aging
| Parent |
| Process in developmental biology |
| Subordinate |
| Cell aging organ aging aging of multicellular organisms |
| Gene Ontology |
|---|
| QuickGO |
The aging is a progressive, irreversible biological process of most multicellular organisms , which gradually to the loss of healthy body and organ functions and finally to biological death leads. Aging is by far the most important risk factor for various diseases such as cancer , coronary artery disease , Alzheimer's disease , Parkinson's disease and chronic kidney failure . The maximum lifetime that an individual can achieve is significantly limited by aging.
Aging as a physiological process is an elementary part of the life of all higher organisms and one of the least understood phenomena in biology . It is generally accepted that a number of different highly complex, in many cases still unexplained mechanisms are responsible for aging. They influence and limit the lifespan of biological systems such as cells , the organs , tissues and organisms built from them. There are many different answers to the question of why organisms age ( aging theories ) , but to this day there is no scientifically accepted comprehensive answer.
The Gerontology , also age and age Swiss stem called, is the science of human life in old age and the aging of the people. The basic biological discipline - without focusing on the human species - is biogerontology .
Definition and demarcation
(1) Aging in progeria (premature aging)
(2) Accelerated aging due to risk factors such as high blood pressure, tobacco smoking, etc. ä.
(2A) after the acute event such as a stroke, without therapeutic measures
(2B) In the case of a therapeutic measure after an acute event an improvement in the vitality and lifespan can be achieved.
(3) A rapid functional impairment with a long phase of disability and care dependency, as is typical in the case of dementia
(4) An example of "normal" aging with only minor impairments even in old age
(5) An ideal-typical aging process
There is no generally accepted scientific definition of aging itself. A broader, more recent definition regards any time-bound change that occurs in the course of an organism's life as aging. This includes both the maturation processes in childhood rated as “positive” and the degenerative phenomena seen negatively in old adults. Derived from this definition, the aging of higher organisms begins immediately after the union of the sperm cell and egg cell and leads to its death. Other gerontologists define aging only in terms of negative changes in an organism over time, for example the loss of function of organs or aging ( senescence ) after growing up ( adolescence ). The German physician and founder of gerontology, Max Bürger , defined aging in 1960 as an irreversible time-dependent change in the structures and functions of living systems . The totality of physical and mental changes from the germ cell to death is called biomorphosis according to Bürger . Which changes can be attributed to aging, however, leaves a lot of room for interpretation. The American gerontologist Leonard Hayflick defines aging as the sum of all changes that occur in an organism during its life and lead to a loss of function of cells, tissues, organs and ultimately death . For Bernard L. Strehler , the aging of a multicellular organism is defined by three conditions:
- Universality : The processes of aging are present in all individuals of a species with the same regularity.
- System immanence : Aging is a manifestation of life. The processes of aging also take place without exogenous factors.
- Irreversibility : aging is always one-way. The changes that take place are irreversible.
Beyond these scientific definitions, aging in humans is a socially complex, multi-dimensional passage through the life span from birth to death. The genetic disposition and the biological changes are the central element of the complex interaction between humans and the environment. The processes involved in aging are subject to subjective, biological, biographical , social and cultural evaluations. Aging itself is a phenomenon with both biological and psychological and social aspects.
In common parlance, aging is largely associated with negative changes, deterioration, deterioration and degeneration of sensory and physical abilities. These changes are better represented as senescence . The term aging should only be used for inanimate matter.
The term age mostly refers to the period of life of older people, that of the "old", and the result of growing old. In contrast, aging is primarily about the processes and mechanisms that lead to old age and that underlie growing old and being old.
- See also: Age as a phase of human life at the end of life, especially the image of old age .
Primary and Secondary Aging
A distinction is made between two forms of aging, primary and secondary aging.
- Primary aging , also called physiological aging, is caused by cellular aging processes that take place in the absence of disease. This form of aging defined for an organism's maximum achievable lifespan (also known as maximum achievable Age ', Eng .: maximum attainable age ). In humans this value is around 120 years (see also: oldest person ) and is provided with the Greek letter ω ( omega , symbol for the end). Other authors put ω at 122.45 years. This is the age Jeanne Calment reached at the time of her death and the highest verified age of any person to date . So far, there are no evidence-based agents (e.g. drugs ) or other treatment methods known that can delay or even prevent primary aging in humans. In various animal models , primary aging could be delayed by certain measures, such as calorie restriction or the administration of rapamycin .
- As a secondary aging on the other hand refers to the impact of external influences which shorten the maximum possible lifespan. These could be illnesses , lack of exercise , malnutrition or the consumption of addictive substances . Secondary aging can thus be influenced by lifestyle .
The subject of this article is essentially primary aging. In practice, the two forms of aging cannot always be clearly distinguished. The Gerontology is the age and age Swiss shaft and treated accordingly all aspects of aging. The biogerontology deals with the biological causes of aging. The geriatrics , however, is the study of the diseases of old people.
Senescence
Senescence ( lat. Senescere , 'to get old', 'to age') is not a synonym for aging. Senescence can be defined as an age-related increase in mortality (death rate) and / or decrease in fertility (fertility). Aging can lead to senescence: Senescence is the degenerative phase of aging. Only when the harmful effects accumulate gradually and slowly should one speak of senescence. Often, however, it is not possible to clearly distinguish between aging and senescence . The beginning of senescence is usually placed after the end of the reproductive phase. This is an arbitrary definition that does not do justice to what happens in different species. Vertebrates show phenomena of senescence such as the accumulation of the age pigment lipofuscin while they are still fertile and water fleas lay fertile eggs until they die despite senescence. A typical characteristic of senescence is the increase in the mortality rate over time.
Many age-related changes in adult organisms have little or no influence on vitality or lifespan. This includes, for example, the graying of the hair due to a reduced expression of the catalase CAT and the two methionine sulfoxide reductases MSRA and MSRB .
The aging of cells (cell aging) is called cell senescence .
Life expectancy and life potential
Both the average life expectancy and the maximum achievable life span ω are very different from organism to organism. Mayflies and Galápagos giant tortoises are extreme examples. The statistically determined life expectancy of an individual is considerably lower for every organism than the maximum life span. The catastrophic death through illness, accidents or predators (predators) means that most organisms in the wild do not come within the range of their value for ω. Only a small proportion of the deaths are age-related. In humans, an increasing convergence of the mean life expectancy of the population with the maximum life span can be observed over their development history, especially over the last 100 years.
Non-biological forms of aging
In addition to biological aging, there are other forms of aging in humans. This includes psychological aging . This is understood to mean the changes in cognitive functions , experiences of knowledge and subjectively experienced demands, tasks and possibilities in life. Aging can also lead to strengths, such as area-specific experiences, strategies for action and knowledge systems.
With social aging , the changes in the social position that occur through reaching a certain age or a certain status passage are defined. Retiring from working life and entering retirement age is the status passage in industrial society with which social aging begins. The aspects of social aging deal with, among others, the disengagement theory (the self-determined withdrawal from social contacts), the activity theory and the continuity theory of aging . The World Health Organization (WHO) has been promoting the attempt to maintain skills in aging and old people and to make them effective in the form of participation through the concept of active aging since the 1990s .
Organisms unaffected by aging
Aging is a process that accompanies many higher organisms throughout their lives and can ultimately lead to their death. Many organisms with differentiated somatic cells (“normal” diploid body cells ) and gametes (germ cells, i.e. haploid cells) with germ line age and are mortal .
Perennial plants are an important exception here, as they are potentially immortal through vegetative reproduction . In the plant kingdom there are a multitude of species that - according to the current state of knowledge - do not age. For example, a common oak that is over a thousand years old produces leaves and acorns of the same quality every year. If the tree dies, it is due to external influences such as fire or fungal attack.
Many lower organisms that do not have a germline do not age and are potentially immortal . One also speaks of a somatic immortality . These potentially immortal organisms include the prokaryotes , many protozoa ( e.g. amoebas and algae ) and species with asexual division (e.g. multicellular cells such as freshwater polyps ( hydra )). In fact, however, these organisms do have a limited lifespan. External factors, such as ecological changes or predators , limit life expectancy considerably and lead to so-called catastrophic death.
Of particular scientific interest are higher organisms which, after they have become adult , appear not to age further and show no signs of senescence. This is known as "negligible senescence" (English. Negligible senescence ). Such organisms are characterized by a rate of reproduction and death that is constant over age; In contrast to aging organisms, their specific mortality remains constant with increasing age. For some species these properties are suggested. These include, for example, the rock bass Sebastes aleutianus (English Rougheye rockfish ), of which a 205-year-old specimen has been identified, and the American pond turtle ( Emydoidea blandingii ). Some authors also see a negligible senescence in the naked mole rat - as the only mammal so far. In general, it is very difficult to prove that a higher species exhibits negligible senescence. Extremely old specimens are very rare, as no species is immune to catastrophic death. Data from animals in captivity have not been available for a sufficiently long period. The postulate of negligible senescence was only made in 1990.
The jellyfish Turritopsos Nutricula is said to be able to renew its cells when its vital functions decline. According to the researcher Ferdinando Boero, once this state has been reached, it can sink to the sea floor and regenerate its cell volume there. She lives without limitation, unless she is killed, for example, by other animals.
In the case of non-aging organisms, the probability of death is independent of age and time. The age-specific mortality rate , i.e. the number of deaths in a certain age group, is therefore constant. The survival curve of non-aging organisms is a straight line in a semi-logarithmic representation .
In the case of "immortal" bacteria or yeasts that split , the daughter cells are largely identical copies of the parent cells. It is debated whether one can really speak of immortality in such cases, since two new individuals emerge. Regardless of this philosophical question, such cells must not show any signs of aging: These would be transferred to the daughter cells, accumulate from generation to generation and ultimately wipe out (eliminate) the entire species. In multicellular cells ( Metazoa ) and budding yeast, on the other hand, aging can take place in the somatic cells or mother cells. The germ cells that are important for the preservation of the species - daughter cells in the case of yeast - must remain intact.
Model organisms in aging research
For basic research on the processes and causes of aging, mainly short-lived species such as fruit flies, roundworms and color mice are used. For example, the effects of potential active substances, diet and other external living conditions as well as manipulations of the genome are examined. When biogerontological experiments began to be carried out with very simple organisms in the 1980s, it was not yet foreseeable that this was - from a genetic point of view - a stroke of luck. It was not until the beginning of the 21st century that the decoding of the genome of various model organisms and humans revealed that a very high number of genes in these species matched. In particular, the genes that have a significant influence on aging are partially highly conserved and enable the research results to be transferred to other species. However, human aging processes that take place over many decades cannot be adequately mapped. For example, fruit flies have different age-related diseases than humans.
Some research groups take a different approach. They study the genome and living conditions of species that are comparatively old. These include in particular the naked mole rat ( Heterocephalus glaber ) and the Little Brown Bat ( Myotis lucifugus ), a North American bat species from the mouse- eared species . The mouse-sized naked mole-rats outperform rodents of the same size with a maximum life span by a factor of nine. They do not have an age-related increase in mortality that is otherwise present in any other mammal. In addition, naked mole rats show only minor age-related changes over their entire lifespan. The reproductive females have constant fertility up to the third decade of life. So far, spontaneous tumors have not been observed in any naked mole rat. The bats, which weigh a maximum of 14 g, can live up to 34 years in the wild. The genome of the bowhead whale , which can live for over 200 years, is also of scientific interest.
In biogerontology, several animal models have become established for research into aging. In addition to the roundworms and fruit flies described below, these include baker's yeast ( Saccharomyces cerevisiae ) and the color mouse.
Caenorhabditis elegans
The adult roundworm Caenorhabditis elegans consists of only 959 somatic cells, all of which are post-mitotic , i.e. no longer capable of dividing. In 2002, more than 50 different mutants were known that show slower primary aging than the wild type and thus achieve a longer life span. Some of the genes identified have a positive effect on the stress resistance of the test animals; others act directly on the metabolic rate and lower it. The influence on the metabolic rate fits directly with the predictions of the disposable soma theory (see below). A mutation in the clk-1 gene (a clock gene in mitochondrial DNA ) of C. elegans can increase its mean lifespan by 50%. In addition to mutations in the mitochondrial DNA, the aging of C. elegans can also be significantly reduced by low temperatures - which directly lower body temperature -, calorie restriction and a reduced expression of insulin or insulin-like growth factors . If all four measures are used at the same time, the life-prolonging effects add up. However, in terms of the mechanism of action, only the calorie restriction and the reduction in temperature are obviously independent parameters.
New studies have shown that the mitochondria-mediated lengthening of life in C. elegans is directly related to the energy metabolism and can be passed on from tissue to tissue, whereby the metabolism of the cell (without mitochondrion) remains unaffected.
Drosophila melanogaster
.jpg)
The fruit fly Drosophila melanogaster is a frequently used model organism for research into the processes of aging. The genome, which is located on only four chromosomes, was completely sequenced as early as 2000 and the time interval between a generation sequence is very short at nine to 14 days.
By a mutation in the mth gene (engl. Methuselah , dt. Methusalem ) increases the life expectancy of these species by 35%. The mutated animals are significantly more resistant to various forms of stress. Also, a partial deactivation of genes that are directly involved in the electron transport chain engage in the mitochondria (ETC genes, engl. Electron transport chain ) increases the life expectancy of D. melanogaster .
Biomarkers for aging
Aging is a dynamic process that not only depends on the species, genotype and phenotype , but also on external influences (secondary aging). For populations , statements about aging can be made from the survival and mortality rates . The death of the individual serves as a very simple “ biomarker ”. This, in turn, can have very different individual causes, including those that are not age-related, which is why death does not provide an individual statement about the current biological age , as it were as a current status. The chronological age of an organism can only provide limited information.
Biomarkers of aging are characteristics that allow a better prediction of the actual functioning of the organism at an older age and are more reliable than chronological age. In other words, the biomarkers of aging reveal true "biological age" in a way that chronological age cannot. Validated biomarkers of aging make it possible to test whether certain interventions are useful for extending lifespan by observing changes in the biomarkers that indicate a low biological age. Ideally, the biomarkers of aging should only examine the biological process of aging, not the predisposition to a particular disease. The measurement of the biomarkers should have as little negative impact on the organism as possible, be reproducible and the results for a short period of time must be directly related to the entire life of the organism. An international research group has discovered a molecular signature for the first time, which determines the biological age and can be determined by a blood test.
The question is, how can the biological age be measured or the progression of aging determined in an individual? The difficulty with this is that aging is a complex, multi-dimensional process. Aging can proceed very differently in the individual dimensions. For example, as people age, memory performance can decrease, but experience-based knowledge can increase at the same time. Physical impairments can be compensated through psychological adjustments in such a way that the well-being remains subjectively stable. Aging can also be very individual in humans.
External, hardly quantifiable, signs of aging in humans are, for example, posture, gait, elasticity of the skin ( wrinkles ) as well as skin and hair color. One of the endeavors of gerontology is to be able to measure age-related functional losses in a standardized manner. This can be done, for example, using biomarkers or the so-called frailty index . Other tests record a variety of different measurement data such as blood pressure, vital capacity, pulse frequency before and after physical exertion, oxygen content in the blood, hand strength, joint mobility, hearing and vision, reaction times, concentration and coordination skills, and memory performance. A frequently used biomarker is lung function . With increasing age, the breathing capacity and the blowing speed decrease. The aim of these tests to determine biological age is to identify risk factors at an early stage and to initiate possible preventive measures. An example of such a standardized procedure is the age scan .
The usefulness of these methods, and the biomarker for aging in general, is controversial. Some authors question its sense, as the nature of aging is still largely unclear. In addition, many processes of aging take place independently of one another in an individual. For example, there is no relationship between graying hair and age-related hearing loss. The rate of aging varies from person to person. Some of the biomarkers are purely disease-associated and a correlation to aging itself is questionable. For example, if lung function is diagnosed, the mortality rate over the next 4 to 20 years is higher than if it is normal. The main causes of death, however, are cardiovascular and malignant and not pulmonary in nature, so that the critics ask whether the measurement of lung function is not more a predictor for the two disease groups cardiovascular and cancer than for aging. In addition, the predictive power of the measured lung function with regard to mortality is no better than the chronological age of the person concerned. Premature mortality from certain diseases can be predicted, but longevity cannot.
Biological clocks, such as the epigenetic clock, are promising biomarkers of aging. Steve Horvath developed a marker that uses the methylation status of DNA to provide information about the age of various tissues and cell types.
In the case of model organisms kept in laboratories, there is currently no reliable biomarker with which individual life expectancy can be predicted. However, it has been shown, for example, that the number of CD4 and CD8 T memory cells (including CD4 cells with P-glycoprotein) and naive T cells provide a good prediction of the expected lifespan of genetically heterogeneous middle-aged mice.
Pathology of aging
Aging is a physiological process and not a disease. The British Medical Journal published a 'List of Non-Diseases' in 2002. The readers chose it, aging '( aging ) to the first digit of the non-disease. Some protagonists from the anti-aging movement , such as Aubrey de Gray , argue that aging is a disease that needs to be combated. The US Food and Drug Administration (FDA) does not see aging as an indication . That is, according to the FDA, aging is not a condition for which any particular medical measure is appropriate.
Aging is not necessarily associated with disease. However, age is an important risk factor for health. The reduced adaptability and resistance of the organism associated with aging leads to an increased susceptibility to malfunction. Chronic diseases are on the increase, often occur together ( multimorbidity ) and increase mortality. The death rate increases exponentially with the increase in physical deficits. Typically, the accumulation of these deficits accelerates in older people before they die.
