Preview

Вавиловский журнал генетики и селекции

Расширенный поиск

Генетика старения и долголетия

https://doi.org/10.18699/VJ16.171

Полный текст:

Аннотация

Продолжительность жизни является комплексным количествен­ ным признаком, вносящим определяющий вклад в дарвиновскую приспособленность. Раскрытие генетической природы долгожи­ тельства – фундаментальная проблема эволюции онтогенеза, эво­ люционной генетики и молекулярной геронтологии. В оптимальных условиях существования продолжительность жизни опреде­ляется скоростью старения. В свою очередь, феномен старения состоит из взаимосвязанных процессов, происходящих на орга­низменном, тканевом, клеточном, молекулярно-генетическом уровнях. Они включают дерегуляцию процессов поддержания гомеостаза, метаболических реакций и передачи внутри- и меж­ клеточных сигналов, накопление неспособных к делению клеток, поврежденных органелл и макромолекул, эпигенетические изме­нения и генетическую нестабильность. Задачей настоящего обзора является обобщение имеющихся сведений об основных генетиче­ских детерминантах продолжительности жизни и старения. Рас­смотрены гены и сигнальные каскады, влияющие на скорость старения через регуляцию стресс-ответа, обмена веществ, роста клеток и организма, поддержание целостности генома и протео­ма, качественного и количественного состава митохондрий, вос­палительного ответа, апоптоза и селекции жизнеспособных клеток, а также циркадных ритмов. Перераспределение энергетических ресурсов между процессами роста и самоподдержания жизнеспо­ собности может запустить либо отключить «программу долгожи­ тельства», обеспечивая повышенную устойчивость к стрессам и замедленное старение организма. На основании анализа геро­протекторного потенциала регуляции активности рассматривае­мых генов были выделены возможные подходы для замедления старения и достижения здорового долголетия. К ним отнесены восстановление гетерохроматина; подавление ретротранспози­ций; устранение клеток с анеуплоидией; восстановление кислот­ности лизосом; удлинение теломер; подавление хронического воспаления; устранение перекрестных сшивок белков; элимина­ция сенесцентных клеток; восстановление уровней НАД+; ингиби­рование mTOR, S6K, TGF-β, AT1; контролируемая активация генов «программы долгожительства» FOXO, AMPK, PGC1α, NRF2.

Об авторах

А. А. Москалев
Федеральное государственное бюджетное учреждение науки Институт биологии Коми научного центра Уральского отделения Российской академии наук; Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования «Сыктывкарский государственный университет им. Питирима Сорокина»; Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования «Московский физико-технический институт (государственный университет)»; Федеральное государственное бюджетное учреждение науки Институт общей генетики им. Н.И. Вавилова Российской академии наук
Россия

Сыктывкар;

Сыктывкар;

Долгопрудный;

Москва



Е. Н. Прошкина
Федеральное государственное бюджетное учреждение науки Институт биологии Коми научного центра Уральского отделения Российской академии наук; Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования «Сыктывкарский государственный университет им. Питирима Сорокина»
Россия
Сыктывкар


А. А. Белый
Федеральное государственное бюджетное учреждение науки Институт биологии Коми научного центра Уральского отделения Российской академии наук; Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования «Сыктывкарский государственный университет им. Питирима Сорокина»
Россия
Сыктывкар


И. А. Соловьев
Федеральное государственное бюджетное учреждение науки Институт биологии Коми научного центра Уральского отделения Российской академии наук; Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования «Сыктывкарский государственный университет им. Питирима Сорокина»
Россия
Сыктывкар


Список литературы

1. Москалев А.А. Старение и гены. СПб.: Наука, 2008.

2. Москалев А.А., Зайнуллин В.Г. Роль reaper-зависимого апоптоза в радиационно-индуцированном изменении продолжительности жизни у Drosophila melanogaster. Радиац. биология. Радиоэкология. 2003;43(2):242-244.

3. Шапошников М.В., Прошкина Е.Н., Шилова Л.А., Москалев А.А. Роль репарации повреждений ДНК в долголетии. М.: Товарищество научных изданий КМК, 2015.

4. Adler A.S., Kawahara T.L., Segal E., Chang H.Y. Reversal of aging by NFkappaB blockade. Cell Cycle. 2008;7(5):556-559.

5. Ahmed S., Passos J.F., Birket M.J., Beckmann T., Brings S., Peters H., Birch-Machin M.A., von Zglinicki T., Saretzki G. Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress. J. Cell Sci. 2008;121(Pt 7):1046-1053. DОI 10.1242/jcs.019372.

6. Åkerfelt M., Morimoto R.I., Sistonen L. Heat shock factors: integrators of cell stress, development and lifespan. Nat. Rev. Mol. Cell Biol. 2010;11(8):545-555.

7. Amsellem V., Gary-Bobo G., Marcos E., Maitre B., Chaar V., Validire P., Stern J.B., Noureddine H., Sapin E., Rideau D., Hue S., Le Corvoisier P., Le Gouvello S., Dubois-Rande J.L., Boczkowski J., Adnot S. Telomere dysfunction causes sustained inflammation in chronic obstructive pulmonary disease. Am. J. Resp. Crit. Care. 2011; 184(12):1358-1366. DОI 10.1164/rccm.201105-0802OC.

8. Anderson R., Prolla T. PGC-1α in aging and anti-aging interventions. BBA-Gen. Subjects. 2009;1790(10):1059-1066.

9. Anisimov V.N., Bartke A. The key role of growth hormone-insulinIGF-1signaling in aging and cancer. Crit. Rev. Oncol. Hematol. 2013;87(3):201-223. DОI 10.1016/j.critrevonc.2013.01.005.

10. Arai Y., Takayama M., Abe Y., Hirose N. Adipokines and aging. J. Atheroscler. Thromb. 2011;18(7):545-550.

11. Argmann C., Dobrin R., Heikkinen S., Auburtin A., Pouilly L., Cock T.-A., Koutnikova H., Zhu J., Schadt E.E., Auwerx J. Pparγ2 is a key driver of longevity in the mouse. PLoS Genet. 2009;5(12): e1000752.

12. Argon Y., Gidalevitz T. Candidate Genes That Affect Aging Through Protein Homeostasis Longevity Genes. New York: Springer, 2015: 45-72.

13. Aschner Y., Downey G.P. Transforming growth factor-beta: master regulator of the respiratory system in health and disease. Am. J. Respir. Cell Mol. Biol. 2016. DОI 10.1165/rcmb.2015-0391TR.

14. Ayyadevara S., Bharill P., Dandapat A., Hu C., Khaidakov M., Mitra S., Shmookler Reis R.J., Mehta J.L. Aspirin inhibits oxidant stress, reduces age-associated functional declines, and extends lifespan of Caenorhabditis elegans. Antioxid. Redox. Sign. 2013;18(5):481-490. DОI 10.1089/ars.2011.4151.

15. Baker D.J., Childs B.G., Durik M., Wijers M.E., Sieben C.J., Zhong J., Saltness R.A., Jeganathan K.B., Verzosa G.C., Pezeshki A., Khazaie K., Miller J.D., van Deursen J.M. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature. 2016; 530(7589):184-189. DОI 10.1038/nature16932.

