Cellular lifespan and senescence: a complex balance between multiple cellular pathways

BioEssays

Volumn 38, Issue , 2016, Pages S33-S44

  Dolivo, David ^a   Hernandez, Sarah ^a   Dominko, Tanja ^a  

^a WORCESTER POLYTECHNIC INSTITUTE   (United States)

Author keywords

antioxidants; lifespan; metabolism; senescence

Indexed keywords

ANTIOXIDANT; GROWTH FACTOR; NICOTINAMIDE ADENINE DINUCLEOTIDE; OXYGEN; SIRTUIN; TELOMERASE;

CELL AGING; CELL DIVISION; CELL METABOLISM; CELL SURVIVAL; DIET RESTRICTION; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; IN VITRO STUDY; INTRACELLULAR SIGNALING; NONHUMAN; REVIEW; SOMATIC CELL; TELOMERE; TISSUE REGENERATION;

EID: 84978811431     PISSN: 02659247     EISSN: 15211878     Source Type: Journal    
DOI: 10.1002/bies.201670906     Document Type: Review

References (155)

1. Carrel A. 1912. Pure cultures of cells. J Exp Med 16: 165–8.
2. Ebeling AH. 1913. The permanent life of connective tissue outside of the organism. J Exp Med 17: 273–85.
3. Strehler E, Eppenberger H, Heizmann C. 1977. Isolation and characterization of parvalbumin from chicken leg-muscle. FEBS Lett 78: 127–33.
4. Witkowski JA. 1980. Dr. Carrel's immortal cells. Med Hist 24: 129–42.
5. Hayflick L, Moorhead PS. 1961. The serial cultivation of human diploid cell strains. Exp Cell Res 25: 585–621.
6. Muñoz-Espín D, Serrano M. 2014. Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol 15: 482–96.
7. Kim RH, Kang MK, Kim T, Yang P, et al. 2015. Regulation of p53 during senescence in normal human keratinocytes. Aging Cell 14: 838–46.
8. Jin B, Wang Y, Wu CL, Liu KY, et al. 2014. PIM-1 modulates cellular senescence and links IL-6 signaling to heterochromatin formation. Aging Cell 13: 879–89.
9. Acosta JC, Banito A, Wuestefeld T, Georgilis A, et al. 2013. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 15: 978–90.
10. Canino C, Mori F, Cambria A, Diamantini A, et al. 2012. SASP mediates chemoresistance and tumor-initiating-activity of mesothelioma cells. Oncogene 31: 3148–63.
11. Biran A, Perelmutter M, Gal H, Burton DG, et al. 2015. Senescent cells communicate via intercellular protein transfer. Genes Dev 29: 791–802.
12. Blackburn EH, Gall JG. 1978. A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. J Mol Biol 120: 33–53.
13. van Deursen JM. 2014. The role of senescent cells in ageing. Nature 509: 439–46.
14. Greider CW, Blackburn EH. 1985. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43: 405–13.
15. Bodnar AG, Ouellette M, Frolkis M, Holt SE, et al. 1998. Extension of life-span by introduction of telomerase into normal human cells. Science 279: 349–52.
16. Yang J, Chang E, Cherry AM, Bangs CD, et al. 1999. Human endothelial cell life extension by telomerase expression. J Biol Chem 274: 26141–8.
17. Vaziri H, Benchimol S. 1998. Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span. Curr Biol 8: 279–82.
18. Rufer N, Migliaccio M, Antonchuk J, Humphries RK, et al. 2001. Transfer of the human telomerase reverse transcriptase (TERT) gene into T lymphocytes results in extension of replicative potential. Blood 98: 597–603.
19. Wootton M, Steeghs K, Watt D, Munro J, et al. 2003. Telomerase alone extends the replicative life span of human skeletal muscle cells without compromising genomic stability. Hum Gene Ther 14: 1473–87.
20. Kim M, Xu L, Blackburn EH. 2003. Catalytically active human telomerase mutants with allele-specific biological properties. Exp Cell Res 288: 277–87.
