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Sirtuins and Aging

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Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

The sirtuin family of proteins (SIRT proteins) are involved in DNA repair, chromatin remodeling, epigenetic regulation of the expression of metabolism genes, the antioxidant system, apoptosis, immuno- and neurogenesis, etc. The aim of this review is to analyze the geroprotective properties of sirtuins in normal and age-associated pathologies. SIRT1, 2, 3, 4, and 6 contribute to increases in life expectancy. SIRT1, 2, 6, and 7 slow cellular aging and maintain the stem cell pool. Sirtuins are potential targets for the treatment of neurodegenerative, oncological, and cardiovascular diseases, metabolic syndrome, and diabetes mellitus. All these diseases are in most cases characteristic of elderly and old people, so the geroprotective effects of sirtuins, realized at the molecular and cellular levels, may play an important role in the treatment of these conditions.

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References

  1. A. E. Pukhalskaia, A. S. Diatlova, N. S. Linkova, et al., “Sirtuins as possible predictors of ageing and the development of Alzheimer’s disease: verifi cation in the hippocampus and saliva,” Bull. Exp. Biol. Med., 169, No. 6, 769–772 (2020).

    Article  Google Scholar 

  2. A. E. Pukhalskaia, A. S. Diatlova, N. S. Linkova, and I. M. Kvetnoy, “Sirtuins: role and regulation of oxidative stress and the pathogenesis of neurodegenerative diseases,” Usp. Fiziol. Nauk., 52, No. 1, 90–104 (2021).

    Google Scholar 

  3. B. H. Ahn, H. S. Kim, S. Song, et al., “A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis,” Proc. Natl. Acad. Sci. USA, 105, No. 38, 14447–14452 (2008), https://doi.org/10.1073/pnas.0803790105.

    Article  PubMed  PubMed Central  Google Scholar 

  4. M. Almeida and R. M. Porter, “Sirtuins and FoxOs in osteoporosis and osteoarthritis,” Bone, 121, 284–292 (2019), https://doi.org/10.1016/j.bone.2019.01.018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. T. Anwar, S. Khosla, and G. Ramakrishna, “Increased expression of SIRT2 is a novel marker of cellular senescence and is dependent on wild type p53 status,” Cell Cycle, 15, No. 14, 1883–1897 (2016), https://doi.org/10.1080/15384101.2016.1189041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. H. Bai, S. Post, P. Kang, and M. Tatar, “Drosophila longevity assurance conferred by reduced insulin receptor substrate chico partially requires d4eBP,” PLoS One, 10, e0134415 (2015), https://doi.org/10.1371/journal.pone.0134415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. A. Benigni, P. Cassis, S. Conti, et al., “Sirt3 deficiency shortens life span and impairs cardiac mitochondrial function rescued by Opa1 gene transfer,” Antioxid. Redox. Signal., 31, No. 17, 1255–1271 (2019), https://doi.org/10.1089/ars.2018.7703.

    Article  CAS  PubMed  Google Scholar 

  8. N. Braidy, G. J. Guillemin, H. Mansour, et al., “Age related changes in NAD+ metabolism oxidative stress and SIRT1 activity in Wistar rats,” PLoS One, 6, No. 4: e19194 (2011), https://doi.org/10.1371/journal.pone.0019194.

  9. N. Braidy, A. Poljak, R. Grant, et al., “Differential expression of sirtuins in the aging rat brain,” Front. Cell. Neurosci., 9, 167 (2015), https://doi.org/10.3389/fncel.2015.00167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. A. Brunet, L. B. Sweeney, J. F. Sturgill, et al., “Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase,” Science, 303, No. 5666), 2011–2015 (2004), https://doi.org/10.1126/science.1094637.

    Article  CAS  PubMed  Google Scholar 

  11. K. Burkewitz, Y. E. Zhang, and W. B. Mair, “AMPK at the nexus of energetics and aging,” Cell Metab., 20, 10–25 (2014), https://doi.org/10.1016/j.cmet.2014.03.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. C. Burnett, S. Valentini, F. Cabreiro, et al., “Absence of effects of Sir2 overexpression on lifespan in, “elegans and Drosophila,” Nature, 477, 482–485 (2011), https://doi.org/10.1038/nature10296.

