Role of sirtuins in epigenetic regulation and aging control

Advances in modern healthcare in developed countries make it possible to extend the human lifespan, which is why maintaining active longevity is becoming increasingly important. After the sirtuin (SIRT) protein family was discovered, it started to be considered as a significant regulator of the physiological processes associated with aging. SIRT has deacetylase, deacylase, and ADP­ribosyltransferase activity and modifies a variety of protein substrates, including chromatin components and regulatory proteins. This multifactorial regulatory system affects many processes: cellular metabolism, mitochondrial functions, epigenetic regulation, DNA repair and more. As is expected, the activity of sirtuin proteins affects the manifestation of classic signs of aging in the body, such as cellular senescence, metabolic disorders, mitochondrial dysfunction, genomic instability, and the disruption of epigenetic regulation. Changes in the SIRT activity in human cells can also be considered a marker of aging and are involved in the genesis of various age­dependent disorders. Additionally, experimental data obtained in animal models, as well as data from population genomic studies, suggest a SIRT effect on life expectancy. At the same time, the diversity of sirtuin functions and biochemical substrates makes it extremely complicated to identify cause­and­effect relationships and the direct role of SIRT in controlling the functional state of the body. However, the SIRT influence on the epigenetic regulation of gene expression during the aging process and the development of disorders is one of the most important aspects of maintaining the homeostasis of organs and tissues. The presented review centers on the diversity of SIRT in humans and model animals. In addition to a brief description of the main SIRT enzymatic and biological activity, the review discusses its role in the epigenetic regulation of chromatin structure, including the context of the development of genome instability associated with aging. Studies on the functional connection between SIRT and longevity, as well as its effect on pathological processes associated with aging, such as chronic inflammation, fibrosis, and neuroinflammation, have been critically analyzed.

1. Aguilera A., García-Muse T. R loops: from transcription byproducts to threats to genome stability. Mol. Cell. 2012;46(2):115-124. DOI 10.1016/j.molcel.2012.04.009

2. Albani D., Ateri E., Mazzuco S., Ghilardi A., Rodilossi S., Biella G., Ongaro F., Antuono P., Boldrini P., Di Giorgi E., Frigato A., Durante E., Caberlotto L., Zanardo A., Siculi M., Gallucci M., Forloni G. Modulation of human longevity by SIRT3 single nucleotide polymorphisms in the prospective study “Treviso Longeva ( TRELONG).” Age (Dordr.). 2014;36(1):469-478. DOI 10.1007/s11357-013-9559-2

3. Bai W., Zhang X. Nucleus or cytoplasm? The mysterious case of SIRT1’s subcellular localization. Cell Cycle. 2016;15(24):33373338. DOI 10.1080/15384101.2016.1237170

4. Banerjee K.Kr., Ayyub C., Ali S.Z., Mandot V., Prasad N.G., KolthurSeetharam U. dSir2 in the adult fat body, but not in muscles, regulates life span in a diet-dependent manner. Cell Rep. 2012;2(6): 1485-1491. DOI 10.1016/j.celrep.2012.11.013

5. Barber M.F., Michishita-Kioi E., Xi Y., Tasselli L., Kioi M., Moqtaderi Z., Tennen R.I., Paredes S., Young N.L., Chen K., Struhl K., Garcia B.A., Gozani O., Li W., Chua K.F. SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nature. 2012;487(7405):114-118. DOI 10.1038/nature11043

6. Bellizzi D., Rose G., Cavalcante P., Covello G., Dato S., De Rango F., Greco V., Maggiolini M., Feraco E., Mari V., Franceschi C., Passarino G., De Benedictis G. A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages. Genomics. 2005;85(2):258-263. DOI 10.1016/j.ygeno.2004.11.003

7. Bergmann L., Lang A., Bross C., Altinoluk-Hambüchen S., Fey I., Overbeck N., Stefanski A., Wiek C., Kefalas A., Verhülsdonk P., Mielke C., Sohn D., Stühler K., Hanenberg H., Jänicke R.U., Scheller J., Reichert A.S., Ahmadian M.R., Piekorz R.P. Subcellular localization and mitotic interactome analyses identify SIRT4 as a centrosomally localized and microtubule associated protein. Cells. 2020; 9(9):1950. DOI 10.3390/cells9091950

8. Bi S., Liu Z., Wu Z., Wang Z., Liu X., Wang S., Ren J., Yao Y., Zhang W., Song M., Liu G.-H., Qu J. SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer. Protein Cell. 2020;11(7):483-504. DOI 10.1007/s13238-020-00728-4

9. Bosch-Presegué L., Raurell-Vila H., Marazuela-Duque A., Kane-Goldsmith N., Valle A., Oliver J., Serrano L., Vaquero A. Stabilization of Suv39H1 by SirT1 is part of oxidative stress response and ensures genome protection. Mol. Cell. 2011;42(2):210-223. DOI 10.1016/j.molcel.2011.02.034

10. Brenner C. Sirtuins are not conserved longevity genes. Life Metab. 2022;1(2):122-133. DOI 10.1093/lifemeta/loac025

11. Bresque M., Cal K., Pérez-Torrado V., Colman L., Rodríguez-Duarte J., Vilaseca C., Santos L., Garat M.P., Ruiz S., Evans F., Dapueto R., Contreras P., Calliari A., Escande C. SIRT6 stabilization and cytoplasmic localization in macrophages regulates acute and chronic inflammation in mice. J. Biol. Chem. 2022;298(3):101711. DOI 10.1016/j.jbc.2022.101711

12. Brunet A., Sweeney L.B., Sturgill J.F., Chua K.F., Greer P.L., Lin Y., Tran H., Ross S.E., Mostoslavsky R., Cohen H.Y., Hu L.S., Cheng H.-L., Jedrychowski M.P., Gygi S.P., Sinclair D.A., Alt F.W., Greenberg M.E. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004;303(5666):20112015. DOI 10.1126/science.1094637

13. Bryk M., Banerjee M., Murphy M., Knudsen K.E., Garfinkel D.J., Curcio M.J. Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast. Genes Dev. 1997;11(2):255-269. DOI 10.1101/gad.11.2.255