16. Baker D.J., Wijshake T., Tchkonia T., LeBrasseur N.K., Childs B.G., van de Sluis B., Kirkland J.L., van Deursen J.M. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011;479(7372):232-236. DОI 10.1038/nature10600.

17. Bar C., Bernardes de Jesus B., Serrano R., Tejera A., Ayuso E., Jimenez V., Formentini I., Bobadilla M., Mizrahi J., de Martino A., Gomez G., Pisano D., Mulero F., Wollert K.C., Bosch F., Blasco M.A. Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction. Nat. Commun. 2014;5:5863. DОI 10.1038/ncomms6863.

18. Basso N., Paglia N., Stella I., de Cavanagh E.M., Ferder L., del Rosario Lores Arnaiz M., Inserra F. Protective effect of the inhibition of the renin-angiotensin system on aging. Regul. Peptides. 2005; 128(3):247-252. DОI 10.1016/j.regpep.2004.12.027.

19. Benigni A., Corna D., Zoja C., Sonzogni A., Latini R., Salio M., Conti S., Rottoli D., Longaretti L., Cassis P., Morigi M., Coffman T.M., Remuzzi G. Disruption of the Ang II type 1 receptor promotes longevity in mice. J. Clin. Invest. 2009;119(3):524-530. DОI 10.1172/JCI36703.

20. Benigni A., Orisio S., Noris M., Iatropoulos P., Castaldi D., Kamide K., Rakugi H., Arai Y., Todeschini M., Ogliari G., Imai E., Gondo Y., Hirose N., Mari D., Remuzzi G. Variations of the angiotensin II type 1 receptor gene are associated with extreme human longevity. Age (Dordr). 2013;35(3):993-1005. DОI 10.1007/s11357-012-9408-8.

21. Bernardes de Jesus B., Vera E., Schneeberger K., Tejera A.M., Ayuso E., Bosch F., Blasco M.A. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol. Med. 2012;4(8):691-704. DОI 10.1002/emmm.201200245.

22. Bian A., Neyra J.A., Zhan M., Hu M.C. Klotho, stem cells, and aging. Clin. Interv. Aging. 2015;10:1233.

23. Biteau B., Karpac J., Hwangbo D., Jasper H. Regulation of Drosophila lifespan by JNK signaling. Exp. Gerontol. 2011;46(5):349-354. DОI 10.1016/j.exger.2010.11.003.

24. Biteau B., Karpac J., Supoyo S., Degennaro M., Lehmann R., Jasper H. Lifespan extension by preserving proliferative homeostasis in Drosophila. PLoS Genet. 2010;6(10):e1001159. DОI 10.1371/journal.pgen.1001159.

25. Bitto A., Wang A.M., Bennett C.F., Kaeberlein M. Biochemical genetic pathways that modulate aging in multiple species. Cold Spring Harb. Persp. Med. 2015;5(11). DОI 10.1101/cshperspect.a025114.

26. Bluher M., Kahn B.B., Kahn C.R. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science. 2003;299(5606):572-574. DОI 10.1126/science.1078223.

27. Boccardi V., Pelini L., Ercolani S., Ruggiero C., Mecocci P. From cellular senescence to Alzheimer’s disease: The role of telomere shortening. Ageing Res. Rev. 2015;22:1-8. DОI 10.1016/j.arr.2015.04.003.

28. Brooks C.L., Gu W. How does SIRT1 affect metabolism, senescence and cancer? Nat. Rev. Cancer. 2009;9(2):123-128.

29. Broom L., Marinova-Mutafchieva L., Sadeghian M., Davis J.B., Medhurst A.D., Dexter D.T. Neuroprotection by the selective iNOS inhibitor GW274150 in a model of Parkinson disease. Free Radic. Biol. Med. 2011;50(5):633-640. DОI 10.1016/j.freeradbiomed.2010.12.026.

30. Budanov A.V., Karin M. p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell. 2008;134(3):451-460. DОI 10.1016/j.cell.2008.06.028.

31. Cai W., He J.C., Zhu L., Chen X., Wallenstein S., Striker G.E., Vlassara H. Reduced oxidant stress and extended lifespan in mice exposed to a low glycotoxin diet: association with increased AGER1 expression. Am. J. Pathol. 2007;170(6):1893-1902. DОI 10.2353/ajpath.2007.061281.

32. Cantó C., Auwerx J. Calorie restriction: is AMPK a key sensor and effector? Physiology. 2011;26(4):214-224.

33. Carrard G., Bulteau A.-L., Petropoulos I., Friguet B. Impairment of proteasome structure and function in aging. Int. J. Biochem. Cell Biol. 2002;34(11):1461-1474.

34. Carrieri G., Marzi E., Olivieri F., Marchegiani F., Cavallone L., Cardelli M., Giovagnetti S., Stecconi R., Molendini C., Trapassi C., De Benedictis G., Kletsas D., Franceschi C. The G/C915 polymorphism of transforming growth factor beta1 is associated with human longevity: a study in Italian centenarians. Aging Cell. 2004;3(6):443-448. DОI 10.1111/j.1474-9728.2004.00129.x.

35. Cha D.R., Han J.Y., Su D.M., Zhang Y., Fan X., Breyer M.D., Guan Y. Peroxisome proliferator-activated receptor-alpha deficiency protects aged mice from insulin resistance induced by high-fat diet. Am. J. Nephrol. 2007;27(5):479-482.

36. Cha Y.I., Kim H.-S. Emerging role of sirtuins on tumorigenesis: possible link between aging and cancer. BMB Reports. 2013;46(9): 429-438.

37. Chang H.C., Guarente L. SIRT1 and other sirtuins in metabolism. Trends Endocrin. Met. 2014;25(3):138-145. DОI 10.1016/j.tem.2013.12.001.

38. Chen D., Guarente L. SIR2: a potential target for calorie restriction mimetics. Trends Mol. Med. 2007;13(2):64-71.

39. Chen H., Zheng X., Zheng Y. Age-associated loss of lamin-B leads to systemic inflammation and gut hyperplasia. Cell. 2014;159(4): 829-843.

40. Cheong J.K., Zhang F., Chua P.J., Bay B.H., Thorburn A., Virshup D.M. Casein kinase 1alpha-dependent feedback loop controls autophagy in RAS-driven cancers. J. Clin. Invest. 2015;125(4):1401-1418. DОI 10.1172/JCI78018.

41. Chondrogianni N., Georgila K., Kourtis N., Tavernarakis N., Gonos E.S. 20S proteasome activation promotes life span extension and resistance to proteotoxicity in Caenorhabditis elegans. The FASEB J. 2015;29(2):611-622.

42. Chondrogianni N., Petropoulos I., Grimm S., Georgila K., Catalgol B., Friguet B., Grune T., Gonos E.S. Protein damage, repair and proteolysis. Mol. Aspects Med. 2014;35:1-71.

43. Clempson A.M., Pollott G.E., Brickell J.S., Bourne N.E., Munce N., Wathes D.C. Polymorphisms in the autosomal genes for mitochondrial function TFAM and UCP2 are associated with performance and longevity in dairy cows. Animal. 2011;5(9):1335-1343. DОI 10.1017/S1751731111000346.

