Does SIRT-1 Mediate Calorie Restriction and Prolong Life? – A Mini Review

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Calorie restriction is the only intervention proved to prolong both average and maximum lifespan in yeast, worms, fish, rodents and possibly primates. Not only does the regimen prolong life, but it also reduces the incident of numerous age-related diseases like diabetes, atherosclerosis or cancer and slows down ageing. Mechanisms by which that is thought to occur have not yet been elucidated, but they probably involve reactive oxygen species signaling, insulin growth factor and transcriptional factors. Here, special emphasis is given to SIRT1 - silent information regulator. There is sound evidence showing that SIRT1 is a key player in mediating physiological response to calorie restriction and that its overexpression is correlated with extended lifespan. The possible mechanism leading to its elevated levels is high NAD/NADH ratio, observed in Sir2 in yeast. SIRT1 increases glucose production, enhances fat mobilization, stimulates angiogenesis, prevents neuronal degeneration and rises insulin sensitivity. Therefore, it seems to be a very beneficial factor activated by such a simple intervention that is calorie restriction.

1. Araki T., Sasaki Y., Milbrandt J., Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science, 2004, 305, 1010-1013.

2. Blüher M., Kahn B.B., Kahn C.R., Extended longevity in mice lacking the insulin receptor in adipose tissue. Science, 2003, 5606, 572-574.

3. Boily G., Seifert E.L., Bevilacqua L., He X.H., Sabourin G., Estey C., et al., SirT1 regulates energy metabolism and response to caloric restriction in mice. PLoS One, 2008, 3, e1759.

4. Bordone L., Cohen D., Robinson A., Motta M.C., van Veen E., Czopik A., et al., SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell, 2007, 6, 759-767.

5. Cantó C., Auwerx J., Caloric restriction, SIRT1 and longevity. Trends Endocrinol. Metab., 2009, 20, 325-331.

6. Chen D., Steele A.D., Lindquist S., Guarente L., Increase in activity during calorie restriction requires Sirt1. Science, 2005, 310, 1641.

7. Chong Z.Z., Lin S.H., Li F., Maiese K., The sirtuin inhibitor nicotinamide enhances neuronal cell survival during acute anoxic injury through AKT, BAD, PARP, and mitochondrial associated “anti- apoptotic’’ pathways. Curr. Neurovasc. Res., 2005, 2, 271-285.

8. Cohen H.Y., Miller C., Bitterman K.J., Wall N.R., Hekking B., Kessler B., et al., Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science, 2004, 305, 390-392.

9. Haigis M.C., Guarente L.P., Mammalian sirtuins-emerging roles in physiology, aging, and calorie restriction. Genes Dev., 2006, 20, 2913-2921.

10. Hebert A.S., Dittenhafer-Reed K.E., Yu W., Bailey D.J., Selen E.S., Boersma M.D., Carson J.J., Tonelli M., Balloon A.J., Higbee A.J., Westphall M.S., Pagliarini D.J., Prolla T.A., Assadi- Porter F., Roy S., Denu J.M., Coon J.J., Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome. Mol. Cell., 2013, 49 186-199.

11. Heilbronn L.K., de Jonge L., Frisard M.I., DeLany J.P., Larson- -Meyer D.E., Rood J., et al., Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial. JAMA, 2006, 295, 1539-1548.

12. Holzenberger M., Dupont J., Ducos B., Leneuve P., Géloën A., Even P.C., IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature, 2003, 421, 182-187.

13. Howitz K.T., Bitterman K.J., Cohen H.Y., Lamming D.W., Lavu S., Wood J.G., et al., Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature, 2003, 425, 191-196.

14. Kaeberlein M., Kirkland K.T., Fields S., Kennedy B.K., Sir2- -independent life span extension by calorie restriction in yeast. PLoS Biol., 2004, 2, e296, 1381-1387.

15. Kim D., Nguyen M.D., Dobbin M.M., et al., SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis. EMBO J., 2007, 26, 3169-3179.

16. Kincaid B., Bossy-Wetzel E., Forever young: SIRT3 a shield against mitochondrial meltdown, aging, and neurodegeneration. Front. Aging Neurosci., 2013, 5, 48.

17. Lin S.J., Ford E., Haigis M., Liszt G., Guarente L., Calorie restriction extends yeast life span by lowering the level of NADH. Genes Dev., 2004, 18, 12-16.

18. Mahlknecht U., Zschoernig B., Involvement of sirtuins in life span and aging related diseases. Adv. Exp. Med. Biol., 2012, 739, 252-261.