21. Zhu J, Wang H, Bishop JM, Blackburn EH. 1999. Telomerase extends the lifespan of virus-transformed human cells without net telomere lengthening. Proc Natl Acad Sci 96: 3723–8.
22. Mukherjee S, Firpo EJ, Wang Y, Roberts JM. 2011. Separation of telomerase functions by reverse genetics. Proc Natl Acad Sci 108: E1363–E71.
23. Palm W, de Lange T. 2008. How shelterin protects mammalian telomeres. Annu Rev Genet 42: 301–34.
24. De Lange T. 2011. How shelterin solves the telomere end-protection problem. Cold Spring Harbor Symposia on Quantitative Biology: Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY. p sqb. 2010.75. 017.
25. Karlseder J, Smogorzewska A, de Lange T. 2002. Senescence induced by altered telomere state, not telomere loss. Science 295: 2446–9.
26. Boccardi V, Razdan N, Kaplunov J, Mundra JJ, et al. 2015. Stn1 is critical for telomere maintenance and long-term viability of somatic human cells. Aging Cell 14: 372–81.
27. Suram A, Kaplunov J, Patel PL, Ruan H, et al. 2012. Oncogene-induced telomere dysfunction enforces cellular senescence in human cancer precursor lesions. EMBO J 31: 2839–51.
28. Sahin E, Colla S, Liesa M, Moslehi J, et al. 2011. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature 470: 359–65.
29. Lindvall C, Hou M, Komurasaki T, Zheng C, et al. 2003. Molecular characterization of human telomerase reverse transcriptase-immortalized human fibroblasts by gene expression profiling activation of the epiregulin gene. Cancer Res 63: 1743–7.
30. Perrault SD, Hornsby PJ, Betts DH. 2005. Global gene expression response to telomerase in bovine adrenocortical cells. Biochem Biophys Res Commun 335: 925–36.
31. Choi J, Southworth LK, Sarin KY, Venteicher AS, et al. 2008. TERT promotes epithelial proliferation through transcriptional control of a Myc-and Wnt-related developmental program. PLoS Genet 4: e10.
32. Ghosh A, Saginc G, Leow SC, Khattar E, et al. 2012. Telomerase directly regulates NF-κB-dependent transcription. Nat Cell Biol 14: 1270–81.
33. Low KC, Tergaonkar V. 2013. Telomerase: central regulator of all of the hallmarks of cancer. Trends Biochem Sci 38: 426–34.
34. Kondoh H, Lleonart ME, Gil J, Wang J, et al. 2005. Glycolytic enzymes can modulate cellular life span. Cancer Res 65: 177–85.
35. Parrinello S, Samper E, Krtolica A, Goldstein J, et al. 2003. Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat Cell Biol 5: 741–7.
36. Brand KA, Hermfisse U. 1997. Aerobic glycolysis by proliferating cells: a protective strategy against reactive oxygen species. FASEB J 11: 388–95.
37. Hinoi E, Takarada T, Tsuchihashi Y, Fujimori S, et al. 2006. A molecular mechanism of pyruvate protection against cytotoxicity of reactive oxygen species in osteoblasts. Mol Pharmacol 70: 925–35.
38. Chen Q, Ames BN. 1994. Senescence-like growth arrest induced by hydrogen peroxide in human diploid fibroblast F65 cells. Proc Natl Acad Sci 91: 4130–4.
39. Passos JF, Nelson G, Wang C, Richter T, et al. 2010. Feedback between p21 and reactive oxygen production is necessary for cell senescence. Mol Syst Biol 6: 347.
40. Gitenay D, Wiel C, Lallet-Daher H, Vindrieux D, et al. 2014. Glucose metabolism and hexosamine pathway regulate oncogene-induced senescence. Cell death & dis 5: e1089.
41. Quijano C, Cao L, Fergusson MM, Romero H, et al. 2012. Oncogene-induced senescence results in marked metabolic and bioenergetic alterations. Cell Cycle 11: 1383–92.