44. Codd V., Nelson C.P., Albrecht E., Mangino M., Deelen J., Buxton J.L., Hottenga J.J., Fischer K., Esko T., Surakka I. Identification of seven loci affecting mean telomere length and their association with disease. Nat. Genet. 2013;45(4):422-427.

45. Cohen H.Y., Miller C., Bitterman K.J., Wall N.R., Hekking B., Kessler B., Howitz K.T., Gorospe M., de Cabo R., Sinclair D.A. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science. 2004;305(5682):390-392.

46. Corpet A., Stucki M. Chromatin maintenance and dynamics in senescence: a spotlight on SAHF formation and the epigenome of senescent cells. Chromosoma. 2014;123(5):423-436. DОI 10.1007/s00412-014-0469-6.

47. Costacou T., Zgibor J.C., Evans R.W., Otvos J., Lopes-Virella M.F., Tracy R.P., Orchard T.J. The prospective association between adiponectin and coronary artery disease among individuals with type 1 diabetes. The pittsburgh epidemiology of diabetes complications study. Diabetologia. 2005;48(1):41-48. DОI 10.1007/s00125-004-1597-y.

48. de Cavanagh E.M., Inserra F., Ferder L. Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition. Am. J. Physiol. Heart Circ. Physiol. 2015;309(1):H15-H44. DОI 10.1152/ajpheart.00459.2014.

49. Demontis F., Patel V.K., Swindell W.R., Perrimon N. Intertissue control of the nucleolus via a myokine-dependent longevity pathway. Cell Rep. 2014;7(5):1481-1494. DОI 10.1016/j.celrep.2014.05.001.

50. Demontis F., Perrimon N. FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell. 2010;143(5):813-825. DОI 10.1016/j.cell.2010.10.007. Dërmaku-Sopjani M., Kolgeci S., Abazi S., Sopjani M. Significance of the anti-aging protein Klotho. Mol. Memb. Biol. 2013;30(8): 369-385.

51. Ding J., Sackmann-Sala L., Kopchick J.J. Mouse models of growth hormone action and aging: a proteomic perspective. Proteomics. 2013;13(3-4):674-685. DОI 10.1002/pmic.201200271.

52. Dominy J.E., Puigserver P. Mitochondrial biogenesis through activation of nuclear signaling proteins. Cold Spring Harb. Persp. Biol. 2013;5(7):a015008.

53. Efeyan A., Zoncu R., Sabatini D.M. Amino acids and mTORC1: from lysosomes to disease. Trends Mol. Med. 2012;18(9):524-533. DОI 10.1016/j.molmed.2012.05.007.

54. Fang E.F., Scheibye-Knudsen M., Chua K.F., Mattson M.P., Croteau D.L., Bohr V.A. Nuclear DNA damage signalling to mitochondria in ageing. Nat. Rev. Mol. Cell Biol. 2016. DОI 10.1038/nrm.2016.14.

55. Feng Z., Lin M., Wu R. The regulation of aging and longevity: a new and complex role of p53. Genes. Cancer. 2011;2(4):443-452. DОI 10.1177/1947601911410223.

56. Fleming T.H., Humpert P.M., Nawroth P.P., Bierhaus A. Reactive metabolites and AGE/RAGE-mediated cellular dysfunction affect the aging process: a mini-review. Gerontology. 2011;57(5):435-443. DОI 10.1159/000322087.

57. Frippiat C., Dewelle J., Remacle J., Toussaint O. Signal transduction in H2O2-induced senescence-like phenotype in human diploid fibroblasts. Free Radic. Biol. Med. 2002;33(10):1334-1346.

58. Gallot Y.S., Durieux A.-C., Castells J., Desgeorges M.M., Vernus B., Plantureux L., Rémond D., Jahnke V.E., Lefai E., Dardevet D. Myostatin gene inactivation prevents skeletal muscle wasting in cancer. Cancer Res. 2014;74(24):7344-7356.

59. Garcia-Martinez J.M., Alessi D.R. mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serumand glucocorticoid-induced protein kinase 1 (SGK1). Biochem. J. 2008;416(3):375-385. DОI 10.1042/BJ20081668.

60. Garg A., Agarwal A.K. Lipodystrophies: disorders of adipose tissue biology. Biochem. Bioph. Acta. 2009;1791(6):507-513. DОI 10.1016/j.bbalip.2008.12.014.

61. Genabai N.K., Ahmad S., Zhang Z., Jiang X., Gabaldon C.A., Gangwani L. Genetic inhibition of JNK3 ameliorates spinal muscular atrophy. Hum. Mol. Genet. 2015;24(24):6986-7004. DОI 10.1093/hmg/ddv401.

62. Goetz R., Ohnishi M., Ding X., Kurosu H., Wang L., Akiyoshi J., Ma J., Gai W., Sidis Y., Pitteloud N., Kuro O.M., Razzaque M.S., Mohammadi M. Klotho coreceptors inhibit signaling by paracrine fibroblast growth factor 8 subfamily ligands. Mol. Cell Biol. 2012;32(10):1944-1954. DОI 10.1128/MCB.06603-11.

63. Goitre L., Trapani E., Trabalzini L., Retta S.F. The Ras superfamily of small GTPases: the unlocked secrets. Methods Mol. Biol. 2014; 1120:1-18. DОI 10.1007/978-1-62703-791-4_1.

64. Green S.J., Scheller L.F., Marletta M.A., Seguin M.C., Klotz F.W., Slayter M., Nelson B.J., Nacy C.A. Nitric oxide: cytokine-regulation of nitric oxide in host resistance to intracellular pathogens. Immunol. Lett. 1994;43(1-2):87-94.

65. Grube K., Burkle A. Poly(ADP-ribose) polymerase activity in mononuclear leukocytes of 13 mammalian species correlates with speciesspecific life span. Proc. Natl Acad. Sci. USA. 1992;89(24):11759-11763.

66. Han J., Ryu S., Moskowitz D.M., Rothenberg D., Leahy D.J., Atzmon G., Barzilai N., Suh Y. Discovery of novel non-synonymous SNP variants in 988 candidate genes from 6 centenarians by target capture and next-generation sequencing. Mech. Ageing Dev. 2013;134(10):478-485. DОI 10.1016/j.mad.2013.01.005.

67. Hannon G.J., Beach D. p15INK4B is a potential effector of TGF-betainduced cell cycle arrest. Nature. 1994;371(6494):257-261. DОI 10.1038/371257a0.

68. Hannum G., Guinney J., Zhao L., Zhang L., Hughes G., Sadda S., Klotzle B., Bibikova M., Fan J.-B., Gao Y. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol. Cell. 2013;49(2):359-367.

69. Harshman L.G., Moore K.M., Sty M.A., Magwire M.M. Stress resistance and longevity in selected lines of Drosophila melanogaster. Neurobiol. Aging. 1999;20(5):521-529.

70. Hart R.W., Setlow R.B. Correlation between deoxyribonucleic acid excision-repair and life-span in a number of mammalian species. Proc. Natl Acad. Sci. USA. 1974;71(6):2169-2173.