14. Bugyei-Twum A., Ford C., Civitarese R., Seegobin J., Advani S.L., Desjardins J.-F., Kabir G., Zhang Y., Mitchell M., Switzer J., Thai K., Shen V., Abadeh A., Singh K.K., Billia F., Advani A., Gilbert R.E., Connelly K.A. Sirtuin 1 activation attenuates cardiac fibrosis in a rodent pressure overload model by modifying Smad2/3 transactivation. Cardiovasc. Res. 2018;114(12):1629-1641. DOI 10.1093/cvr/cvy131

15. Burnett C., Valentini S., Cabreiro F., Goss M., Somogyvári M., Piper M.D., Hoddinott M., Sutphin G.L., Leko V., McElwee J.J., Vazquez-Manrique R.P., Orfila A.-M., Ackerman D., Au C., Vinti G., Riesen M., Howard K., Neri C., Bedalov A., Kaeberlein M., Sőti C., Partridge L., Gems D. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature. 2011;477(7365): 482-485. DOI 10.1038/nature10296

16. Cacabelos R., Carril J., Cacabelos N., Kazantsev A., Vostrov A., Corzo L., Cacabelos P., Goldgaber D. Sirtuins in Alzheimer’s disease: SIRT2-related genophenotypes and implications for pharmacoepigenetics. Int. J. Mol. Sci. 2019;20(5):1249. DOI 10.3390/ijms20051249

17. Chatzidoukaki O., Stratigi K., Goulielmaki E., Niotis G., AkalestouClocher A., Gkirtzimanaki K., Zafeiropoulos A., Altmüller J., Topalis P., Garinis G.A. R-loops trigger the release of cytoplasmic ssDNAs leading to chronic inflammation upon DNA damage. Sci. Adv. 2021;7(47):eabj5769. DOI 10.1126/sciadv.abj5769

18. Chen S., Seiler J., Santiago-Reichelt M., Felbel K., Grummt I., Voit R. Repression of RNA polymerase I upon stress is caused by inhibition of RNA-dependent deacetylation of PAF53 by SIRT7. Mol. Cell.

19. ;52(3):303-313. DOI 10.1016/j.molcel.2013.10.010

20. Crossley M.P., Song C., Bocek M.J., Choi J.-H., Kousorous J., Sathirachinda A., Lin C., Brickner J.R., Bai G., Lans H., Vermeulen W., Abu-Remaileh M., Cimprich K.A. R-loop-derived cytoplasmic RNA-DNA hybrids activate an immune response. Nature. 2023; 613(7942):187-194. DOI 10.1038/s41586-022-05545-9

21. Curry A.M., White D.S., Donu D., Cen Y. Human sirtuin regulators: The “success” stories. Front. Physiol. 2021;12:752117. DOI 10.3389/fphys.2021.752117

22. Diao Z., Ji Q., Wu Z., Zhang W., Cai Y., Wang Z., Hu J., Liu Z., Wang Q., Bi S., Huang D., Ji Z., Liu G.-H., Wang S., Song M., Qu J. SIRT3 consolidates heterochromatin and counteracts senescence. Nucleic Acids Res. 2021;49(8):4203-4219. DOI 10.1093/nar/gkab161

23. Diaz-Perdigon T., Belloch F.B., Ricobaraza A., Elboray E.E., Suzuki T., Tordera R.M., Puerta E. Early sirtuin 2 inhibition prevents age- related cognitive decline in a senescence-accelerated mouse model. Neuropsychopharmacology. 2020;45(2):347-357. DOI 10.1038/s41386-019-0503-8

24. Du J., Zhou Y., Su X., Yu J.J., Khan S., Jiang H., Kim J., Woo J., Kim J.H., Choi B.H., He B., Chen W., Zhang S., Cerione R.A., Auwerx J., Hao Q., Lin H. Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science. 2011;334(6057):806-809. DOI 10.1126/science.1207861

25. Du Y., Hu H., Hua C., Du K., Wei T. Tissue distribution, subcellular localization, and enzymatic activity analysis of human SIRT5 isoforms. Biochem. Biophys. Res. Commun. 2018;503(2):763-769. DOI 10.1016/j.bbrc.2018.06.073

26. El Ramy R., Magroun N., Messadecq N., Gauthier L.R., Boussin F.D., Kolthur-Seetharam U., Schreiber V., McBurney M.W., Sassone-Corsi P., Dantzer F. Functional interplay between Parp-1 and SirT1 in genome integrity and chromatin-based processes. Cell. Mol. Life Sci. 2009;66(19):3219-3234. DOI 10.1007/s00018-009-0105-4

27. Eldridge M.J.G., Pereira J.M., Impens F., Hamon M.A. Active nuclear import of the deacetylase Sirtuin-2 is controlled by its C-terminus and importins. Sci. Rep. 2020;10(1):2034. DOI 10.1038/s41598020-58397-6

28. Eskandarian H.A., Impens F., Nahori M.-A., Soubigou G., Coppée J.-Y., Cossart P., Hamon M.A. A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. Science. 2013; 341(6145):1238858. DOI 10.1126/science.1238858

29. Etchegaray J.-P., Chavez L., Huang Y., Ross K.N., Choi J., MartinezPastor B., Walsh R.M., Sommer C.A., Lienhard M., Gladden A., Kugel S., Silberman D.M., Ramaswamy S., Mostoslavsky G., Hochedlinger K., Goren A., Rao A., Mostoslavsky R. The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine. Nat. Cell Biol. 2015; 17(5): 545-557. DOI 10.1038/ncb3147

30. Fabrizio P., Gattazzo C., Battistella L., Wei M., Cheng C., McGrew K., Longo V.D. Sir2 blocks extreme life-span extension. Cell. 2005; 123(4):655-667. DOI 10.1016/j.cell.2005.08.042

31. Fahie K., Hu P., Swatkoski S., Cotter R.J., Zhang Y., Wolberger C. Side chain specificity of ADP-ribosylation by a sirtuin. FEBS J. 2009;276(23):7159-7176. DOI 10.1111/j.1742-4658.2009.07427.x

32. Figarska S.M., Vonk J.M., Boezen H.M. SIRT1 polymorphism, longterm survival and glucose tolerance in the general population. PLoS One. 2013;8(3):e58636. DOI 10.1371/journal.pone.0058636