  13. A. Cardinale, M. C. de Stefano, C. Mollinari, et al., “Biochemical characterization of sirtuin 6 in the brain and its involvement in oxidative stress response,” Neurochem. Res., 40, No. 1, 59–69 (2015), https://doi.org/10.1007/s11064-014-1465-1.

    Article  CAS  PubMed  Google Scholar 

  14. C. Chen, M. Zhou, Y. Ge, and X. Wang, “SIRT1 and aging related signaling pathways,” Mech. Aging Dev., 187, 111215 (2020), https://doi.org/10.1016/j.mad.2020.111215.

    Article  CAS  PubMed  Google Scholar 

  15. S. H. Cho, J. A. Chen, F. Sayed, et al., “SIRT1 deficiency in microglia contributes to cognitive decline in aging and neurodegeneration via epigenetic regulation of IL-1 beta,” J. Neurosci., 35, 807–818 (2015), https://doi.org/10.1523/JNEUROSCI.2939-14.2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. N. D’Onofrio, M. Vitiello, R. Casale, et al., “Sirtuins in vascular diseases: emerging roles and therapeutic potential,” Biochim. Biophys. Acta, 1852, No. 7, 1311–1322 (2015), https://doi.org/10.1016/j.bbadis.2015.03.001.

    Article  CAS  PubMed  Google Scholar 

  17. W. Dang, “The controversial world of sirtuins,” Drug Discov. Today Technol., 12, e9–e17 (2014), https://doi.org/10.1016/j.ddtec.2012.08.003.

    Article  PubMed  PubMed Central  Google Scholar 

  18. M. A. Deprez, E. Eskes, J. Winderickx, and T. Wilms, “The TORC1-Sch9 pathway as a crucial mediator of chronological lifespan in the yeast Saccharomyces cerevisiae,” FEMS Yeast Res., 18, 18 (2018), https://doi.org/10.1093/femsyr/foy048.

    Article  CAS  Google Scholar 

  19. A. J. Donato, K. A. Magerko, B. R. Lawson, et al., “SIRT-1 and vascular endothelial dysfunction with ageing in mice and humans,” J. Physiol., 589, 4545–4554 (2011), https://doi.org/10.1113/jphysiol.2011.211219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. J. Du, Y. Zhou, X. Su, et al., “Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase,” Science, 334, 806–809 (2011), https://doi.org/10.1126/science.1207861.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. J. R. Edwards, D. S. Perrien, N. Fleming, et al., “Silent information regulator (Sir)T1 inhibits NF-κB signaling to maintain normal skeletal remodeling,” J. Bone Miner. Res, 28, No. 4, 960–969 (2013), https://doi.org/10.1002/jbmr.1824.

    Article  CAS  PubMed  Google Scholar 

  22. E. F. Fang, S. Lautrup, Y. J. Hou, et al., “NAD+ in aging: molecular mechanisms and translational implications,” Trends Mol. Med., 23, 899–916 (2017), https://doi.org/10.1016/j.molmed.2017.08.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. L. W. Finley, A. Carracedo, J. Lee, et al., “SIRT3 opposes reprogramming of Cancer Cell metabolism through HIF1α destabilization,” Cancer Cell, 19, No. 3, 416–428 (2011), https://doi.org/10.1016/j.ccr.2011.02.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. R. A. Frye, “Phylogenetic classifi cation of prokaryotic and eukaryotic Sir2-like proteins,” Biochem. Biophys. Res. Commun, 273, No. 2, 793–798 (2000), https://doi.org/10.1006/bbrc.2000.3000.

    Article  CAS  PubMed  Google Scholar 

  25. A. García-Aguilar, C. Guillén, M. Nellist, et al., “TSC2 N-terminal lysine acetylation status affects to its stability modulating mTORC1 signaling and autophagy,” Biochim. Biophys. Acta, 1863, No. 11, 2658–2667 (2016), https://doi.org/10.1016/j.bbamcr.2016.08.006.