19. Moynihan K.A., Grimm A.A., Plueger M.M., Bernal-Mizrachi E., Ford E., Cras-Méneur C., Permutt M.A., Imais S.I., Increased dosage of mammalian Sir2 in pancreatic cells enhances glucose-stimulated insulin secretion in mice. Cell Metab., 2005, 2, 105-117.

20. Nisoli E., Tonetto C., Cardile A., Cozzi V., Bracale R., Tedesco L., et al., Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science, 2005, 310, 314-317.

21. Osborne B., Cooney G.J., Turner N., Are sirtuin deacylase enzymes important modulators of mitochondrial energy metabolism? Biochim. Biophys. Acta, 2014, 1840, SI, 1295-1302.

22. Page M.M., Robb E.L., Salway K.D., Stuart J.A., Mitochondrial redox metabolism: Aging, longevity and dietary effects. Mech. Ageing Dev., 2010, 131, SI, 242-252.

23. Pfl uger P.T., Herranz D., Velasco-Miguel S., Serrano M., Tschöp M.H., Sirt1 protects against high-fat diet-induced metabolic damage. Proc. Natl. Acad. Sci. USA, 2008, 105, 9793-9798.

24. Price N.L., Games A.P., Ling A.J.Y., et al., SIRT1 is required for AMPK activation and the benefi cial effects of resveratrol on mitochondrial function. Cell Metab., 2012, 15, 675-690.

25. Picard F., Kurtev M., Chung N., Topark-Ngarm A., Senawong T., Machado De Oliveira R., et al., Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature, 2004, 429, 771-776.

26. Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W., Label-free quantitative proteomics of the lysine acetylome in mitochondria identifi es substrates of SIRT3 metabolic pathways. Proc. Natl. Acad. Sci. USA, 2013, 110, 6601-6606.

27. Raval A.P., Dave K.R., Pérez-Pinzón M.A., Resveratrol mimics ischemic preconditioning in the brain. J. Cereb. Blood Flow Metab., 2006, 26, 1141-1147.

28. Redman L., Ravussin E., Caloric restriction in humans: impact on physiological, psychological and behavioral outcomes. Antioxid. Redox Signal., 2011, 14, 275-287.

29. Ritz B.W., Akran I., Nogusa S., Gardner E.M., Energy restriction impairs natural killer cell function and increases the severity of infl uenza infection in young adult male C57BL/6 mice. J. Nutr., 2008, 138, 2269-2275.

30. Rodgers J.T., Puigserver P., Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1. Proc. Natl. Acad. Sci. USA, 2007, 104, 12861-12866.

31. Sacher G.A., Life table modifi cations and life prolongation. 1997, in: Handbook of the Biology of Aging (eds. C.E. Finch, L. Hayfl ick). New York: van Nostrand Reinold, pp. 582-638.

32. Sack M.N., Finkel T., Mitochondrial metabolism, sirtuins, and aging. Cold Spring Harb. Perspect. Biol., 2012; 4, 12, e013102.

33. Sakamoto J., Miura T., Shimamoto K., Horio Y., Predominant expression of Sir2alpha, an NAD-dependent histone deacetylase, in the embryonic mouse heart and brain. FEBS Lett., 2004, 556, 281-286.

34. Valerio A., Boroni F., Benarese M., Sarnico I., Ghisi V., Bresciani L.G., et al., NFkappaB pathway: a target for preventing beta-amyloid (Ab)-induced neuronal damage and Abeta42 production. Eur. J. Neurosci., 2006, 23, 1711-1720.

35. Vergnes B., Sereno D., Madjidian-Sereno N., Lemesre J.L., Ouaissi A., Cytoplasmic SIR2 homologue overexpression promotes survival of Leishmania parasites by preventing programmed cell death. Gene, 2002, 296, 139-150.

36. Westphal C.H., Dipp M.A., Guarente L., A therapeutic role for sirtuins in diseases of aging? Trends Biochem. Sci., 2007, 32, 555-560.

37. Yeung F., Hoberg J.E., Ramsey C.S., Keller M.D., Jones D.R., Frye R.A., et al., Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J., 2004, 23, 2369-2380.

38. Zhang C.Y., Baffy G., Perret P., Krauss S., Peroni O., Grujic D., et al., Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell, 2001, 105, 745-755. Submitted: 31 January 2014. Revised: 23 March 2014. Accepted: 14 April 2014. Published on-line: 25 July 2014.

Polish Journal of Food and Nutrition Sciences

The Journal of Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn

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