33. Finkel T., Deng C.-X., Mostoslavsky R. Recent progress in the biology and physiology of sirtuins. Nature. 2009;460(7255):587-591. DOI 10.1038/nature08197

34. Flachsbart F., Croucher P.J.P., Nikolaus S., Hampe J., Cordes C., Schrei ber S., Nebel A. Sirtuin 1 (SIRT1) sequence variation is not associated with exceptional human longevity. Exp. Gerontol. 2006; 41(1):98-102. DOI 10.1016/j.exger.2005.09.008

35. Ford E., Voit R., Liszt G., Magin C., Grummt I., Guarente L. Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. Genes Dev. 2006;20(9):1075-1080. DOI 10.1101/gad.399706

36. Frye R.A. Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. Biochem. Biophys. Res. Commun. 1999;260(1):273-279. DOI 10.1006/bbrc.1999.0897

37. Frye R.A. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem. Biophys. Res. Commun. 2000;273(2): 793-798. DOI 10.1006/bbrc.2000.3000

38. Gottschling D.E., Aparicio O.M., Billington B.L., Zakian V.A. Position effect at S. cerevisiae telomeres: Reversible repression of Pol II transcription. Cell. 1990;63(4):751-762. DOI 10.1016/0092-8674(90)90141-Z

39. Gray S.G., Ekström T.J. The human histone deacetylase family. Exp. Cell Res. 2001;262(2):75-83. DOI 10.1006/excr.2000.5080

40. Griswold A.J., Chang K.T., Runko A.P., Knight M.A., Min K.-T. Sir2 mediates apoptosis through JNK-dependent pathways in Drosophila. Proc. Natl. Acad. Sci. USA. 2008;105(25):8673-8678. DOI 10.1073/pnas.0803837105

41. Haigis M.C., Mostoslavsky R., Haigis K.M., Fahie K., Christodoulou D.C., Murphy A.J., Valenzuela D.M., Yancopoulos G.D., Karow M., Blander G., Wolberger C., Prolla T.A., Weindruch R., Alt F.W., Guarente L. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic β cells. Cell. 2006;126(5):941-954. DOI 10.1016/j.cell.2006.06.057

42. Hall H. R-loops in neuronal aging. Aging. 2023;15(17):8535-8536. DOI 10.18632/aging.205070

43. Heo J., Lim J., Lee S., Jeong J., Kang H., Kim Y., Kang J.W., Yu H.Y., Jeong E.M., Kim K., Kucia M., Waigel S.J., Zacharias W., Chen Y., Kim I.-G., Ratajczak M.Z., Shin D.-M. Sirt1 regulates DNA methylation and differentiation potential of embryonic stem cells by antagonizing Dnmt3l. Cell Rep. 2017;18(8):1930-1945. DOI 10.1016/j.celrep.2017.01.074

44. Herranz D., Muñoz-Martin M., Cañamero M., Mulero F., MartinezPastor B., Fernandez-Capetillo O., Serrano M. Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat. Commun. 2010;1(1):3. DOI 10.1038/ncomms1001

45. Hirvonen K., Laivuori H., Lahti J., Strandberg T., Eriksson J.G., Hackman P. SIRT6 polymorphism rs117385980 is associated with longevity and healthy aging in Finnish men. BMC Med. Genet. 2017; 18(1):41. DOI 10.1186/s12881-017-0401-z

46. Hou T., Tian Y., Cao Z., Zhang J., Feng T., Tao W., Sun H., Wen H., Lu Xiaopeng, Zhu Q., Li M., Lu X., Liu B., Zhao Y., Yang Y., Zhu W.-G. Cytoplasmic SIRT6-mediated ACSL5 deacetylation impedes nonalcoholic fatty liver disease by facilitating hepatic fatty acid oxidation. Mol. Cell. 2022;82(21):4099-4115.e9. DOI 10.1016/j.molcel.2022.09.018

47. Ianni A., Hoelper S., Krueger M., Braun T., Bober E. Sirt7 stabilizes rDNA heterochromatin through recruitment of DNMT1 and Sirt1. Biochem. Biophys. Res. Commun. 2017;492(3):434-440. DOI 10.1016/j.bbrc.2017.08.081

48. Imai S., Armstrong C.M., Kaeberlein M., Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000;403(6771):795-800. DOI 10.1038/35001622

49. Imaoka N., Hiratsuka M., Osaki M., Kamitani H., Kambe A., Fukuoka J., Kurimoto M., Nagai S., Okada F., Watanabe T., Ohama E., Kato S., Oshimura M. Prognostic significance of sirtuin 2 protein nuclear localization in glioma: an immunohistochemical study. Oncol. Rep . 2012;28(3):923-230. DOI 10.3892/or.2012.1872

50. Isaka Y. Targeting TGF-β signaling in kidney fibrosis. Int. J. Mol. Sci. 2018;19(9):2532. DOI 10.3390/ijms19092532

51. Ivy J.M., Klar A.J., Hicks J.B. Cloning and characterization of four SIR genes of Saccharomyces cerevisiae. Mol. Cell. Biol. 1986;6(2): 688-702. DOI 10.1128/MCB.6.2.688

52. Jeong J., Juhn K., Lee H., Kim S.-H., Min B.-H., Lee K.-M., Cho M.- H., Park G.-H., Lee K.-H. SIRT1 promotes DNA repair activity and deacetylation of Ku70. Exp. Mol. Med. 2007;39(1):8-13. DOI 10.1038/emm.2007.2

53. Jia B., Chen J., Wang Q., Sun X., Han J., Guastaldi F., Xiang S., Ye Q., He Y. SIRT6 promotes osteogenic differentiation of adipose-derived mesenchymal stem cells through antagonizing DNMT1. Front. Cell Dev. Biol. 2021;9:648627. DOI 10.3389/fcell.2021.648627

54. Jiang H., Khan S., Wang Y., Charron G., He B., Sebastian C., Du J., Kim R., Ge E., Mostoslavsky R., Hang H.C., Hao Q., Lin H. SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine. Nature. 2013;496(7443):110-113. DOI 10.1038/nature12038

55. Jiao F., Gong Z. The beneficial roles of SIRT1 in neuroinflammationrelated diseases. Oxid. Med. Cell. Longev. 2020;2020:6782872. DOI 10.1155/2020/6782872