    Article  CAS  PubMed  Google Scholar 

  26. H. S. Ghosh, M. McBurney, and P. D. Robbins, “SIRT1 negatively regulates the mammalian target of rapamycin,” PLoS One, 5, No. 2, e9199 (2010), https://doi.org/10.1371/journal.pone.0009199.

  27. J. Guo, M. Shao, F. Lu, et al., “Role of SIRT1 plays in nucleus pulposus cells and intervertebral disc degeneration,” Spine (Phila Pa 1976), 49, No. 13, E757–E766 (2017), https://doi.org/10.1097/BRS.0000000000001954.

  28. M. C. Haigis and L. P. Guarente, “Mammalian sirtuins-emerging roles in physiology, aging, and calorie restriction,” Genes Dev., 20, 2913–2921 (2006), https://doi.org/10.1101/gad.1467506.

    Article  CAS  PubMed  Google Scholar 

  29. M. C. Haigis, R. Mostoslavsky, K. M. Haigis, et al., “SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta Cells,” Cell, 126, 941–954 (2006), https://doi.org/10.1016/j.cell.2006.06.057.

    Article  CAS  PubMed  Google Scholar 

  30. P. Han, Z. Tang, J. Yin, et al., “Pituitary adenylate cyclase-activating polypeptide protects against β-amyloid toxicity,” Neurobiol. Aging, 35, No. 9, 2064–2071 (2014), https://doi.org/10.1016/j.neurobiolaging.2014.03.022.

    Article  CAS  PubMed  Google Scholar 

  31. M. D. Hirschey, T. Shimazu, E. “Jing, et al., “SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome,” Mol. Cell., 44, No. 2, 177–190 (2011), https://doi.org/10.1016/j.molcel.2011.07.019.

  32. M. D. Hirschey, T. Shimazu, E. Goetzman, et al., “SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation,” Nature, 464, No. 7285), 121–125 (2010), https://doi.org/10.1038/nature08778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Y. S. Hori, A. Kuno, R. Hosoda, and Y. Horio, “Regulation of FOXOs and p53 by SIRT1 modulators under oxidative stress,” PLoS One, 8, No. 9, e73875 (2013), https://doi.org/10.1371/journal.pone.0073875.

  34. R. H. Houtkooper, E. Pirinen, and J. Auwerx, “Sirtuins as regulators of metabolism and healthspan,” Nat. Rev. Mol. Cell. Biol., 13, 225–238 (2012), https://doi.org/10.1038/nrm3293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. M. E. Hubbi, H. Hu, Kshitiz et al, “Sirtuin-7 inhibits the activity of hypoxia-inducible factors,” J. Biol. Chem., 288, No. 29, 20768–20775 (2013), https://doi.org/10.1074/jbc.M113.476903.

  36. S. M. Jeon, “Regulation and function of AMPK in physiology and diseases,” Exp. Mol. Med., 48, e245 (2016), https://doi.org/10.1038/emm.2016.81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. E. S. Jung, H. Choi, and H. Song, et al., “p53-dependent SIRT6 expression protects Aβ42-induced DNA damage,” Sci. Rep., 6, 25628 (2016), https://doi.org/10.1038/srep25628.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. M. Kaeberlein, M. McVey, and L. Guarente, “The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms,” Genes Dev., 13, No. 19, 2570–2580 (1999), https://doi.org/10.1101/gad.13.19.2570.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. S. Kaluski, M. Portillo, and A. Besnard, et al., “Neuroprotective Functions for the Histone Deacetylase SIRT6,” Cell Rep., 18, No. 13, 3052–3062 (2017), https://doi.org/10.1016/j.celrep.2017.03.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Y. Kanfi, S. Naiman, and G. Amir, et al., “The sirtuin SIRT6 regulates lifespan in male mice,” Nature, 483, No. 7388, 218–221 (2012), https://doi.org/10.1038/nature10815.