71. Hartmann N., Reichwald K., Wittig I., Drose S., Schmeisser S., Luck C., Hahn C., Graf M., Gausmann U., Terzibasi E., Cellerino A., Ristow M., Brandt U., Platzer M., Englert C. Mitochondrial DNA copy number and function decrease with age in the short-lived fish Nothobranchius furzeri. Aging Cell. 2011;10(5):824-831. DОI 10.1111/j.1474-9726.2011.00723.x.

72. He C., Tsuchiyama S.K., Nguyen Q.T., Plyusnina E.N., Terrill S.R., Sahibzada S., Patel B., Faulkner A.R., Shaposhnikov M.V., Tian R., Tsuchiya M., Kaeberlein M., Moskalev A.A., Kennedy B.K., Polymenis M. Enhanced longevity by ibuprofen, conserved in multiple species, occurs in yeast through inhibition of tryptophan import. PLoS Genet. 2014;10(12):e1004860. DОI 10.1371/journal.pgen.1004860.

73. Hepple R.T., Baker D.J., McConkey M., Murynka T., Norris R. Caloric restriction protects mitochondrial function with aging in skeletal and cardiac muscles. Rejuv. Res. 2006;9(2):219-222.

74. Herranz D., Munoz-Martin M., Canamero M., Mulero F., MartinezPastor B., Fernandez-Capetillo O., Serrano M. Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat. Commun. 2010;1:3. DОI 10.1038/ncomms1001.

75. Herskovits A.Z., Guarente L. SIRT1 in neurodevelopment and brain senescence. Neuron. 2014;81(3):471-483. DОI 10.1016/j.neuron.2014.01.028.

76. Hollander M.C., Sheikh M.S., Bulavin D.V., Lundgren K., AugeriHenmueller L., Shehee R., Molinaro T.A., Kim K.E., Tolosa E., Ashwell J.D., Rosenberg M.P., Zhan Q., Fernandez-Salguero P.M., Morgan W.F., Deng C.X., Fornace A.J., Jr. Genomic instability in Gadd45a-deficient mice. Nat. Genet. 1999;23(2):176-184. DОI 10.1038/13802.

77. Hsu A.L., Murphy C.T., Kenyon C. Regulation of aging and agerelated disease by DAF-16 and heat-shock factor. Science. 2003; 300(5622):1142-1145. DОI 10.1126/science.1083701.

78. Hu M.C., Shi M., Zhang J., Pastor J., Nakatani T., Lanske B., Razzaque M.S., Rosenblatt K.P., Baum M.G., Kuro-o M. Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. The FASEB J. 2010;24(9):3438-3450.

79. Hulmi J.J., Oliveira B.M., Silvennoinen M., Hoogaars W.M., Pasternack A., Kainulainen H., Ritvos O. Exercise restores decreased physical activity levels and increases markers of autophagy and oxidative capacity in myostatin/activin-blocked mdx mice. Am. J. Physiol. Endoc. Metab. 2013;305(2):E171-E182.

80. Icreverzi A., de la Cruz A.F., Walker D.W., Edgar B.A. Changes in neuronal CycD/Cdk4 activity affect aging, neurodegeneration, and oxidative stress. Aging Cell. 2015;14(5):896-906. DОI 10.1111/acel.12376.

81. Jäger S., Handschin C., Pierre J., Spiegelman B.M. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α. Proc. Natl Acad. Sci. 2007;104(29):12017-12022.

82. Jazwinski S.M., Yashin A.I. Aging and health – a systems biology perspective. Introduction. Interdiscip. Top Gerontol. 2015;40:VII-XII.

83. Jewell J.L., Russell R.C., Guan K.L. Amino acid signalling upstream of mTOR. Nat. Rev. Mol. Cell Biol. 2013;14(3):133-139. DОI 10.1038/nrm3522.

84. Junnila R.K., List E.O., Berryman D.E., Murrey J.W., Kopchick J.J. The GH/IGF-1 axis in ageing and longevity. Nat. Rev. Endocrinol. 2013;9(6):366-376. DОI 10.1038/nrendo.2013.67.

85. Kanfi Y., Naiman S., Amir G., Peshti V., Zinman G., Nahum L., BarJoseph Z., Cohen H.Y. The sirtuin SIRT6 regulates lifespan in male mice. Nature. 2012;483(7388):218-221. DОI 10.1038/nature10815.

86. Kanfi Y., Peshti V., Gozlan Y.M., Rathaus M., Gil R., Cohen H.Y. Regulation of SIRT1 protein levels by nutrient availability. FEBS Lett. 2008;582(16):2417-2423. DОI 10.1016/j.febslet.2008.06.005.

87. Katewa S.D., Akagi K., Bose N., Rakshit K., Camarella T., Zheng X., Hall D., Davis S., Nelson C.S., Brem R.B., Ramanathan A., Sehgal A., Giebultowicz J.M., Kapahi P. Peripheral circadian clocks mediate dietary restriction-dependent changes in lifespan and fat metabolism in Drosophila. Cell Metab. 2016;23(1):143-154. DОI 10.1016/j.cmet.2015.10.014.

88. Katsimpardi L., Litterman N.K., Schein P.A., Miller C.M., Loffredo F.S., Wojtkiewicz G.R., Chen J.W., Lee R.T., Wagers A.J., Rubin L.L. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science. 2014;344(6184):630-634. DОI 10.1126/science.1251141.

89. Keane M., Semeiks J., Webb A.E., Li Y.I., Quesada V., Craig T., Madsen L.B., van Dam S., Brawand D., Marques P.I., Michalak P., Kang L., Bhak J., Yim H.S., Grishin N.V., Nielsen N.H., Heide-Jorgensen M.P., Oziolor E.M., Matson C.W., Church G.M., Stuart G.W., Patton J.C., George J.C., Suydam R., Larsen K., Lopez-Otin C., O’Connell M.J., Bickham J.W., Thomsen B., de Magalhaes J.P. Insights into the evolution of longevity from the bowhead whale genome. Cell Rep. 2015;10(1):112-122. DОI 10.1016/j.celrep.2014.12.008.

90. Kenyon C., Chang J., Gensch E., Rudner A., Tabtiang R. A C. elegans mutant that lives twice as long as wild type. Nature. 1993; 366(6454):461-464. DОI 10.1038/366461a0.

91. Khan M.H., Ligon M., Hussey L.R., Hufnal B., Farber R. 2nd., Munkácsy E., Rodriguez A., Dillow A., Kahlig E., Rea S.L. TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants. Aging (Albany NY). 2013;5(10):741-758.

92. Khapre R.V., Kondratova A.A., Patel S., Dubrovsky Y., Wrobel M., Antoch M.P., Kondratov R.V. BMAL1-dependent regulation of the mTOR signaling pathway delays aging. Aging (Albany NY). 2014; 6(1):48-57.

93. Kim E.B., Fang X., Fushan A.A., Huang Z., Lobanov A.V., Han L., Marino S.M., Sun X., Turanov A.A., Yang P., Yim S.H., Zhao X., Kasaikina M.V., Stoletzki N., Peng C., Polak P., Xiong Z., Kiezun A., Zhu Y., Chen Y., Kryukov G.V., Zhang Q., Peshkin L., Yang L., Bronson R.T., Buffenstein R., Wang B., Han C., Li Q., Chen L., Zhao W., Sunyaev S.R., Park T.J., Zhang G., Wang J., Gladyshev V.N. Genome sequencing reveals insights into physiology and longevity of the naked mole rat. Nature. 2011;479(7372):223-227. DОI 10.1038/nature10533.