56. Julien C., Tremblay C., Émond V., Lebbadi M., Salem N., Bennett D.A., Calon F. Sirtuin 1 reduction parallels the accumulation of tau in Alzheimer disease. J. Neuropathol. Exp. Neurol. 2009;68(1):48-58. DOI 10.1097/NEN.0b013e3181922348

57. Kaeberlein M., McVey M., Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 1999;13(19):2570-2580. DOI 10.1101/gad.13.19.2570

58. Kawahara T.L.A., Michishita E., Adler A.S., Damian M., Berber E., Lin M., McCord R.A., Ongaigui K.C.L., Boxer L.D., Chang H.Y., Chua K.F. SIRT6 links histone H3 lysine 9 deacetylation to NF-κBdependent gene expression and organismal life span. Cell. 2009; 136(1):62-74. DOI 10.1016/j.cell.2008.10.052

59. Kim S., Bi X., Czarny-Ratajczak M., Dai J., Welsh D.A., Myers L., Welsch M.A., Cherry K.E., Arnold J., Poon L.W., Jazwinski S.M. Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity. Biogerontology. 2012;13(2):119-131. DOI 10.1007/s10522-011-9360-5

60. Kiran S., Chatterjee N., Singh S., Kaul S.C., Wadhwa R., Ramakrishna G. Intracellular distribution of human SIRT7 and mapping of the nuclear/nucleolar localization signal. FEBS J. 2013;280(14):3451-3466. DOI 10.1111/febs.12346

61. Kumar R., Mohan N., Upadhyay A.D., Singh A.P., Sahu V., Dwivedi S., Dey A.B., Dey S. Identification of serum sirtuins as novel noninvasive protein markers for frailty. Aging Cell. 2014;13(6):975-980. DOI 10.1111/acel.12260

62. Laurent G., German N.J., Saha A.K., de Boer V.C.J., Davies M., Koves T.R., Dephoure N., Fischer F., Boanca G., Vaitheesvaran B., Lovitch S.B., Sharpe A.H., Kurland I.J., Steegborn C., Gygi S.P., Muoio D.M., Ruderman N.B., Haigis M.C. SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase. Mol. Cell. 2013;50(5):686-698. DOI 10.1016/j.molcel.2013.05.012

63. Lee N., Kim D.-K., Kim E.-S., Park S.J., Kwon J.-H., Shin J., Park S.- M., Moon Y.H., Wang H.J., Gho Y.S., Choi K.Y. Comparative interactomes of SIRT6 and SIRT7: Implication of functional links to aging. Proteomics. 2014;14(13-14):1610-1622. DOI 10.1002/pmic.201400001

64. Leng S., Huang W., Chen Y., Yang Ya., Feng D., Liu W., Gao T., Ren Y., Huo M., Zhang J., Yang Yu., Wang Y. SIRT1 coordinates with the CRL4B complex to regulate pancreatic cancer stem cells to promote tumorigenesis. Cell Death Differ. 2021;28(12):3329-3343. DOI 10.1038/s41418-021-00821-z

65. Li T., Garcia-Gomez A., Morante-Palacios O., Ciudad L., Özkara mehmet S., Van Dijck E., Rodríguez-Ubreva J., Vaquero A., Balles tar E. SIRT1/2 orchestrate acquisition of DNA methylation and loss of histone H3 activating marks to prevent premature activation of inflammatory genes in macrophages. Nucleic Acids Res. 2020;48(2): 665-681. DOI 10.1093/nar/gkz1127

66. Li Z., Li H., Zhao Z.-B., Zhu W., Feng P.-P., Zhu X.-W., Gong J.-P. SIRT4 silencing in tumor-associated macrophages promotes HCC development via PPARδ signalling-mediated alternative activation of macrophages. J. Exp. Clin. Cancer Res. 2019;38(1):469. DOI 10.1186/s13046-019-1456-9

67. Lin R., Yan D., Zhang Y., Liao X., Gong G., Hu J., Fu Y., Cai W. Common variants in SIRT1 and human longevity in a Chinese population. BMC Med. Genet. 2016a;17(1):31. DOI 10.1186/s12881-016-0293-3

68. Lin R., Zhang Y., Yan D., Liao X., Gong G., Hu J., Fu Y., Cai W. Lack of association between polymorphisms in the SIRT6 gene and longevity in a Chinese population. Mol. Cell. Probes. 2016b;30(2): 79-82. DOI 10.1016/j.mcp.2016.01.005

69. Liu Z.-H., Zhang Ya., Wang X., Fan X.-F., Zhang Yu., Li X., Gong Y.- Sh., Han L.-P. SIRT1 activation attenuates cardiac fibrosis by endothelial-to-mesenchymal transition. Biomed. Pharmacother. 2019;118:109227. DOI 10.1016/j.biopha.2019.109227

70. LoBianco F.V., Krager K.J., Carter G.S., Alam S., Yuan Y., Lavoie E.G., Dranoff J.A., Aykin-Burns N. The role of Sirtuin 3 in radiationinduced long-term persistent liver injury. Antioxidants. 2020;9(5): 409. DOI 10.3390/antiox9050409

71. Lombard D.B., Alt F.W., Cheng H.-L., Bunkenborg J., Streeper R.S., Mostoslavsky R., Kim J., Yancopoulos G., Valenzuela D., Murphy A., Yang Y., Chen Y., Hirschey M.D., Bronson R.T., Haigis M., Guarente L.P., Farese R.V., Weissman S., Verdin E., Schwer B. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol. Cell. Biol. 2007;27(24):8807-8814. DOI 10.1128/MCB.01636-07

72. Luo J., Nikolaev A.Y., Imai S., Chen D., Su F., Shiloh A., Guarente L., Gu W. Negative control of p53 by Sir2α promotes cell survival under stress. Cell. 2001;107(2):137-148. DOI 10.1016/S0092-8674(01)00524-4

73. Maity S., Muhamed J., Sarikhani M., Kumar S., Ahamed F., Spurthi K.M., Ravi V., Jain A., Khan D., Arathi B.P., Desingu P.A., Sundaresan N.R. Sirtuin 6 deficiency transcriptionally up-regulates TGF-β signaling and induces fibrosis in mice. J. Biol. Chem. 2020; 295(2): 415-434. DOI 10.1074/jbc.RA118.007212

