Sirtuins

from Wikipedia, the free encyclopedia

Sirtuins , also Sir2-like proteins , are a family of multifunctional enzymes from the group of histone deacetylases ( HDAC , EC  3.5.1.98 ). They occur evolutionarily highly conserved in all living things such as bacteria , yeast , worms , insects , mammals and humans, as well as in viruses . While most simple organisms - such as bacteria - have only one or a few sirtuins, yeasts have four and humans have seven different of these enzymes.

The name Sirtuin derived from the gene Sir2 ( s ilent mating type i nformation r egulation 2) from yeast, which is responsible for cellular regulation.

Class III histone deacetylases act on acetylated lysine residues in protein substrates such as B. histone proteins and deacetylate them via an NAD + -dependent mechanism. However, recent studies have shown that they can also remove other acyl residues such as myristoyl and palmitoyl and should therefore be referred to as deacylases. Furthermore, with the exception of Sirt4, a second catalytic mechanism has been described for human sirtuins, ADP-ribosylation ( EC  2.4.2.31 ). This is made responsible for the regulation of aging processes, transcription, apoptosis and stress resistance.

Sirtuin species

Sirtuins are classified according to their amino acid sequence . The following sirtuins are known:

Art Name in humans Name in yeast Name in mice
Yes Sirt1 (Gen:  SIRT1 ) Sir2 or Sir2p, Hst1 or Hst1p Sir2-beta
Ib Sirt2 , Sirt3 Hst2 or Hst2p Sir2l2, Sir2l3
Ic Hst3 or Hst3p, Hst4 or Hst4p
II Sirt4 SIRT4
III Sirt5 SIRT5
IVa Sirt6 SIRT6
IVb Sirt7 SIRT7
U < Discovered in Gram-positive bacteria

Sirtuin substrates

Deacetylation of the classic substrates of sirtuins, the lysine ends of the histones , leads to a change in the basicity of the nitrogen in the lysine residue. With a free amine at the end of the from the histone outstanding nitrogen termini which therefore tortuous condensed DNA more strongly to the protein complex so that the transcription is disturbed by other enzymes or prevented. This results in a gene silencing of the corresponding gene segment, which manifests itself in a reduced expression of the enzymes encoded in this locus. Other important substrates, the activity of which can be modulated by deacetylation or ADP-ribosylation, are shown in the table:

Sirtuin Known substrates Biological function mechanism credentials
Sirt1 AceCS1, Atg5, Atg7, Atg8, BCL6 , B-catenin, FOXO1 , FOXO3a, FOXO4, HES-1, HEY-1, HIC-1, histone H1 (K26), histone H3 (K9, K14), histone H4 (K16 ), H2A.z, HIV Tat Protein, Ku70, LXR, MEF MyoD, NF-κB , p300 / CBP, p53 , p73, PCAF , PGC-1a, Rb, TAFi68 cellular metabolism , increase in insulin response , glucose homeostasis, neuroprotection, anti-inflammatory, cardioprotective, cancer-promoting / inhibiting ?, stimulates HIV transcription, antioxidant, cell protection / aging ADP ribosyl transferase, deacylase
Sirt2 α-tubulin, FOXO1, Foxo3a, histone H3 (K14), histone H4 (K16), p53 Mitosecheckpoint , Mitosestop in the cell cycle , tumor suppressor ( gliomas ), Adipocytendifferentierung , regulation of cellular stress, inhibition of cell adhesion, migration, axon growth ADP ribosyl transferase, deacylase
Sirt3 AceCS2, glutamate dehydrogenase , isocitrate dehydrogenase 2, histone H4 (K16) Mitochondrial NAD + utilization, thermogenesis, cellular metabolism, apoptosis, cell protection / aging ADP ribosyl transferase, deacylase
Sirt4 Glutamate dehydrogenase Mitochondrial NAD + utilization, regulation of insulin secretion ADP ribosyl transferase
Sirt5 Cytochrome c , CPS1 , UOX Regulation of glycolysis Deacylase
Sirt6 Histone H3 (K9, K18, K56), CtIP, NPM1, PKM2, GCN5, TNFα , PARP1 , KAP1, Sirt6 Cellular metabolism, maintenance of telomeres , cell protection / aging ADP ribosyl transferase, deacylase
Sirt7 p53 , NPM1, histone H3, PAF53 Activation of RNA polymerase I, cardiac stress resistance, cell protection / aging Deacetylase