Aging is currently mostly not a primary cause of death : Cellular changes caused by aging and the resulting organic changes increase the likelihood of dying from an illness of old age or an illness that is not critical at a young age. Typical age-related diseases are many cardiovascular diseases , diseases of the brain vessels, bronchitis , type II diabetes mellitus , osteoporosis , osteoarthritis and cancer . Age-related diseases are one of the main reasons why the maximum life span can only very rarely be reached.
From a physiological point of view, aging is characterized by a slow and progressive loss of various body functions, which affects all organ systems. The point in time when these functions cease to exist varies greatly from one organ to the next. In humans, for example, the glomerular filtration rate (GFR) of the kidneys (kidney performance) already decreases in childhood, while the speed of nerve conduction only decreases after the age of 30. In the area of internal medicine , in addition to the GFR, the decrease in the vital capacity of the lung function, the maximum oxygen uptake capacity , the tidal volume , the blood flow in the brain and liver and the heartbeat volume can be observed. The most important neurological change is a declining memory function . The endocrine system produces fewer hormones . The digestive tract reduces the secretion of digestive enzymes and the utilization of nutrients decreases - as does the peristalsis of the intestine . In addition to these organ-specific changes, there is a systemic loss of structural proteins , which manifests itself primarily as a loss of muscle mass , connective tissue and subcutaneous fat.
The following table gives an overview of the most important age-related changes.
| Organ / system | Age-related changes | Possible consequences |
|---|---|---|
| Sense organs | Eyes: Presbyopia , lens opacity | decreased accommodation , decrease in vision |
| Ears: high frequency losses (presbycusis) ( depending on the environment) | limited word discrimination in background noise | |
| Endocrine system | impaired glucose tolerance | increased blood sugar level in acute illnesses |
| Decrease in vitamin D absorption and activation in the skin | u. a. Osteopenia | |
| Decrease in thyroxine excretion and production | reduced thyroxine dose necessary in hypothyroidism | |
| Decrease in blood estrogen levels in women | Menopause , menopause | |
| Decrease in testosterone - estradiol - quotient in men | ||
|
Cardiovascular system and respiratory tract |
decreasing adaptation of the arteries, increasing systolic and diastolic blood pressure (depending on the environment and lifestyle) | orthostatic problems |
| delayed blood pressure regulation | ||
| Limitation of the heartbeat volume | Stress can only be compensated by increasing the heart rate | |
| Decrease in lung elasticity | decreasing oxygen partial pressure | |
| Genitourinary tract | Perception of thirst decreases, the perception of satiety increases | increased risk of desiccosis |
| Urinary bladder : tone increases, capacity decreases | more frequent urination , usually with a shortened urge time; increased water loss | |
| Kidney : glomerular filtration rate decreases | insufficient elimination of drugs and drugs | |
| benign prostatic hyperplasia (benign enlargement of the prostate ) | nocturnal urination , urinary retention | |
| Blood and immune systems |
Decrease in bone marrow reserve (suspected) | decreased immune response |
| decreasing function of T-lymphocytes | ||
| Increase in autoantibodies | ||
| Musculoskeletal system | Decrease in muscle mass | reduced mobility and strength |
| Skeletal muscles decrease | ||
| Ligaments , tendons, and muscles are less flexible | ||
| Decrease in the mineral content of the bones | increased susceptibility to fractures | |
| the mobility of the joints decreases | ||
| Nervous system | Decrease in ganglion cells and neurotransmitters | Impaired metabolic processes;
Slowed down information processing |
| Reduction of phospholipids in cell membranes | increased intake of harmful substances | |
| Impairment of the function of the receptors | decreased absorption of glucose | |
| Loss of neurons in the hippocampus by up to 20–30% by the age of 80 | decreased memory performance | |
| Decreased electrophysiological activity |
In Germany, as in many other industrial nations, life expectancy has almost doubled over the past 100 years. The main reasons for this are improved hygiene conditions , a reduction in the death rate of newborns and more effective therapies and prevention of a large number of acute diseases. In the United States in 1900, the three leading causes of death were influenza / pneumonia , tuberculosis, and gastroenteritis / diarrhea, accounting for 31% of all deaths . In 2002 in the same country with heart disease , cancer and stroke , three clearly age-associated diseases were the most common causes of death, accounting for 61% of all deaths. The consequence of this development is that more and more people are getting older. However, these measures have not changed the maximum life span of around 120 years. The gerontologist Leonard Hayflick assumes that this value has remained constant over the last 100,000 years of human history.
Genetic influences
_on_cloth,_close-up_from_front.jpg)
Most scientists justify the extreme differences for ω in the individual species with a genetic determination, which is, however, controversial. When programmed aging refers to the genetically controlled Biomorphose (also ontogeny ) and differentiation. The genetic control for these two processes is indisputable. In contrast, the discussion as to whether there is programmed senescence and whether this is the cause of the differences in ω between individual species is very controversial .
There is widespread consensus that within a species, aging and life expectancy are influenced by certain genes. In humans, both, apart from lifestyle and other external influences, are partly determined by genetics. The proportion of genetic disposition in life expectancy is estimated at 20 to 30%. Statistically speaking, the probability of death (mortality rate) increases exponentially in humans up to around the age of 92. For even older age groups, it flattens out again. The increase in mortality is slowing down ( late-life mortality deceleration ), but is by no means decreasing . This means a deviation from the “law of mortality” formulated by Benjamin Gompertz in 1825 ( Gompertz-Makeham model ). Women and men over the age of 92 form a separate group with regard to mortality. The genetic make-up (“age genes”) and the immune system, which is important for recognizing and destroying cancer cells, are generally held responsible for this phenomenon . The influence of genetic makeup on longevity has been clearly demonstrated in humans and a large number of model organisms. Accordingly, children with very old parents reach an older age on average than people whose parents died earlier. It is known from research on twins that the mean difference in lifespan of dizygoti twins is twice as high as that of genetically identical identical twins .
Conversely, the genetic disposition with regard to aging cannot be used to infer a genetic program aging or a specific “aging gene” that promotes the aging of an organism. Such a disadvantageous gene would have long since been selected by evolution after a mutation that would render it functionless - if it did not offer an advantage for the entire species. There are no genes for aging, at least in humans. The genetics of aging are highly complex. Aging is caused by the continual accumulation of somatic damage resulting from the body's limited investment in its maintenance and repair. Repair mechanisms, such as DNA repair and the fight against oxidative stress , are controlled by genes, which thereby influence the longevity and aging of the organism. There may also be adaptations to the consequences of aging: in rats, the expression of megalin in the kidneys is increased with age, probably to compensate for the increasing number of defects in the large protein.
In natural habitats, the mortality of organisms - with the exception of humans - is mainly due to external causes (catastrophic death). Aging is a side effect that rarely occurs in the wild, as most organisms die before that. From this it can be deduced that a genetic “death program” as a result of evolutionary selection is very unlikely. Aging is less due to deterministic (future events are determined by preconditions) than to stochastic processes (temporally ordered, random processes).
In some seminal organisms there is a form of programmed death (reproductive death). The best known is the life cycle of the Pacific salmon ( Oncorhynchus ), which hardly or no food at all during their spawning migration. The body is subject to significant hormonal changes and the animals perish shortly after they have reproduced in the spawning waters. Similar behaviors are known from octopuses ( Octopoda ). The males of the Australian broad-footed pouch mice ( Antechinus ) die after mating, ultimately caused by an overproduction of testosterone and cortisol .
In 2018, scientists from the German Cancer Research Center (DKFZ) in Heidelberg discovered a protein called TXNIP (thioredoxin-interacting protein), which is a central control point in the aging process. It controls the life span of an individual - from the fly to the human.
Mutations That Can Affect Aging
The aging phenomenon has a genetic background. The roundworm Caenorhabditis elegans has a maximum life span (ω) of a few weeks. For ω, humans reach a value of around 120 years. Both species have a common ancestor in their tribal history . If one assumes that this ancestor had a value for ω similar to that of C. elegans , this means that over the course of millions of years evolution through mutation and selection has increased the value by over 2000 times. One of the problems studied by biogerontology is to identify the genes responsible for this. In the laboratory, the value of ω can be shortened or lengthened in model organisms, such as C. elegans , by specifically activating or deactivating certain genes ( gene knockin or gene knockout ). In the wild, spontaneous mutations can affect genes that have an immediate impact on aging. This can be observed in humans as well as in other organisms.
Progeria
The term progeria summarizes some extremely rare hereditary diseases that are characterized by the aging of the affected patients accelerated by a factor of five to ten. These diseases are caused by spontaneous point mutations. The so-called Hutchinson-Gilford syndrome affects around 40 children worldwide with a mean life expectancy of around 14 years. Some of the typical age-associated hereditary diseases such as heart attacks or strokes are particularly common in children with progeria and are the main cause of death. In contrast, the risk of developing cancer or Alzheimer's disease is not increased. Progeria is therefore not a disease that corresponds directly to accelerated aging. Because of these differences between progeria and normal aging, there is a controversial discussion as to whether progeria is really a form of accelerated aging. At the molecular biological level, sufficient data have now been obtained to confirm the hypothesis of accelerated aging, at least for Hutchinson-Gilford syndrome. For example, parallels were found in the instability of the genome and telomere degradation.
Dyskeratosis congenita is a special form of progeria . In this very rare hereditary disease, the function of the enzyme telomerase is directly or indirectly affected by a mutation. Due to the limited activity of telomerase, the telomeres at the ends of the chromosomes of the affected patient are broken down more quickly. Among other things, the patients age faster than normal, have fragile bones, underdeveloped testicles and show a predisposition to cancer.
Dwarf mice
Dwarf mice are mutants of the Mus musculus species ( house mouse , or their cultivated form, color mouse , genus : mice) and should not be confused with the dwarf mice ( Micromys minutus ) from the Micromys genus . Due to a spontaneous gene mutation, these animals show a deficit of growth hormones . Thus, the production can, for example, insulin-like growth factors (IGF-1), thyrotropin ( TSHB ) and prolactin ( PRL ) may be reduced by over 99%. For the Dwarf mice, this mutation means that they age much more slowly and their lifespan is 68% (females) and 49% (males) higher than in animals of the same species without mutation. As a trade-off (compensation) in these animals - according to the life history theory - a reduced growth and lower fertility can be observed. The females of the Ames and Snell Dwarf mice are sterile and the males have low fertility. The body weight is 67% less than that of the wild type .
Since the late 1980s, such mice have been specifically produced in the laboratory using gene knockout . In addition, a large number of genetic modifications were made to mice and other organisms, in which the values of ω could be increased or decreased.
For example, mice in which the apoptosis inducer p66Shc was switched off have a 30% longer life expectancy, which is caused by a higher resistance to oxidative stress .
FOXO3
A working group led by the Kiel scientist Almut Nebel analyzed the genome of 388 centenarian Germans in comparison with 731 younger people. They found that a certain genotype of the FOXO3 gene is particularly common in centenarians. In the press, terms such as longevity gene , age gene , old man's gene or methuselah gene were used. A year earlier, another working group had already found that the FOXO3 genotype has a significant influence on a person's life expectancy. Studies in other countries come to the same conclusion.
The gene product of FOXO3 acts as a transcription factor directly on the gene expression of sirtuin-1 . Sirtuin-1 is increasingly released during the calorie restriction, which causes delayed aging and a longer life expectancy in a large number of model organisms. Sirtuin-1 in turn inhibits mTOR ( mammalian target of rapamycin ) and can be activated by certain substances such as resveratrol .
Gerontogenic
In the two model organisms Caenorhabditis elegans (roundworm) and Drosophila melanogaster ( fruit fly ), which are important for biogerontology , several genes could be identified which - if deactivated - can significantly increase the maximum life expectancy of these animals. Such genes are called gerontogens . They are considered evidence that aging is regulated by specific genes.
Aging theories
Aging is the result of stochastic processes and a genetic program. It starts on the molecular level and continues on all superordinate levels (levels, in green) until death. In the middle (in red) the results of the aging processes are shown. The right column lists the measurable parameters.
To this day, there is no generally scientifically accepted answer to clarify the question of why all higher organisms age. For higher organisms - including humans - there is no natural law that inevitably “prescribes” this process for aging and the resulting death.
The American evolutionary biologist George C. Williams formulated this in 1957 with the words:
"It is really surprising that - after the miracle of embryogenesis has been accomplished - a complex metazoon fails because of the seemingly much simpler task of simply maintaining what has already been created."
The causes of primary aging are very complex and complex. As a result, there were around 300 different theories about aging in 1990, but none of them are able to explain aging alone. The aging theories can be divided into two main groups: evolution and damage theories. At present, most researchers see the theories of evolution as the best model for explaining why humans and other organisms age, even if these theories still have some weaknesses.
The rate of aging determines the maximum life expectancy of an individual. There are slight differences within a species and considerable differences between individual species. For example, there is a difference of almost two orders of magnitude between the two mammals, the house mouse and the bowhead whale . The structure of the body cells, the elementary building blocks of both species, is largely the same. From a functional point of view, there are hardly any differences between the organs and tissues made up of cells. The decisive differences lie in the genome, even if this shows a very high degree of similarity in its entirety.
The maximum life span is determined by a large number of very different genes. These genes are obviously not selected and they do not directly affect the process of aging. Aging itself is essentially the result of the accumulation of somatic damage, as only limited resources (energy) are used to maintain the soma. These resources are limited and need to be divided between self-preservation, growth and reproduction. In addition, there are pleiotropic genes that are beneficial for the organism at a young age, but have detrimental effects with increasing age.
The scientifically based theories of aging are very controversial in the scientific community . So far there is no general consensus. The opinions of the various camps differ widely. For example, the two renowned British researchers Sir Richard Peto and Sir Richard Doll even come to the extreme statement regarding aging:
“ There is no such thing as aging - old age is associated with disease, but it does not cause it. "
The majority of gerontologists do not share this opinion. On the other side of the extremes are gerontologists who reduce aging to simple damage theories such as telomere breakdown, oxidative damage from free radicals, or mitochondrial aging.
The following are the main categories of aging theories.
Damage theories
Harm theories are among the most popular and widely spread theories of aging. According to them, aging is a process caused by the sum of damage caused by destructive processes such as oxidation, wear and tear or the accumulation of harmful by-products of metabolism. Organisms then age - to put it simply - similar to a car or an exterior color. The most common theory for this is the on the rate-of-living theory -building free-radical theory of aging by Denham Harman . It also serves as an explanatory model for the development of diseases such as cancer, arteriosclerosis, diabetes mellitus and Alzheimer's. After initial rejection, the theory became immensely popular in the 1990s. Antioxidants , which are able to scavenge free radicals in the laboratory as radical scavengers , have been seen as potential active substances against aging and age-related diseases. This euphoria has now subsided - at least in gerontology. There are a number of experimental results in support of the free radical theory. In comparative studies of different species, it was found that life expectancy correlates very strongly with the ability of cells to withstand oxidative stress. On the other hand, some basic experimental observations are completely contrary to this theory. For example, high levels of oxidative damage were found in the cells of the comparatively long-lived naked mole rat. A markedly reduced expression of essential elements of the antioxidant system , for example manganese superoxide dismutase (MnSOD), induced by gene knockout , increases the incidence of cancer, but does not accelerate the aging of the test animals. In addition, in a large number of clinical studies no positive effects could be found when taking antioxidants. Anti-aging products that rely on the antioxidant effect probably have no effect on humans. Michael Ristow's working group goes one step further and was able to show that free radicals are necessary to set mitohormesis in motion. As a result, the cell achieves an increased defense capacity against free radicals in a kind of "training". Antioxidants, on the other hand, prevent mitohormesis.
According to the error catastrophe (of aging) theory (AE: error catastrophe (of aging) ), first developed by Leslie Orgel in 1963 , there are two types of proteins within a cell: those that carry out metabolic functions and those that are involved in information processes. Damage in a metabolic protein is therefore not relevant for the cell, since it is just one wrong protein among many other (right) ones. Errors in the molecular 'copying processes' ( transcription and translation ) of proteins, which in turn are involved in protein synthesis, could trigger a whole cascade of errors in the cell. The theory is that the number of errors in the amino acid sequence of a cell's proteins, which increases with age , is ultimately the cause of aging. The accumulation of errors ultimately leads to cell death. So far there is no experimental evidence for the failure-catastrophe theory; a number of test results speak against the theory. However, it was also not Orgel's intention to set up a new aging theory with his theory.
As descriptive theories, harm theories offer an explanation for the processes involved in aging, but no answer to why organisms age. In addition, the comparison with the aging of a dead object is wrong in the approach: Organisms represent dynamic systems with a constant exchange of substances; they struggle against entropy throughout their lives ( Henri Bergson ).
In about seven years the human body replaces 90% of the components it is made of. Body cells have a variety of repair mechanisms. For example, more than 55,000 single-strand breaks, 12,000 base losses, 200 deaminations and 10 double-strand breaks occur in the genome of each individual human body cell, which are largely repaired by appropriate mechanisms. Dead cells in organs can be replaced by newly formed ones and some species are even able to completely restore lost body parts. The theories of damage do not provide an answer to the question of why these undoubtedly existing repair processes are only insufficiently used in many organisms.