74. Mao Z., Hine C., Tian X., Van Meter M., Au M., Vaidya A., Seluanov A., Gorbunova V. SIRT6 promotes DNA repair under stress by activating PARP1. Science. 2011;332(6036):1443-1446. DOI 10.1126/science.1202723

75. Mathias R.A., Greco T.M., Oberstein A., Budayeva H.G., Chakrabarti R., Rowland E.A., Kang Y., Shenk T., Cristea I.M. Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity. Cell. 2014;159(7):1615-1625. DOI 10.1016/j.cell.2014.11.046

76. Michishita E., Park J.Y., Burneskis J.M., Barrett J.C., Horikawa I. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol. Biol. Cell. 2005;16(10): 4623-4635. DOI 10.1091/mbc.e05-01-0033

77. Michishita E., McCord R.A., Berber E., Kioi M., Padilla-Nash H., Damian M., Cheung P., Kusumoto R., Kawahara T.L.A., Barrett J.C., Chang H.Y., Bohr V.A., Ried T., Gozani O., Chua K.F. SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature. 2008;452(7186):492-496. DOI 10.1038/nature06736

78. Mizumoto T., Yoshizawa T., Sato Y., Ito T., Tsuyama T., Satoh A., Araki S., Tsujita K., Tamura M., Oike Y., Yamagata K. SIRT7 deficiency protects against aging-associated glucose intolerance and extends lifespan in male mice. Cells. 2022;11(22):3609. DOI 10.3390/cells11223609

79. Moniot S., Schutkowski M., Steegborn C. Crystal structure analysis of human Sirt2 and its ADP-ribose complex. J. Struct. Biol. 2013; 182(2):136-143. DOI 10.1016/j.jsb.2013.02.012

80. North B.J., Verdin E. Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during mitosis. PLoS One. 2007;2(8):e784. DOI 10.1371/journal.pone.0000784

81. North B.J., Marshall B.L., Borra M.T., Denu J.M., Verdin E. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol. Cell. 2003;11(2):437-444. DOI 10.1016/S1097-2765(03)00038-8

82. Ong A.L.C., Ramasamy T.S. Role of Sirtuin1-p53 regulatory axis in aging, cancer and cellular reprogramming. Ageing Res. Rev. 2018; 43:64-80. DOI 10.1016/j.arr.2018.02.004

83. Palomer X., Román-Azcona M.S., Pizarro-Delgado J., Planavila A., Villarroya F., Valenzuela-Alcaraz B., Crispi F., Sepúlveda-Martínez Á., Miguel-Escalada I., Ferrer J., Nistal J.F., García R., Davidson M.M., Barroso E., Vázquez-Carrera M. SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation. Signal Transduct. Target. Ther. 2020;5(1):14. DOI 10.1038/s41392-020-0114-1

84. Paredes S., Angulo-Ibanez M., Tasselli L., Carlson S.M., Zheng W., Li T.-M., Chua K.F. The epigenetic regulator SIRT7 guards against mammalian cellular senescence induced by ribosomal DNA instability. J. Biol. Chem. 2018;293(28):11242-11250. DOI 10.1074/jbc.AC118.003325

85. Peng L., Yuan Z., Ling H., Fukasawa K., Robertson K., Olashaw N., Koomen J., Chen J., Lane W.S., Seto E. SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters its activities. Mol. Cell. Biol. 2011;31(23):4720-4734. DOI 10.1128/MCB.06147-11

86. Pereira J.M., Chevalier C., Chaze T., Gianetto Q., Impens F., Matondo M., Cossart P., Hamon M.A. Infection reveals a modification of SIRT2 critical for chromatin association. Cell Rep. 2018;23(4): 1124-1137. DOI 10.1016/j.celrep.2018.03.116

87. Piracha Z.Z., Saeed U., Kim J., Kwon H., Chwae Y.-J., Lee H.W., Lim J.H., Park S., Shin H.-J., Kim K. An alternatively spliced Sirtuin 2 isoform 5 inhibits Hepatitis B virus replication from cccDNA by repressing epigenetic modifications made by histone lysine methyltransferases. J. Virol. 2020;94(16):e00926-20. DOI 10.1128/JVI.00926-20

88. Pruitt K.D., Harrow J., Harte R.A., Wallin C., Diekhans M., Maglott D.R., Searle S., … Wu W., Birney E., Haussler D., Hubbard T., Ostell J., Durbin R., Lipman D. The consensus coding sequence (CCDS) project: Identifying a common protein-coding gene set for the human and mouse genomes. Genome Res. 2009;19(7):13161323. DOI 10.1101/gr.080531.108

89. Pukhalskaia A.E., Dyatlova A.S., Linkova N.S., Kozlov K.L., Kvetnaia T.V., Koroleva M.V., Kvetnoy I.M. Sirtuins as possible predictors of aging and Alzheimer’s disease development: verification in the hippocampus and saliva. Bull. Exp. Biol. Med. 2020;169(6):821824. DOI 10.1007/s10517-020-04986-4

90. Pukhalskaia A.E., Kvetnoy I.M., Linkova N.S., Diatlova A.S., Gutop E.O., Kozlov K.L., Paltsev M.A. Sirtuins and aging. Uspekhi Fizio logicheskikh Nauk = Progress in Physiological Science. 2022; 53(1):16-27. DOI 10.31857/S0301179821040056 (in Russian)

91. Quan Y., Park W., Jin J., Kim W., Park S.K., Kang K.P. Sirtuin 3 activation by honokiol decreases unilateral ureteral obstruction-induced renal inflammation and fibrosis via regulation of mitochondrial dynamics and the renal NF-κB-TGF-β1/Smad signaling pathway. Int. J. Mol. Sci. 2020;21(2):402. DOI 10.3390/ijms21020402

92. Rack J.G.M., VanLinden M.R., Lutter T., Aasland R., Ziegler M. Constitutive nuclear localization of an alternatively spliced Sirtuin-2 isoform. J. Mol. Biol. 2014;426(8):1677-1691. DOI 10.1016/j.jmb. 2013.10.027