meaning

Due to their ability to modify numerous enzymes and proteins that play a key role in various diseases, sirtuins have become the focus of research in recent years. Above all, the fact that numerous target proteins also play a role in the pathological mechanisms of degenerate cells ( cancer ) gives rise to hope for new therapeutic options for certain types of cancer. Enzymes that play a role in Alzheimer's disease , Parkinson's disease , diabetes mellitus and obesity are also found among the substrates of sirtuins. Their influence on cell aging could provide a better understanding of the aging processes in human cells.

Critical consideration

Because of their life-extending effect on microorganisms, sirtuins are repeatedly referred to in the press as "anti-aging enzymes". These effects of increased Sirt1 activity could be shown in experiments with yeast and the results on other model organisms confirmed by experiments with the sirtuin activator resveratrol . However, these studies cannot simply be transferred to humans, since the extension of the life of the microorganisms is essentially based on calorie restriction . Experiments on mice could not show any prolongation of life, but age-related degenerative diseases could be significantly delayed.

Individual evidence

  1. ↑ Entry on sirtuins. In: Römpp Online . Georg Thieme Verlag, accessed on September 4, 2013.
  2. ↑ Bernd Kleine-Gunk: Resveratrol. Key to a long life? . In: Pharmaceutical newspaper . 29/2007.
  3. ↑ Poonam Bheda, Hui Jing, Cynthia Wolberger , Hening Lin: The Substrate Specificity of Sirtuins. In: Annual Review of Biochemistry. 85, 2016, p. 405, doi : 10.1146 / annurev-biochem-060815-014537 .
  4. ^ RA Frye: Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. In: Biochem. Biophys. Res. Commun. Volume 273, 2000, pp. 793-798. PMID 10873683 .
  5. ↑ Eva Bober: Can sirtuins counteract the aging process? Research report 2008, Max Planck Institute for Heart and Lung Research .
  6. ↑ R. Mostoslavsky include: Genomic instability and aging-like phenotype in the absence of mammalian SIRT6 . In: Cell . tape 124 , no. 2 , 2006, p. 315-329 , doi : 10.1016 / j.cell.2005.11.044 , PMID 16439206 .
  7. ↑ H. Vaziri, SK Dessain, E. Ng Eaton, SI Imai, RA Frye, TK Pandita, L. Guarente, RA Weinberg: hSIR2 (SIRT1) functions as an NAD-dependent p53 deacetylase. In: Cell. 107, 2001, pp. 149-159.
  8. ↑ J. Luo, AY Nikolaev, S. Imai, D. Chen, F. Su, A. Shiloh, L. Guarente, W. Gu: Negative control of p53 by Sir2alpha promotes cell survival under stress. In: Cell. 107, 2001, pp. 137-148.
  9. ^ S. Nemoto, MM Fergusson, T. Finkel: SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1 {alpha}. In: J Biol Chem . 280, 2005, pp. 16456-16460.
  10. ^ Y. Yang, H. Hou, EM Haller, SV Nicosia, W. Bai: Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation. In: EMBO J . 24, 2005, pp. 1021-1032.
  11. ↑ MC Motta, N. Divecha, M. Lemieux, C. Kamel, D. Chen, W. Gu, Y. Bultsma, M. McBurney, Guarente, L. Mammalian: SIRT1 represses forkhead transcription factors. In: Cell. 116, 2004, pp. 551-563.