94. Kleinert H., Wallerath T., Fritz G., Ihrig-Biedert I., Rodriguez-Pascual F., Geller D.A., Forstermann U. Cytokine induction of NO synthase II in human DLD-1 cells: roles of the JAK-STAT, AP-1 and NF-kappaB-signaling pathways. Br. J. Pharmacol. 1998;125(1):193-201. DОI ß10.1038/sj.bjp.0702039.

95. Klichko V.I., Chow E.S., Kotwica-Rolinska J., Orr W.C., Giebultowicz J.M., Radyuk S.N. Aging alters circadian regulation of redox in Drosophila. Front. Genet. 2015;6:83. DОI 10.3389/fgene.2015.00083.

96. Kolovou G., Kolovou V., Vasiliadis I., Giannakopoulou V., Mihas C., Bilianou H., Kollia A., Papadopoulou E., Marvaki A., Goumas G., Kalogeropoulos P., Limperi S., Katsiki N., Mavrogeni S. The frequency of 4 common gene polymorphisms in nonagenarians, centenarians, and average life span individuals. Angiology. 2014;65(3): 210-215. DОI 10.1177/0003319712475075.

97. Kondratov R.V., Kondratova A.A., Gorbacheva V.Y., Vykhovanets O.V., Antoch M.P. Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock. Genes. Dev. 2006;20(14):1868-1873. DОI 10.1101/gad.1432206.

98. Kourtis N., Tavernarakis N. Cellular stress response pathways and ageing: intricate molecular relationships. EMBO J. 2011;30(13): 2520-2531.

99. Kruegel U., Robison B., Dange T., Kahlert G., Delaney J.R., Kotireddy S., Tsuchiya M., Tsuchiyama S., Murakami C.J., Schleit J. Elevated proteasome capacity extends replicative lifespan in Saccharomyces cerevisiae. PLoS Genet. 2011;7(9):e1002253.

100. Kumar S., Dietrich N., Kornfeld K. Angiotensin converting enzyme (ACE) inhibitor extends Caenorhabditis elegans Life Span. PLoS Genet. 2016;12(2):e1005866. DОI 10.1371/journal.pgen.1005866.

101. Le Bourg E. The somatotropic axis may not modulate ageing and longevity in humans. Biogerontology. 2016;17(2):421-429. DОI 10.1007/s10522-015-9632-6.

102. Lee S.-J., Hwang A.B., Kenyon C. Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr. Biol. 2010a;20(23):2131-2136.

103. Lee Y.H., Lee H.Y., Kim T.G., Lee N.H., Yu M.K., Yi H.K. PPARgamma maintains homeostasis through autophagy regulation in dental pulp. J. Dent. Res. 2015;94(5):729-737. DОI 10.1177/0022034515573833.

104. Lee Y.H., Lee N.H., Bhattarai G., Yun J.S., Kim T.I., Jhee E.C., Yi H.K. PPARγ inhibits inflammatory reaction in oxidative stress induced human diploid fibloblast. Cell Biochem. Funct. 2010b;28(6): 490-496.

105. Leiser S.F., Kaeberlein M. The hypoxia-inducible factor HIF-1 functions as both a positive and negative modulator of aging. Biol. Chem. 2010;391(10):1131-1137.

106. Lewis K.N., Mele J., Hornsby P.J., Buffenstein R. Stress resistance in the naked mole-rat: the bare essentials – a mini-review. Gerontology. 2012;58(5):453-462. DОI 10.1159/000335966.

107. Lewis K.N., Wason E., Edrey Y.H., Kristan D.M., Nevo E., Buffenstein R. Regulation of Nrf2 signaling and longevity in naturally long-lived rodents. Proc. Natl Acad. Sci. USA. 2015;112(12):3722-3727. DОI 10.1073/pnas.1417566112.

108. Liu S.F., Ye X., Malik A.B. Inhibition of NF-kappaB activation by pyrrolidine dithiocarbamate prevents In vivo expression of proinflammatory genes. Circulation. 1999;100(12):1330-1337.

109. Longo V.D. The Ras and Sch9 pathways regulate stress resistance and longevity. Exp. Gerontol. 2003;38(7):807-811.

110. Lopez-Lluch G., Hunt N., Jones B., Zhu M., Jamieson H., Hilmer S., Cascajo M., Allard J., Ingram D., Navas P. Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency. Proc. Natl Acad. Sci. USA. 2006;103(6):1768-1773.

111. Lopez-Otin C., Blasco M.A., Partridge L., Serrano M., Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-1217. DОI 10.1016/j.cell.2013.05.039.

112. Lorenzini A., Johnson F.B., Oliver A., Tresini M., Smith J.S., Hdeib M., Sell C., Cristofalo V.J., Stamato T.D. Significant correlation of species longevity with DNA double strand break recognition but not with telomere length. Mech. Ageing Dev. 2009;130(11-12):784-792. DОI 10.1016/j.mad.2009.10.004.

113. Luo S., Shaw W.M., Ashraf J., Murphy C.T. TGF-beta Sma/Mab signaling mutations uncouple reproductive aging from somatic aging. PLoS Genet. 2009;5(12):e1000789. DОI 10.1371/journal.pgen.1000789.

114. Luzi L., Confalonieri S., Di Fiore P.P., Pelicci P.G. Evolution of Shc functions from nematode to human. Curr. Opin. Genet. Dev. 2000;10(6):668-674.

115. Manya H., Akasaka-Manya K., Endo T. Klotho protein deficiency and aging. Geriatr. Gerontol. Int. 2010;10(s1):S80-S87.

116. 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. DОI 10.1126/science.1202723.

117. Marin-Garcia J. Mitochondrial DNA repair: a novel therapeutic target for heart failure. Heart Fail Rev. 2016. DОI 10.1007/s10741-016-9543-x.

118. Martín-Montalvo A., Villalba J.M., Navas P., De Cabo R. NRF2, cancer and calorie restriction. Oncogene. 2011;30(5):505-520.

119. Maslov A.Y., Ganapathi S., Westerhof M., Quispe-Tintaya W., White R.R., Van Houten B., Reiling E., Dollé M.E., Steeg H., Hasty P. DNA damage in normally and prematurely aged mice. Aging Cell. 2013;12(3):467-477.

120. Masternak M.M., Bartke A. PPARs in calorie restricted and genetically long-lived mice. PPAR Res. 2006;2007.

121. Matsuda T., Kanki T., Tanimura T., Kang D., Matsuura E.T. Effects of overexpression of mitochondrial transcription factor A on lifespan and oxidative stress response in Drosophila melanogaster. Biochem. Bioph. Res. Commun. 2013;430(2):717-721. DОI 10.1016/j.bbrc.2012.11.084.

122. McPherron A., Lawler A., Lee S. Regulation of skeletal muscle massin micebyanew TGF-ß superfamily member. Nature. 1997;5(1):83-90.