93. Rajamohan S.B., Pillai V.B., Gupta M., Sundaresan N.R., Birukov K.G., Samant S., Hottiger M.O., Gupta M.P. SIRT1 promotes cell survival under stress by deacetylation-dependent deactivation of poly(ADPribose) polymerase 1. Mol. Cell. Biol. 2009;29(15):4116-4129. DOI 10.1128/MCB.00121-09

94. Ramadani-Muja J., Gottschalk B., Pfeil K., Burgstaller S., Rauter T., Bischof H., Waldeck-Weiermair M., Bugger H., Graier W.F., Malli R. Visualization of Sirtuin 4 distribution between mitochondria and the nucleus, based on bimolecular fluorescence self-complementation. Cells. 2019;8(12):1583. DOI 10.3390/cells8121583

95. Ren Y., Du C., Yan L., Wei J., Wu H., Shi Y., Duan H. CTGF siRNA ameliorates tubular cell apoptosis and tubulointerstitial fibrosis in obstructed mouse kidneys in a Sirt1-independent manner. Drug Des. Devel. Ther. 2015;9:4155-4171. DOI 10.2147/DDDT.S86748

96. Rogina B., Helfand S.L. Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc. Natl. Acad. Sci. USA. 2004;101(45):15998-16003. DOI 10.1073/pnas.040418410

97. Roichman A., Elhanati S., Aon M.A., Abramovich I., Di Francesco A., Shahar Y., Avivi M.Y., Shurgi M., Rubinstein A., Wiesner Y., Shuchami A., Petrover Z., Lebenthal-Loinger I., Yaron O., Lyashkov A., Ubaida-Mohien C., Kanfi Y., Lerrer B., Fernández-Marcos P.J., Serrano M., Gottlieb E., de Cabo R., Cohen H.Y. Restoration of energy homeostasis by SIRT6 extends healthy lifespan. Nat. Commun. 2021;12(1):3208. DOI 10.1038/s41467-021-23545-7

98. Rothgiesser K.M., Erener S., Waibel S., Lüscher B., Hottiger M.O. SIRT2 regulates NF-κB-dependent gene expression through deacetylation of p65 Lys310. J. Cell Sci. 2010;123(24):4251-4258. DOI 10.1242/jcs.073783

99. Satoh A., Brace C.S., Rensing N., Cliften P., Wozniak D.F., Herzog E.D., Yamada K.A., Imai S. Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. Cell Metab. 2013;18(3):416-430. DOI 10.1016/j.cmet.2013.07.013

100. Sauve A.A., Wolberger C., Schramm V.L., Boeke J.D. The biochemistry of sirtuins. Annu. Rev. Biochem. 2006;75:435-465. DOI 10.1146/annurev.biochem.74.082803.133500

101. Sayers E.W., Bolton E.E., Brister J.R., Canese K., Chan J., Comeau D.C., Connor R., Funk K., Kelly C., Kim S., Madej T., Marchler-Bauer A., Lanczycki C., Lathrop S., Lu Z., Thibaud-Nissen F., Murphy T., Phan L., Skripchenko Y., Tse T., Wang J., Williams R., Trawick B.W., Pruitt K.D., Sherry S.T. Database resources of the national center for biotechnology information. Nucleic Acids Res. 2022;50(D1):D20-D26. DOI 10.1093/nar/gkab1112

102. Schmeisser K., Mansfeld J., Kuhlow D., Weimer S., Priebe S., Heiland I., Birringer M., Groth M., Segref A., Kanfi Y., Price N.L., Schmeisser S., Schuster S., Pfeiffer A.F.H., Guthke R., Platzer M., Hoppe T., Cohen H.Y., Zarse K., Sinclair D.A., Ristow M. Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. Nat. Chem. Biol. 2013;9(11):693-700. DOI 10.1038/nchembio.1352

103. Sengupta A., Haldar D. Human sirtuin 3 (SIRT3) deacetylates histone H3 lysine 56 to promote nonhomologous end joining repair. DNA Repair (Amst.). 2018;61:1-16. DOI 10.1016/j.dnarep.2017.11.003

104. Simon M., Yang J., Gigas J., Earley E.J., Hillpot E., Zhang L., Zagorulya M., Tombline G., Gilbert M., Yuen S.L., Pope A., Van Meter M., Emmrich S., Firsanov D., Athreya A., Biashad S.A., Han J., Ryu S., Tare A., Zhu Y., Hudgins A., Atzmon G., Barzilai N., Wolfe A., Moody K., Garcia B.A., Thomas D.D., Robbins P.D., Vijg J., Seluanov A., Suh Y., Gorbunova V. A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A. EMBO J. 2022;41(21):e110393. DOI 10.15252/embj.2021110393

105. Simonet N.G., Thackray J.K., Vazquez B.N., Ianni A., EspinosaAlcantud M., Morales-Sanfrutos J., Hurtado-Bagès S., Sabidó E., Buschbeck M., Tischfield J., De La Torre C., Esteller M., Braun T., Olivella M., Serrano L., Vaquero A. SirT7 auto-ADP-ribosylation regulates glucose starvation response through mH2A1. Sci. Adv. 2020;6(30):eaaz2590. DOI 10.1126/sciadv.aaz2590

106. Sinclair D.A., Guarente L. Extrachromosomal rDNA circles – a cause of aging in yeast. Cell. 1997;91(7):1033-1042. DOI 10.1016/S0092-8674(00)80493-6

107. Smith J.S., Brachmann C.B., Celic I., Kenna M.A., Muhammad S., Starai V.J., Avalos J.L., Escalante-Semerena J.C., Grubmeyer C., Wolberger C., Boeke J.D. A phylogenetically conserved NAD+dependent protein deacetylase activity in the Sir2 protein family. Proc. Natl. Acad. Sci. USA. 2000;97(12):6658-6663. DOI 10.1073/pnas.97.12.6658

108. Soerensen M., Dato S., Tan Q., Thinggaard M., Kleindorp R., Beekman M., Suchiman H.E.D., Jacobsen R., McGue M., Stevnsner T., Bohr V.A., de Craen A.J.M., Westendorp R.G.J., Schreiber S., Slagboom P.E., Nebel A., Vaupel J.W., Christensen K., Christiansen L. Evidence from case-control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity. Age (Dordr.). 2013;35(2):487-500. DOI 10.1007/s11357-011-9373-7