  12. ^ A. van der Horst, LG Tertoolen, LM de Vries-Smits, RA Frye, RH Medema, BM Burgering : FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2 (SIRT1). In: J Biol Chem. 279, 2004, pp. 28873-28879.
  13. ↑ I. Mattagajasingh, CS Kim, A. Naqvi, T. Yamamori, TA Hoffman, SB Jung, J. DeRicco, K. Kasuno, K. Irani: SIRT1 Promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. In: Proc Natl Acad Sci USA . 104, 2007, pp. 14855-14860.
  14. ↑ X. Zhao, T. Sternsdorf, TA Bolger, RM Evans, TP Yao: Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications. In: Mol Cell Biol. 25, 2005, pp. 8456-8464.
  15. ↑ S. Pagans, A. Pedal, BJ North, K. Kaehlcke, BL Marshall, A. Dorr, C. Hetzer-Egger, P. Henklein, R. Frye, MW McBurney, H. Hruby, M. Jung, E. Verdin, M. Ott: SIRT1 regulates HIV transcription via Tat deacetylation. In: PLoS Biol . 3, 2005, p. E41.
  16. ^ WC Hallows, S. Lee, JM Denu: Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. In: Proc Natl Acad Sci US A. 103, 2006, pp. 10230-10235.
  17. ↑ JT Rodgers, C. Lerin, W. Haas, SP Gygi, BM Spiegelman, P. Puigserver: Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. In: Nature . 434, 2005, pp. 113-118.
  18. ↑ X. Li, S. Zhang, G. Blander, JG Tse, M. Krieger, L. Guarente: SIRT1 deacetylates and positively regulates the nuclear receptor LXR. In: Mol Cell. 28, 2007, pp. 91-106.
  19. ^ IH Lee, L. Cao, R. Mostoslavsky, DB Lombard, J. Liu, NE Bruns, M. Tsokos, FW Alt, T. Finkel: A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. In: Proc Natl Acad Sci US A. 105, 2008, pp. 3374-3379.
  20. ^ HY Cohen, C. Miller, KJ Bitterman, NR Wall, B. Hekking, B. Kessler, KT Howitz, M. Gorospe, R. de Cabo, DA Sinclair: Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. In: Science . 305, 2004, pp. 390-392.
  21. ^ S. Nemoto, MM Fergusson, T. Finkel: Nutrient availability regulates SIRT1 through a forkhead-dependent pathway. In: Science. 306, 2004, pp. 2105-2108.
  22. ↑ N. Stankovic-Valentin, S. Deltour, J. Seeler, S. Pinte, G. Vergoten, C. Guerardel, A. Dejean, D. Leprince: An acetylation / deacetylation-SUMOylation switch through a phylogenetically conserved psiKXEP motif in the tumor suppressor HIC1 regulates transcriptional repression activity. In: Mol Cell Biol. 27, 2007, pp. 2661-2675.
  23. ↑ B. Heltweg, T. Gatbonton, AD Schuler, J. Posakony, H. Li, S. Goehle, R. Kollipara, RA Depinho, Y. Gu, JA Simon, A. Bedalov: Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. In: Cancer Res . 66, 2006, pp. 4368-4377.
  24. ^ S. Wong, JD Weber: Deacetylation of the retinoblastoma tumor suppressor protein by SIRT1. In: Biochem J . 407, 2007, pp. 451-460.
  25. ^ A. Vaquero, M. Scher, D. Lee, H. Erdjument-Bromage, P. Tempst, D. Reinberg: Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin. In: Mol Cell. 16, 2004, pp. 93-105.
  26. ↑ K. Pruitt, RL Zinn, JE Ohm, KM McGarvey, SH Kang, DN Watkins, JG Herman, SB Baylin: Inhibition of SIRT1 reactivates silenced cancer genes without loss of promoter DNA hypermethylation. In: PLoS Genet . 2, 2006, p. E40
  27. ^ B. Chen, DM Nelson, Y. Sadovsky: N-myc down-regulated gene 1 modulates the response of term human trophoblasts to hypoxic injury. In: J Biol Chem. 281, 2006, pp. 2764-2772.
