Kalori Kısıtlamasının Sirtüinler Aracılığı ile Yaşam Süresine Etkisi: SIRT1 ve SIRT3

Year 2022, Volume: 7 Issue: 2, 351 - 357, 31.05.2022

Ebru Şurgun

Abstract

Maya Sir2 proteininin memeli organizmadaki homoloğu olan sirtüin protein ailesi 7 üyeden oluşmaktadır (SIRT1-7). Sir2 benzerliği en yüksek olan Sirtüin-1 (SIRT1), aktivasyonunun metabolizmaya sağladığı pozitif etkiler nedeniyle dikkat çekmektedir. Sirtüinlerin hücredeki farklı lokalizasyonları, işlevlerinde de çeşitliliğe neden olarak enerji homeostazından DNA onarım mekanizmalarına kadar geniş bir etki alanı sağlamaktadır. Sirtüinlerin keşfedilen ilk regülatörü hücresel nikotinamid adenin dinükleotid (NAD) molekülü olmuştur. Organizmanın normalden az enerji alımına maruz kalması sonucu, oluşan bu kısıtlılık hücrede NAD+/NADH oranının NAD+ lehine değişmesine neden olmaktadır. Oluşan bu yeni denge, mayalardan memelilere her düzeydeki organizmada artmış sirtüin aktivasyonu sonucu uzamış yaşam süresi ile ilişkili bulunmuştur. Deasetilasyon işlevleri keşfedildikten sonra, sirtüinler ‘NAD-bağımlı deasetilaz’lar olarak da anılmaya başlamıştır. Düşük organizmalarda çoğunlukla histon proteinlerinin lizin rezidülerini deasetile etmekle sınırlı olsalar da, sirtünlerin memeli organizmasında çok çeşitli protein hedefleri mevcuttur. Bu derleme makalenin amacı, diyete bağlı değişiklikler ile indüklenebilen sirtüin proteinlerinin önemine dair genel bir bakış açısı sağlamak ve pozitif metabolik işlevleri ile öne çıkan SIRT1 ve SIRT3’ün bazı hedef substratları aracılığıyla metabolizma üzerindeki etkilerini özetlemektir.

Keywords

Sirtüin, enerji, SIRT1, deasetilasyon, epigenetik

Thanks

Bu derleme makalenin oluşturulmasında bilimsel danışmanlık yapan ve yayınlanmak üzere gönderilmeden önce taslakta düzeltme desteği veren danışmanım Dr. Esra Karalar Beyaz’a teşekkürlerimle.

Effect of Energy Restriction on Lifespan via Sirtuins: SIRT1 and SIRT3

Abstract

Sirtuin protein family, the homologue of the yeast Sir2 protein in the mammalian organism, consists of 7 members (SIRT1-7). Sirtuin-1 (SIRT1), which has the highest Sir2 similarity, draws attention due to the positive effects of its activation on metabolism. The different localizations of sirtuins in the cell cause diversity in their functions, providing a wide range of effects from energy homeostasis to DNA repair mechanisms. The first discovered regulator of sirtuins was cellular NAD molecule. As a result of the organism’s exposure to less energy intake than normal, this restriction causes the NAD+/ NADH ratio in the cell to change in favor of NAD+. This new balance has been found to be associated with prolonged lifespan as a result of increased sirtuin activation in organisms at all levels, from yeasts to mammals. After the deacetylation functions were discovered, sirtuins were also referred to as ‘NAD-dependent deacetylase’. Despite being often limited to deacetylate lysine residues of histone proteins in lower organisms, sirtuins have a wide variety of protein targets in the mammalian organism. The purpose of this review article is to provide an overview of the importance of sirtuin proteins that can be induced by dietary changes and to summarize the effects of SIRT1 and SIRT3, which stand out with their positive metabolic functions, on metabolism through some target substrates.