42. Reis RJS, Xu L, Lee H, Chae M, et al. 2011. Modulation of lipid biosynthesis contributes to stress resistance and longevity of C. elegans mutants. Aging (Albany NY) 3: 125.
43. Aird KM, Zhang G, Li H, Tu Z, et al. 2013. Suppression of nucleotide metabolism underlies the establishment and maintenance of oncogene-induced senescence. Cell reports 3: 1252–65.
44. Aird KM, Worth AJ, Snyder NW, Lee JV, et al. 2015. ATM couples replication stress and metabolic reprogramming during cellular senescence. Cell reports 11: 893–901.
45. James EL, Michalek RD, Pitiyage GN, de Castro AM, et al. 2015. Senescent human fibroblasts show increased glycolysis and redox homeostasis with extracellular metabolomes that overlap with those of irreparable DNA damage, aging, and disease. J Proteome Res 14: 1854–71.
46. Jones RG, Plas DR, Kubek S, Buzzai M, et al. 2005. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 18: 283–93.
47. Jiang P, Du W, Mancuso A, Wellen KE, et al. 2013. Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence. Nature 493: 689–93.
48. Ma W, Sung HJ, Park JY, Matoba S, et al. 2007. A pivotal role for p53: balancing aerobic respiration and glycolysis. J Bioenerg Biomembr 39: 243–6.
49. Li H, Jogl G. 2009. Structural and biochemical studies of TIGAR (TP53-induced glycolysis and apoptosis regulator). J Biol Chem 284: 1748–54.
50. Matoba S, Kang J-G, Patino WD, Wragg A, et al. 2006. p53 regulates mitochondrial respiration. Science 312: 1650–3.
51. Zhou S, Kachhap S, Singh KK. 2003. Mitochondrial impairment in p53-deficient human cancer cells. Mutagenesis 18: 287–92.
52. Gottlieb E, Vousden KH. 2010. p53 regulation of metabolic pathways. Cold Spring Harb Perspect Biol 2: a001040.
53. Longo VD, Antebi A, Bartke A, Barzilai N, et al. 2015. Interventions to Slow Aging in Humans: Are We Ready? Aging cell.
54. Mair W, Dillin A. 2008. Aging and survival: the genetics of life span extension by dietary restriction. Annu Rev Biochem 77: 727–54.
55. Tokunaga C, Yoshino K-i, Yonezawa K. 2004. mTOR integrates amino acid-and energy-sensing pathways. Biochem Biophys Res Commun 313: 443–6.
56. Johnson SC, Rabinovitch PS, Kaeberlein M. 2013. mTOR is a key modulator of ageing and age-related disease. Nature 493: 338–45.
57. Pospelova TV, Leontieva OV, Bykova TV, Zubova SG, et al. 2012. Suppression of replicative senescence by rapamycin in rodent embryonic cells. Cell Cycle 11: 2402–7.
58. Demidenko ZN, Zubova SG, Bukreeva EI, Pospelov VA, et al. 2009. Rapamycin decelerates cellular senescence. Cell Cycle 8: 1888–95.
59. Amiel E, Everts B, Fritz D, Beauchamp S, et al. 2014. Mechanistic target of rapamycin inhibition extends cellular lifespan in dendritic cells by preserving mitochondrial function. J Immunol 193: 2821–30.
60. Dulic V. 2013. Senescence regulation by mTOR. Methods in Molecular Biology 965: 15–35.
61. Blagosklonny MV. 2014. Geroconversion: irreversible step to cellular senescence. Cell Cycle 13: 3628–35.
62. Guarente L. 2013. Calorie restriction and sirtuins revisited. Genes Dev 27: 2072–85.
63. Giblin W, Skinner ME, Lombard DB. 2014. Sirtuins: guardians of mammalian healthspan. Trends Genet 30: 271–86.
64. Kanfi Y, Naiman S, Amir G, Peshti V, et al. 2012. The sirtuin SIRT6 regulates lifespan in male mice. Nature 483: 218–21.