Telomere Hypothesis of Aging
The telomere hypothesis of aging builds on the Hayflick limit found by Leonard Hayflick in 1965 . The hypothesis was put forward by Calvin Harley in 1991 . According to this hypothesis, the telomeres have a decisive function for the aging of a cell and thus for the entire organism. From the time of birth, the telomeres at the chromosome ends shorten roughly parallel to age: the more cell divisions a cell has undergone, the shorter the telomeres are. Elizabeth Blackburn discovered that telomerase allows an organism to restore telomeres to a limited extent. However, environmental influences can also shorten the telomere length. Towards the end of aging, the rate of cell division slows down, and above a certain telomere length, the cell no longer divides at all. She becomes senescent. The point in time at which a cell reaches this stage depends on the one hand on the cell type and on the other hand on the species.
The shortening of the telomeres can be observed in a large number of mitotically active tissues. These include above all the skin fibroblasts , the peripheral blood cells, the epithelia of the gastrointestinal tract, cells of the adrenal gland in the kidney cortex , the liver and the spleen . In mitotically inactive organs such as the brain and the heart muscle , the telomere lengths are largely constant over the entire period of aging. For a number of chronic diseases of various organs, increased telomere shortening has been demonstrated. For example in the endothelium in atherosclerosis and in the hepatocytes in chronic liver diseases.
There is a correlation between the number of cell divisions limited by the telomere length and the maximum life span ω of an organism. The proliferation potential (cell division capacity) is higher in long-lived organisms.
| species | ω [a] |
maximum number of cell divisions |
|---|---|---|
| Galápagos giant tortoise | 175 | 125 |
| human | 110 | 60 |
| Domestic horse | 46 | 82 |
| Domestic chicken | 30th | 35 |
| Domestic cat | 28 | 92 |
| kangaroo | 16 | 46 |
| American mink | 10 | 34 |
| House mouse | 4th | 28 |
Dolly the sheep is seen as evidence for the telomere hypothesis of aging . Dolly was cloned from a somatic cell in a five year old sheep . In the donor sheep, the telomeres in the removed cell were already considerably shortened due to a large number of divisions. Dolly died well before the median life expectancy of a sheep and showed an early onset and rapid process of aging.
In patients with Werner syndrome , a rare hereditary disease with accelerated aging, the cells can only divide about twenty times on average and then become senescent.
In the model organism Caenorhabditis elegans , on the other hand, telomere length has no influence on aging. The long-lived daf-2 and the short-lived daf-16 mutants can have short or long telomeres, neither of which changes the life span of the animals.
Cell aging, cellular senescence - cancer or aging
Until the 1950s, aging was understood as the slow wear and tear of cells, the tissues and organs formed from them and the body built from them. The molecular causes of aging were not recognized or understood. After it was possible to cultivate mammalian cells in vitro , it became possible to analyze and understand the molecular changes. It was not until 1961 that Leonard Hayflick's experiments revealed that normal human cells cannot divide as often as they want and are not immortal. Human fibroblasts from fetuses can divide 60 to 80 times in a cell culture ; the same cells from an older adult, however, only 10 to 20 times. This process of cell aging is called cellular or replicative senescence . The cells remain in the G 1 phase of the cell cycle , the S phase is no longer reached. The cells continue to function normally, but no longer replicate. Many of these cells are then also fully differentiated , that is, they have taken on their specific final physiological function. The senescent cells are then also resistant to programmed cell death, apoptosis . The number of divisions permitted for a cell is preprogrammed in the DNA via telomeres . In animals with a short life span, the cells can divide less often than in animals with a longer life span.
Not all cells in the body become senescent. If this were the case, there would be no wound healing, for example . Some of the cells therefore do not become senescent: the stem cells . Differentiated cells can form from these undifferentiated progenitor cells. The proportion of stem cells is very high during the embryonic phase and decreases continuously with increasing age. However, they are present throughout life, for example to replace or form cells in the skin, the intestinal mucosa and the immune system. In addition to stem cells, gametes (germ cells) and cancer cells are also excluded from cellular senescence and can - if necessary - divide as often as required.
In addition to reaching the Hayflick limit, cellular senescence can also be activated by irreparable damage to the DNA. This damage can be caused, for example, by reactive oxygen species (free radicals), which can also attack lipids ( lipid peroxidation ) and proteins ( protein oxidation ) within the cells. The resulting reaction products, such as the age pigment lipofuscin, can often only be broken down insufficiently and accumulate in the cell. Depending on the extent of the damage, the cell either becomes prematurely senescent or, in the case of more severe damage - if it is still able to divide - initiates apoptosis. These measures prevent too many damaged cells from accumulating in the organism. The reason for the two measures (premature senescence or apoptosis) is - according to the prevailing explanatory model - that the degeneration of cells and thus the development of cancer cells should be prevented. Senescence is regulated by the two proteins p53 (“guardian of the genome”) and pRB ( retinoblastoma protein ). Defects in the two tumor suppressor genes TP53 and RB1 , which code for p53 and pRB, respectively , can switch off the senescence program and programmed cell death and lead to cancer. Hence, cells that can bypass both the senescence program and apoptosis are cancer cells.
Mice in which the expression of p53 is deliberately downregulated (gene knockdown) therefore very easily develop spontaneous tumors. If, on the other hand, p53 is overexpressed in them , the likelihood of cancer is significantly reduced, as expected. However, this is associated with the effect that the life expectancy of the animals is significantly shortened by early signs of aging, such as osteoporosis and universal atrophy of the organs.
From this fact, some research groups conclude that aging is the price to pay for the extensive avoidance of cancer . TP53 is a tightly regulated gene. Both an excess and a lack of p53 are detrimental to the organism. p53 has pleiotropic properties for the organism : in adolescence it is advantageous for the organism because it prevents cancer, but later it is disadvantageous because it ages more quickly.
Apoptosis and cellular changes
Aging can be understood as a conflict between the 'individual' cell and the 'community' organism. From an evolutionary point of view, the long-term reproduction of the entire organism is more important than the perfect repair of an individual cell. The organism, i.e. the majority of cells, uses programmed cell death - apoptosis - to defend itself against individual cells that deviate from the “norm”. This defense strategy is an essential element in building an organism out of a group of cells.
Cellular senescence and apoptosis are the tools to suppress malignant changes in cells. On the other hand, both processes are inevitably linked to aging. Aging is obviously an antagonistic pleiotropic process to suppress degeneration of cells. The role that apoptosis plays in aging is still largely unclear and controversial. Apparently, significant amounts of muscle fiber cells (myocytes) of the heart muscle and skeletal muscles are broken down by apoptosis processes during aging . This may be caused by mitochondrial damage, for example from oxidative stress.
During aging, the membrane potential, the lipid content and the fluidity of the cells change. The number of mitochondria in the cells decreases. These cellular changes can be found in all mammals.
Inflammatory aging
The increased release of proinflammatory cytokines in older people is referred to as inflammatory aging ( AE : inflammaging ). This release leads to mild systemic and chronic inflammation. This process has been linked to a number of age-related diseases and is itself seen as a cause of aging. Inflammations are - so the hypothesis - helpful for the organism at a young age, since they considerably improve the chances of survival against pathogens , but according to the theory of antagonistic pleiotropy , they are more harmful to the organism in old age. This thesis is supported by the fact that administration of the immunosuppressant rapamycin can significantly extend life expectancy in mice.
From an evolutionary point of view, the survival of an organism is important at least until the end of its reproductive phase. Most organisms (including humans) died before reaching the end of the reproductive phase. The deleterious effects of inflammatory aging were thus very rare. A selection against this age of inflammation, which shortens the life span and which only occurs after the reproductive phase, would therefore not be possible.
Evolution theories of aging
In contrast to proximate theories , such as harm theories , which provide explanatory models for how an organism ages, the theories of aging based on the theory of evolution attempt to answer the question of why ( ultimate theories ). According to these theories, aging is a result of the evolutionary process. The first living things that arose on earth did not age. Aging emerged in the course of evolution as a property of higher living beings.
These theories can explain a number of phenomena associated with aging. Correspondences between theory and experiment could also be obtained in various model organisms .
There is currently no general evolutionary explanation for aging. A trait that limits lifespan and also limits fertility has a negative impact on Darwin's fitness . Even Darwin was aware of this problem and assumed that the limited lifespan of the higher organisms must have a benefit that more than compensates for the disadvantage of aging and the associated death. Darwin could not answer what the benefit is.
Programmed aging
The first evolutionary theories of aging emerged immediately after evolutionary theory in the 19th century. In 1881, the German biologist August Weismann saw aging and - as a consequence - death as a necessity that had arisen out of evolution because it served the survival of the species. According to this, aging ensures that the previous generations are not in competition with their offspring for food and living space. The old make room for the young, so to speak, so that they have better chances in the “struggle for existence”. Weismann argued that immortality was useless to an individual because sooner or later they would be killed anyway by an accident or by the accumulation of injuries that were not fully healed over time. The latter in particular would lead to older organisms that would be less fit than the younger ones. The older would then withhold resources from the younger, which would be better invested in the younger. The death of old organisms as a result of senescence would therefore be a selection advantage for the species.
However, Weismann could not find a Darwinian mechanism for his thesis. In addition, his assumption that organisms cannot show complete healing was a circular argument. Animals of a species that do not reach advanced age as prey in the wild can show various signs of aging in captivity when they have exceeded their mean natural lifespan; even if they never had the opportunity to show these signs of age in the course of their evolutionary history. For these reasons, Weismann gave up his hypothesis a few years later. Nevertheless, Weismann's hypothesis can still be found today in a number of publications outside the field of biogerontology.
The theory of programmed aging has been experiencing a renaissance since the beginning of the 21st century. Studies on model organisms such as baker's yeast have shown that at least in this unicellular organism there is a form of 'programmed and altruistic aging and death' ( programmed and altruistic aging and death ). When about 90 to 99% of the individuals of Saccharomyces cerevisiae have died in a culture, a small mutated subpopulation is created that uses the nutrients released by the dead cells and continues to develop. Because the molecular mechanisms that control aging are very similar in many animal models, it is believed that programmed aging could also be present in higher eukaryotes . As a prime example of the advocates is programmed aging while the Pacific salmon . Several theories of programmed aging have been developed. Some are based on group selection and kin selection , others on evolvability . This adjustment dependent theories (engl. Adaptive theories ) are in contradiction to the subject of the subsequent adjustment independent theories (engl. Non-adaptive theories ).
Classic evolution theories of aging
Natural selection decreases with age. In the wild, due to a variety of factors, very few individuals even reach the realm of aging. For example, nine out of ten house mice die before they are 10 months old, while the same species in captivity reaches an average age of 24 months.
The European robin ( Erithacus rubecula ) has an average mortality rate of 0.6 per year. That means that 60% of the animals die every year. From markings and observations in the wild, it was possible to calculate that only one out of 60,000 robins can come within the range of their previously determined maximum life expectancy of twelve years. It is still largely unclear in which range the maximum life expectancy of a robin really lies. Other birds do more than double this value with no signs of senescence. A long service life means high biological costs , that is, a greater need for energy. Most species have therefore "traded" a long lifespan for a high reproductive rate at a young age. Their reproduction follows the so-called r-strategy . This means that they invest their resources in a large number of offspring and less in their own growth and repair mechanisms to maintain the soma. But even the - relatively few - species that follow the K strategy rarely reach their maximum lifespan ω in the wild. Chimpanzees ( Pan troglodytes ) live on average 23 (males) and 30 (females) years old in captivity. 20% even reach an age of 50 years. In contrast, life expectancy in the wild for the closest human relatives is only eight years, and almost no specimen is 50 years old. The survival curve of the first humans ( Homo ) was largely the same as that of today's chimpanzees. A further investment in growth and, above all, in maintaining homeostasis , which was favored by the selection, could not take place - the great majority of individuals died catastrophically before they came into the area of aging. In general, in all species in the wild, only very few individuals reach old age to build up sufficient selection pressure against aging. This is also known by a Selection shade (Engl. Selection shadow ).
According to the theory of evolution, species with a lower probability of catastrophic death, for example because they have few predators, should live longer. These species would have enough time to develop protective mechanisms to maintain homeostasis, for example through the establishment of antioxidative protective mechanisms in the cells or through better regulation of the expression of oncogenes . This is the case, among other things, for birds, which - compared to mammals of the same size - have a life expectancy that is five to ten times longer. The same applies to bats , turtles and humans , for example . Even within a species, the elimination of predators can steer evolution towards slower aging. An example of this is the northern opossum ( Didelphis virginiana ) in Virginia . A population of these marsupials, cut off from the mainland for 4500 years, has a significantly reduced number of predators. These specimens age significantly more slowly than the mainland population.
The idea of the selection shadow was first published by the British geneticist JBS Haldane . In his 1942 book New paths in genetics , he looked at the hereditary disease Huntington's disease . From the fact that this fatal disease typically only occurs after the third decade of life, Haldane concluded that it only exists because in the times of our ancestors - even before the beginning of agriculture - it could not trigger any selective effect. Haldane further postulated that natural selection in the later stages of life, typically after the end of the reproductive phase, is only a weak force. Few people would have reached the age of 40 or more before civilization began. Their genetically determined, life-threatening diseases, which only broke out in old age, could not contribute to evolution through natural selection.
Peter Medawar took Haldane's ideas and developed in 1952, the mutation accumulation theory (Engl. Mutation accumulation theory ) after which accumulate an organism harmful mutations in the course of life (accumulate), which ultimately cause is what is perceived as aging . Due to the lower selection pressure on old organisms in populations in which most individuals die before they reach the range of maximum life expectancy, repair mechanisms would hardly prevail. However, this process is mostly limited to individual development and inheritance of such mutations is rare.
In 1957, George C. Williams developed the theory of antagonistic pleiotropy from the considerations on mutation accumulation . According to her, antagonistic pleiotropic genes are responsible for the aging of organisms that reproduce sexually. Pleiotropic are genes that cause different appearances under different conditions . Antagonistic (opposite) in this context means that some pleiotropic genes under the conditions in a young organism have beneficial effects for reproduction, but harmful effects under the conditions in the same, aged organism - which this theory sees as the reason for aging. Since the harmful effects of such genes often only occur after the offspring have been created and thus the genes have been passed on, they have only minor negative effects on the reproductive success of their carriers. According to Williams, harmful mutations that only show their effect in old age accumulate more frequently in the genome of an organism if these mutations provide the organism with reproductive advantages at an early stage of life. The term antagonistic pleiotropy was coined in 1982 by Michael R. Rose .
William D. Hamilton reformulated the theory. As organisms age, their contribution to reproduction decreases as their fertility decreases over time. Selection therefore leads to higher mortality rates in older organisms. Without these differences in fertility between young and old organisms, there would be no evolutionary reason why organisms age and thus more easily develop life-shortening diseases, for example. However, these considerations contradict the observation that some living beings - especially humans - can enjoy the best of health even after the end of their reproductive phase, if they cannot make a direct contribution to reproduction. This fact can be explained by the fact that many living beings invest not only in birth, but also in rearing their offspring. Investments can also be made in the grandchildren's generation (see also grandmother hypothesis ). In the bottlenose dolphin ( Tursiops truncatus ), for example, the grandparents supervise, protect and nurse their grandchildren.
The disposable soma theory proposed by Tom Kirkwood in 1977 is based on the two theories proposed by Medawar and Williams. In addition, there are also aspects of life history theory . In principle, every organism has repair mechanisms. Some species, such as the Mexican tailed amphibian axolotl ( Ambystoma mexicanum ), are able to completely restore lost body parts. It would not violate any natural law if a higher organism - such as humans - could completely replace aged, degenerated cells or entire organs and thus potentially be immortal. Such mechanisms are partially present, but their function, especially with increasing age, is insufficient. At first glance, such an organism should be favored by evolution. But it is not. Rather, it is exactly the opposite. Only limited resources are available to each organism. According to the life history theory, he has to divide these into:
- own growth
- Self-preservation
- Reproduction
Every investment in one of these competing processes means a scarcity of resources in one of the other two processes (called trade-off , English for ' conflict of interests '). Each organism adapts its life cycle strategy to the amount and distribution of available resources in its habitat. There is a large variety of life cycle strategies. The body (the soma ) keeps the effort for self-preservation at a level just high enough to be in good condition for normal life expectancy in the wild - and not to neglect the other two processes, but not so high that he can live without certain death. According to Kirkwood , the Soma is disposable , which means that there is no need for genetic optimization.
A number of observations in different species confirm the evolution theories of aging, in particular the theory of antagonistic pleiotropy and the disposable soma theory; For example, experiments with the model organism Drosophila melanogaster in the 1980s.
For species living in the wild, there is still relatively little data to allow the theories to be tested. By 2008, the mechanisms underlying the aging process had been investigated in only five vertebrate species living in the wild. For example, in the guillemot ( Uria aalge ), the mute swan ( Cygnus olor ), the gray seal ( Halichoerus grypus ) and the red deer ( Cervus elaphus ), matches were found with the predictions of the evolutionary theories of aging. Birds are particularly suitable as free-living vertebrates.
The survival curves of all living things in the wild show that catastrophic death - for example from predators, diseases or dramatically changing living conditions - is the norm. An investment in a potential immortality would be a bad investment under these conditions. For the survival of the species, investing in its own growth - for example to have fewer predators - or in more offspring is the better investment of resources. The survival curve of many people has only deviated from that of other species in the wild for an evolutionarily insignificant short period of time. In this short period of time, no fundamental changes in the life cycle strategy could take place through natural selection.
Gender differences in aging
For most mammals, including humans, and insects, the life expectancy of males is significantly shorter than that of females.