109. Song C., Hotz-Wagenblatt A., Voit R., Grummt I. SIRT7 and the DEAD-box helicase DDX21 cooperate to resolve genomic R loops and safeguard genome stability. Genes Dev. 2017;31(13):13701381. DOI 10.1101/gad.300624.117

110. Subramani P., Nagarajan N., Mariaraj S., Vilwanathan R. Knockdown of sirtuin6 positively regulates acetylation of DNMT1 to inhibit NOTCH signaling pathway in non-small cell lung cancer cell lines. Cell. Signal. 2023;105:110629. DOI 10.1016/j.cellsig.2023.110629

111. Sun L., Fang J. Macromolecular crowding effect is critical for maintaining SIRT1’s nuclear localization in cancer cells. Cell Cycle. 2016;15(19):2647-2655. DOI 10.1080/15384101.2016.1211214

112. Sundaresan N.R., Bindu S., Pillai V.B., Samant S., Pan Y., Huang J.-Y., Gupta M., Nagalingam R.S., Wolfgeher D., Verdin E., Gupta M.P. SIRT3 blocks aging-associated tissue fibrosis in mice by deacetylating and activating glycogen synthase kinase 3β. Mol. Cell. Biol. 2016;36(5):678-692. DOI 10.1128/MCB.00586-15

113. Tan M., Peng C., Anderson K.A., Chhoy P., Xie Z., Dai L., Park J., Chen Y., Huang H., Zhang Y., Ro J., Wagner G.R., Green M.F., Madsen A.S., Schmiesing J., Peterson B.S., Xu G., Ilkayeva O.R., Muehlbauer M.J., Braulke T., Mühlhausen C., Backos D.S., Olsen C.A., McGuire P.J., Pletcher S.D., Lombard D.B., Hirschey M.D., Zhao Y. Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab. 2014;19(4):605-617. DOI 10.1016/ j.cmet.2014.03.014

114. Taylor J.R., Wood J.G., Mizerak E., Hinthorn S., Liu J., Finn M., Gordon S., Zingas L., Chang C., Klein M.A., Denu J.M., Gorbunova V., Seluanov A., Boeke J.D., Sedivy J.M., Helfand S.L. Sirt6 regulates lifespan in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA. 2022;119(5):e2111176119. DOI 10.1073/pnas.2111176119

115. TenNapel M.J., Lynch C.F., Burns T.L., Wallace R., Smith B.J., Button A., Domann F.E. SIRT6 minor allele genotype is associated with >5-year decrease in lifespan in an aged cohort. PLoS One. 2014;9(12):e115616. DOI 10.1371/journal.pone.0115616

116. Tian X., Firsanov D., Zhang Z., Cheng Y., Luo L., Tombline G., Tan R., Simon M., Henderson S., Steffan J., Goldfarb A., Tam J., Zheng K., Cornwell A., Johnson A., Yang J.-N., Mao Z., Manta B., Dang W., Zhang Z., Vijg J., Wolfe A., Moody K., Kennedy B.K., Bohmann D., Gladyshev V.N., Seluanov A., Gorbunova V. SIRT6 is responsible for more efficient DNA double-strand break repair in long-lived species. Cell. 2019;177(3):622-638.e22. DOI 10.1016/j.cell.2019.03.043

117. Tissenbaum H.A., Guarente L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature. 2001;410(6825):227230. DOI 10.1038/35065638

118. Tsai Y.-C., Greco T.M., Boonmee A., Miteva Y., Cristea I.M. Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription. Mol. Cell. Proteomics. 2012;11(5):60-76. DOI 10.1074/mcp.A111.015156

119. van der Horst A., Tertoolen L.G.J., de Vries-Smits L.M.M., Frye R.A., Medema R.H., Burgering B.M.T. FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2SIRT1. J. Biol. Chem. 2004;279(28):28873-28879. DOI 10.1074/jbc.M40 1138200

120. Van Meter M., Kashyap M., Rezazadeh S., Geneva A.J., Morello T.D., Seluanov A., Gorbunova V. SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age. Nat. Commun. 2014;5(1):5011. DOI 10.1038/ncomms6011

121. Vaquero A., Scher M., Lee D., Erdjument-Bromage H., Tempst P., Reinberg D. Human sirt1 interacts with histone H1 and promotes formation of facultative heterochromatin. Mol. Cell. 2004;16(1): 93-105. DOI 10.1016/j.molcel.2004.08.031

122. Vaquero A., Scher M.B., Lee D.H., Sutton A., Cheng H.-L., Alt F.W., Serrano L., Sternglanz R., Reinberg D. SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. Genes Dev.

123. ;20(10):1256-1261. DOI 10.1101/gad.1412706

124. Vaquero A., Scher M., Erdjument-Bromage H., Tempst P., Serrano L., Reinberg D. SIRT1 regulates the histone methyl-transferase SUV39H1 during heterochromatin formation. Nature. 2007; 450(7168):440-444. DOI 10.1038/nature06268

125. Vaziri H., Dessain S.K., Eaton E.N., Imai S.-I., Frye R.A., Pandita T.K., Guarente L., Weinberg R.A. hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase. Cell. 2001;107(2):149-159. DOI 10.1016/S0092-8674(01)00527-X

126. Vazquez B.N., Thackray J.K., Simonet N.G., Kane‐Goldsmith N., Martinez‐Redondo P., Nguyen T., Bunting S., Vaquero A., Tischfield J.A., Serrano L. SIRT7 promotes genome integrity and modulates nonhomologous end joining DNA repair. EMBO J. 2016;35(14):14881503. DOI 10.15252/embj.201593499

127. Vazquez B.N., Fernández-Duran I., Vaquero A. Sirtuins in hematopoiesis and blood malignancies. Chapter 23. In: Maiese K. (Ed.). Sirtuin Biology in Medicine. Academic Press, 2021;373-391. DOI 10.1016/B978-0-12-814118-2.00020-3

128. Viswanathan M., Guarente L. Regulation of Caenorhabditis elegans lifespan by sir-2.1 transgenes. Nature. 2011;477(7365):E1-E2. DOI 10.1038/nature10440

129. Wang L., Xu C., Johansen T., Berger S.L., Dou Z. SIRT1 – a new mammalian substrate of nuclear autophagy. Autophagy. 2021;17(2):593-595. DOI 10.1080/15548627.2020.1860541