  28. ↑ JM Dai, ZY Wang, DC Sun, RX Lin, SQ Wang: SIRT1 interacts with p73 and suppresses p73-dependent transcriptional activity. In: J Cell Physiol . 210, 2007, pp. 161-166.
  29. ↑ T. Takata, F. Ishikawa: Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression. In: Biochem Biophys Res Commun. 301, 2003, pp. 250-257.
  30. ^ V. Muth, S. Nadaud, I. Grummt, R. Voit: Acetylation of TAF (I) 68, a subunit of TIF-IB / SL1, activates RNA polymerase I transcription. In: EMBO J. 20, 2001, pp. 1353-1362.
  31. ^ BJ North, BL Marshall, MT Borra, JM Denu, E. Verdin: The human Sir2 ortholog, SIRT2, is an NAD + -dependent tubulin deacetylase. In: Mol Cell. 11, 2003, pp. 437-444.
  32. ↑ E. Jing, S. Gesta, CR Kahn: SIRT2 regulates adipocyte differentiation through FoxO1 acetylation / deacetylation. In: Cell Metab . 6, 2007, pp. 105-114.
  33. ↑ F. Wang, M. Nguyen, FX Qin, Q. Tong: SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. In: Aging Cell. 6, 2007, pp. 505-514.
  34. ↑ YH Jin, YJ Kim, DW Kim, KH Baek, BY Kang, CY Yeo, KY Lee: Sirt2 interacts with 14-3-3 beta / gamma and down-regulates the activity of p53. In: Biochem Biophys Res Commun. 368, 2008, pp. 690-695.
  35. ^ A. Vaquero, R. Sternglanz, D. Reinberg: NAD + -dependent deacetylation of H4 lysine 16 by class III HDACs. In: Oncogene . 26, 2007, pp. 5505-5520.
  36. ^ BJ North, BL Marshall, MT Borra, JM Denu, E. Verdin: The human Sir2 ortholog, SIRT2, is an NAD + -dependent tubulin deacetylase. In: Mol Cell. 11, 2003, pp. 437-444.
  37. ↑ as heavy, J. Bunke Borg, RO Verdin, JS Andersen, E. Verdin: Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. In: Proc Natl Acad Sci US A. 103, 2006, p 10224-10229.
  38. ↑ C. Schlicker, M. Gertz, P. Papatheodorou, B. Kachholz, CF Becker, C. Steegborn: Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. In: J Mol Biol. 382, 2008, pp. 790-801.
  39. ↑ N. Ahuja, B. Schwer, S. Carobbio, D. Waltregny, BJ North, V. Castronovo, P. Maechler, E. Verdin: Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase. In: J Biol Chem. 282, 2007, pp. 33583-33592.
  40. ↑ MC Haigis, R. Mostoslavsky, KM Haigis, K. Fahie, DC Christodoulou, AJ Murphy, DM Valenzuela, GD Yancopoulos, M. Karow, G. Blander, C. Wolberger, TA Prolla, R. Weindruch, FW Alt, L Guarente: SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. In: Cell. 126, 2006, pp. 941-954.
  41. ↑ C. Schlicker, M. Gertz, P. Papatheodorou, B. Kachholz, CF Becker, C. Steegborn: Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. In: J Mol Biol. 382, 2008, pp. 790-801.
  42. ↑ Chao Peng, Zhike Lu, Zhongyu Xie, Zhongyi Cheng, Yue Chen: The First Identification of Lysine Malonylation Substrates and Its Regulatory Enzyme . In: Molecular & Cellular Proteomics . tape 10 , no. 12 , December 1, 2011, ISSN  1535-9476 , p. M111.012658 , doi : 10.1074 / mcp.M111.012658 , PMID 21908771 , PMC 3237090 (free full text) - ( mcponline.org [accessed April 7, 2017]).
  43. ↑ Yuya Nishida, Matthew J. Rardin, Chris Carrico, Wenjuan He, Alexandria K. Sahu: SIRT5 Regulates both Cytosolic and Mitochondrial Protein Malonylation with Glycolysis as a Major Target . In: Molecular Cell . tape 59 , no. 2 , July 16, 2015, ISSN  1097-4164 , p. 321-332 , doi : 10.1016 / j.molcel.2015.05.022 , PMID 26073543 , PMC 4571487 (free full text).