In humans, the difference in life expectancy between the sexes is between six and eight years, depending on the country. In order to draw conclusions about biological differences in the aging of the sexes, further influencing factors must be recorded and deducted, i.e. non-biological differences between the sexes that have a life-shortening effect (e.g. smoking, drinking behavior, accidental death in traffic, death from war missions ). This fact is rarely taken into account in non-scientific publications, so that it is often concluded on the basis of the death rate alone that men succumb to old age more quickly than women. Scientific analyzes on the subject, however, have come up with different results: According to L. Mealey, the lower average life expectancy of men is actually largely caused by different rates of aging and an earlier and more progressive senescence . Other studies, however, suggest gender-related differences in lifestyle as the cause of the shorter life expectancy of men, which also correlate with the regional differences in age- and gender-related death rates. A study that deals with the evaluation of specialist literature on the subject of aging indicates that, contrary to popular belief, women age faster than men and thus the different life expectancy does not reflect the biological aging pattern.
For most avian taxa , the opposite is true of the majority of mammals and insects: Most males grow older than females.
The reasons for the gender differences in aging in the zoological classes mentioned are obviously dependent on several factors. Various explanatory models for this largely unexplained phenomenon have been established.
Asymmetrical inheritance patterns
Some theories to explain the phenomenon are based on asymmetrical inheritance patterns. So the unguarded X-hypothesis (“hypothesis of the unprotected X chromosome ”). Male mammals are hemizygous , meaning they have two different sex chromosomes (X and Y ). The females, on the other hand, are homozygous . They are equipped with two identical sex chromosomes (X and X). In males there is only one X chromosome (the "unprotected X chromosome"), while in females the X chromosome is redundant. Disadvantageous mutations on the X chromosome are therefore always effective in males, which - according to the hypothesis - should result in a higher mortality rate. So far there has been no experimental verification or falsification of the hypothesis. However, it agrees with the observation that the males of most avian taxa have a longer life expectancy, since in birds the males are homozygous ( Z + Z ) and the females are hemizygous (Z + W).
Another hypothesis is based on an asymmetrical pattern of inheritance of mitochondrial DNA , which in most organisms is only passed on from mother to offspring. This genome is therefore only selected in the females and so further optimized. It can therefore - according to the hypothesis - under certain circumstances develop suboptimal properties in males, which lead to increased mortality. The mitochondria play an active role in aging. They have a direct impact on the mortality rate and the maximum life span, which fits this hypothesis. However, it cannot be explained why males live longer than females in many bird species.
Evolutionary hypotheses
In sexual selection , males are chosen by females of the same species and thereby gain an advantage over their peers in terms of reproduction. This can be at the expense of other functions, such as the self-preservation of the soma. Pleiotropic genes, which give males advantages for reproduction but tend to have a negative effect in old age, are another evolutionary explanatory model.
Another evolutionary explanatory model assumes that in polygynous species there is fierce competition between the males for the females. This has a direct impact on the growth and behavior of males who invest more resources in mating strategies, for example to have a competitive advantage over other males or to keep competitors away from their female. The selection pressure should therefore be higher in males than in females, which is reflected in higher mortality rates over most of their lifespan. In the case of monogamous species, the difference in aging between the sexes and, derived from this, the mean life expectancy should be smaller. A comparison between six monogamous and six polygynous species resulted in convincing evidence for this hypothesis.
Aging psychology
The physical and psychological aspects of aging are not necessarily synchronized. Physical degenerative processes can sometimes take place at the same time as an increase in mental agility. Parallel to a possible decline in memory performance ( fluid intelligence ), clear reflective performances ( crystalline intelligence ) that are largely unaffected by this can be observed. Overall, the aging process shows itself in a slowing down of the behavioral reactions controlled by the CNS and can proceed very differently from person to person.
Change in cognitive skills
Cognitive-mental abilities to process information are inevitably linked to human experience and behavior. It is assumed that different cognitive abilities are subject to different aging processes. Studies have shown that crystalline intelligence ( e.g. vocabulary ) remains stable or even develops further into old age, whereas fluid intelligence (e.g. working memory ) deteriorates with increasing age.
The following changes in the cognitive area can occur:
| Cognitive ability | Change process |
|---|---|
| Information acquisition and processing | Decreasing recording and processing speed (increase in delays in the encoding and processing of information, and in the selection of a reaction) |
| Decreasing information processing capacity (decrease in the amount of information that can be recorded and processed at the same time) | |
| reaction | Decreasing reaction speed already from the age of 20 due to decreasing speed in the transmission of nerve impulses and information processing |
| Increased sensitivity to interference with overstimulation, distractions and irritations | |
| coordination | Performing tasks simultaneously or in quick succession is becoming increasingly difficult due to reduced information processing capacity and reaction speed |
| Memory performance | Declining STM and LTM , such as episodic memory, semantic memory (eg. As names) |
| Less efficient and spontaneous use of mnemonic techniques (e.g. " donkey bridges ") | |
| Slower and more ineffective decoding processes (longer time to retrieve information from memory, increase in susceptibility to interference due to distraction and interruptions) | |
| Learn | Longer learning times by slowing down information processing, but once learned can be retained just as well as with younger people |
| Decreasing ability to learn with certain learning content: Greater difficulties in learning new schemes (which do not build on existing knowledge or which correspond to expectations) than with younger people |
Factors such as genetics, diet, stress levels, and physiological and mental fitness can slow down the cognitive aging process.
Genetics itself is largely fixed and thus defines an upper limit for cognitive performance. However, epigenetics offers opportunities to make the most of the genetically determined framework. In studies with microorganisms such. B. be shown that caloric restriction has a positive effect on insulin metabolism.
The processes progress differently and can be actively slowed down. Targeted training (" brain jogging ") and physical exercise can mobilize cognitive performance reserves even in old age.
A new study suggests that not only fitness but also cognitive performance is related to lung health. 832 test persons were observed over 19 years. Pulmonary function tests as well as cognitive tests were performed. The results were compared with each other. While poorer lung function does not seem to affect memory, it does affect problem-solving skills and processing speed. The researchers have not yet been able to find an explicit reason for this connection.
According to a US study published in 2010, according to the term "age wisdom ", wisdom actually increases with age, regardless of cognitive performance .
Age wisdom describes the assumed phenomenon that older people get better in some cognitive areas due to increasing life experience. As already mentioned, z. B. crystalline intelligence with age. Older people are also more likely to refer to more global argumentation patterns that require multiple perspectives and can encourage compromise.
Developmental aspects
The development possibilities of the personality are largely independent of external conditions such as age, stage of life, health and illness. In developmental psychology , aging represents the interaction between regression on the one hand and the development and stabilization of personality and performance characteristics on the other.
Social psychological aspects
The role of the elderly in society is changing rapidly due to the increase in the average age and the declining birth rates in most western industrialized countries. As a result of this shift in proportions, the relationship between the generations and their respective understanding of roles changes. Overall, the presence of older people and their self-confidence in society has increased. This can be seen, for example, in the increased number of leisure activities for senior citizens and in the public discussion of the long-term taboo topic of sexuality in old age .
Clinical-psychological aspects
With increasing lifespan, the number of decisive life events also increases. One of the most critical is the death of one's life partner. At the same time, life perspectives change in old age with regard to lifespan, health, social integration, mobility, etc. These circumstances place increased demands on the ability to process such events. The most common mental illness in old age is depression . Maintaining meaningful activities and maintaining social contacts play a central role in overcoming crises.
As people age, many people feel a need to reflect on their life, to appreciate it for how it went, and to see it as meaningful. A life review that reconciles with one's own life can u. a. can be achieved in a life review therapy ( Maercker & Forstmeier 2013).
Further mental aspects for promoting health in old age and for maintaining possible life expectancy can be found in the next chapter "Measures against aging: Mental influences ".
Measures against aging
The situation of aging, especially in humans, which is often described with the words everyone wants to get old, but nobody wants to be old, is the basis for an entire industry: anti-aging . Much of the advice is focused on the healthy and happy lifestyle possible.
Measures against aging must distinguish between primary and secondary aging. A number of rules of conduct, such as a healthy, balanced diet, not tobacco consumption and regular exercise, can minimize secondary aging in humans.
Many results from animal experiments are hardly transferable to humans. Human aging processes, which take place over many decades, cannot be adequately represented with organisms that have significantly shorter life expectancies. Controlled clinical studies, ideally double- blind studies , on humans can hardly be carried out or only with great effort . They would have to be carried out over decades with statistically sufficiently large populations. Ethical concerns, extremely high costs and risks stand in the way of testing. Side effects of an antiaging agent that healthy people would have to take for many decades would not be tolerated and would prevent approval.
To many people, extending the life span only makes sense if the quality of life is correspondingly high for the period gained. In this context, we are talking about healthy or successful aging.
Calorie restriction
In a large number of model organisms it has been shown that primary aging can be delayed by a considerable reduction in food intake ( calorie restriction ). The calorie restriction increases the mean and maximum life expectancy. Age-associated diseases are weakened or delayed. Evidence that calorie restriction delays primary aging and increases life expectancy in primates is still pending. Several studies with rhesus monkeys produced contradicting results. In humans, the laboratory results for the most important biomarkers in subjects living with a calorie restriction suggest this. The asceticism required for calorie restriction is, however, impractical for most people.
The exact causes for the life-prolonging effect of the calorie restriction have not yet been finally clarified. What is certain is that neither the catabolic rate per kilogram of body mass nor the amount of free radicals is reduced. Both indications that the mechanisms from the damage theories play no role in this case. From an evolutionary point of view, the disposable soma theory provides an explanatory model. The calorie restriction causes a shift in the r / K strategy in the body in the direction of self-preservation at the expense of reduced reproduction. The external condition of little food is a signal that reproduction is unfavorable at this point in time. In order to bridge this period of lack of food, the organism may only change (age) a little in order to be able to reproduce later. The stress caused by starvation leads to an active adaptation via the self-interest principle of the cells. The stress response of the cells can be detected via an altered gene expression. The genes that are increasingly expressed include the heat shock proteins (HSP) from the Hsp70 and Sirtuin-1 families . On the other hand, a reduced expression of pro-inflammatory genes can be detected.
Even with intermittent fasting , in which the total nutrient intake does not have to be reduced over time and body weight is maintained, a higher life expectancy and a lower rate of age-related diseases can be observed in a number of model organisms.
Active ingredients
Aging is not a disease as per the Food and Drug Administration . As a result, new active ingredients that would potentially be effective against aging currently only have a chance of approval if they are effective (therapy) or have a preventive effect (prevention) against diseases. There is currently no approved drug that is effective against aging. So far, no substance has been scientifically proven - regardless of its approval status - that it can delay or even stop aging in humans. Regardless of this, a gray market has developed with dubious promises of salvation for a number of potential, but also proven ineffective or even disadvantageous substances. Examples are the "anti-aging hormones" dehydroepiandrosterone (DHEA), testosterone, somatotropin and melatonin . In most cases, the supposedly positive effects are based only on the observation that the levels of certain hormones continue to drop with increasing age and - as a presumably logical conclusion - that hormone replacement could bring about a youthful state. In many cases, the relationship between cause and effect is unclear: Is the decreasing hormone release a consequence of aging and therefore possibly a sensible physiological process, or do the falling hormone levels cause aging? The discussion about the administration of hormones in old age is very controversial. See also hormone replacement therapy .
To date, there has been no evidence of any effectiveness against aging in humans for all active ingredients based on hormones. Animal experiment data and the theory of evolution suggest that the administration of growth and sex hormones - due to the pleiotropic effects of these substances - would lead to life-shortening rather than life-prolonging effects.
In an animal model, the immunosuppressant sirolimus (rapamycin) was found for the first time in 2009 in a study in which the life expectancy of a species of mammal (colored mouse) could be demonstrably extended. The maximum life expectancy of the test animals could be increased by 9% (males) and 14% (females). In contrast to the calorie restriction, there is also a life-prolonging effect in old experimental animals with an age of 20 months - which corresponds to an age of around 60 in humans. The inhibition of mTOR , an enzyme important for the survival, growth, division and motility of cells, by rapamycin evidently triggers a signal cascade that is very similar to that of calorie restriction. These results cannot simply be transferred to humans. Rapamycin also has significant side effects , particularly affecting the immune system. The test animals - like the control group - were kept under largely sterile and air-conditioned conditions in the laboratory.
A study by Michael Ristow published in 2011 suggests a connection between an increased intake of the trace element lithium and a lower mortality rate. In a study in Japan, areas with a comparatively high occurrence of the element in drinking water were found to be significantly higher than the general life expectancy. In the laboratory experiment, an increase in the average life expectancy of the nematode Caenorhabditis elegans was also demonstrated after treatment with an equivalent dose of the trace element. This provides the first clues for a possible connection in humans as well, but not yet a conclusion.
Genetic Approaches
Molecular biology has made significant strides with the decoding of the human genome at the beginning of the 21st century. It also identified genes that are directly involved in the processes of aging. It is currently impossible to foresee when and how aging can be influenced by molecular biological interventions in the future. Which potentials exist in principle could be shown in model organisms such as the Dwarf mice or Caenorhabditis elegans .
Mental influences
In 1979, the American social psychologist Ellen J. Langer started an experiment in which men between the ages of 70 and early 80 spent a week in a simulated environment from 1959. One group was also given the task of actively empathizing with this time and what moved it at that time - all events after 1959 should be thematically taboo. The result was astonishing in that both mentally and physically manifested abilities such as eyesight and joint mobility had improved; and this was particularly evident in the group that had actively dealt with their lives during this time. It is possible that moving back in time and looking at the younger self had increased the participant's expectation of self-efficacy - i.e. the expectation of being able to do certain things - and promoted these positive effects. These and other results are u. a. Subject of a specialist article in Perspectives on Psychological Science magazine published in 2010 and has been taken up in several popular scientific papers.
The epidemiologist and social medicine specialist Becca R. Levy from Yale University evaluated the lifespan of 650 people who were asked in a 1979 survey to tick positive or negative statements about age as applicable. Over 20 years later, the analysis found that those who tended to be positive about aging lived an average of 7.5 years longer than those who showed negative attitudes.
Aging from a medical history perspective
The interest in aging and the fight against its negative effects is likely to be almost as old as humanity itself. Fulgentius (Mythographus) took in "sermones antiqui" from the historical work of Cincius Alimentus his quote from Gorgias: "Anyone who longed for the end of his days as a Tattergreis, escaped, if not death, at least from frailty." The text of Cincius is the first written discussion of age in the Latin culture. The next thing to be mentioned is Lucilius and then Juvenal .
Preserving youth, extending life or even eternal life are ancient human dreams that can be found in a multitude of mythical or religious traditions.
The traditions deal, for example, with fountains of youth as a source of eternal youth or eternal life. A herb that gives eternal life was sought by Gilgamesh in the epic of the same name around 3000 BC. The golden apples of the Hesperides gave the gods of Greek mythology eternal youth. Tithonos was granted eternal life by Zeus at the request of Eos , but Eos also forgot to ask for eternal youth, so that Tithonos aged and shrank to a cicada . This theme was later taken up and varied by Jonathan Swift in Gulliver's Travels with the Immortal Struldbrugs .
The first book of Moses in the Old Testament reports on the tree of life , to the fruits of which Adam and Eve no longer had access after they were driven out of paradise - they had previously forbidden to eat the fruits of the tree of knowledge . This is an early religious approach to explaining human mortality. Genesis also provides an indication of the maximum human life span:
“Then said the Lord: My spirit should not remain in man forever, because he is also flesh; therefore its lifetime should be 120 years. "
The Edwin Smith Papyrus describes formulas against age spots and wrinkles on the skin. With Hippocrates of Kos , Aristotle and Galenus prophylaxis for old age can be found in the form of diet and moderation. Aristotle tries to prevent or at least delay the consumption of the "inner warmth" that is life for him. Galenus founded the gerocomy (medical treatment of the elderly) and thus provided old people's and nursing homes in Roman Constantinople . Right up to modern times, opinions as to whether aging was a disease were very controversial. For Aristotle, aging was a natural disease and for Seneca it was even incurable . Terence meant Senectus ipsa morbus (est) , dt. 'Old age itself is a disease'. For Galenus, aging was not a disease, as he viewed disease as contrary to nature . Paracelsus saw self-poisoning in aging in the 16th century . Ignatz Leo Nascher , the father of modern geriatrics , always emphasized that aging is not a disease.
Until the Renaissance, attempts were made to treat male old age with Sunamitism . The physical “vapors” of a virgin who was put in bed with the treated old man - without sexual intercourse taking place - should have a rejuvenating effect. This form of therapy goes back to the Old Testament .
At the end of the 18th century, the German doctor Christoph Wilhelm Hufeland founded macrobiotics . His book Macrobiotics or The Art of Extending Human Life , published in 1796, was a worldwide success.
Until well into the 20th century, some doctors assumed that aging was primarily caused by a "regression of the sex glands". In some cases, this led to “therapeutic approaches” that now seem absurd, such as injected testicular extracts from various species. Charles-Édouard Brown-Séquard worked towards the end of the 19th century with subcutaneous injections of testicular extracts from guinea pigs and dogs , the so-called Brown-Séquard elixir , with which he had also "rejuvenated" himself. Serge Voronoff first implanted sliced testicles of a chimpanzee into a patient's scrotum on June 12, 1920 . The thin disks should promote the union of the xenograft with the patient's tissue. Worldwide, the number of these interventions ran into the thousands. In Austria, Eugen Steinach worked on a variant of Vornoff's transplants. Voronoff later also transplanted monkey ovaries (unsuccessfully) into women to prevent menopause . When the effects promised by Voronoff did not materialize in the patients - the short-term successes observed today are essentially attributed to the placebo effect - Vornoff's transplant method fell out of fashion. When testosterone was identified as the active substance of the testes a few years later, hopes for the revitalization and rejuvenation of men sprang up again. The hoped-for effect did not materialize. Testosterone did not increase the life expectancy of the test animals. Due to the pleiotropic effect of testosterone, the opposite is more the case.