123. Mendias C.L., Bakhurin K.I., Gumucio J.P., Shallal-Ayzin M.V., Davis C.S., Faulkner J.A. Haploinsufficiency of myostatin protects against aging-related declines in muscle function and enhances the longevity of mice. Aging Cell. 2015;14(4):704-706.

124. Merino M.M., Rhiner C., Lopez-Gay J.M., Buechel D., Hauert B., Moreno E. Elimination of unfit cells maintains tissue health and prolongs lifespan. Cell. 2015;160(3):461-476. DОI 10.1016/j.cell.2014.12.017.

125. Miller M.D., Crotty M., Giles L.C., Bannerman E., Whitehead C., Cobiac L., Daniels L.A., Andrews G. Corrected arm muscle area: an independent predictor of long-term mortality in community-dwelling older adults? J. Am. Geriatr. Soc. 2002;50(7):1272-1277.

126. Min J.-N., Whaley R.A., Sharpless N.E., Lockyer P., Portbury A.L., Patterson C. CHIP deficiency decreases longevity, with accelerated aging phenotypes accompanied by altered protein quality control. Mol. Cell. Biol. 2008;28(12):4018-4025.

127. Morrow G., Samson M., Michaud S., Tanguay R.M. Overexpression of the small mitochondrial Hsp22 extends Drosophila life span and increases resistance to oxidative stress. The FASEB J. 2004;18(3): 598-599.

128. Moskalev A.A., Aliper A.M., Smit-McBride Z., Buzdin A., Zhavoronkov A. Genetics and epigenetics of aging and longevity. Cell Cycle. 2014;13(7):1063-1077. DОI 10.4161/cc.28433.

129. Moskalev A., Plyusnina E., Shaposhnikov M., Shilova L., Kazachenok A., Zhavoronkov A. The role of D-GADD45 in oxidative, thermal and genotoxic stress resistance. Cell Cycle. 2012;11(22):4222-4241. DОI 10.4161/cc.22545.

130. Moskalev A.A., Proshkina E.N., Shaposhnikov M.V. Chapter 2. Gadd45 Proteins in Aging and Longevity of Mammals and Drosophila. Life Extension Lessons from Drosophila. Cham: Springer, 2015:39-65.

131. Moskalev A., Shaposhnikov M. Pharmacological inhibition of NF-kappaB prolongs lifespan of Drosophila melanogaster. Aging (Albany NY). 2011;3(4):391-394.

132. Moskalev A., Shaposhnikov M., Turysheva E. Life span alteration after irradiation in Drosophila melanogaster strains with mutations of Hsf and Hsps. Biogerontology. 2009;10(1):3-11. DОI 10.1007/s10522-008-9147-5.

133. Mostoslavsky R., Chua K.F., Lombard D.B., Pang W.W., Fischer M.R., Gellon L., Liu P., Mostoslavsky G., Franco S., Murphy M.M., Mills K.D., Patel P., Hsu J.T., Hong A.L., Ford E., Cheng H.L., Kennedy C., Nunez N., Bronson R., Frendewey D., Auerbach W., Valenzuela D., Karow M., Hottiger M.O., Hursting S., Barrett J.C., Guarente L., Mulligan R., Demple B., Yancopoulos G.D., Alt F.W. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell. 2006;124(2):315-329. DОI 10.1016/j.cell.2005.11.044.

134. Neufeld-Cohen A., Robles M.S., Aviram R., Manella G., Adamovich Y., Ladeuix B., Nir D., Rousso-Noori L., Kuperman Y., Golik M., Mann M., Asher G. Circadian control of oscillations in mitochondrial rate-limiting enzymes and nutrient utilization by PERIOD proteins. Proc. Natl Acad. Sci. USA. 2016;113(12):E1673-E1682. DОI 10.1073/pnas.1519650113.

135. Oh S.W., Mukhopadhyay A., Svrzikapa N., Jiang F., Davis R.J., Tissenbaum H.A. JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc. Natl Acad. Sci. USA. 2005;102(12):4494-4499. DОI 10.1073/pnas.0500749102.

136. Olovnikov A.M. A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J. Theor. Biol. 1973;41(1): 181-190.

137. Onken B., Driscoll M. Metformin induces a dietary restriction–like state and the oxidative stress response to extend C. elegans healthspan via AMPK, LKB1, and SKN-1. PLoS ONE. 2010;5(1):e8758.

138. Oudit G.Y., Liu G.C., Zhong J., Basu R., Chow F.L., Zhou J., Loibner H., Janzek E., Schuster M., Penninger J.M., Herzenberg A.M., Kassiri Z., Scholey J.W. Human recombinant ACE2 reduces the progression of diabetic nephropathy. Diabetes. 2010;59(2):529-538. DОI 10.2337/db09-1218.

139. Pall M.L., Levine S. Nrf2, a master regulator of detoxification and also antioxidant, anti-inflammatory and other cytoprotective mechanisms, is raised by health promoting factors. Sheng Li Xue Bao. 2015;67(1):1-18.

140. Perkins N.D. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat. Rev. Mol. Cell Biol. 2007;8(1):49-62. DОI 10.1038/nrm2083.

141. Piaceri I., Bagnoli S., Tedde A., Sorbi S., Nacmias B. Ataxia-telangiectasia mutated (ATM) genetic variant in Italian centenarians. Neurol. Sci. 2013;34(4):573-575. DОI 10.1007/s10072-012-1188-5.

142. Picca A., Pesce V., Fracasso F., Joseph A.M., Leeuwenburgh C., Lezza A.M. Aging and calorie restriction oppositely affect mitochondrial biogenesis through TFAM binding at both origins of mitochondrial DNA replication in rat liver. PLoS ONE. 2013;8(9):e74644. DОI 10.1371/journal.pone.0074644.

143. Pickering A.M., Lehr M., Miller R.A. Lifespan of mice and primates correlates with immunoproteasome expression. J. Clin. Invest. 2015;125(5):2059-2068.

144. Plyusnina E.N., Shaposhnikov M.V., Moskalev A.A. Increase of Drosophila melanogaster lifespan due to D-GADD45 overexpression in the nervous system. Biogerontology. 2011;12(3):211-226. DОI 10.1007/s10522-010-9311-6.

145. Pyo J.-O., Yoo S.-M., Ahn H.-H., Nah J., Hong S.-H., Kam T.-I., Jung S., Jung Y.-K. Overexpression of Atg5 in mice activates autophagy and extends lifespan. Nat. Commun. 2013;4.

146. Rakshit K., Giebultowicz J.M. Cryptochrome restores dampened circadian rhythms and promotes healthspan in aging Drosophila. Aging. Cell. 2013;12(5):752-762. DОI 10.1111/acel.12100.

147. Ramasamy R., Shekhtman A., Schmidt A.M. The multiple faces of RAGE – opportunities for therapeutic intervention in aging and chronic disease. Expert. Opin. Ther. Targets. 2016;20(4):431-446. DОI 10.1517/14728222.2016.1111873.

148. Regenhardt R.W., Mecca A.P., Desland F., Ritucci-Chinni P.F., Ludin J.A., Greenstein D., Banuelos C., Bizon J.L., Reinhard M.K., Sumners C. Centrally administered angiotensin-(1-7) increases the survival of stroke-prone spontaneously hypertensive rats. Exp. Physiol. 2014;99(2):442-453. DОI 10.1113/expphysiol.2013.075242.