    Article  CAS  PubMed  Google Scholar 

  41. C. L. Kao, L. K. Chen, Y. L. Chang, et al., “Resveratrol protects human endothelium from H2O2- induced oxidative stress and senescence via SIRT1 activation,” J. Atheroscler. Thromb, 17, 970–979 (2010), https://doi.org/10.5551/jat.4333.

    Article  CAS  PubMed  Google Scholar 

  42. A. A. Kendrick, M. Choudhury, S. M. Rahman, et al., “Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation,” Biochem. J., 433, No. 3, 505–514 (2011), https://doi.org/10.1042/BJ20100791.

    Article  CAS  PubMed  Google Scholar 

  43. B. K. Kennedy, M. Gotta, D. A. Sinclair, et al., “Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in, “cerevisiae,” Cell, 89, No. 3, 381–391 (1997), https://doi.org/10.1016/s0092-8674(00)80219-6.

  44. M. Kim, J. S. Lee, J. E. Oh, et al., “SIRT3 Overexpression Attenuates Palmitate-Induced Pancreatic β-Cell Dysfunction,” PLoS One, 10, No. 4, e0124744 (2015), https://doi.org/10.1371/journal.pone.0124744.

  45. S. Kiran, T. Anwar, M. Kiran, and G. Ramakrishna, “Sirtuin 7 in cell proliferation, stress and disease: Rise of the Seventh Sirtuin!,” Cell. Signal., 27, No. 3, 673–682 (2015), https://doi.org/10.1016/j.cellsig.2014.11.026.

    Article  CAS  PubMed  Google Scholar 

  46. M. Kitada, Y. Ogura, and D. Koya, “The protective role of SIRT1 in vascular tissue: its relationship to vascular aging and atherosclerosis,” Aging (Albany NY), 8, No. 10, 2290–2307 (2016), 10.18632/aging.101068.

  47. M. Kitada, Y. Ogura, I. Monno, and D. Koya, “Sirtuins and type 2 diabetes: role in inflammation, oxidative stress, and mitochondrial function,” Front. Endocrinol. (Lausanne), 10, 187 (2019), https://doi.org/10.3389/fendo.2019.00187.

    Article  PubMed  Google Scholar 

  48. M. A. Klein and J. M. Denu, “Biological and catalytic functions of sirtuin 6 as targets for small-molecule modulators,” J. Biol. Chem., 295, No. 32, 11021–11041 (2020), https://doi.org/10.1074/jbc.REV120.011438.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. S. Kugel and R. Mostoslavsky, “Chromatin and beyond: the multitasking roles for SIRT6,” Trends Biochem. Sci., 39, No. 2, 72–81 (2014), https://doi.org/10.1016/j.tibs.2013.12.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. S. Kugel, C. Sebastián, J. Fitamant, et al., “SIRT6 suppresses pancreatic cancer through control of Lin28b,” Cell, 165, No. 6, 1401–1415 (2016), https://doi.org/10.1016/j.cell.2016.04.033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. A. Lang, S. Grether-Beck, M. Singh, et al., “MicroRNA-15b regulates mitochondrial ROS production and the senescence-associated secretory phenotype through sirtuin 4/SIRT4,” Aging (Albany NY), 8, No. 3, 484–505 (2016), 10.18632/aging.100905.

  52. I. R. Lanza, D. K. Short, and K. R. Short, et al., “Endurance exercise as a countermeasure for aging,” Diabetes, 57, No. 11, 2933–2942 (2008), https://doi.org/10.2337/db08-0349.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. F. Li and L. Liu, “SIRT5 defi ciency enhances susceptibility to kainate-induced seizures and exacerbates hippocampal neurodegeneration not through mitochondrial antioxidant enzyme SOD2,” Front. Cell. Neurosci, 10, 171 (2016), https://doi.org/10.3389/fncel.2016.00171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. C. J. Lim, Y. M. Lee, S. G. Kang, et al., “Aquatide activation of SIRT1 reduces cellular senescence through a SIRT1-FOXO1-autophagy axis,” Biomol. Ther. (Seoul), 25, No. 5, 511–518 (2017), https://doi.org/10.4062/biomolther.2017.119.