The Swiss doctor Paul Niehans followed a similar path, who invented what is known as 'cellular therapy' ( fresh cell therapy ) using cell suspensions from sheep fetuses . The procedure had a certain widespread use until the 1980s and was found mainly through the treatment of numerous celebrities, such as Konrad Adenauer , Pius XII. and Hirohito , in the tabloid press attention. To date, there is no scientific evidence of the effectiveness of fresh cell therapy.
- See also: Research on the oldest people (longevity, centenarians and centenarians - English supercentenarians ; data on maximum life span)
further reading
Journals on aging
- Experimental Gerontology. Elsevier , since 1964
- Mechanisms of Aging and Development. Elsevier, since 1972
- Aging International. Springer , since 1974
- Neurobiology of Aging. Elsevier, since 1980
- Archives of Gerontology and Geriatrics. Elsevier, since 1982
- Journal of Cross-Cultural Gerontology. Springer, since 1986
- Journal of Aging Studies. Elsevier, since 1987
- Gerontology. S. Karger , since 1998
- Journal of Gerontology and Geriatrics. Springer, since 1998
- Journal of Aging and Identity. Springer, 1998-2002
- Biogerontology. Springer, since 2000
- Aging Research Reviews. Elsevier, since 2002
- Immunity & Aging. Journal in Open Access , articles under CC-by-sa , since 2004
- European Journal of Aging. Springer, since 2004
- GeroScience Verlag Springer, since 2005 (continuation of the Journal of the American Aging Association )
- European Review of Aging and Physical Activity. Springer, since 2006
- International Journal of Gerontology. Elsevier, since 2007
- Journal of Population Aging. Springer, since 2008
- Journal of Nutrition, Health & Aging. Springer, since 2008
- Aging. Journal in Open Access , articles under CC-by-sa , since 2009
Reference books
- A. Motel-Klingebiel, S. Wurm and C. Tesch-Römer (eds.): Aging in change. Findings of the German Age Survey (DEAS). Kohlhammer, 2010, ISBN 978-3-17-021595-5 .
- Norman S. Wolf (Ed.): Comparative Biology of Aging. Springer, 2010, ISBN 978-90-481-3464-9 .
- J. Kocka and U. Staudinger (eds.): Won Years - Recommendations of the Academy Group on Aging in Germany. (PDF; 5.6 MB), Nova Acta Leopoldinam, Volume 107, 2009, ISBN 978-3-8047-2550-8 .
- V. L. Bengtson et al. a .: Handbook of theories of aging. Springer, 2009, ISBN 978-0-8261-6251-9 limited preview in Google book search (English)
- A. Baudisch: Inevitable aging ?: contributions to evolutionary-demographic theory. Springer, 2008, ISBN 978-3-540-76655-1 , limited preview in the Google book search
- P. Gruss (Ed.): The future of aging: the answer of science. CH Beck , 2007, ISBN 978-3-406-55746-0 , limited preview in the Google book search (a report by the Max Planck Society)
- A. Kruse : Age: What's true? Herder , 2007, ISBN 978-3-451-05750-2
- U. Lehr : Psychology of Aging. Edition 11, Quelle & Meyer , 2006, ISBN 3-494-01432-9
- E. J. Masoro and SN Austad (Eds.): Handbook of the biology of aging. 6th edition, Academic Press, 2006, ISBN 0-12-088387-2 limited preview in Google Book Search (English)
- R. Arking: The biology of aging. 3rd edition, Oxford University Press, 2006, ISBN 0-19-516739-2
- R. Schulz: The Encyclopedia of Aging. Volume 1 + 2, Edition 4, Springer, 2006, ISBN 0-8261-4843-3 , limited preview in the Google book search (English)
- D. Ganten and K. Ruckpaul (eds.): Molecular medical principles of age-specific diseases. Springer, 2004, ISBN 3-540-00858-6 restricted preview in the Google book search
- A. Kruse : Encyclopedia of Gerontology. Huber , 2004, ISBN 3-456-83108-0
- PB Baltes , J. Mittelstraß , UM Staudinger (Ed.): Age and Aging: An interdisciplinary study text on gerontology. Walter de Gruyter , 1994, ISBN 3-11-014408-5 limited preview in the Google book search
- MR Rose : Evolutionary Biology of Aging. Oxford University Press, 1994, ISBN 0-19-509530-8
- H. Reimann and H. Reimann: The age: introduction to gerontology. Lucius & Lucius , 1994, ISBN 3-432-92893-9 limited preview in Google Book Search
- Commission on Life Sciences (Ed.): Aging in today's Environment. National Academy Press, 1987 (English)
- MS Kanungo: Biochemistry of Aging , Academic Press, 1980, ISBN 0-12-396450-4 (English)
- A. Weismann: Essays on inheritance and related biological questions. G. Fischer, Jena 1892
Review articles and book contributions
- PJ Hornsby: Senescence and life span. In: Pflügers Archive - European Journal of Physiology . Volume 459, Number 2, January 2010, pp. 291-299, doi: 10.1007 / s00424-009-0723-6 . PMID 19763609
- M. Muers: Aging: Predicting long life. In: Nature Reviews Genetics . 11, 2010, p. 530. doi: 10.1038 / nrg2833 PMID 20628349
- L. Fontana et al. a .: Extending healthy life span - from yeast to humans. In: Science . 328, 2010, pp. 321-326. PMID 20395504
- Hans-Jörg Ehni: Can you imagine Elina Makropoulos as a happy person? A contribution to the ethical debate about the individual value of a longer life. In: L. Honnefelder u. a. (Ed.): Yearbook for Science and Ethics. Walter de Gruyter, 2009, ISBN 978-3-11-020884-9 , pp. 47-70. limited preview in Google Book search
- G. Campisi et al. a .: Pathophysiology of age-related diseases. In: Immunity & Aging. 6, 2009, 12 doi: 10.1186 / 1742-4933-6-12 ( Open Access )
- O. Fernandez-Capetillo: Intrauterine programming of aging free. In: EMBO reports. 11, 2009, pp. 32-36. doi: 10.1038 / embor.2009.262
- E. Derhovanessian et al. a .: Immunity, aging and cancer. In: Immunity & Aging. 5, 2008, 11 doi: 10.1186 / 1742-4933-5-11 ( Open Access )
- Alexander Bürkle u. a .: Pathophysiology of aging, longevity and age related diseases. In: Immunity & Aging. 4, 2007, 4 doi: 10.1186 / 1742-4933-4-4 ( Open Access )
- Gundolf Keil : Aging and old age in antiquity. In: Current Gerontology 13, 1983, pp. 47-52.
Popular science
- Uta Henschel: The Secret of the Methuselah Animals. In: Spiegel Online , May 21, 2005.
- Rafaela von Bredow : Aging research: The abolition of dying . In: Der Spiegel . No. 30 , 2005 ( online ).
- Markus Becker: Researchers find a path to the fountain of youth. In: Spiegel Online , April 14, 2004.
- Luise Wagner-Roos u. a .: Forever young. In: Focus. 5, 1996, dated January 29, 1996.
Web links
- N. Podbregar: What makes us age? scinexx.de, April 16, 2010
- M. Platzer: Why do we age? Possibilities & Limits of Aging Research. (PDF; 3.8 MB) Leibniz Institute for Age Research
- Leibniz Research Association Healthy Aging
- Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI) eV
- German Center for Age Issues
- German age survey
- German Society for Gerontology and Geriatrics
- American Federation for Aging Research (English)
Footnotes
- ↑ Original quote: It is indeed remarkable that after a seemingly miraculous feat of morphogenesis a complex metazoan should be unable to perform the much simpler task of merely maintaining what is already formed.
- ↑ Original quote: There is no such thing as aging - old age is associated with disease, but does not cause it.
- ↑ According to Marcus Tullius Ciceros Cato maior de senectute , 4 (Ger. Cato the Elder on old age): Quo in genere est in primis senectus, quam ut adipiscantur omnes optant, eandem accusant adeptam; tanta est stultitiae inconstantia atque perversitas. (German: "This includes especially the age that everyone wants to reach, but about which they complain when they have reached it.")
Individual evidence
- ↑ S. Ruppert: Age and Law (MPG). In: Activity report 2008. Max Planck Institute for European Legal History, Frankfurt am Main
- ↑ M. Raschke: The development of the life staircase. GRIN Verlag, 2010, ISBN 978-3-640-58370-6 , p. 6. Limited preview in the Google book search
- ↑ M. Kaeberlein, PS Rabinovitch, GM Martin: Healthy aging: The ultimate preventative medicine. In: Science. Volume 350, number 6265, December 2015, pp. 1191–1193, doi: 10.1126 / science.aad3267 , PMID 26785476 , PMC 4793924 (free full text) (review)
- ↑ J. Krutmann: Environment-induced aging processes. In: Annual Report 2008. German Research Foundation
- ↑ a b c d H. Niedermüller, G. Hofecker: Lifespan: Genetic determination and life-extending strategies. In: D. Ganten, K. Ruckpaul (Hrsg.): Molecular medical principles of age-specific diseases. Verlag Springer, 2004, ISBN 3-540-00858-6 restricted preview in the Google book search
- ↑ a b c d R. F. Schmidt, F. Lang, G. Thews: Physiologie des Menschen. Verlag Springer, 2005, ISBN 3-540-21882-3 , 2005 limited preview in the Google book search
- ^ PB Baltes , J. Mittelstraß , UM Staudinger : Age and Aging: An interdisciplinary study text on gerontology. Verlag Walter de Gruyter, 1994, ISBN 3-11-014408-5 , p. 96. Restricted preview in the Google book search
- ↑ a b R. L. Bowen, CS Atwood: Living and dying for sex. A theory of aging based on the modulation of cell cycle signaling by reproductive hormones. (PDF; 373 kB) In: Gerontology. 50, 2004, pp. 265-290. PMID 15331856 (Review).
- ^ A b c F. W. Schwartz : The Public Health Book. Elsevier, Urban & Fischer Verlag, 2003, ISBN 3-437-22260-0 , p. 163. Restricted preview in the Google book search
- ↑ EI Masoro: Aging: Current Concepts. In: Handbook of Physiology. Section 11: Aging, Oxford University Press, 1995, ISBN 0-19-507722-9 , pp. 3-21.
- ↑ M. Bürger : Aging and Illness. Thieme publishing house, 1954
- ↑ a b P. M. Kappeler: Behavioral biology. Verlag Springer, 2008, ISBN 978-3-540-68776-4 , p. 62. Restricted preview in the Google book search
- ↑ Universitas. Volume 13, issues 7-12, Wissenschaftliche Verlagsgesellschaft, 1958, p. 739.
- ↑ M. Bürger: Aging and illness as a problem of biomorphosis. 4th edition, Thieme, Leipzig 1960.
- ↑ UMS Röhl: Older people as a fringe group in the diaspora community - in sociological and Christian ethical discussions. GRIN Verlag, 2009, ISBN 978-3-640-44681-0 , p. 7. limited preview in Google book search
- ↑ a b c T. Braun: Aging of Gastrophysa viridula (DeGeer). Dissertation, Albert-Ludwigs-Universität Freiburg, 2008, p. 4 f.
- ↑ a b c T. Anlasik: Influence of dietary habits on the antioxidant status in healthy people. Dissertation, Heinrich Heine University Düsseldorf, 2009
- ↑ L. Hayflick: Biological aging is no longer an unsolved problem. In: Ann NY Acad Sci. 1100, 2007, pp. 1-13. PMID 17460161 (Review)
- ↑ a b J. Türk: Theoretical Aging Mechanisms II. University of Kaiserslautern, 2003.
- ^ BL Strehler : Time, cells, and aging. 2nd edition, Academic Press, 1977, ISBN 0-12-673260-4 .
- ^ F. Schulz-Nieswandt : Social policy and age. Verlag W. Kohlhammer, 2006, ISBN 3-17-018142-4 limited preview in the Google book search
- ^ PB Baltes , MM Baltes : Gerontology: Concept, challenge and focal points. In: PB Baltes, J. Mittelstraß (ed.): Future of aging and social development. Verlag W. de Gruyter, 1992, ISBN 3-11-013248-6 , pp. 1-34.
- ^ A. Baudisch: How Aging is shaped by Trade-offs. ( Memento of the original from July 31, 2010 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. MPIDR Working Paper, Max Planck Institute for Demographic Research, 2009.
- ↑ a b P. B. Medawar : An Unsolved Problem of Biology. In: Uniqueness of the Individual. HK Lewis, London 1952, pp. 44-70.
- ↑ a b c d e K. G. Collatz : Altern. In: Wissenschaft-Online. Spektrum Akademischer Verlag, accessed on August 8, 2010.
- ^ PB Baltes , MM Baltes : Gerontology: Concept, challenge and focal points. In: PB Baltes, J. Mittelstraß , UM Staudinger : Age and Aging: An interdisciplinary study text on gerontology. Verlag Walter de Gruyter, 1994, ISBN 3-11-014408-5 , p. 9. Restricted preview in the Google book search
- ↑ M. Tostlebe: Disproportionality of the activities of the mitochondrial respiratory chain complexes in the myocardium and in the skeletal muscles in old age. Dissertation, Martin Luther University Halle-Wittenberg, 2005, p. 1.
- ^ MJ Levitt: Biology of Aging. Florida International University, accessed September 1, 2010.
- ^ I. Kohler: Can Frailty Models Explain Mortality Differentials by Socioeconomic Status? IUSSP conference 2001.
- ↑ JO Holloszy, L. Fontana: Caloric Restriction in Humans. In: Exp Gerontol. 42, 2007, pp. 709-712. doi: 10.1016 / j.exger.2007.03.009 ; PMID 17482403 ; PMC 2020845 (free full text).
- ↑ a b c David E. Harrison, Randy Strong, Zelton Dave Sharp, James F. Nelson, Clinton M. Astle, Kevin Flurkey, Nancy L. Nadon, J. Erby Wilkinson, Krystyna Frenkel, Christy S. Carter, Marco Pahor, Martin A. Javors, Elizabeth Fernandez, Richard A. Miller: Rapamycin fed late in life extends lifespan in genetically heterogeneous mice . In: Nature . tape 460 , no. 7253 , 2009, p. 392-395 , doi : 10.1038 / nature08221 , PMID 19587680 . ; PMC 2786175 (free full text).
- ↑ Page no longer available , search in web archives: Explanation of terms on the subject of senior sports. (PDF; 1.1 MB) In: Newsletter Network Health and Exercise Switzerland. 2, 2005, p. 46.
- ^ HH Dickhuth : Sports medicine for doctors. Deutscher Ärzteverlag, 2007, ISBN 978-3-7691-0472-1 , p. 601. Restricted preview in Google book search
- ↑ E. Freiberger, D. Schöne: Fall prophylaxis in old age: Basics and modules for planning courses. Deutscher Ärzteverlag, 2010, ISBN 978-3-7691-0557-5 , p. 9. Limited preview in Google book search
- ^ Karlheinz Idelberger : Orthopedics and Geriatrics. In: Archives for Orthopedic and Trauma Surgery. 59, pp. 66-73. doi: 10.1007 / BF00416274
- ↑ A. Baudisch: Hamilton's indicators of the force of selection. In: PNAS . 102, 2005, pp. 8263-8268; PMID 15919822 ; PMC 1140481 (free full text).
- ↑ RF Evert u. a .: Esau's plant anatomy. R. Langenfeld-Heyser (Ed.), Verlag Walter de Gruyter, 2009, ISBN 978-3-11-020592-3 , p. 103. Restricted preview in the Google book search
- ↑ a b c d e f C. E. Finch : Longevity, Senescence, and the Genome. University of Chicago Press, 1994, ISBN 0-226-24889-5 , p. 521. Limited preview in Google Book Search
- ↑ JM Wood et al. a .: Senile hair graying: H2O2-mediated oxidative stress affects human hair color by blunting methionine sulfoxide repair. In: FASEB J 23, 2009, pp. 2065-2075. doi: 10.1096 / fj.08-125435 PMID 19237503 .
- ^ A b P. Doubt: Age, Health, and Health Expenditures - A New View. (PDF; 86 kB) In: GGW. 1, 2001, pp. 6-12.
- ^ A b N. Lange: Concepts of aging and rehabilitation among very old nursing home residents. GRIN Verlag, 2007, ISBN 978-3-638-74293-1 limited preview in the Google book search
- ↑ a b c M. Martin, M. Kliegel: Psychological foundations of gerontology. W. Kohlhammer Verlag, 2008, ISBN 978-3-17-020602-1 limited preview in the Google book search
- ^ E. Cumming, WE Henry: A formal statement of disengagement theory. In: Growing old: The process of disengagement. Basic Books, New York 1961.
- ↑ a b B. J. Zwaan: The evolutionary genetics of aging and longevity. In: Heredity. 82, 1999, pp. 589-597. doi: 10.1046 / j.1365-2540.1999.00544.x PMID 10383679 (Review).