  44. ↑ Takashi Nakagawa, David J. Lomb, Marcia C. Haigis, Leonard Guarente: SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle . In: Cell . tape 137 , no. 3 , May 1, 2009, ISSN  1097-4172 , p. 560-570 , doi : 10.1016 / j.cell.2009.02.026 , PMID 19410549 , PMC 2698666 (free full text).
  45. ↑ Minjia Tan, Chao Peng, Kristin A. Anderson, Peter Chhoy, Zhongyu Xie: Lysine glutarylation is a protein posttranslational modification regulated by SIRT5 . In: Cell Metabolism . tape 19 , no. 4 , April 1, 2014, ISSN  1932-7420 , p. 605–617 , doi : 10.1016 / j.cmet.2014.03.014 , PMID 24703693 , PMC 4108075 (free full text).
  46. ↑ Yasuhiko Nakamura, Masahito Ogura, Kasane Ogura, Daisuke Tanaka, Nobuya Inagaki: SIRT5 deacetylates and activates urate oxidase in liver mitochondria of mice . In: FEBS Letters . tape 586 , no. 23 , November 30, 2012, ISSN  1873-3468 , p. 4076-4081 , doi : 10.1016 / j.febslet.2012.10.009 .
  47. ↑ E. Michishita, RA McCord, E. Berber, M. Kioi, H. Padilla-Nash, M. Damian, P. Cheung, R. Kusumoto, TL Kawahara, JC Barrett, HY Chang, VA Bohr, T. Ried, O. Gozani, KF Chua: SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. In: Nature. 452, 2008, pp. 492-496.
  48. ↑ Bo Yang, Bernadette MM Zwaans, Mark Eckersdorff, David B. Lombard: The sirtuin SIRT6 deacetylates H3 K56Ac in vivo to promote genomic stability . In: Cell Cycle . tape 8 , no. 16 , August 15, 2009, ISSN  1538-4101 , p. 2662-2663 , doi : 10.4161 / cc.8.16.9329 , PMID 19597350 , PMC 2728171 (free full text).
  49. ↑ Luisa Tasselli, Yuanxin Xi, Wei Zheng, Ruth I Tennen, Zaneta Odrowaz: SIRT6 deacetylates H3K18ac at pericentric chromatin to prevent mitotic errors and cellular senescence . In: Nature Structural & Molecular Biology . tape 23 , no. 5 , p. 434-440 , doi : 10.1038 / nsmb.3202 .
  50. ↑ Abderrahmane Kaidi, Brian T. Weinert, Chunaram Choudhary, Stephen P. Jackson: Human SIRT6 Promotes DNA End Resection Through CtIP Deacetylation . In: Science . tape 329 , no. 5997 , September 10, 2010, ISSN  0036-8075 , p. 1348-1353 , doi : 10.1126 / science.1192049 , PMID 20829486 , PMC 3276839 (free full text) - ( sciencemag.org [accessed April 7, 2017]).
  51. ↑ Namgyu Lee, Dae-Kyum Kim, Eung-Sam Kim, Sung Jin Park, Jung-Hee Kwon: Comparative interactomes of SIRT6 and SIRT7: Implication of functional links to aging . In: PROTEOMICS . tape 14 , no. 13-14 , July 1, 2014, ISSN  1615-9861 , p. 1610-1622 , doi : 10.1002 / pmic.201400001 .
  52. ↑ John E. Dominy, Yoonjin Lee, Mark P. Jedrychowski, Helen Chim, Michael J. Jurczak: The deacetylase Sirt6 activates the acetyltransferase GCN5 and suppresses hepatic gluconeogenesis . In: Molecular Cell . tape 48 , no. 6 , December 28, 2012, ISSN  1097-4164 , p. 900–913 , doi : 10.1016 / j.molcel.2012.09.030 , PMID 23142079 , PMC 3534905 (free full text).
  53. ↑ Hong Jiang, Saba Khan, Yi Wang, Guillaume Charron, Bin He: SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine . In: Nature . tape 496 , no. 7443 , April 4, 2013, ISSN  1476-4687 , p. 110–113 , doi : 10.1038 / nature12038 , PMID 23552949 , PMC 3635073 (free full text).
