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Time commands age to destroy beauty , oil painting by Pompeo Batoni from 1746
Process in developmental biology
Cell aging
organ aging
aging of multicellular organisms
Gene Ontology
The age of man. Such representations, also known as life stairs , were very popular from the 17th century. The human life course was usually presented in ten steps of ten years each. The climax of life was set at the fifth decade, as it was assumed that man would come closest to perfection at this age.

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

The biological age of an organism (here in humans) is characterized by its vitality. After birth, this value increases to a maximum in the development phase. In senescence it falls continuously and reaches zero with death. A standardized time axis results in similar curves for all mammals and vertebrates .
Examples of different aging processes:
(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.

Primary and Secondary Aging

A distinction is made between two forms of aging, primary and secondary aging.

Ann Pouder (1807–1917) on her 110th birthday. She is one of the few people who has come within the range of the maximum attainable age.
  • 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.


The ages and death. Painting by Hans Baldung around 1540

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

Freshwater polyps (here Hydra viridis ) do not know aging and can theoretically get any age under optimal environmental conditions.
Getting on in years Neapolitan Mastiff
Relationship between survival (bottom) and mortality rates (top) using the example of a population of males of the species Drosophila melanogaster at 25 ° C: The exponential increase in the mortality curve with increasing age is a characteristic of aging. The dashed lines represent a hypothetical population with the same maximum age that is not aging. The mortality curve would be a straight line: the probability of death would be the same at any point in time.

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

Naked mole rats reach a maximum life span nine times higher than mice of the same size

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 roundworm 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

The black-bellied fruit fly ( Drosophila melanogaster , ♂)

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

A spirometer can be used to assess lung function in humans, which decreases with age. Lung function is one of many 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

The prevalence of three typical age-associated diseases (osteoarthritis, cancer and heart disease) as a function of age. In comparison, asthma , a disease with no age association
Physiological changes in various organ systems depending on age. The scale is not linear in the range from 0 to 10 years.
The decrease in substance and function with aging in humans. The starting value (100%) is set for an age of 30 years. The bars show the percentage of substance / function retained at the age of 80.

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
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
Development of life expectancy in Germany with a prognosis for the year 2040: The curve approaches the shape of a rectangle. One therefore speaks of a "rectangularization of the life expectancy curve".

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

In the case of Antechinus agilis , a species of marsupial from the genus of the broad-footed pouch mice, the male dies immediately after mating from the consequences of an overproduction of testosterone and cortisol.

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.


A child with Hutchinson-Gilford syndrome (an inherited disease that causes premature aging).

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 .


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 .


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

The dependence of the maximum life expectancy of captive mammals on their body mass. The double logarithmic representation clearly shows that larger mammals tend to live longer than smaller ones. Exceptions to this rule are, for example, bats and marsupials.
The hierarchy of aging processes.
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."

- George C. Williams, 1957

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. "

- Richard Peto and Richard Doll, 1997

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

Telomeres (red fluorescent) on the ends of human chromosomes (blue) under a fluorescence microscope
The telomeres of the clone sheep Dolly were shortened at birth. The short lifespan and the early aging process of Dolly is attributed to it.

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
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

The possible influence of the expression of the tumor suppressor gene p53 on aging and the development of cancer. An increase in the expression of p53 reduces the incidence of cancer but increases the rate of aging. A reduced expression causes exactly the opposite: reduced aging, but higher risk of cancer.

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.

The survival curves (simplified) for five different organisms (humans in industrialized countries, elephants, crows, crocodiles and dandelions)

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

The survival rate (l x ) and the reproduction rate (m x , top), as well as the probability of reproduction and the proportion of surviving reproduction (bottom) at an individual age (x-axis) of a hypothetical non-aging population. The reproduction probability at age x is the product of l x and m x . The proportion of surviving reproduction can be seen as a measure of the strength of natural selection at age x. The influence of natural selection decreases with increasing age, as very few individuals can reproduce at an advanced age. Most die first. Disadvantageous genes can escape natural selection if their disadvantageous effects only appear in the so-called selection shadow.

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 functional differentiation of life expenditure. In the course of evolution, each species has its own life cycle strategy.

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

The mortality rate as a function of age and gender in the USA in 1999: At a young age, the rates between the sexes differ relatively strongly due to non-age-related effects, such as accidental death. However, the frequency in absolute numbers (logarithmic Y-axis) is quite low here. A mortality value of 0.001 at the age of 20 means that every thousandth (= 0.1%) of the age group has died within one year.
Elderly British couple; anonymous photography, 1860s

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

Effects of calorie restriction on the survival rate of laboratory mice (KR = calorie restriction in% of food reduction)

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

Rapamycin (shown here in the rod model ) is the only active ingredient so far that has been proven to extend the life expectancy of a mammalian species (the house mouse)

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.

Elderly Couple (Oklahoma, 1914)

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 first anti-aging recipes are described in the Edwin Smith papyrus (approx. 17th century BC, with texts from 3000 to 2500 BC) .
Depiction of a fountain of
youth by Lucas Cranach the Elder Ä. from 1546 (painted at the age of 74)

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. "

- ( Gen 6,3  EU )

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.

further reading

Journals on aging

Reference books

Review articles and book contributions

Popular science

Web links

Commons : Aging  - collection of pictures, videos and audio files
Wikiquote: Aging  - Quotes
Wiktionary: Aging  - explanations of meanings, word origins, synonyms, translations


  1. 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.
  2. Original quote: There is no such thing as aging - old age is associated with disease, but does not cause it.
  3. 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

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