- ↑ DE Martinez: Mortality patterns suggest lack of senescence in hydra. In: Exp Gerontol. 33, 1998, pp. 217-225. PMID 9615920 .
- ↑ E. Voland : Why do we age? The biological evolution of impermanence. ( Memento of the original from May 24, 2010 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. (PDF; 200 kB). In: H. Heller (ed.): Measured time - felt time. LIT-Verlag, Münster 2006, ISBN 3-8258-9588-2 , pp. 43-62. limited preview in Google Book search.
- ↑ GM Cailliet et al. a .: Age determination and validation studies of marine fishes: do deep-dwellers live longer? In: Exp Gerontol. 36, 2001, pp. 739-764. PMID 11295512 .
- ↑ a b J. C. Guerin: Emerging area of aging research: long-lived animals with “negligible senescence”. In: Ann NY Acad Sci. 1019, 2004, pp. 518-520. PMID 15247078 (Review).
- ↑ a b Rochelle Buffenstein: Negligible senescence in the longest living rodent, the naked mole-rat: insights from a successfully aging species . In: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology . tape 178 , no. 4 , 2008, ISSN 0174-1578 , p. 439-445 , doi : 10.1007 / s00360-007-0237-5 , PMID 18180931 .
- ^ CE Finch: Update on slow aging and negligible senescence - a mini-review. In: Gerontology. 55, 2009, pp. 307-313. PMID 19439974 (Review).
- ↑ Nadja Podbregar, Dieter Lohmann: In focus: marine worlds . Springer, Berlin / Heidelberg 2014, p. 127 , doi : 10.1007 / 978-3-642-37720-4 .
- ↑ DIE WELT: An immortal jellyfish renews itself . In: THE WORLD . February 28, 1999 ( welt.de [accessed October 26, 2017]).
- ↑ a b c T. B. Kirkwood , MR Rose : Evolution of senescence: late survival sacrificed for reproduction . In: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences . tape 332 , no. 1262 , 1991, ISSN 0962-8436 , pp. 15-24 , doi : 10.1098 / rstb.1991.0028 , PMID 1677205 .
- ^ A b L. Hayflick: The illusion of cell immortality. In: British Journal of Cancer . 83, 2000, pp. 841-846; PMID 10970682 ; PMC 2374692 (free full text).
- ^ DB Danner, HC Schröder: Biology of Aging (ontogenesis and evolution). In: PB Baltes, J. Mittelstraß, UM Staudinger: Age and Aging: An interdisciplinary study text on gerontology. Verlag Walter de Gruyter, 1994, ISBN 3-11-014408-5 , p. 103. Restricted preview in the Google book search.
- ↑ a b c T. B. Kirkwood, CE Finch CE: Aging: the old worm turns more slowly. In: Nature. 419, 2002, pp. 794-795. PMID 12397339
- ↑ A. Antebi: Aging: when less is more. In: Nature. 447, 2007, pp. 536-537. PMID 17538604
- ↑ a b c d S. Nikolaus, S. Schreiber: Molecular mechanisms for the control of life expectancy. In: Dtsch med Wochenschr. 129, 2004, pp. 903-907. doi: 10.1055 / s-2004-823037
- ↑ R. Buffenstein: The naked mole-rat: a new long-living model for human aging research. In: J Gerontol A Biol Sci Med Sci. 60, 2005, pp. 1369-1377. PMID 16339321 (Review)
- ^ SN Austad: Comparative biology of aging. In: J Gerontol A Biol Sci Med Sci. 64, 2009, pp. 199-201. PMID 19223603 PMC 2655036 (free full text) (Review)
- ↑ Ancient harpoon discovered in dead whale. In: Spiegel Online. June 13, 2007.
- ^ SN Austad: Methusaleh's Zoo: how nature provides us with clues for extending human health span. In: J Comp Pathol. 142, 2010, pp10-21. PMID 19962715 (Review)
- ↑ S. Hekimi et al. a .: Genetics of lifespan in C. elegans: molecular diversity, physiological complexity, mechanistic simplicity. In: Trends Genet. 17, 2001, pp. 712-718. PMID 11718925 (Review)
- ^ GJ Lithgow, GA Walker: Stress resistance as a determinate of C. elegans lifespan. In: Mech Aging Dev. 123, 2002, pp. 765-771. PMID 11869734 (Review)
- ^ TB Kirkwood, SN Austad: Why do we age? In: Nature. 408, 2000, pp. 233-238. PMID 11089980 (Review)
- ↑ A. Olsen et al. a .: Using Caenorhabditis elegans as a model for aging and age-related diseases. In: Ann NY Acad Sci. 1067, 2006, pp. 120-128. PMID 16803977 (Review)
- ↑ A. Wong et al. a .: Mutations in the clk-1 gene of Caenorhabditis elegans affect developmental and behavioral timing. In: Genetics. 139, 1995, pp. 1247-1259. PMID 7768437 PMC 1206454 (free full text)
- ↑ B. Lakowski, p hekimi: Determination of life-span in Caenorhabditis elegans by four clock genes. In: Science. 272, 1996, pp. 1010-1013. PMID 8638122
- ↑ L. Guarente: Aging. What makes us tick? In: Science . 275, 1997, pp. 943-944. doi: 10.1126 / science.275.5302.943 PMID 9053999 (Review)
- ↑ K. Yen, CV Mobbs: Evidence for only two independent pathways for decreasing senescence in Caenorhabditis elegans. In: Age (Dordr). 32, 2010, pp. 39-49. PMID 19662517
- ^ J. Durieux, S. Wolff, A. Dillin: The cell-non-autonomous nature of electron transport chain-mediated longevity. In: Cell. Volume 144, Number 1, January 2011, pp. 79-91. doi: 10.1016 / j.cell.2010.12.016 . PMID 21215371 . PMC 3062502 (free full text).
- ↑ KG Iliadi, GL Boulianne: Age-related behavioral changes in Drosophila. In: Ann NY Acad Sci. 1197, 2010, pp. 9-18. PMID 20536827 (Review)
- ↑ YJ Lin et al. a .: Extended life-span and stress resistance in the Drosophila mutant methuselah. In: Science. 282, 1998, pp. 943-946. doi: 10.1126 / science.282.5390.943 PMID 9794765
- ↑ JM Copeland et al. a .: Extension of Drosophila life span by RNAi of the mitochondrial respiratory chain. In: Curr Biol. 19, 2009, pp. 1591-1598. PMID 19747824
- ↑ J. H. Hur et al. a .: Aging: Dial M for Mitochondria. In: Aging (Albany NY). 2 ,. 2010, pp. 69-73. PMID 20228940 (review); PMC 2837206 (free full text).
- ↑ a b c George T. Baker, III and Richard L. Sprott: Biomarkers of aging . In: EXPERIMENTAL GERONTOLOGY . 23, No. 4-5, 1988, pp. 223-239. PMID 3058488 .
- ↑ Sanjana Sood et al. A novel multi-tissue RNA diagnostic of healthy aging relates to cognitive health status. In: Genome Biology. 16 (2015), No. 1, p. 185
- ↑ a b T. Gunzelmann: Can aging be measured? Pp. 59-77. doi : 10.1007 / 978-3-211-78390-0_5 In: WD Oswald u. a. (Ed.): Gerontopsychology. 2008, ISBN 978-3-211-75685-0 . limited preview in Google Book search
- ↑ a b c d e D. P. Clark and NJ Pazdernik: Aging and apoptosis. In: Molecular Biotechnology. 2009, pp. 523-550, doi : 10.1007 / 978-3-8274-2189-0_20 ISBN 978-3-8274-2128-9 .
- ↑ AB Mitnitski et al. a .: Frailty, fitness and late-life mortality in relation to chronological and biological age. In: BMC Geriatr. 2, 2002, 1; PMID 11897015 ; PMC 88955 (free full text).
- ↑ D. Jones et al. a .: Evaluation of a frailty index based on a comprehensive geriatric assessment in a population based study of elderly Canadians. In: Aging Clin Exp Res. 17, 2005, pp. 465-471. PMID 16485864 .
- ↑ a b S. D. Searle u. a .: A standard procedure for creating a frailty index. In: BMC Geriatr. 8, 2008, p. 24; PMID 18826625 ; PMC 2573877 (free full text).
- ↑ Age Scan determines the exact biological age. In: Die Welt from October 14, 2000.
- ↑ TH Beaty u. a .: Impaired pulmonary function as a risk factor for mortality. In: Am J Epidemiol. 116, 1982, pp. 102-113. PMID 7102646 .
- ^ Commission on Life Sciences (editor): Aging in today's environment. National Academy Press, 1987, pp. 40 f.
- ↑ Horvath S: DNA methylation age of human tissues and cell types . In: Genome Biology . 14, no.R115, 2013.
- ^ RA Miller: Biomarkers of aging: Prediction of longevity by using age-sensitive T-cell subset determinations in a middle-aged, genetically heterogeneous mouse population . In: JOURNALS OF GERONTOLOGY . 56, No. 4, 2001, pp. B180-B186. PMID 11283189 .
- ^ A b U. Brandenburg, JP Domschke: Aging is not a disease. In: The future looks old. 2007, ISBN 978-3-8349-9532-2 , pp. 69-71. doi : 10.1007 / 978-3-8349-9532-2_4
- ↑ R. Smith: In search of "non-disease". In: BMJ. 324, 2002, pp. 883-885. doi: 10.1136 / bmj.324.7342.883 ; PMID 11950739 .
- ↑ Speakers Aubrey de Gray: Seeker of immortality. at ted.com , accessed August 9, 2010
- ↑ A. de Gray, M. Rae: Never old! transcript Verlag, 2010, ISBN 978-3-8376-1336-0 , pp. 27f. limited preview in Google Book search
- ↑ S. Heuer: "Aging is a disease" In: Technologie Review. 2, 2010.
- ↑ a b c d C. J. Kenyon: The genetics of aging. In: Nature. 464, 2010, pp. 504-512. doi: 10.1038 / nature08980 PMID 20336132 (Review)
- ↑ K. Rockwood, A. Mitnitski: Frailty in relation to the accumulation of deficits. In: J Gerontol Biol Sci Med Sci. 62A, 2007, pp. 722-727; PMID 17634318
- ↑ a b A. Kulminski et al. a .: Cumulative index of health disorders as an indicator of aging-associated processes in the elderly: Results from analyzes of the National Long Term Care Survey. In: Mech Aging Dev. 128, 2007, pp. 250-258. doi: 10.1016 / j.mad.2006.12.004 ; PMID 17223183 ; PMC 1866299 (free full text).
- ↑ K. Rockwood et al. a .: Long-term risks of death and institutionalization of elderly people in relation to deficit accumulation at age 70. In: J Am Geriatr Soc. 54, 2006, pp. 975-979. doi: 10.1111 / j.1532-5415.2006.00738.x ; PMID 16776795 .
- ↑ G. Grupe et al. a .: anthropology. Verlag Springer, 2004, ISBN 3-540-21159-4 , p. 287. Restricted preview in the Google book search
- ^ WC Orr u. a .: Aging and neural control of the GI tract: IV. Clinical and physiological aspects of gastrointestinal motility and aging. ( Memento of the original from July 9, 2008 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. In: Am J Physiol-Gastroint Liver Physiol . 283, 2002, pp. G1226-G1231. PMID 12433662
- ↑ MF Holick: Environmental factors that influence the cutaneous production of vitamin D. In: Am J Clin Nutr. 61, 19995, pp. 638S-645S. PMID 7879731
- ^ A b E. Nieschlag : Andrology: Fundamentals and clinics of reproductive health of men. Verlag, Springer, 2009, ISBN 978-3-540-92962-8 , p. 246. Restricted preview in the Google book search
- ↑ Y. Gorina et al. a .: Trends in Causes of Death among Older Persons in the United States. (PDF; 359 kB) In: Aging Trends. No. 6, National Center for Health Statistics, 2006, based on data from Deaths: Leading Causes of 2002. NVSR, Vol. 53, No. 17.
- ↑ A. Fischer: The 100-year-olds remain the exception for the time being. In: The world. February 20, 2001
- ^ A. Ruiz-Torres: Introduction. In: D. Ganten, K. Ruckpaul (Hrsg.): Molecular medical principles of age-specific diseases. Verlag Springer, 2004, ISBN 3-540-00858-6 , p. 4. Restricted preview in the Google book search
- ↑ AM Herskind u. a .: The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870-1900. In: Hum Genet. 97, 1996, pp. 319-323. PMID 8786073
- ^ B. Gompertz: On the nature of the function expressive of the law of human mortality and on a new mode of determining life contingencies. In: Philos Trans R Soc Lond. 115, 1825, pp. 513-585. doi: 10.1098 / rstl.1825.0026
- ↑ Expertise on the fourth report on the elderly by the Federal Government. Volume 1, German Center for Age Issues (Ed.), Vincentz Network GmbH & Co KG, 2002, ISBN 3-87870-921-8 , p. 37. Restricted preview in Google book search
- ↑ a b c H. W. Wahl , A. Kruse : Future aging: Individual and social setting the course. Verlag Springer, 2009, ISBN 978-3-8274-2058-9 , pp. 112-113. limited preview in Google Book search
- ^ TB Kirkwood : Understanding aging from an evolutionary perspective. In: J Intern Med. 263, 2008, pp. 117-127. PMID 18226090
- ↑ Odera K, Goto S, Takahashi R: Age-related change of endocytic receptors megalin and cubilin in the kidney in rats . In: Biogerontology . 8, No. 5, October 2007, pp. 505-15. doi : 10.1007 / s10522-007-9093-7 . PMID 17453355 .
- ↑ T. Hofmann: Cellular senescence - when cells retire. ( Memento of the original from March 28, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Lecture from December 13, 2005
- ^ A b c T. C. Goldsmith: The Evolution of Aging. (PDF; 2.5 MB) 3rd edition, Azinet, 2010, ISBN 978-0-9788709-0-4 , limited preview in the Google book search for the 2nd edition from 2006.
- ↑ R. Naylor et al. a .: Boom and bust: a review of the physiology of the marsupial genus Antechinus. In: J Comp Physiol B. 178, 2008, pp. 545-562. PMID 18210128 (Review)
- ↑ a b T. Schmidt u. a .: Physiological potentials of longevity and health in an evolutionary and cultural context - basic requirements for a productive life. ( Memento from January 12, 2012 in the Internet Archive ) In: M. Baltes, L. Montada (Ed.): Productive life in old age. Campus-Verlag, 1996, ISBN 3-593-35456-X , pp. 69-130.
- ↑ Key molecule of aging discovered , PM DKFZ of June 20, 2018, accessed on June 21, 2018
- ↑ P. Scaffidi et al. a .: The Cell Nucleus and Aging: Tantalizing Clues and Hopeful Promises. In: PLoS Biology . 3, 2005, e395 doi: 10.1371 / journal.pbio.0030395 PMID 16277559 ( Open Access )
- ↑ M. Eriksson et al. a .: Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. In: Nature . 423, 2003, pp. 293-298. PMID 12714972
- ↑ CR Burtner, BK Kennedy: Progeria syndromes and aging: what is the connection? In: Nature Reviews Molecular Cell Biology . 11, 2010, pp. 567-578. doi: 10.1038 / nrm2944 PMID 20651707 (Review)
- ^ V. Gupta, A. Kumar: Dyskeratosis congenita. In: Adv Exp Med Biol. 685, 2010, pp. 215-219. PMID 20687509 (Review)
- ↑ H. Breitsameter: Holistic proteome analysis of the adrenal gland bGH and IGFBP-2 transgenic mice. (PDF; 4.3 MB) Dissertation, LMU Munich, 2007, p. 8.
- ^ A. Bartke, H. Brown-Borg: Life extension in the dwarf mouse. In: Curr Top Dev Biol. 63, 2004, pp. 189-225. PMID 15536017 (Review)
- ↑ CE Finch: The Biology of Human Longevity: Inflammation, Nutrition, and Aging in the Evolution of Lifespans. Academic Press, 2007, ISBN 978-0-12-373657-4 limited preview in Google Book Search
- ^ L. Guarente: Mutant mice live longer. In: Nature. 402, 1999, pp. 243-245. doi: 10.1038 / 46185 PMID 10580490
- ↑ RR Behringer et al. a .: Dwarf mice produced by genetic ablation of growth hormone-expressing cells. In: Genes Dev. 2, 1988, pp. 453-461. PMID 3286373
- ^ GJ Lithgow, JK Andersen: The real Dorian Gray mouse. In: Bioessays. 22, 2000, pp. 410-413. PMID 10797480 (Review)
- ↑ Stress sensor as guardian of the suicide program. In: scinexx. dated April 16, 2008, accessed September 1, 2010
- ↑ Live longer with the "longevity gene". Press release of the Christian-Albrechts-Universität zu Kiel from February 2nd, 2009
- ↑ On the trail of the Methuselah gene. In: The star. February 3, 2009.
- ↑ The 100-year-old gene. In: Focus. February 3, 2009.
- ↑ G. Schütte: In search of the Methuselah genes. In: The world. August 24, 2009.
- ^ BJ Willcox et al. a .: FOXO3A genotype is strongly associated with human longevity In: PNAS. 105, 2008, pp. 13987-13992. doi: 10.1073 / pnas.0801030105 ; PMID 18765803 ; PMC 2544566 (free full text)
- ↑ CV Anselmi: Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. In: Rejuvenation Res. 12, 2009, pp. 95-104. PMID 19415983
- ^ S. Nemoto et al. a .: Nutrient availability regulates SIRT1 through a forkhead-dependent pathway. In: Science. 306, 2004, pp. 2105-2108. PMID 15604409
- ↑ HS Ghosh et al. a .: SIRT1 negatively regulates the mammalian target of rapamycin. In: PLOS ONE . 5, 2010, e9199. PMID 20169165 PMC 2821410 (free full text).