Keywords

Sirtuin, energy, SIRT1, deacetylation, epigenetic

References

• McCay CM, Crowell MF, Maynard LA. The effect of retarded growth upon the length of life span and upon the ultimate body size: one figure. J Nutr. 1935; 10(1): 63–79. Available from: https://doi.org/10.1093/ jn/10.1.63
• Guarente L, Picard F. Calorie restriction--the SIR2 connection. Cell. 2005; 120(4): 473–82. Available from: https://doi.org/10.1016/j. cell.2005.01.029
• Berdichevsky A, Viswanathan M, Horvitz, HR, Guarente L. C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span. Cell. 2006; 125(6): 1165–77. Available from: https://doi. org/10.1016/j.cell.2006.04.036
• Nogueiras R, Habegger KM, Chaudhary N, Finan B, Banks AS, Dietrich MO, Horvath T L et al. Sirtuin 1 and sirtuin 3: physiological modulators of metabolism. Physiol Rev. 2012; 92(3): 1479–514. Available from: https:// doi.org/10.1152/physrev.00022.2011
• Silvestre MF, Viollet B, Caton PW, Leclerc J, Sakakibara I, Foretz M, Holness MC et al. The AMPK-SIRT signaling network regulates glucose tolerance under calorie restriction conditions. Life Sci. 2014; 100(1): 55–0. Available from: https://doi.org/10.1016/j.lfs.2014.01.080
• Yu W, Qin J, Chen C, Fu Y, Wang W. Moderate calorie restriction attenuates age associated alterations and improves cardiac function by increasing SIRT1 and SIRT3 expression. Mol Med Rep. 2018; 18(4): 4087–94. Available from: https://doi.org/10.3892/mmr.2018.9390
• Michan S, Sinclair D. Sirtuins in mammals: insights into their biological function. Biochem J. 2007; 404(1): 1–13. Available from: https://doi. org/10.1042/BJ20070140
• Grabowska W, Sikora E, Bielak-Zmijewska A. Sirtuins, a promising target in slowing down the ageing process. Biogerontology. 2017; 18(4): 447–76. Available from: https://doi.org/10.1007/s10522-017-9685-9
• Lee SH, Lee JH, Lee HY, Min KJ. Sirtuin signaling in cellular senescence and aging. BMB Rep. 2019; 52(1): 24–34. Available from: https://doi. org/10.5483/BMBRep.2019.52.1.290
• Teixeira M, Sanchez-Lopez E, Espina M, Garcia ML, Durazzo A, Lucarini M, Novellino E et al. Sirtuins and SIRT6 in carcinogenesis and in diet. Int J Mol Sci. 2019; 20(19): 4945. Available from: https://doi. org/10.3390/ijms20194945
• Hubbard BP, Sinclair DA. Small molecule SIRT1 activators for the treatment of aging and age-related diseases. Trends Pharmacol Sci. 2014; 35(3): 146–54. Available from: https://doi.org/10.1016/j. tips.2013.12.004
• Asghari S, Asghari-Jafarabadi M, Somi MH, Ghavami SM, Rafraf M. Comparison of calorie-restricted diet and resveratrol supplementation on anthropometric indices, metabolic parameters, and serum Sirtuin-1 levels in patients with nonalcoholic fatty liver disease: a randomized controlled clinical trial. J Am Coll Nutr. 2018; 37(3): 223–33. Available from: https://doi.org/10.1080/07315724.2017.1392264
• Baysal A. Beslenme. 16th ed. Ankara: Hatipoğlu Yayınevi; 2015. 566p.
• Alberts B, Johnson A, Lewis J, Morgan D, Raff M, Roberts K, Walter P. Molecular Biology of The Cell. 6th ed. USA: Garland Science; 2015. 1342p.
• McClure JM, Wierman MB, Maqani N, Smith JS. Isonicotinamide enhances Sir2 protein-mediated silencing and longevity in yeast by raising intracellular NAD+ concentration. J Biol Chem. 2012; 15;287(25): 20957-66. Available from: https://doi.org/10.1074/jbc.M112.367524
• Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011; 14(4): 528–36. Available from: https://doi.org/10.1016/j.cmet.2011.08.014
• Zhao L, Cao J, Hu K, He X, Yun D, Tong T, Han L. Sirtuins and their biological relevance in aging and age-related diseases. Aging Dis. 2020; 11(4): 927–45. Available from: https://doi.org/10.14336/AD.2019.0820
• Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012; 7;13(4): 225-38. Available from: https://doi.org/10.1038/nrm3293
• Schemies J, Uciechowska U, Sippl W, Jung M. NAD(+) -dependent histone deacetylases (sirtuins) as novel therapeutic targets. Med Res Rev. 2010; 30(6): 861–89. Available from: https://doi.org/10.1002/med.20178
• Yu W, Zhou HF, Lin RB, Fu YC, Wang W. Short term calorie restriction activates SIRT1 4 and 7 in cardiomyocytes in vivo and in vitro. Mol Med Rep. 2014; 9(4): 1218–24. Available from: https://doi.org/10.3892/ mmr.2014.1944
• Drew LJ, Hen R. Food for thought: linking caloric intake to behavior via sirtuin activity. Cell. 2011; 147(7): 1436–7. Available from: https://doi. org/10.1016/j.cell.2011.11.052
• Libert S, Pointer K, Bell EL, Das A, Cohen DE, Asara JM, Kapur K et al. SIRT1 activates MAO-A in the brain to mediate anxiety and exploratory drive. Cell. 2011; 147(7): 1459–72. Available from: https:// doi.org/10.1016/j.cell.2011.10.054
• Sun C, Zhang F, Ge X, Yan T, Chen X, Shi X, Zhai Q. SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab. 2007; 6(4): 307–19. Available from: https://doi. org/10.1016/j.cmet.2007.08.014
• Kitada M, Ogura Y, Monno I, Koya D. Sirtuins and type 2 diabetes: role in inflammation, oxidative stress, and mitochondrial function. Front Endocrinol (Lausanne). 2019; 10: 187. Available from: https://doi. org/10.3389/fendo.2019.00187
• Chen D, Bruno J, Easlon E, Lin SJ, Cheng HL, Alt FW, Guarente L. Tissue-specific regulation of SIRT1 by calorie restriction. Genes Dev. 2008; 22(13): 1753–7. Available from: https://doi.org/10.1101/gad.1650608
• Kim HS, Patel K, Muldoon-Jacobs K, Bisht KS, Aykin-Burns N, Pennington JD, van der Meer R et al. SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell. 2010; 17(1): 41–52. Available from: https://doi.org/10.1016/j.ccr.2009.11.023
• Sebaa R, Johnson J, Pileggi C, Norgren M, Xuan J, Sai Y, Tong Q et al. SIRT3 controls brown fat thermogenesis by deacetylation regulation of pathways upstream of UCP1. Mol Metab. 2019; 25:35-49. Available from: https://doi.org/10.1016/j.molmet.2019.04.008
• Hirschey MD, Shimazu T, Goetzman E, Jing E, Schwer B, Lombard DB, Grueter CA et al. SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature. 2010; 464(7285): 121–5. Available from: https://doi.org/10.1038/nature08778
• Yuan H, Marmorstein R. Structural basis for sirtuin activity and inhibition. J Biol Chem. 2012; 14;287(51): 42428-35. Available from: https://doi.org/10.1074/jbc.R112.372300
• Sauve AA. Sirtuin chemical mechanisms. Biochim Biophys Acta. 2010; 1804(8): 1591–603. Available from: https://doi.org/10.1016/j. bbapap.2010.01.021
• Toiber D, Sebastian C, Mostoslavsky R. Characterization of nuclear sirtuins: molecular mechanisms and physiological relevance. Handb Exp Pharmacol. 2011; 206: 189–224. Available from: https://doi. org/10.1007/978-3-642-21631-2_9