    Article  CAS  PubMed  Google Scholar 

  55. C. H. Lin, J. Chen, B. Ziman, et al., “Endostatin and kidney fi brosis in aging: a case for antagonistic pleiotropy?” Am. J. Physiol. Heart Circ. Physiol., 306, No. 12, H1692–H1699 (2014), https://doi.org/10.1152/ajpheart.00064.2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. G. Liszt, E. Ford, M. Kurtev, and L. Guarente, “Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase,” J. Biol. Chem., 280, 21313–21320 (2005), https://doi.org/10.1074/jbc.M413296200.

    Article  CAS  PubMed  Google Scholar 

  57. L. Liu, C. Peritore, J. Ginsberg, et al., “Protective role of SIRT5 against motor defi cit and dopaminergic degeneration in MPTPinduced mice model of Parkinson’s disease,” Behav. Brain Res., 281, 215–221 (2015), https://doi.org/10.1016/j.bbr.2014.12.035.

    Article  CAS  PubMed  Google Scholar 

  58. D. B. Lombard and B. M. Zwaans, “SIRT3: as simple as it seems?” Gerontology, 60, No. 1, 56–64 (2014), https://doi.org/10.1159/000354382.

    Article  CAS  PubMed  Google Scholar 

  59. H. Luo, W. C. Mu, and R. Karki, et al., “Mitochondrial stress-initiated aberrant activation of the NLRP3 infl ammasome regulates the functional deterioration of hematopoietic stem cell aging,” Cell Rep., 26, 945–954 (2019), https://doi.org/10.1016/j.celrep.2018.12.101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. X. Y. Luo, S. L. Qu, and Z. H. Tang, et al., “SIRT1 in cardiovascular aging,” Clin. Chim. Acta, 437, 106–114 (2014), https://doi.org/10.1016/j.cca.2014.07.019.

    Article  CAS  PubMed  Google Scholar 

  61. Y. X. Luo, X. Tang, X. Z. An, et al., “SIRT4 accelerates Ang IIinduced pathological cardiac hypertrophy by inhibiting manganese superoxide dismutase activity,” Eur. Heart J., 38, No. 18, 1389–1398 (2017), https://doi.org/10.1093/eurheartj/ehw138.

    Article  CAS  PubMed  Google Scholar 

  62. S. Masri, P. Rigor, M. Cervantes, et al., “Partitioning circadian transcription by SIRT6 leads to segregated control of cellular metabolism,” Cell, 158, No. 3, 659–672 (2014), https://doi.org/10.1016/j.cell.2014.06.050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. E. McDonnell, B. S. Peterson, H. M. Bomze, and M. D. Hirschey, “SIRT3 regulates progression and development of diseases of aging,” Trends Endocrinol. Metab., 26, No. 9, 486–492 (2015), https://doi.org/10.1016/j.tem.2015.06.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Z. Min, J. Gao, and Y. Yu, “The roles of mitochondrial sirt4 in cellular metabolism,” Front. Endocrinol. (Lausanne), 9, 783 (2019), https://doi.org/10.3389/fendo.2018.00783.

    Article  PubMed  Google Scholar 

  65. M. Mohrin, J. Shin, Y. Liu, et al., “Stem cell aging. A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging,” Science, 347, No. 6228, 1374–1377 (2015), https://doi.org/10.1126/science.aaa2361.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. R. Mostoslavsky, K. F. Chua, D. B. Lombard, et al., “Genomic instability and aging-like phenotype in the absence of mammalian SIRT6,” Cell, 124, No. 2, 315–329 (2006), https://doi.org/10.1016/j.cell.2005.11.044.

    Article  CAS  PubMed  Google Scholar 

  67. M. C. Motta, N. Divecha, M. Lemieux, et al., “Mammalian SIRT1 represses forkhead transcription factors,” Cell, 116, 551–563 (2004), https://doi.org/10.1016/s0092-8674(04)00126-6.