- ^ TE Johnson et al. a .: Gerontogenes mediate health and longevity in nematodes through increasing resistance to environmental toxins and stressors. In: Exp Gerontol. 35, 2000, pp. 687-694. PMID 11053658 (Review)
- ↑ L. Guarente, C. Kenyon: Genetic pathways that regulate aging in model organisms. In: Nature. 408, 2000, pp. 255-262. PMID 11089983 (Review)
- ^ SN Austad: Diverse aging rates in metazoans: targets for functional genomics. In: Mech Aging Dev. 126, 2005, pp. 43-49. PMID 15610761 (Review)
- ↑ JR Speakman: Body size, energy metabolism and lifespan. In: J Exp Biol. 208, 2005, pp. 1717-1730. PMID 15855403 (Review)
- ↑ JP de Magalhães: Comparative Biology of Aging. 2008, accessed August 21, 2010
- ↑ W. Tanner: Aging and death from the perspective of biology. In: Biology in Our Time . 10, 1980, pp. 45-51. doi: 10.1002 / biuz.19800100206
- ^ A b G. C. Williams: Pleiotropy, Natural Selection, and the Evolution of Senescence. In: evolution. 11, 1957, pp. 398-411.
- ^ ZA Medvedev: An attempt at a rational classification of theories of aging. In: Biol Rev Camb Philos Soc. 65, 1990, pp. 375-398. PMID 2205304
- ^ KA Hughes and RM Reynolds: Evolutionary and mechanistic theories of aging. In: Annu Rev Entomol. 50, 2005, pp. 421-445. PMID 15355246 (Review)
- ↑ The Info Guide to Aging theories of aging. (PDF; 186 kB) 2006, accessed on September 1, 2010
- ↑ a b c T. BL Kirkwood : A systematic look at an old problem. In: Nature . 451, 2008, pp. 644-647. doi: 10.1038 / 451644a PMID 18256658
- ↑ R. Peto et al. a .: There is no such thing as aging, and cancer is not related to it. In: A. Likhachev et al. a. (Ed.): Age-related factors in carcinogenesis. Oxford Univ. Press, IARC, 1986, ISBN 92-832-1158-8 , pp. 43-53. (IARC Scientific Publication 58)
- ^ R. Peto , R. Doll : There is no such thing as aging. In: BMJ. 315, 1997, pp. 1030-1032. PMID 9366723 PMC 2127679 (free full text)
- ↑ M. Gilca et al. a .: The oxidative hypothesis of senescence. In: J Postgrad Med. 53, 2007, pp. 207-213. PMID 17700000 (Review)
- ↑ P. Kapahi: Positive correlation between mammalian life span and cellular resistance to stress. In: Free Radic Biol Med. 26, 1999, pp. 495-500. PMID 10218637
- ↑ B. Andziak et al. a .: High oxidative damage levels in the longest-living rodent, the naked mole-rat. In: Aging Cell. 5, 2006, pp. 463-471. PMID 17054663
- ↑ H. van Remmen et al. a .: Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. In: Physiological Genomics . 16, 2003, pp. 29-37. PMID 14679299
- ↑ N. Heinen: The fairy tale of the protective vitamin pills. In: The world . May 11, 2009.
- ↑ G. Bjelakovic et al. a .: Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention. In: JAMA. 297, 2007, pp. 842-857. (Review)
- ↑ TJ Schulz u. a .: Glucose Restriction Extends Caenorhabditis elegans Life Span by Inducing Mitochondrial Respiration and Increasing Oxidative Stress. In: Cell Metabolism . 6, 2007, pp. 280-293. doi: 10.1016 / j.cmet.2007.08.011
- ↑ LE Orgel: The maintenance of the accuracy of protein synthesis and its relevance to aging. In: PNAS. 49, 1963, pp. 517-521. PMID 13940312 PMC 299893 (free full text)
- ↑ LE Organ: The maintenance of the accuracy of protein synthesis and its relevance to aging: a correction. In PNAS 67, 1970, p. 1476. PMID 5274472
- ↑ LE organ: Aging of clones of mammalian cells. In: Nature. 243, 1973, pp. 441-445. PMID 4591306
- ^ The Orgel's Error Catastrophe Theory of Aging and Longevity. Retrieved September 3, 2010
- ^ Science of Aging: Leslie Orgel Proposes the "Error Catastrophe" Theory of Aging. Retrieved March 19, 2014
- ↑ W. Ries and M. Bürger : Methods and findings in aging research. Akademie-Verlag, 1986, ISBN 3-05-500095-1
- ^ V. Becker, H. Schipperges : Entropy and Pathogenesis. Verlag Springer, 1993, ISBN 3-540-56528-0 , p. 50.
- ↑ Vincent Ziswiler: Life on the germ line. In: NZZ Folio . 12, 1997.
- ↑ K. Ott and R. Döring: Theory and practice of strong sustainability. Metropolis-Verlag, 2008, ISBN 3-89518-695-3 , p. 216.
- ↑ DS Goodsell: How cells work: Economy and production in the molecular world. Verlag Springer, 2010, ISBN 3-8274-2453-4 , p. 30. Restricted preview in the Google book search
- ↑ R. Prinzinger : Programmed aging: the theory of maximal metabolic scope. How does the biological clock tick? In: EMBO Rep. 6, 2005, p. S1419. doi: 10.1038 / sj.embor.7400425 PMID 15995655 PMC 1369273 (free full text)
- ↑ J. Türk: Theoretical Aging Mechanisms II. University of Kaiserslautern, 2003.
- ^ Science.ca: Calvin Harley. Retrieved September 3, 2010
- ↑ C. B. Harley et al. a .: The telomere hypothesis of cellular aging. In: Exp Gerontol. 27, 1992, pp. 375-382. PMID 1459213
- ↑ C. B. Harley et al. a .: Telomeres shorten during the aging of human fibroblasts. In: Nature . 345, 1990, pp. 458-460 PMID 2342578
- ↑ Chromosomes don't lie. Interview with Elizabeth Blackburn. NZZ on Sunday, March 26, 2017, accessed on March 29, 2017
- ↑ C. Behl: Molecular Foundations of Aging - An Introduction. In: Molecular medical principles of age-specific diseases. D. Ganten and K. Ruckpaul (eds.), Verlag Springer, 2004, ISBN 3-540-00858-6 , pp. 67-86. limited preview in Google Book search
- ^ RC Allsopp and C. B. Harley: Evidence for a critical telomere length in senescent human fibroblasts. In: Exp Cell Res . 219, 1995, pp. 130-136. PMID 7628529
- ↑ H. Satoh et al. a .: Telomere shortening in peripheral blood cells was related with aging but not with white blood cell count. In: Jpn J Hum Genet. 41, 1996, pp. 413-417. PMID 9088112
- ↑ RM Cawthon et al. a .: Association between telomere length in blood and mortality in people aged 60 years or older. In: Lancet . 361, 2003, pp. 393-395. PMID 12573379
- ↑ E. Furugori et al. a .: Telomere shortening in gastric carcinoma with aging despite telomerase activation. In: J Cancer Res Clin Oncol. 126, 2000, pp. 481-485. PMID 10961392
- ↑ L. Yang et al. a .: Telomere shortening and decline in replicative potential as a function of donor age in human adrenocortical cells. In: Mech Aging Dev. 122, 2001, pp. 1685-1694. PMID 11557273
- ↑ A. Melk et al. a .: Telomere shortening in kidneys with age. In: J Am Soc Nephrol. 11, 2000, pp. 444-453. PMID 10703668
- ↑ H. Aikata et al. a .: Telomere reduction in human liver tissues with age and chronic inflammation. In: Exp Cell Res. 256, 2000, pp. 578-582. PMID 10772830
- ↑ a b K. Takubo et al. a .: Telomere lengths are characteristic in each human individual. In: Exp Gerontol. 37, 2002, pp. 523-531. PMID 11830355
- ↑ NJ Samani et al. a .: Telomere shortening in atherosclerosis. In: Lancet . 358, 2001, pp. 472-473. PMID 11513915
- ↑ T. Kitada: Telomere shortening in chronic liver diseases. In: Biochem Biophys Res Commun . 211, 1995, pp. 33-39. PMID 7779103
- ^ SU Wiemann: Telomere shortening in human liver cirrhosis and the influence of telomere shortening in the context of chronic liver damage on survival, organ homeostasis and the development of hepatocellular carcinomas in the mouse model. Dissertation, University of Hanover, 2004, p. 8f.
- ↑ a b J. Lund: Theories of aging: telomeres and senescence. University of Kentucky, Fall 2008
- ↑ G. Vogel: In contrast to Dolly, cloning resets telomere clock in cattle. In: Science . 288, pp. 586-587. doi: 10.1126 / science.288.5466.586 PMID 10798984
- ↑ S. Chang: A mouse model of Werner Syndrome: what can it tell us about aging and cancer? In: Int J Biochem Cell Biol. 37, 2005, pp. 991-999. PMID 15743673 (Review)
- ↑ M. Raices et al. a .: Uncoupling of Longevity and Telomere Length in C. elegans. In: PLoS Genet . 1, 2005, e30. doi: 10.1371 / journal.pgen.0010030 PMID 16151516 .
- ↑ a b G. Ferbeyre, SW Lowe: Aging: The price of tumor suppression? In: Nature . 415, 2002, pp. 26-27. PMID 11780097
- ↑ L. Hayflick, PS Moorhead: The serial cultivation of human diploid cell strains. In: Exp Cell Res. 25, 1961, pp. 585-621. doi: 10.1016 / 0014-4827 (61) 90192-6 PMID 13905658
- ^ Leonard Hayflick: Cell Aging. In: Ann. Rev. Geront. Geriatric. 1, 1980, pp. 26-67.
- ↑ LA Donehower et al. a .: Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumors. In: Nature. 356, 1992, pp. 215-221. PMID 1552940
- ↑ SD Tyner et al .: p53 mutant mice that display early aging-associated phenotypes. In: Nature. 415, 2002, pp. 45-53. doi: 10.1038 / 415045a PMID 11780111
- ^ J. Campisi: Aging and cancer: the double-edged sword of replicative senescence. In: J Am Geriatric Soc. 45, 1997, pp. 482-488. PMID 9100719 (Review)
- ^ J. Campisi: Cancer, aging and cellular senescence. In: In Vivo. 14, 2000, pp. 183-188. PMID 10757076
- ↑ Ungewitter, H. Scrable: Antagonistic pleiotropy and p53. In: Mech Aging Dev. 130, 2009, pp. 10-17. doi: 10.1016 / j.mad.2008.06.002 PMID 18639575 PMC 2771578 (free full text) (review)
- ↑ J. Campisi: Senescent cells, tumor suppression, and organizational aging: good citizens, bad neighbors. In: Cell. 120, 2005, pp. 513-522. PMID 15734683 (Review)
- ↑ LJ Miller and J. Marx: Apoptosis. In: Science 281, 1998, p. 1301. doi: 10.1126 / science.281.5381.1301
- ^ JC Ameisen: The Evolutionary Origin and Role of Programmed Cell Death in Single Celled Organisms: A New View of Executioners, Mitochondria, Host-Pathogen Interactions and the Role of Death in the Process of Natural Selection. In: A. Lockshin et al. a. (Ed.): When Cells Die. Wiley-Liss, 1998, ISBN 978-0-471-16569-9 .
- ^ A b M. Pollack, C. Leeuwenburgh: Apoptosis and aging: role of the mitochondria . In: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences . tape 56 , no. 11 , 2001, ISSN 1079-5006 , p. B475-482 , PMID 11682568 . (Review)
- ↑ C. Franceschi et al. a .: Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. In: Mech Aging Dev. 128, 2007, pp. 92-105. PMID 17116321 (Review)
- ↑ C. Franceschi et al. a .: inflammation. An evolutionary perspective on immunosenescence. In: Ann NY Acad Sci. 908, 2000, pp. 244-254. PMID 10911963 (Review)
- ↑ G. Candore et al. a .: Biology of longevity: role of the innate immune system. In: Rejuvenation Res. 9, 2006, pp. 143-148. PMID 16608411 (Review)
- ↑ C. Caruso et al. a .: Aging, longevity, inflammation, and cancer. In: Ann NY Acad Sci. 1028, 2004, pp. 1-13. PMID 15915584 (Review)
- ^ C. Franceschi: Inflammaging as a major characteristic of old people: can it be prevented or cured? In: Nutr Rev. 65, 2007, pp. S173-176. PMID 18240544 (Review)
- ↑ a b T. B. Kirkwood: The origins of human aging. In: Philos Trans R Soc Lond B Biol Sci. 352, 1997, pp. 1765-1772. PMID 9460059 (review); PMC 1692133 (free full text)
- ↑ a b c d M. R. Rose u. a .: Evolution of aging since Darwin. (PDF; 239 kB) In: J Genet. 87, 2008, pp. 363-371. PMID 19147926 .
- ↑ A. Weismann: About the duration of life. Verlag G. Fischer, Jena, 1882, (2008 edition: ISBN 978-0-559-76312-0 )
- ↑ TB Kirkwood and T. Cremer: Cytogerontology since 1881: a reappraisal of August Weismann and a review of modern progress. In: Hum Genet. 60, 1982, pp. 101-121. PMID 7042533
- ↑ S. Knell, M. Weber: Menschliches Leben. Verlag Walter de Gruyter, 2009, pp. 55–108. (Chapter 2: Metaphysics of Aging) ISBN 978-3-11-021983-8 doi: 10.1515 / 9783110219845.55 p. 59.
- ^ PB Medawar: An unsolved problem of biology. Lewis, London 1952.
- ↑ a b T. O. Monaco, PS Silveira: Aging is not Senescence: A Short Computer Demonstration and Implications for Medical Practice. In: Clinics (Sao Paulo). 64, 2009, pp. 451-457. PMID 19488612 ; PMC 2694250 (free full text)
- ↑ I. Semsei: On the nature of aging. In: Mech Aging Dev. 117, 2000, pp. 93-108. PMID 10958926 (Review)
- ↑ P. Fabrizio et al. a .: Superoxide is a mediator of an altruistic aging program in Saccharomyces cerevisiae. In: J Cell Biol . 166, 2004, pp. 1055-1067. PMID 15452146 PMC 2172019 (free full text)
- ↑ VD Longo u. a .: Programmed and altruistic aging. (PDF; 341 kB) In: Nature Reviews Genetics. 6, 2005, pp. 866-872. doi: 10.1038 / nrg1706 PMID 16304601 (Review)
- ↑ Programmed vs. Non-Programmed Aging Theory Controversy. www.programmed-aging.org, accessed September 1, 2010
- ^ A b c d P. Ljubuncic, AZ Reznick: The evolutionary theories of aging revisited - a mini-review. In: Gerontology. 55, 2009, pp. 205-216. PMID 19202326 (Review)
- ↑ M. R. Rose et al. a .: Hamilton's Forces of Natural Selection after forty years. In: evolution. 61, 2007, pp. 1265-1276. PMID 17542838
- ^ WD Hamilton : The molding of senescence by natural selection. In: J Theoretical Biology. 12, 1966, pp. 12-45. PMID 6015424
- ↑ B. Dyke et al. a .: Model life table for captive chimpanzees. In: Am J Primatol. 37, 1995, pp. 25-37. doi: 10.1002 / ajp.1350370104
- ↑ K. Hill et al. a .: Mortality rates among wild chimpanzees. In: J Hum Evol. 40, 2001, pp. 437-450. PMID 11322804
- ↑ SN Austad: Retarded senescence in an insular population of Virginia opossums. In: J Zool. 229, 1993, pp. 695-708. doi: 10.1111 / j.1469-7998.1993.tb02665.x
- ^ JBS Haldane : New paths in genetics. Harper & brothers, New York / London 1942.