65. Kaeberlein M, McVey M, Guarente L. 1999. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13: 2570–80.
66. Tissenbaum HA, Guarente L. 2001. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410: 227–30.
67. Burnett C, Valentini S, Cabreiro F, Goss M, et al. 2011. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 477: 482–5.
68. Schmeisser K, Mansfeld J, Kuhlow D, Weimer S, et al. 2013. Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. Nat Chem Biol 9: 693–700.
69. Whitaker R, Faulkner S, Miyokawa R, Burhenn L, et al. 2013. Increased expression of Drosophila Sir 2 extends life span in a dose-dependent manner. Aging (Albany NY) 5: 682.
70. Satoh A, Brace CS, Rensing N, Cliften P, et al. 2013. Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. Cell Metab 18: 416–30.
71. Mattison JA, Roth GS, Beasley TM, Tilmont EM, et al. 2012. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489: 318–321.
72. Colman RJ, Beasley TM, Kemnitz JW, Johnson SC, et al. 2014. Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun 5: 1–5.
73. Huang J, Gan Q, Han L, Li J, et al. 2008. SIRT1 overexpression antagonizes cellular senescence with activated ERK/S6k1 signaling in human diploid fibroblasts. PLoS One 3: e1710.
74. Zu Y, Liu L, Lee MY, Xu C, et al. 2010. SIRT1 promotes proliferation and prevents senescence through targeting LKB1 in primary porcine aortic endothelial cells. Circ Res 106: 1384–93.
75. Vaziri H, Dessain SK, Eaton EN, Imai S-I, et al. 2001. hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase. Cell 107: 149–59.
76. Li M, Luo J, Brooks CL, Gu W. 2002. Acetylation of p53 inhibits its ubiquitination by Mdm2. J Biol Chem 277: 50607–11.
77. Imai S-I, Armstrong CM, Kaeberlein M, Guarente L. 2000. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403: 795–800.
78. Ying W. 2008. NAD+/NADH and NADP+/NADPH in cellular functions and cell death: regulation and biological consequences. Antioxid Redox Signal 10: 179–206.
79. Ho C, van der Veer E, Akawi O, Pickering JG. 2009. SIRT1 markedly extends replicative lifespan if the NAD+ salvage pathway is enhanced. FEBS Lett 583: 3081–5.
80. Lim C-S, Potts M, Helm RF. 2006. Nicotinamide extends the replicative life span of primary human cells. Mech Ageing Dev 127: 511–4.
81. Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, et al. 2002. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J Biol Chem 277: 45099–107.
82. Chen H, Liu X, Zhu W, Chen H, et al. 2014. SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating telomere shelterin. Front aging neurosci 6: 103.
83. Massudi H, Grant R, Braidy N, Guest J, et al. 2012. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue.
84. Braidy N, Guillemin GJ, Mansour H, Chan-Ling T, et al. 2011. Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in Wistar rats. PLoS One 6: e19194.
85. Singh N, Ogburn C, Wolf N, van Belle G, et al. 2001. DNA double-strand breaks in mouse kidney cells with age. Biogerontology 2: 261–70.
86. Sedelnikova OA, Horikawa I, Zimonjic DB, Popescu NC, et al. 2004. Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks. Nat Cell Biol 6: 168–70.
87. Mitchell P. 1976. Vectorial chemistry and the molecular mechanics of chemiosmotic coupling: power transmission by proticity. Biochem Soc Trans 4: 399.
88. Eaton S, Middleton B, Sherratt HSA, Pourfarzam M, et al. 2002. Control of Mitochondrial β-Oxidation at the Levels of [NAD+]/[NADH] and CoA Acylation. Advances in Experimental Medicine and Biology 466: 145–154.
89. Gomes AP, Price NL, Ling AJ, Moslehi JJ, et al. 2013. Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 155: 1624–38.
90. Tsang F, James C, Kato M, Myers V, et al. 2015. Reduced Ssy1-Ptr3-Ssy5 (SPS) signaling extends replicative life span by enhancing NAD+ homeostasis in Saccharomyces cerevisiae. J Biol Chem 290: 12753–64.