    Article  CAS  PubMed  Google Scholar 

  68. R. Nogueiras, K. M. Habegger, N. Chaudhary, et al., “Sirtuin 1 and sirtuin 3: physiological modulators of metabolism,” Physiol. Rev., 92, No. 3, 1479–1514 (2012), https://doi.org/10.1152/physrev.00022.2011.

    Article  CAS  PubMed  Google Scholar 

  69. B. J. North, M. A. Rosenberg, and K. B. Jeganathan, et al., “SIRT2 induces the checkpoint kinase BubR1 to increase lifespan,” EMBO J., 33, No. 13, 1438–1453 (2014), 10.15252/embj.201386907.

  70. C. O’Callaghan and A. Vassilopoulos, “Sirtuins at the crossroads of stemness, aging, and cancer,” Aging Cell, 16, No. 6, 1208–1218 (2017), https://doi.org/10.1111/acel.12685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. C. O’Callaghan, and A. Vassilopoulos, “Sirtuins at the crossroads of stemness, aging, and cancer,” Aging Cell, 16, No. 6, 1208–1218 (2017), https://doi.org/10.1111/acel.12685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. X. Ou, M. R. Lee, X. Huang, et al., “SIRT1 positively regulates autophagy and mitochondria function in embryonic Stem Cells under oxidative stress,” Stem Cells, 32, 1183–1194 (2014), https://doi.org/10.1002/stem.1641.

    Article  CAS  PubMed  Google Scholar 

  73. H. Pan, D. Guan, X. Liu, et al., “SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2,” Cell Res., 26, No. 2, 190–205 (2016), https://doi.org/10.1038/cr.2016.4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. S. Paredes, M. Angulo-Ibanez, L. Tasselli, et al., “The epigenetic regulator SIRT7 guards against mammalian cellular senescence induced by ribosomal DNA instability,” J. Biol. Chem., 293, No. 28, 11242–11250 (2018), https://doi.org/10.1074/jbc.AC118.003325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. S. Parik, S. Tewary, C. Ayyub, and U. Kolthur-Seetharam, “Loss of mitochondrial SIRT4 shortens lifespan and leads to a decline in physical activity,” J. Biosci, 43, No. 2, 243–247 (2018).

    Article  CAS  PubMed  Google Scholar 

  76. J. Park, Y. Chen, D. X. Tishkoff, et al., “SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways,” Mol. Cell., 50, 919–930 (2013), https://doi.org/10.1016/j.molcel.2013.06.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. R. Paulin, P. Dromparis, G. Sutendra, et al., “Sirtuin 3 defi ciency is associated with inhibited mitochondrial function and pulmonary arterial hypertension in rodents and humans,” Cell Metab., 20, No. 5, 827–839 (2014), https://doi.org/10.1016/j.cmet.2014.08.011.

    Article  CAS  PubMed  Google Scholar 

  78. A. Salminen, K. Kaarniranta, and A. Kauppinen, “Crosstalk between oxidative stress and SIRT1: impact on the aging process,” Int. J. Mol. Sci., 14, No. 2, 3834–3859 (2013), https://doi.org/10.3390/ijms14023834.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. A. Satoh, C. S. Brace, N. Rensing, et al., “SIRT1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH,” Cell Metab., 18, 416–430 (2013), https://doi.org/10.1016/j.cmet.2013.07.013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. J. Shih, L. Liu, A. Mason, et al., “Loss of SIRT4 decreases GLT-1- dependent glutamate uptake and increases sensitivity to kainic acid,” J. Neurochem., 131, No. 5, 573–581 (2014), https://doi.org/10.1111/jnc.12942.

    Article  CAS  PubMed  Google Scholar 

  81. D. M. Silberman, K. Ross, and P. H. Sande, et al., “SIRT6 is required for normal retinal function,” PLoS One, 9, No. 6, e98831 (2014), https://doi.org/10.1371/journal.pone.0098831.

  82. W. Song, Y. Song, B. Kincaid, et al., “Mutant SOD1G93A triggers mitochondrial fragmentation in spinal cord motor neurons: neuroprotection by SIRT3 and PGC-1α,” Neurobiol. Dis., 51, 72–81 (2013), https://doi.org/10.1016/j.nbd.2012.07.004.