149. Rera M., Bahadorani S., Cho J., Koehler C.L., Ulgherait M., Hur J.H., Ansari W.S., Lo T., Jr., Jones D.L., Walker D.W. Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog. Cell Metab. 2011;14(5):623-634. DОI 10.1016/j.cmet.2011.09.013.

150. Ropelle E.R., Pauli J.R., Cintra D.E., da Silva A.S., De Souza C.T., Guadagnini D., Carvalho B.M., Caricilli A.M., Katashima C.K., Carvalho-Filho M.A., Hirabara S., Curi R., Velloso L.A., Saad M.J., Carvalheira J.B. Targeted disruption of inducible nitric oxide synthase protects against aging, S-nitrosation, and insulin resistance in muscle of male mice. Diabetes. 2013;62(2):466-470. DОI 10.2337/db12-0339.

151. Rubinsztein D.C., Mariño G., Kroemer G. Autophagy and aging. Cell. 2011;146(5):682-695.

152. Salminen A., Kaarniranta K. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res. Rev. 2012;11(2):230-241. DОI 10.1016/j.arr.2011.12.005.

153. Santos E.L., de Picoli Souza K., da Silva E.D., Batista E.C., Martins P.J., D’Almeida V., Pesquero J.B. Long term treatment with ACE inhibitor enalapril decreases body weight gain and increases life span in rats. Biochem. Pharmacol. 2009;78(8):951-958. DОI 10.1016/j.bcp.2009.06.018.

154. 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.

155. Seim I., Fang X., Xiong Z., Lobanov A.V., Huang Z., Ma S., Feng Y., Turanov A.A., Zhu Y., Lenz T.L., Gerashchenko M.V., Fan D., Hee Yim S., Yao X., Jordan D., Xiong Y., Ma Y., Lyapunov A.N., Chen G., Kulakova O.I., Sun Y., Lee S.G., Bronson R.T., Moskalev A.A., Sunyaev S.R., Zhang G., Krogh A., Wang J., Gladyshev V.N. Genome analysis reveals insights into physiology and longevity of the Brandt’s bat Myotis brandtii. Nat. Commun. 2013;4:2212. DОI 10.1038/ncomms3212.

156. Shaposhnikov M.V., Moskalev A.A., Plyusnina E.N. Effect of PARP-1 overexpression and pharmacological inhibition of NF-kB on the lifespan of Drosophila melanogaster. Adv. Gerontol. 2011;24(3): 405-419.

157. Shaposhnikov M., Proshkina E., Shilova L., Zhavoronkov A., Moskalev A. Lifespan and stress resistance in Drosophila with overexpressed DNA repair genes. Sci. Rep. 2015;5:15299. DОI 10.1038/srep15299.

158. Shaw W.M., Luo S., Landis J., Ashraf J., Murphy C.T. The C. elegans TGF-beta Dauer pathway regulates longevity via insulin signaling. Curr. Biol. 2007;17(19):1635-1645. DОI 10.1016/j.cub.2007.08.058.

159. Simmonds R.E., Foxwell B.M. Signalling, inflammation and arthritis: NF-kappaB and its relevance to arthritis and inflammation. Rheumatology (Oxford). 2008;47(5):584-590. DОI 10.1093/rheumatology/kem298.

160. Simonsen A., Cumming R.C., Brech A., Isakson P., Schubert D.R., Finley K.D. Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy. 2008;4(2):176-184.

161. Sinha M., Jang Y.C., Oh J., Khong D., Wu E.Y., Manohar R., Miller C., Regalado S.G., Loffredo F.S., Pancoast J.R., Hirshman M.F., Lebowitz J., Shadrach J.L., Cerletti M., Kim M.J., Serwold T., Goodyear L.J., Rosner B., Lee R.T., Wagers A.J. Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle. Science. 2014;344(6184):649-652. DОI 10.1126/science.1251152.

162. Slack C., Alic N., Foley A., Cabecinha M., Hoddinott M.P., Partridge L. The Ras-Erk-ETS-signaling pathway is a drug target for longevity. Cell. 2015;162(1):72-83. DОI 10.1016/j.cell.2015.06.023.

163. 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. A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family. Proc. Natl Acad. Sci. 2000;97(12):6658-6663.

164. Snell T.W., Johnston R.K., Rabeneck B., Zipperer C., Teat S. Joint inhibition of TOR and JNK pathways interacts to extend the lifespan of Brachionus manjavacas (Rotifera). Exp. Gerontol. 2014;52:55-69. DОI 10.1016/j.exger.2014.01.022.

165. Solovyev I.A., Dobrovolskaya E.V., Moskalev A.A. Genetic control of circadian rhythms and aging. Russ. J. Genet. 2016;52(4):343-361.

166. Stenesen D., Suh J.M., Seo J., Yu K., Lee K.-S., Kim J.-S., Min K.-J., Graff J.M. Adenosine nucleotide biosynthesis and AMPK regulate adult life span and mediate the longevity benefit of caloric restriction in flies. Cell Metab. 2013;17(1):101-112.

167. Sung B., Park S., Yu B.P., Chung H.Y. Amelioration of age-related inflammation and oxidative stress by PPARγ activator: suppression of NF-κB by 2, 4-thiazolidinedione. Exp. Gerontol. 2006;41(6): 590-599.

168. Swindell W.R., Masternak M.M., Kopchick J.J., Conover C.A., Bartke A., Miller R.A. Endocrine regulation of heat shock protein mRNA levels in long-lived dwarf mice. Mech. Ageing Dev. 2009;130(6):393-400.

169. Sykiotis G.P., Bohmann D. Keap1/Nrf2 signaling regulates oxidative stress tolerance and lifespan in Drosophila. Dev. Cell. 2008;14(1): 76-85. DОI 10.1016/j.devcel.2007.12.002.

170. Symphorien S., Woodruff R.C. Effect of DNA repair on aging of transgenic Drosophila melanogaster: I. mei-41 locus. J. Gerontol. A Biol. Sci. Med. Sci. 2003;58(9):B782-B787.

171. Szwergold B.S., Miller C.B. Potential of birds to serve as a pathologyfree model of type 2 diabetes, Part 1. Is the apparent absence of the rage gene a factor in the resistance of avian organisms to chronic hyperglycemia? Rejuv. Res. 2014;17(1):54-61. DОI 10.1089/rej.2013.1498.

172. Tan Q., Soerensen M., Kruse T.A., Christensen K., Christiansen L. A novel permutation test for case-only analysis identifies epistatic effects on human longevity in the FOXO gene family. Aging Cell. 2013;12(4):690-694. DОI 10.1111/acel.12092.

173. Tan V.P., Miyamoto S. Nutrient-sensing mTORC1: Integration of metabolic and autophagic signals. J. Mol. Cell Cardiol. 2016). DОI 10.1016/j.yjmcc.2016.01.005.

174. Tatar M., Kopelman A., Epstein D., Tu M.P., Yin C.M., Garofalo R.S. A mutant Drosophila insulin receptor homolog that extends lifespan and impairs neuroendocrine function. Science. 2001;292(5514): 107-110. DОI 10.1126/science.1057987.