- ↑ KA Hughes et al. a .: A test of evolutionary theories of aging. In: PNAS 99, 2002, pp. 14286-14291. PMID 12386342 PMC 137876 (free full text)
- ↑ R. Czepel: "Oldies but Goldies": new evolutionary theory of aging. In: science.ORF.at , accessed on September 1, 2010
- ^ RD Lee: Rethinking the evolutionary theory of aging: transfers, not births, shape senescence in social species. In: PNAS. 100, 2003, pp. 9637-9642. PMID 12878733 ; PMC 170970 (free full text)
- ↑ E. Voland: Aging and the life course - an evolutionary biological outline. In: H. Künemund, M. Szydlik (Ed.): Generations. Vs Verlag, ISBN 978-3-531-15413-8 , p. 26. Restricted preview in the Google book search
- ↑ F. Dziock: Survival strategies and food specialization in predatory hover flies (Diptera, Syrphidae). Dissertation, University of Osnabrück, 2002
- ↑ TBL Kirkwood : How can we live forever? In: BMJ. 313, 1996, p. 1571. PMID 8990987 ; PMC 2359091 (free full text)
- ^ TB Kirkwood : Evolution of Aging. In: Mech Aging Dev. 123, 2002, pp. 737-745. PMID 11869731
- ^ MR Rose : Laboratory evolution of postponed senescence in Drosophila melanogaster. In: Evolution 38, 1984, pp. 1004-1010. doi: 10.2307 / 2408434
- ↑ MR Rose : Making SENSE: strategies for engineering negligible senescence evolutionarily. In: Rejuvenation Res 11, 2008, pp. 527-534. PMID 18393654
- ↑ DH Nussey et al. a .: The rate of senescence in maternal performance increases with early-life fecundity in red deer. In: Ecol Lett 9, 2006, pp. 1342-1350. PMID 17118008 PMC 2366114 (free full text)
- ↑ a b A. Charmantier u. a .: Age-dependent genetic variance in a life-history trait in the mute swan. In: Proc R Soc B 273, 2006, pp. 225-232. doi: 10.1098 / rspb.2005.3294 PMID 16555791 PMC 1560027 (free full text)
- ^ TE Reed: Reproductive senescence in a long-lived seabird: rates of decline in late-life performance are associated with varying costs of early reproduction. In: Am Nat 171, 2008, pp. E89-E101. PMID 18173366
- ↑ WD Bowen et al. a .: Reproductive performance in gray seals: age-related improvement and senescence in a capital breeder. In: J Anim Ecol 75, 2006, pp. 1340-1351. PMID 17032366
- ↑ DH Nussey et al. a .: Testing for genetic trade-offs between early- and late-life reproduction in a wild red deer population. In: Proc Biol Sci 275, 2008, pp. 745-750. PMID 18211877 PMC 2366114 (free full text) ( Open Access )
- ^ DJ Holmes and MA Ottinger: Birds as long-lived animal models for the study of aging. In: Exp Gerontol 38, 2003, pp. 1365-1375. doi: 10.1016 / j.exger.2003.10.018 PMID 14698817 (Review)
- ↑ DJ Holmes et al. a .: Reproductive aging in female birds. In: Exp Gerontol 38, 2003, pp. 751-756. doi: 10.1016 / S0531-5565 (03) 00103-7 PMID 12855282
- ↑ RM Nesse , GC Williams : On Darwinian Medicine. (PDF; 90 kB) In: Life Science Research. 3, 1999, pp. 1-17.
- ^ SN Austad : Why we age: what science is discovering about the body's journey throughout life. J. Wiley & Sons, 1997, ISBN 0-471-29646-5
- ↑ CW Fox et al. a .: The genetic architecture of life span and mortality rates: gender and species differences in inbreeding load of two seed-feeding beetles. In: Genetics. 174, 2006, pp. 763-773. PMID 16888331 PMC 1602065 (free full text)
- ↑ DE Promislow: Costs of Sexual Selection in Natural Populations of Mammals. In: Proc R Soc Lond B. 247, 1992, pp. 203-210. doi: 10.1098 / rspb.1992.0030
- ↑ A. A. Maklakov et al. a .: Sexual selection affects lifespan and aging in the seed beetle. In: Aging Cell. 6, 2007, pp. 739-744. PMID 17725688
- ^ L. Mealey: Sex differences: developmental and evolutionary strategies. Academic Press, 2000, ISBN 0-12-487460-6
- ↑ Gerry McCartney, Lamia Mahmood, Alastair H Leyland, G David Batty, Kate Hunt: Contribution of smoking-related and alcohol-related deaths to the gender gap in mortality: evidence from 30 European countries (PDF; 158 kB), January 12 2011
-
↑ Brent M. Graves, Mac Strand, Alec R. Lindsay: A reassessment of sexual dimorphism in human senescence: Theory, evidence, and causation. In: American Journal of Human Biology. Volume 18, No. 2, 2006, pp. 161-168, doi: 10.1002 / ajhb.20488 .
Women age faster than men. On: Wissenschaft.de from June 7, 2006. - ↑ A. Liker and T. Székely: Mortality costs of sexual selection and parental care in natural populations of birds. In: evolution. 59, 2005, pp. 890-897. PMID 15926698
- ^ IP Owens and PM Bennett: Mortality Costs of Parental Care and Sexual Dimorphism in Birds. In: Proc R Soc Lond B. 257, 1994, pp. 1-8. doi: 10.1098 / rspb.1994.0086
- ↑ a b c T. Bilde u. a .: Sex differences in the genetic architecture of lifespan in a seed beetle: extreme inbreeding extends male lifespan. In: BMC Evolutionary Biology. 9, 2009, 33. doi: 10.1186 / 1471-2148-9-33 PMID 19200350 ( Open Access )
- ^ R. Trivers : Social evolution. Verlag Benjamin / Cummings, 1985, ISBN 0-8053-8507-X
- ↑ J. Tower: Sex-specific regulation of aging and apoptosis. In: Mech Aging Dev. 127, 2006, pp. 705-718. PMID 16764907 (Review)
- ↑ AC James and JW Ballard: Mitochondrial genotype affects fitness in Drosophila simulans. In: Genetics. 164, 2003, pp. 187-194. PMID 12750331 PMC 1462568 (free full text)
- ^ A b T. H. Clutton-Brock and K. Isvaran: Sex differences in aging in natural populations of vertebrates. In: Proc Biol Sci 274, 2007, pp. 3097-3104. doi: 10.1098 / rspb.2007.1138 PMID 17939988 PMC 2293943 (free full text)
- ^ RL Trivers: Parental investment and sexual selection. In: B. Campbell (Ed.): Sexual selection and the descent of man. Aldine-Atherton Verlag, 1972, pp. 136-179.
- ↑ JL Horn, RB Cattell: Refinement and test of the theory of fluid and crystallized general intelligences. In: Journal of educational psychology. Volume 57, Number 5, October 1966, pp. 253-270, ISSN 0022-0663 . PMID 5918295 .
- ↑ a b Changes in Age: The Process of Aging ( Memento of May 16, 2013 in the Internet Archive ). Humboldt University Berlin, July 29, 2007.
- ↑ Sven Thönes, Michael Falkenstein, Patrick D. Gajewski: Multitasking in aging: ERP correlates of dual-task costs in young versus low, intermediate, and high performing older adults . In: Neuropsychologia . tape 119 , October 1, 2018, ISSN 0028-3932 , p. 424-433 , doi : 10.1016 / j.neuropsychologia.2018.09.003 ( sciencedirect.com [accessed September 19, 2019]).
- ↑ Erik Kirk, Dominic N. Reeds, Brian N. Finck, Mitra S. Mayurranjan, Bruce W. Patterson: Dietary Fat and Carbohydrates Differentially Alter Insulin Sensitivity During Caloric Restriction . In: Gastroenterology . tape 136 , no. 5 , May 1, 2009, ISSN 0016-5085 , p. 1552–1560 , doi : 10.1053 / j.gastro.2009.01.048 ( sciencedirect.com [accessed September 19, 2019]).
- ↑ Memory: Gaps in memory - With brain jogging, the memory performance of older people can be mobilized . In: Der Spiegel . No. 37 , 1990, pp. 256-259 ( online ).
- ↑ Brain in old age: movement slows down wasting . In: Spiegel Online . Article on neurology.org , October 13, 2010
- ↑ CF Emery, D. Finkel, NL Pedersen: Pulmonary Function as a Cause of Cognitive Aging Archived from the original on April 9, 2016. Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. In: Psychological Science . 23, No. 9, 2012, pp. 1024-1032. Retrieved October 9, 2012.
- ↑ Poorer Lung Health Leads to Age-Related Changes in Brain Function . In: Science Daily
- ^ I. Grossmann, J. Na u. a .: Reasoning about social conflicts improves into old age. In: Proceedings of the National Academy of Sciences . Volume 107, Number 16, April 2010, pp. 7246-7250, ISSN 1091-6490 . doi: 10.1073 / pnas.1001715107 . PMID 20368436 . PMC 2867718 (free full text).
- ↑ hda / ddp: Psychology: Wisdom actually comes with age. In: Spiegel Online. dated April 6, 2010
- ↑ Andreas Maercker & Simon Forstmeier (eds.): The life review in therapy and counseling. Berlin, Springer, 2013.
- ↑ W. Köhler (Ed.): Aging and lifetime. In: Nova acta Leopoldina. Volume 81, 314, 1999, German Academy of Natural Scientists Leopoldina, ISBN 3-8304-5073-7 .
- ^ M. Künzel: The influence of physical activity on the aging process with special consideration of the two most common diseases of civilization that lead to death: cancer and cardiovascular diseases. ( Memento of the original from November 7, 2017 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Written term paper, University of Regensburg, 2008.
- ↑ Klaus R. Schroeter : The myth of successful aging . Kiel 2010 (presentation by the author at the annual conference of the German Society for Geriatric Dentistry)
- ↑ R. Weindruch u. a .: The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. In: Journal of Nutrition. 116, 1986, pp. 641-654. PMID 3958810
- ↑ EJ Masoro: Caloric restriction: A key to understanding and Modulating aging. Research profiles in aging. Verlag Elsevier Science B.V., 2003, ISBN 0-444-51162-8
- ↑ R. Walford and R. Weindruch: The retardation of aging and disease by dietary restriction. Charles C. Thomas Publisher, 1988, ISBN 0-398-05496-7
- ↑ EJ Masoro: Dietary restriction and aging. In: J Am Geriatr Soc. 41, 1993, pp. 994-999. PMID 8409187
- ↑ JA Mattison, GS Roth et al. a .: Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. In: Nature. Volume 489, Number 7415, September 2012, pp. 318-321. doi: 10.1038 / nature11432 . PMID 22932268 .
- ↑ L. Fontana et al. a .: Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. In: PNAS. 101, 2004, pp. 6659-6663. PMID 15096581
- ↑ L. Fontana et al. a .: Calorie restriction or exercise: effects on coronary heart disease risk factors. A randomized, controlled trial. In: Am J Physiol-Endocrinol Metab . 293, 2007, pp. E197-202. PMID 17389710
- ↑ E. P. Weiss et al. a .: Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial. In: Am J Clin Nutr. 84, 2006, pp. 1033-1042. PMID 17093155 PMC 1941677 (free full text)
- ↑ D. E. Larson-Meyer et al. a .: Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects. In: Diabetes Care . 29, 2006, pp. 1337-1344. PMID 16732018
- ↑ T. E. Meyer et al. a .: Long-term caloric restriction ameliorates the decline in diastolic function in humans. In: J Am College Cardiol. 47, 2006, pp. 398-402. PMID 16412867
- ↑ a b c H. Liu u. a .: Systematic review: the safety and efficacy of growth hormone in the healthy elderly. In: Ann Intern Med. 146, 2007, pp. 104-115. PMID 17227934
- ^ RJ Mc Carter and J. Palmer: Energy metabolism and aging: a lifelong study of Fischer 344 rats. In: Am J Physiol. 263, 1992, pp. E448-452. PMID 1415524
- ↑ K. Hounthoofd et al. a .: No reduction of metabolic rate in food restricted Caenorhabditis elegans. In: Experimental Gerontology. 37, 2002, pp. 1359-1369. PMID 12559405
- ↑ R. Pamplona et al. a .: Oxidative, glycoxidative and lipoxidative damage to rat heart mitochondrial proteins is lower after 4 months of caloric restriction than in age-matched controls. In: Mech Aging Dev. 123, 2002, pp. 1437-1346. PMID 12425950
- ↑ S. Miwa et al. a .: Lack of correlation between mitochondrial reactive oxygen species production and life span in Drosophila. In: Ann NY Acad Sci. 1019, 2004, pp. 388-391. PMID 15247051 (Review)
- ↑ EJ Masoro: Overview of caloric restriction and aging. In: Mech Aging Dev. 126, 2005, pp. 913-922. PMID 15885745 (Review)
- ↑ Y. Higami et al. a .: Adipose tissue energy metabolism: altered gene expression profile of mice subjected to long-term caloric restriction. In: FASEB J. 18, 2003, pp. 415-417. PMID 14688200
- ↑ J. Türk: Caloric restriction and life expectancy - A mathematical model. University of Kaiserslautern, December 10, 2004
- ↑ JA Ehrenfried u. a .: Caloric restriction increases the expression of heat shock protein in the gut. In: Ann Surg. 223, 1996, pp. 592-599. PMID 8651750 PMC 1235189 (free full text)
- ↑ C. Cantó and J. Auwerx: Caloric restriction, SIRT1 and longevity. In: Trends Endocrinol Metab. 20, 2009, pp. 325-331. PMID 19713122
- ↑ Y. Higami et al. a .: Energy restriction lowers the expression of genes linked to inflammation, the cytoskeleton, the extracellular matrix, and angiogenesis in mouse adipose tissue. In: J Nutr. 136, 2006, pp. 343-352. PMID 16424110
- ↑ RM Anderson et al. a .: Caloric restriction and aging: studies in mice and monkeys. In: Toxicol Pathol . 37, 2009, pp. 47-51. PMID 19075044 (Review)
- ↑ E. J. Masoro et al. a .: Action of food restriction in delaying the aging process. In: PNAS . 79, 1982, pp. 4239-4241. PMID 6955798
- ↑ R. M. Anson et al. a .: Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. In: PNAS . 100, 2003, pp. 6216-6220. PMID 12724520 ; PMC 156352 (free full text)
- ↑ a b c D. Heutling, H. Lehnert : Hormone Therapy and Anti-Aging - Is there an indication? In: The internist . 49, 2008, pp. 570-580. doi: 10.1007 / s00108-008-2110-3 . PMID 18389196 .
- ↑ A. Römmler: Adrenopause and dehydroepiandrosterone: pharmacotherapy versus substitution. In: Gynäkol Obstetric Rundsch. 43, 2003, pp. 79-90. doi: 10.1159 / 000069165
- ^ OT Wolf: Effects of Dehydroepiandrostone (DHEA) Replacement on Cognitive Performance in Humans: Four Placebo Controlled Double Blind Studies. Verlag Cuvillier, 1998, ISBN 3-89712-062-3
- ^ MR Rose : Adaptation, aging, and genomic information. (PDF; 322 kB) In: Aging. 1, 2009, pp. 444-450. PMID 2015752 (Review, in Open Access )
- ^ J. Rice: First Drug Shown to Extend Life Span in Mammals. In: Technology Review. July 8, 2009
- ↑ MV Blagosklonny Validation of anti-aging drugs by treating age-related diseases. (PDF; 273 kB) In: Aging. 1, 2009, pp. 281–288, PMID 20157517 , PMC 2806014 (free full text) (review, in open access )
- ↑ K. Zarse, T. Terao and a .: Low-dose lithium uptake promotes longevity in humans and metazoans. In: European Journal of Nutrition . Volume 50, Number 5, August 2011, pp. 387-389, ISSN 1436-6215 . doi: 10.1007 / s00394-011-0171-x . PMID 21301855 . PMC 3151375 (free full text).
- ↑ T. Rabe, T. Strowitzki: Anti-aging medicine on the way to science. In: Health. Heidelberger Jahrbücher, 2007, Volume 50, pp. 351–377. doi : 10.1007 / 978-3-540-48562-9_20
- ↑ C. Werner: Emotions influence aging so drastically. In: The world. 7 August 2010
- ↑ Perspectives on Psychological Science: "The Influence of Age-Related Cues on Health and Longevity", Langer, Chung, Hsu 2010
- ^ BR Levy, MD Slade et al. a .: Longevity increased by positive self-perceptions of aging. In: Journal of personality and social psychology. Volume 83, Number 2, August 2002, pp. 261-270, ISSN 0022-3514 . PMID 12150226 .
- ^ RH Wilkins: Neurosurgical Classic-XVII Edwin Smith Surgical Papyrus. In: Journal of Neurosurgery. 1964, pp. 240-244.
- ^ Ed. R. Helm (Leipzig), 1898; rev. J. Préaux, 1979
- ↑ Udo Jongebloed: Aging and senescence of the phloem and the leaf by Ricinus communis L. Bayreuth 2003, DNB 96798372X , urn : nbn: de: bvb: 703-opus-340 (dissertation, University of Bayreuth).
- ↑ a b c d H. P. Meier-Baumgartner: Geriatrics - Origin, Claim and Reality. In: European Journal of Geriatrics. 11, 2009, pp. 93-97.
- ^ Terence: Phormio. 4, 1, 19
- ↑ Bible quote: 1 Kings 1,1-4 EU
- ↑ CW Hufeland: Macrobiotics or The Art of Extending Human Life. 8th edition, Verlag Georg Reimer, 1860. limited preview in the Google book search
- ↑ D. Platt: Age-related organ changes and their significance for pharmacotherapy. In: Natural Sciences. 70, 1983, pp. 15-22. doi: 10.1007 / BF00365952
- ↑ E. Steinach: Rejuvenation through experimental revitalization of the aging pubertal gland. In: Endocrinology. 5, 1921, p. 238. doi: 10.1210 / endo-5-2-238
- ↑ T. Gillyboeuf: The Famous Doctor Who inserts Monkey Glands in Millionaires. In: The Journal of the EE Cummings Society. 2000, pp. 44-45.
- ↑ C. Sengoopta: Rejuvenation and the prolongation of life: science or quackery? In: Perspectives in Biology and Medicine. 37, 1993, p. 55.
- ↑ D. Hamilton: The Monkey Gland Affair. Chatto & Windus, London 1986.
- ↑ D. Schultheiss: A Brief History of Testosterone. In: Der Urologe A. 49, pp. 51-55. doi: 10.1007 / s00120-009-2199-6
- ↑ C. López-Otín, EP Diamandis: Breast and prostate cancer: an analysis of common epidemiology, genetic and biochemical features. In: Endocr Rev . 19, 1998, pp. 365-396. PMID 9715372 (Review).
- ^ P. Niehans: 20 years of cellular therapy. Urban and Schwarzenberg Publishing House, 1952