    Article  CAS  PubMed  Google Scholar 

  83. S. Sun, Z. Liu, Y. Feng, et al., “Sirt6 deacetylase activity regulates circadian rhythms via Per2,” Biochem. Biophys. Res. Commun, 511, No. 2, 234–238 (2019), https://doi.org/10.1016/j.bbrc.2019.01.143.

    Article  CAS  PubMed  Google Scholar 

  84. N. R. Sundaresan, M. Gupta, G. Kim, et al., “Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice,” J. Clin. Invest., 119, No. 9, 2758–2771 (2009), https://doi.org/10.1172/JCI39162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. B. Sung, J. W. Chung, H. R. Bae, et al., “Humulus japonicus extract exhibits antioxidative and anti-aging effects via modulation of the AMPK-SIRT1 pathway,” Exp. Ther. Med., 9, No. 5, 1819–1826 (2015), https://doi.org/10.3892/etm.2015.2302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. B. L. Tang, “Is SIRT6 Activity neuroprotective and how does it differ from SIRT1 in this regard?” Front. Cell. Neurosci., 11, 165 (2017), https://doi.org/10.3389/fncel.2017.00165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Y. Tao, C. Huang, Y. Huang, et al., “SIRT4 suppresses inflammatory responses in human umbilical vein endothelial cells,” Cardiovasc. Toxicol, 15, No. 3, 217–223 (2015), https://doi.org/10.1007/s12012-014-9287-6.

    Article  CAS  PubMed  Google Scholar 

  88. J. Tian and L. Yuan, “Sirtuin 6 inhibits colon cancer progression by modulating PTEN/AKT signaling,” Biomed. Pharmacother., 106, 109–116 (2018), https://doi.org/10.1016/j.biopha.2018.06.070.

    Article  CAS  PubMed  Google Scholar 

  89. D. Tomaselli, C. Steegborn, A. Mai, and D. Rotili, “Sirt4: A multifaceted enzyme at the crossroads of mitochondrial metabolism and cancer,” Front. Oncol., 10, 474 (2020), https://doi.org/10.3389/fonc.2020.00474.

    Article  PubMed  PubMed Central  Google Scholar 

  90. R. A. H. van de Ven, D. Santos, and M. C. Haigis, “Mitochondrial sirtuins and molecular mechanisms of aging,” Trends Mol. Med., 23, No. 4, 320–331 (2017), https://doi.org/10.1016/j.molmed.2017.02.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. H. Vaziri, S. K. Dessain, E. Ng Eaton, et al., “HSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase,” Cell, 107, No. 2, 149–159 (2001), https://doi.org/10.1016/s0092-8674(01)00527-x.

    Article  CAS  PubMed  Google Scholar 

  92. N. Wang, Z. Luo, M. Jin, et al., “Exploration of age-related mitochondrial dysfunction and the anti-aging effects of resveratrol in zebrafish retina,” Aging (Albany NY), 11, No. 10, 3117–3137 (2019), 10.18632/aging.101966.

  93. Y. Wang, J. Yang, T. Hong, et al., “SIRT2: Controversy and multiple roles in disease and physiology,” Ageing Res. Rev., 100961 (2019), https://doi.org/10.1016/j.arr.2019.100961.

  94. J. G. Wood, B. Schwer, P. C. Wickremesinghe, et al., “Sirt4 is a mitochondrial regulator of metabolism and lifespan in Drosophila melanogaster,” Proc. Natl. Acad. Sci. USA, 115, No. 7, 1564–1569 (2018), https://doi.org/10.1093/geroni/igy023.345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. J. J. Wu, J. Liu, E. B. Chen, et al., “Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression,” Cell Rep., 4, 913–920 (2013), https://doi.org/10.1016/j.celrep.2013.07.030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. D. Xu, X. Jiang, H. He, et al., “SIRT2 functions in aging, autophagy, and apoptosis in post-maturation bovine oocytes,” Life Sci., 232, 116639 (2019), https://doi.org/10.1016/j.lfs.2019.116639.