91. Page RL, Ambady S, Holmes WF, Vilner L, et al. 2009. Induction of stem cell gene expression in adult human fibroblasts without transgenes. Cloning Stem Cells 11: 417–26.
92. Kole D, Ambady S, Page RL, Dominko T. 2014. Maintenance of multipotency in human dermal fibroblasts treated with Xenopus laevis egg extract requires exogenous fibroblast growth factor-2. Cell Reprogramming (Formerly“ Cloning and Stem Cells”) 16: 18–28.
93. Levenstein ME, Ludwig TE, Xu RH, Llanas RA, et al. 2006. Basic fibroblast growth factor support of human embryonic stem cell self-renewal. Stem Cells 24: 568–74.
94. Kurz DJ, Hong Y, Trivier E, Huang H-L, et al. 2003. Fibroblast growth factor-2, but not vascular endothelial growth factor, upregulates telomerase activity in human endothelial cells. Arterioscler Thromb Vasc Biol 23: 748–54.
95. Mohammadi M, Dionne C, Li W, Li N, et al. 1992. Point mutation in FGF receptor eliminates phosphatidylinositol hydrolysis without affecting mitogenesis. Nature 358: 681–684.
96. Mohammadi M, Dikic I, Sorokin A, Burgess W, et al. 1996. Identification of six novel autophosphorylation sites on fibroblast growth factor receptor 1 and elucidation of their importance in receptor activation and signal transduction. Mol Cell Biol 16: 977–89.
97. Shaulian E, Resnitzky D, Shifman O, Blandino G, et al. 1997. Induction of Mdm2 and enhancement of cell survival by bFGF. Oncogene 15: 2717–25.
98. Ries S, Biederer C, Woods D, Shifman O, et al. 2000. Opposing effects of Ras on p53: transcriptional activation of mdm2 and induction of p19ARF. Cell 103: 321–30.
99. Kashpur O, LaPointe D, Ambady S, Ryder EF, et al. 2013. FGF2-induced effects on transcriptome associated with regeneration competence in adult human fibroblasts. BMC Genomics 14: 656.
100. Milman S, Atzmon G, Huffman DM, Wan J, et al. 2014. Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity. Aging Cell 13: 769–71.
101. Blüher M, Kahn BB, Kahn CR. 2003. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299: 572–4.
102. Holzenberger M, Dupont J, Ducos B, Leneuve P, et al. 2003. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421: 182–7.
103. Cao SX, Dhahbi JM, Mote PL, Spindler SR. 2001. Genomic profiling of short-and long-term caloric restriction effects in the liver of aging mice. Proc Natl Acad Sci 98: 10630–5.
104. Murphy CT, McCarroll SA, Bargmann CI, Fraser A, et al. 2003. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424: 277–83.
105. Garigan D, Hsu A-L, Fraser AG, Kamath RS, et al. 2002. Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics 161: 1101–12.
106. Li Y, Wang W-J, Cao H, Lu J, et al. 2009. Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations. Hum Mol Genet 18: 4897–904.
107. Lunetta KL, D'Agostino RB, Karasik D, Benjamin EJ, et al. 2007. Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study. BMC Med Genet 8: S13.
108. Flachsbart F, Caliebe A, Kleindorp R, Blanché H, et al. 2009. Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc Natl Acad Sci 106: 2700–5.
109. Anselmi CV, Malovini A, Roncarati R, Novelli V, et al. 2009. Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Res 12: 95–104.
110. Willcox BJ, Donlon TA, He Q, Chen R, et al. 2008. FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci 105: 13987–92.
111. Pawlikowska L, Hu D, Huntsman S, Sung A, et al. 2009. Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity. Aging Cell 8: 460–72.
112. Tran D, Bergholz J, Zhang H, He H, et al. 2014. Insulin-like growth factor-1 regulates the SIRT1-p53 pathway in cellular senescence. Aging Cell 13: 669–78.
113. Brunet A, Datta SR, Greenberg ME. 2001. Transcription-dependent and -independent control of neuronal survival by the PI3K–Akt signaling pathway. Curr Opin Neurobiol 11: 297–305.