175. Taylor R.C., Dillin A. Aging as an event of proteostasis collapse. Cold Spring Harbor Persp. Biol. 2011;3(5):a004440.

176. Tian J., Yan Z., Wu Y., Zhang S.L., Wang K., Ma X.R., Guo L., Wang J., Zuo L., Liu J.Y., Quan L., Liu H.R. Inhibition of iNOS protects endothelial-dependent vasodilation in aged rats. Acta Pharmacol. Sin. 2010;31(10):1324-1328. DОI 10.1038/aps.2010.111.

177. Tomaru U., Takahashi S., Ishizu A., Miyatake Y., Gohda A., Suzuki S., Ono A., Ohara J., Baba T., Murata S. Decreased proteasomal activity causes age-related phenotypes and promotes the development of metabolic abnormalities. Am. J. Pathol. 2012;180(3):963-972.

178. Tran H., Brunet A., Grenier J.M., Datta S.R., Fornace A.J., Jr., DiStefano P.S., Chiang L.W., Greenberg M.E. DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein. Science. 2002;296(5567):530-534. DОI 10.1126/science.1068712.

179. Tsurumi A., Li W.X. Global heterochromatin loss: a unifying theory of aging? Epigenetics. 2012;7(7):680-688. DОI 10.4161/epi.20540.

180. Tsutsui M., Shimokawa H., Otsuji Y., Ueta Y., Sasaguri Y., Yanagihara N. Nitric oxide synthases and cardiovascular diseases: insights from genetically modified mice. Circ. J. 2009;73(6):986-993.

181. Twumasi-Boateng K., Wang T.W., Tsai L., Lee K.H., Salehpour A., Bhat S., Tan M.W., Shapira M. An age-dependent reversal in the protective capacities of JNK signaling shortens Caenorhabditis elegans lifespan. Aging Cell. 2012;11(4):659-667. DОI 10.1111/j.1474-9726.2012.00829.x.

182. Tyner S.D., Venkatachalam S., Choi J., Jones S., Ghebranious N., Igelmann H., Lu X., Soron G., Cooper B., Brayton C., Park S.H., Thompson T., Karsenty G., Bradley A., Donehower L.A. p53 mutant mice that display early ageing-associated phenotypes. Nature. 2002;415(6867):45-53. DОI 10.1038/415045a.

183. Ulgherait M., Rana A., Rera M., Graniel J., Walker D.W. AMPK modulates tissue and organismal aging in a non-cell-autonomous manner. Cell Reports. 2014;8(6):1767-1780.

184. Ungar L., Harari Y., Toren A., Kupiec M. Tor complex 1 controls telomere length by affecting the level of Ku. Curr. Biol. 2011;21(24): 2115-2120. DОI 10.1016/j.cub.2011.11.024.

185. Ungvari Z., Ridgway I., Philipp E.E., Campbell C.M., McQuary P., Chow T., Coelho M., Didier E.S., Gelino S., Holmbeck M.A., Kim I., Levy E., Sosnowska D., Sonntag W.E., Austad S.N., Csiszar A. Extreme longevity is associated with increased resistance to oxidative stress in Arctica islandica, the longest-living non-colonial animal. J. Gerontol. A Biol. Sci. Med. Sci. 2011;66(7):741-750. DОI 10.1093/gerona/glr044.

186. Vajapey R., Rini D., Walston J., Abadir P. The impact of age-related dysregulation of the angiotensin system on mitochondrial redox balance. Front. Physiol. 2014;5:439. DОI 10.3389/fphys.2014.00439.

187. Van Deursen J.M. The role of senescent cells in ageing. Nature. 2014;509(7501):439-446. DОI 10.1038/nature13193.

188. 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;5:5011. DОI 10.1038/ncomms6011.

189. Vermeulen C.J., Van De Zande L., Bijlsma R. Resistance to oxidative stress induced by paraquat correlates well with both decreased and increased lifespan in Drosophila melanogaster. Biogerontology. 2005;6(6):387-395. DОI 10.1007/s10522-005-4903-2.

190. Wang M.C., Bohmann D., Jasper H. JNK signaling confers tolerance to oxidative stress and extends lifespan in Drosophila. Dev. Cell. 2003;5(5):811-816.

191. Wang Y., Sun Z. Antiaging gene Klotho regulates endothelin-1 levels and endothelin receptor subtype B expression in kidneys of spontaneously hypertensive rats. J. Hypertens. 2014;32(8):1629-1636.

192. Weiss A., Attisano L. The TGFbeta superfamily signaling pathway. Wiley Interdiscip. Rev. Dev. Biol. 2013;2(1):47-63. DОI 10.1002/wdev.86.

193. White T.A., LeBrasseur N.K. Myostatin and sarcopenia: opportunities and challenges – A mini-review. Gerontology. 2014;60(4):289-293.

194. Willcox B.J., Tranah G.J., Chen R., Morris B.J., Masaki K.H., He Q., Willcox D.C., Allsopp R.C., Moisyadi S., Poon L.W., Rodriguez B., Newman A.B., Harris T.B., Cummings S.R., Liu Y., Parimi N., Evans D.S., Davy P., Gerschenson M., Donlon T.A. The FoxO3 gene and cause-specific mortality. Aging Cell. 2016. DОI 10.1111/acel.12452.

195. Xia H., Suda S., Bindom S., Feng Y., Gurley S.B., Seth D., Navar L.G., Lazartigues E. ACE2-mediated reduction of oxidative stress in the central nervous system is associated with improvement of autonomic function. PLoS ONE. 2011;6(7):e22682. DОI 10.1371/journal.pone.0022682.

196. Xie J., Yoon J., An S.-W., Kuro-o M., Huang C.-L. Soluble Klotho protects against uremic cardiomyopathy independently of fibroblast growth factor 23 and phosphate. J. Am. Soc. Nephrol. 2015;26(5): 1150-1160.

197. Yonekura H., Yamamoto Y., Sakurai S., Watanabe T., Yamamoto H. Roles of the receptor for advanced glycation endproducts in diabetes-induced vascular injury. J. Pharmacol. Sci. 2005;97(3):305-311.

198. Zhang G., Li J., Purkayastha S., Tang Y., Zhang H., Yin Y., Li B., Liu G., Cai D. Hypothalamic programming of systemic ageing involving IKK-beta, NF-kappaB and GnRH. Nature. 2013;497(7448):211-216. DОI 10.1038/nature12143.

199. Zhang R., Chen H.-Z., Liu D.-P. The four layers of aging. Cell Systems. 2015;1(3):180-186.

200. Zhao G., Hatting M., Nevzorova Y.A., Peng J., Hu W., Boekschoten M.V., Roskams T., Muller M., Gassler N., Liedtke C., Davis R.J., Cubero F.J., Trautwein C. Jnk1 in murine hepatic stellate cells is a crucial mediator of liver fibrogenesis. Gut. 2014;63(7): 1159-1172. DОI 10.1136/gutjnl-2013-305507.


Просмотров: 909


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 2500-0462 (Print)
ISSN 2500-3259 (Online)