    Article  CAS  PubMed  Google Scholar 

  97. S. Yamamura, Y. Izumiya, S. Araki, et al., “Cardiomyocyte Sirt (Sirtuin) 7 ameliorates stress-induced cardiac hypertrophy by interacting with and deacetylating GATA4,” Hypertension, 75, No. 1, 98–108 (2020), https://doi.org/10.1161/HYPERTENSIONAHA.119.13357.

    Article  CAS  PubMed  Google Scholar 

  98. B. Yang, X. Fu, L. Shao, et al., “Aberrant expression of SIRT3 is conversely correlated with the progression and prognosis of human gastric cancer,” Biochem. Biophys. Res. Commun, 443, No. 1, 156– 160 (2014), https://doi.org/10.1016/j.bbrc.2013.11.068.

    Article  CAS  PubMed  Google Scholar 

  99. M. Yang, Y. Peng, W. Liu, et al., “Sirtuin 2 expression suppresses oxidative stress and senescence of nucleus pulposus cells through inhibition of the p53/p21 pathway,” Biochem. Biophys. Res. Commun, 513, No. 3, 616–622 (2019), https://doi.org/10.1016/j.bbrc.2019.03.200.

    Article  CAS  PubMed  Google Scholar 

  100. F. Yeung, J. E. Hoberg, C. S. Ramsey, et al., “Modulation of NFkappa B-dependent transcription and cell survival by the SIRT1 deacetylase,” EMBO J., 23, No. 12, 2369–2380 (2004), https://doi.org/10.1038/sj.emboj.7600244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. W. You, D. Rotili, T. M. Li, et al., “Structural basis of sirtuin 6 activation by synthetic small molecules,” Angew. Chem. Int. Ed. Engl., 56, No. 4, 1007–1011 (2017), https://doi.org/10.1002/anie.201610082.

    Article  CAS  PubMed  Google Scholar 

  102. M. J. Zarzuelo, R. López-Sepúlveda, M. Sánchez, et al., “SIRT1 inhibits NADPH oxidase activation and protects endothelial function in the rat aorta: implications for vascular aging,” Biochem. Pharmacol., 85, No. 9, 1288–1296 (2013), https://doi.org/10.1016/j.bcp.2013.02.015.

    Article  CAS  PubMed  Google Scholar 

  103. L. Zeng, Y. Yang, and Y. Hu, et al., “Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model,” PLoS One, 9, No. 2, e88019 (2014), https://doi.org/10.1371/journal.pone.0088019.

  104. C. Z. Zhang, L. Liu, M. Cai, et al., “Low SIRT3 expression correlates with poor differentiation and unfavorable prognosis in primary hepatocellular carcinoma,” PLoS One, 7, No. 12, e51703 (2012), https://doi.org/10.1371/journal.pone.0051703.

  105. H. Zhang, X. Yang, and X. Pang, et al., “Genistein protects against ox- LDL-induced senescence through enhancing SIRT1/LKB1/AMPKmediated autophagy flux in HUVECs,” Mol. Cell Biochem., 455, No. 1–2, 127–134 (2019), https://doi.org/10.1007/s11010-018-3476-8.

    Article  CAS  PubMed  Google Scholar 

  106. Y. Zhang, S. L. Mi, and N. Hu, et al., “Mitochondrial aldehyde dehydrogenase 2 accentuates aging-induced cardiac remodeling and contractile dysfunction: role of AMPK, SIRT1, and mitochondrial function,” Free Radic. Biol. Med., 71, 208–220 (2014), https://doi.org/10.1016/j.freeradbiomed.2014.03.018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Translated from Uspekhi Fiziologicheskikh Nauk, Vol. 53, No. 1, pp. 16–27, January–March, 2022.

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Pukhalskaia, A.E., Kvetnoy, I.M., Linkova, N.S. et al. Sirtuins and Aging. Neurosci Behav Physi 52, 1482–1490 (2022). https://doi.org/10.1007/s11055-023-01379-8

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