• Ong A, Ramasamy TS. Role of Sirtuin1-p53 regulatory axis in aging, cancer and cellular reprogramming. Ageing Res Rev. 2018; 43: 64–80. Available from: https://doi.org/10.1016/j.arr.2018.02.004
• Zhang Z, Lin J, Nisar M, Chen T, Xu T, Zheng G, Wang C et al. The Sirt1/P53 axis in diabetic intervertebral disc degeneration pathogenesis and therapeutics. Oxid Med Cell Longev. 2019; 7959573. Available from: https://doi.org/10.1155/2019/7959573
• Kume S, Uzu T, Horiike K, Chin-Kanasaki M, Isshiki K, Araki S, Sugimoto T et al. Calorie restriction enhances cell adaptation to hypoxia through Sirt1- dependent mitochondrial autophagy in mouse aged kidney. J Clin Invest. 2010; 120(4): 1043-55. Available from: https://doi.org/10.1172/JCI41376
• Jeong J, Juhn K, Lee H, Kim SH, Min BH, Lee KM, Cho MH et al. SIRT1 promotes DNA repair activity and deacetylation of Ku70. Exp Mol Med. 2007; 39(1): 8–13. Available from: https://doi.org/10.1038/emm.2007.2
• Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004; 303(5666): 2011–5. Available from: https:// doi.org/10.1126/science.1094637
• Rahman S, Islam R. Mammalian Sirt1: insights on its biological functions. Cell Commun Signal. 2011; 9(11). Available from: https://doi. org/10.1186/1478-811X-9-11
• Luo H, Chiang HH, Louw M, Susanto A, Chen D. Nutrient sensing and the oxidative stress response. Trends Endocrinol Metab. 2017; 28(6): 449–60. Available from: https://doi.org/10.1016/j.tem.2017.02.008
• Qiang L, Wang L, Kon N, Zhao W, Lee S, Zhang Y, Rosenbaum M et al. Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Pparγ. Cell. 2012; 3;150(3): 620-32. Available from: https://doi.org/10.1016/j.cell.2012.06.027
• Liu L, Zhang T, Hu J, Ma R, He B, Wang M, Wang Y. Adiponectin/SIRT1 Axis Induces White Adipose Browning After Vertical Sleeve Gastrectomy of Obese Rats with Type 2 Diabetes. Obes Surg. 2020; 30(4): 1392-403. Available from: https://doi.org/10.1007/s11695-019-04295-4
• Wang H, Qiang L, Farmer SR. Identification of a domain within peroxisome proliferator-activated receptor gamma regulating expression of a group of genes containing fibroblast growth factor 21 that are selectively repressed by SIRT1 in adipocytes. Mol Cell Biol. 2008; 28(1): 188–200. Available from: https://doi.org/10.1128/MCB.00992-07
• Chen JH, Ouyang C, Ding Q, Song J, Cao W, Mao L. A moderate low-carbohydrate low-calorie diet improves lipid profile, insulin sensitivity and adiponectin expression in rats. Nutrients. 2015; 11;7(6): 4724-38. Available from: https://doi.org/10.3390/nu7064724
• Waldman M, Cohen K, Yadin D, Nudelman V, Gorfil D, Laniado- Schwartzman M, Kornwoski R et al. Regulation of diabetic cardiomyopathy by caloric restriction is mediated by intracellular signaling pathways involving ‘SIRT1 and PGC-1α’. Cardiovasc Diabetol. 2018; 2;17(1): 111. Available from: https://doi.org/10.1186/s12933-018-0754-4
• Olmos Y, Sánchez-Gómez FJ, Wild B, García-Quintans N, Cabezudo S, Lamas S, Monsalve M. SirT1 regulation of antioxidant genes is dependent on the formation of a FoxO3a/PGC-1α complex. Antioxid Redox Signal. 2013; 1;19(13): 1507-21. Available from: https://doi. org/10.1089/ars.2012.4713
• Ponugoti B, Kim DH, Xiao Z, Smith Z, Miao J, Zang M, Wu SY et al. SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism. J Biol Chem. 2010; 285(44): 33959–70. Available from: https://doi.org/10.1074/jbc.M110.122978