130. Wang R.-H., Sengupta K., Li C., Kim H.-S., Cao L., Xiao C., Kim S., Xu X., Zheng Y., Chilton B., Jia R., Zheng Z.-M., Appella E., Wang X.W., Ried T., Deng C.-X. Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell. 2008;14(4):312-323. DOI 10.1016/j.ccr.2008.09.001

131. Whitaker R., Faulkner S., Miyokawa R., Burhenn L., Henriksen M., Wood J.G., Helfand S.L. Increased expression of Drosophila Sir2 extends life span in a dose-dependent manner. Aging. 2013;5(9): 682-691. DOI 10.18632/aging.100599

132. Willcox B.J., Donlon T.A., He Q., Chen R., Grove J.S., Yano K., Masaki K.H., Willcox D.C., Rodriguez B., Curb J.D. FOXO3A genotype is strongly associated with human longevity. Proc. Natl. Acad. Sci. USA. 2008;105(37):13987-13992. DOI 10.1073/pnas.0801030105

133. Woo S.J., Lee S.-M., Lim H.S., Hah Y.-S., Jung I.D., Park Y.-M., Kim H.-O., Cheon Y.-H., Jeon M.-G., Jang K.Y., Kim K.M., Park B.- H., Lee S.-I. Myeloid deletion of SIRT1 suppresses collagen-induced arthritis in mice by modulating dendritic cell maturation. Exp. Mol. Med. 2016;48(3):e221. DOI 10.1038/emm.2015.124

134. Woo S.J., Noh H.S., Lee N.Y., Cheon Y.-H., Yi S.M., Jeon H.M., Bae E.J., Lee S.-I., Park B.-H. Myeloid sirtuin 6 deficiency accelerates experimental rheumatoid arthritis by enhancing macrophage activation and infiltration into synovium. EBioMedicine. 2018;38: 228-237. DOI 10.1016/j.ebiom.2018.11.005

135. Wood J.G., Schwer B., Wickremesinghe P.C., Hartnett D.A., Burhenn L., Garcia M., Li M., Verdin E., Helfand S.L. Sirt4 is a mitochondrial regulator of metabolism and lifespan in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA. 2018;115(7):1564-1569. DOI 10.1073/pnas.1720673115

136. Wu Q.J., Zhang T.N., Chen H.H., Yu X.F., Lv J.L., Liu Y.Y., Liu Y.S., Zheng G., Zhao J.Q., Wei Y.F., Guo J.Y., Liu F.H., Chang Q., Zhang Y.X., Liu C.G., Zhao Y.H. The sirtuin family in health and disease. Signal Transduct. Target. Ther. 2022;7(1):402. DOI 10.1038/s41392-022-01257-8

137. Xu C., Wang L., Fozouni P., Evjen G., Chandra V., Jiang J., Lu C., Nicastri M., Bretz C., Winkler J.D., Amaravadi R., Garcia B.A., Adams P.D., Ott M., Tong W., Johansen T., Dou Z., Berger S.L. SIRT1 is downregulated by autophagy in senescence and ageing. Nat. Cell Biol. 2020;22(10):1170-1179. DOI 10.1038/s41556-020-00579-5

138. Yang Y., Hou H., Haller E.M., Nicosia S.V., Bai W. Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation. EMBO J. 2005;24(5):1021-1032. DOI 10.1038/sj.emboj.7600570

139. Yeung F., Hoberg J.E., Ramsey C.S., Keller M.D., Jones D.R., Frye R.A., Mayo M.W. Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 2004; 23(12):2369-2380. DOI 10.1038/sj.emboj.7600244

140. Zhang J., Fang L., Lu Z., Xiong J., Wu M., Shi L., Luo A., Wang S. Are sirtuins markers of ovarian aging? Gene. 2016;575(2 Pt. 3):680-686. DOI 10.1016/j.gene.2015.09.043

141. Zhang P.-Y., Li G., Deng Z.-J., Liu L.-Y., Chen L., Tang J.-Z., Wang Y.- Q., Cao S.-T., Fang Y.-X., Wen F., Xu Y., Chen X., Shi K.- Q., Li W.-F., Xie C., Tang K.-F. Dicer interacts with SIRT7 and regulates H3K18 deacetylation in response to DNA damaging agents. Nucleic Acids Res. 2016;44(8):3629-3642. DOI 10.1093/nar/gkv1504

142. Zhang W.-G., Bai X.-J., Chen X.-M. SIRT1 variants are associated with aging in a healthy Han Chinese population. Clin. Chim. Acta. 2010;411(21-22):1679-1683. DOI 10.1016/j.cca.2010.06.030

143. Zhang X., Spiegelman N.A., Nelson O.D., Jing H., Lin H. SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation. eLife. 2017;6:e25158. DOI 10.7554/eLife.25158

144. Zhang X., Ameer F.S., Azhar G., Wei J.Y. Alternative splicing increases sirtuin gene family diversity and modulates their subcellular localization and function. Int. J. Mol. Sci. 2021;22(2):473. DOI 10.3390/ijms22020473

145. Zhang Y., Connelly K.A., Thai K., Wu X., Kapus A., Kepecs D., Gilbert R.E. Sirtuin 1 activation reduces transforming growth factorβ1-induced fibrogenesis and affords organ protection in a model of progressive, experimental kidney and associated cardiac disease. Am. J. Pathol. 2017;187(1):80-90. DOI 10.1016/j.ajpath.2016.09.016

146. Zhao Y., Wang H., Poole R.J., Gems D. A fln-2 mutation affects lethal pathology and lifespan in C. elegans. Nat. Commun. 2019;10(1): 5087. DOI 10.1038/s41467-019-13062-z

147. Zhong L., D’Urso A., Toiber D., Sebastian C., Henry R.E., Vadysirisack D.D., Guimaraes A., Marinelli B., Wikstrom J.D., Nir T., Clish C.B., Vaitheesvaran B., Iliopoulos O., Kurland I., Dor Y., Weissleder R., Shirihai O.S., Ellisen L.W., Espinosa J.M., Mostoslavsky R. The histone deacetylase SIRT6 regulates glucose homeostasis via Hif1α. Cell. 2010;140(2):280-293. DOI 10.1016/j.cell.2009.12.041