114. Miyauchi H, Minamino T, Tateno K, Kunieda T, et al. 2004. Akt negatively regulates the in vitro lifespan of human endothelial cells via a p53/p21-dependent pathway. EMBO J 23: 212–20.
115. Packer L, Fuehr K. 1977. Low oxygen concentration extends the lifespan of cultured human diploid cells. Nature 267: 423–425.
116. Poulios E, Trougakos IP, Chondrogianni N, Gonos ES. 2007. Exposure of human diploid fibroblasts to hypoxia extends proliferative life span. Ann N Y Acad Sci 1119: 9–19.
117. Yatabe N, Kyo S, Maida Y, Nishi H, et al. 2004. HIF-1-mediated activation of telomerase in cervical cancer cells. Oncogene 23: 3708–15.
118. Nishi H, Nakada T, Kyo S, Inoue M, et al. 2004. Hypoxia-inducible factor 1 mediates upregulation of telomerase (hTERT). Mol Cell Biol 24: 6076–83.
119. Zhang Y, Shao Z, Zhai Z, Shen C, et al. 2009. The HIF-1 hypoxia-inducible factor modulates lifespan in C. elegans. PLoS One 4: e6348.
120. Mehta R, Steinkraus KA, Sutphin GL, Ramos FJ, et al. 2009. Proteasomal regulation of the hypoxic response modulates aging in C. elegans. Science 324: 1196–8.
121. Raices M, Maruyama H, Dillin A, Karlseder J. 2005. Uncoupling of longevity and telomere length in C. elegans. PLoS Genet 1: e30.
122. Chen QM, Prowse KR, Tu VC, Purdom S, et al. 2001. Uncoupling the senescent phenotype from telomere shortening in hydrogen peroxide-treated fibroblasts. Exp Cell Res 265: 294–303.
123. Kashino G, Kodama S, Nakayama Y, Suzuki K, et al. 2003. Relief of oxidative stress by ascorbic acid delays cellular senescence of normal human and Werner syndrome fibroblast cells. Free Radical Biol Med 35: 438–43.
124. Hwang W-S, Park S-H, Kim H-S, Kang H-J, et al. 2007. Ascorbic acid extends replicative life span of human embryonic fibroblast by reducing DNA and mitochondrial damages. Nutr res pract 1: 105–12.
125. Yang HH, Hwangbo K, Zheng MS, Son J-K, et al. 2014. Inhibitory effects of juglanin on cellular senescence in human dermal fibroblasts. J Nat Med 68: 473–80.
126. Yang HH, Hwangbo K, Zheng MS, Cho JH, et al. 2014. Inhibitory effects of (−)-loliolide on cellular senescence in human dermal fibroblasts. Arch Pharm Res 1–9.
127. Im W, Chung J-Y, Bhan J, Lim J, et al. 2012. Sun ginseng protects endothelial progenitor cells from senescence associated apoptosis. J ginseng res 36: 78.
128. Yang HH, Son J-K, Jung B, Zheng M, et al. 2011. Epifriedelanol from the root bark of Ulmus davidiana inhibits cellular senescence in human primary cells. Planta Med-Nat Prod MedPlant Res 77: 441.
129. Yang HH, Hwangbo K, Zheng MS, Cho JH, et al. 2014. Quercetin-3-O-β-d-glucuronide isolated from Polygonum aviculare inhibits cellular senescence in human primary cells. Arch Pharm Res 37: 1219–33.
130. Yang HH, Jung B, Kim J-R. 2010. Identification of plant extracts that inhibit cellular senescence in human fibroblasts, endothelial cells, and vascular smooth muscle cells. J Korean Soc for Appl Biol Chem 53: 584–92.
131. Ma D, Stokes K, Mahngar K, Domazet-Damjanov D, et al. 2014. Inhibition of stress induced premature senescence in presenilin-1 mutated cells with water soluble Coenzyme Q 10. Mitochondrion 17: 106–15.
132. Schriner SE, Linford NJ, Martin GM, Treuting P, et al. 2005. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308: 1909–11.