• Verma M, Gupta SJ, Chaudhary A, Garg VK. Protein tyrosine phosphatase 1B inhibitors as antidiabetic agents - A brief review. Bioorg Chem. 2017; 70: 267-83. Available from: https://doi.org/10.1016/j.bioorg.2016.12.004
• Qiu X, Brown K, Hirschey MD, Verdin E, Chen D. Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab. 2010; 12(6): 662–7. Available from: https://doi.org/10.1016/j. cmet.2010.11.015
• Someya S, Yu W, Hallows WC, Xu J, Vann JM, Leeuwenburgh C, Tanokura M et al. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell. 2010; 143(5): 802–12. Available from: https://doi.org/10.1016/j.cell.2010.10.002
• Chen Y, Zhang J, Lin Y, Lei Q, Guan KL, Zhao S, Xiong Y. Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS. EMBO Rep. 2011; 12(6): 534–41. Available from: https://doi.org/10.1038/embor.2011.65
• Wang Z, Zhang L, Liang Y, Zhang C, Xu Z, Zhang L, Fuji R et al. Cyclic AMP mimics the anti-ageing effects of calorie restriction by up-regulating sirtuin. Sci Rep. 2015; 5: 12012. Available from: https://doi. org/10.1038/srep12012
• Hammer SS, Vieira CP, McFarland D, Sandler M, Levitsky Y, Dorweiler TF, Lydic TA et al. Fasting and fasting-mimicking treatment activate SIRT1/LXRα and alleviate diabetes-induced systemic and microvascular dysfunction. Diabetologia. 2021; 10.1007/s00125-021-05431-5. Available from: https://doi.org/10.1007/s00125-021-05431-5
• Paramesha B, Anwar MS, Meghwani H, Maulik SK, Arava SK, Banerjee SK. Sirt1 and Sirt3 activation improved cardiac function of diabetic rats via modulation of mitochondrial function. Antioxidants. 2021; 10(3): 338. Available from: https://doi.org/10.3390/antiox10030338
• Ghadimi M, Foroughi F, Hashemipour S, Nooshabadi MR, Ahmadi MH, Yari MG, Kavianpour M et al. Decreased insulin resistance in diabetic patients by influencing Sirtuin1 and Fetuin-A following supplementation with ellagic acid: a randomized controlled trial. Diabetol Metab Syndr. 2021; 13(1): 16. Available from: https://doi. org/10.1186/s13098-021-00633-8
• Lee SH, Min KJ. Caloric restriction and its mimetics. BMB Rep. 2013; 46(4): 181–7. Available from: https://doi.org/10.5483/ bmbrep.2013.46.4.033
• Redman LM, Smith SR, Burton JH, Martin CK, Il’yasova D, Ravussin E. Metabolic slowing and reduced oxidative damage with ustained caloric restriction support the rate of living and oxidative damage theories of aging. Cell Metab. 2018; 27(4): 805–15.e4. Available from: https://doi. org/10.1016/j.cmet.2018.02.019
• Rappou E, Jukarainen S, Tuikka R, Kaye S, Heinonen S, Hakkarainen A, Lunbom J et al. Weight loss is associated with increased NAD/SIRT1 expression but reduced PARP activity in white adipose tissue. J Clin Endocrinol Metab. 2016; 101(3): 1263–73. Available from: https://doi. org/10.1210/jc.2015-3054
• Moschen AR, Wieser V, Gerner RR, Bichler A, Enrich B, Moser P, Ebenbichler CF et al. Adipose tissue and liver expression of SIRT1, 3, and 6 increase after extensive weight loss in morbid obesity. J Hepatol. 2013; 59(6): 1315-22. Available from: https://doi.org/10.1016/j. jhep.2013.07.027
• Mariani S, Fiore D, Persichetti A, Basciani S, Lubrano C, Poggiogalle E, Genco A et al. Circulating SIRT1 increases after intragastric balloon fat loss in obese patients. Obes Surg. 2016; 26(6): 1215-20. Available from: https://doi.org/10.1007/s11695-015-1859-4