  54. ↑ Zhiyong Mao, Christopher Hine, Xiao Tian, ​​Michael Van Meter, Matthew Au: SIRT6 Promotes DNA Repair Under Stress by Activating PARP1 . In: Science . tape 332 , no. 6036 , June 17, 2011, ISSN  0036-8075 , p. 1443–1446 , doi : 10.1126 / science.1202723 , PMID 21680843 ( sciencemag.org [accessed April 7, 2017]).
  55. ↑ Michael Van Meter, Mehr Kashyap, Sarallah Rezazadeh, Anthony J. Geneva, Timothy D. Morello: SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age . In: Nature Communications . tape 5 , 23 September 2014, ISSN  2041-1723 , doi : 10.1038 / ncomms6011 , PMID 25247314 , PMC 4185372 (free full text).
  56. ↑ Gregory Liszt, Ethan Ford, Martin Kurtev, Leonard Guarente: Mouse Sir2 Homolog SIRT6 Is a Nuclear ADP-ribosyltransferase . In: Journal of Biological Chemistry . tape 280 , no. 22 , June 3, 2005, ISSN  0021-9258 , p. 21313-21320 , doi : 10.1074 / jbc.M413296200 , PMID 15795229 ( jbc.org [accessed April 7, 2017]).
  57. ↑ O. Vakhrusheva, C. Smolka, P. Gajawada, S. Kostin, T. Boettger, T. Kubin, T. Braun, E. Bober: Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice. In: Circ Res . 102, 2008, pp. 703-710.
  58. ↑ Namgyu Lee, Dae-Kyum Kim, Eung-Sam Kim, Sung Jin Park, Jung-Hee Kwon: Comparative interactomes of SIRT6 and SIRT7: Implication of functional links to aging . In: PROTEOMICS . tape 14 , no. 13-14 , July 1, 2014, ISSN  1615-9861 , p. 1610-1622 , doi : 10.1002 / pmic.201400001 .
  59. ↑ Matthew F. Barber, Eriko Michishita-Kioi, Yuanxin Xi, Luisa Tasselli, Mitomu Kioi: SIRT7 left H3K18 deacetylation to maintenance of oncogenic transformation . In: Nature . doi : 10.1038 / nature11043 , PMID 22722849 , PMC 3412143 (free full text).
  60. ↑ Sifan Chen, Jeanette Seiler, Magaly Santiago-Reichelt, Kerstin Felbel, Ingrid Grummt: Repression of RNA polymerase I upon stress is caused by inhibition of RNA-dependent deacetylation of PAF53 by SIRT7 . In: Molecular Cell . tape 52 , no. 3 , November 7, 2013, ISSN  1097-4164 , p. 303-313 , doi : 10.1016 / j.molcel.2013.10.010 , PMID 24207024 .
  61. ↑ DW Lamming, M. Latorre-Esteves, O. Medvedik, SN Wong, FA Tsang, C. Wang, SJ Lin, DA Sinclair: HST2 mediates SIR2-independent life-span extension by calorie restriction. In: Science. 309, 2005, pp. 1861-1864.
  62. ^ SJ Lin, PA Defossez, L. Guarente: Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. In: Science. 289, 2000, pp. 2126-2128.
  63. ↑ JG Wood, B. Rogina, S. Lavu, K. Howitz, SL Helfand, M. Tatar, D. Sinclair: Sirtuin activators mimic caloric restriction and delay aging in metazoans. In: Nature. 430, 2004, pp. 686-689.
  64. ↑ DR Valenzano, E. Terzibasi, T. Genade, A. Cattaneo, L. Domenici, A. Cellerino: Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. In: Curr Biol. 16, 2006, pp. 296-300.
  65. ↑ KJ Pearson, JA Baur, KN Lewis, L. Peshkin, NL Price, N. Labinskyy, WR Swindell, D. Kamara, RK Minor, E. Perez, HA Jamieson, Y. Zhang, SR Dunn, K. Sharma, N Pleshko, LA Woollett, A. Csiszar, Y. Ikeno, D. Le Couteur, PJ Elliott, KG Becker, P. Navas, DK Ingram, NS Wolf, Z. Ungvari, DA Sinclair, R. de Cabo: Resveratrol delays age -related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. In: Cell Metab. 8, 2008, pp. 157-168.

literature

See also

Web links