133. Halliwell B. 2014. Cell culture, oxidative stress, and antioxidants: avoiding pitfalls. Biomed j 37: 99.
134. Clanton TL. 2007. Hypoxia-induced reactive oxygen species formation in skeletal muscle. J Appl Physiol 102: 2379–88.
135. Duranteau J, Chandel NS, Kulisz A, Shao Z, et al. 1998. Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes. J bio chem 273: 11619–24.
136. Wu W, Platoshyn O, Firth AL, Yuan JX-J. 2007. Hypoxia divergently regulates production of reactive oxygen species in human pulmonary and coronary artery smooth muscle cells. Am J Physiol-Lung Cell Mol Physio 293: L952–L9.
137. D'Autréaux B, Toledano MB. 2007. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8: 813–24.
138. Barja G, Herrero A. 2000. Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals. FASEB J 14: 312–8.
139. Castro MdR, Suarez E, Kraiselburd E, Isidro A, et al. 2012. Aging increases mitochondrial DNA damage and oxidative stress in liver of rhesus monkeys. Exp Gerontol 47: 29–37.
140. Mecocci P, MacGarvey U, Kaufman AE, Koontz D, et al. 1993. Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. Ann Neurol 34: 609–16.
141. Khaidakov M, Heflich RH, Manjanatha MG, Myers MB, et al. 2003. Accumulation of point mutations in mitochondrial DNA of aging mice. Mutation Res/Fundam Mol Mech Mutagen 526: 1–7.
142. Kujoth G, Hiona A, Pugh T, Someya S, et al. 2005. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309: 481–4.
143. Wang Y, Michikawa Y, Mallidis C, Bai Y, et al. 2001. Muscle-specific mutations accumulate with aging in critical human mtDNA control sites for replication. Proc Natl Acad Sci 98: 4022–7.
144. Yun J, Finkel T. 2014. Mitohormesis. Cell Metab 19: 757–66.
145. Schulz TJ, Zarse K, Voigt A, Urban N, et al. 2007. Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab 6: 280–93.
146. Zarse K, Schmeisser S, Groth M, Priebe S, et al. 2012. Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial L-proline catabolism to induce a transient ROS signal. Cell Metab 15: 451–65.
147. Yang N-C, Song T-Y, Chen M-Y, Hu M-L. 2011. Effects of 2-deoxyglucose and dehydroepiandrosterone on intracellular NAD+ level, SIRT1 activity and replicative lifespan of human Hs68 cells. Biogerontology 12: 527–36.
148. Schmeisser S, Schmeisser K, Weimer S, Groth M, et al. 2013. Mitochondrial hormesis links low-dose arsenite exposure to lifespan extension. Aging Cell 12: 508–17.
149. Leontieva OV, Natarajan V, Demidenko ZN, Burdelya LG, et al. 2012. Hypoxia suppresses conversion from proliferative arrest to cellular senescence. Proc Natl Acad Sci 109: 13314–8.
150. Monickaraj F, Aravind S, Nandhini P, Prabu P, et al. 2013. Accelerated fat cell aging links oxidative stress and insulin resistance in adipocytes. J Biosci 38: 113–22.
151. Golde TE, Miller VM. 2009. Proteinopathy-induced neuronal senescence: a hypothesis for brain failure in Alzheimer's and other neurodegenerative diseases. Alzheimers Res Ther 1: 5.
152. Laberge R-M, Awad P, Campisi J, Desprez P-Y. 2012. Epithelial-mesenchymal transition induced by senescent fibroblasts. Cancer Microenvironment 5: 39–44.
153. Khan S, CHuTuRGOON AA, NAiDOO DP. 2012. Telomeres and atherosclerosis: review article. Cardiovasc J Afr 23: 563–71.
154. Sousa-Victor P, Gutarra S, García-Prat L, Rodriguez-Ubreva J, et al. 2014. Geriatric muscle stem cells switch reversible quiescence into senescence. Nature 506: 316–21.
155. Tchkonia T, Zhu Y, van Deursen J, Campisi J, et al. 2013. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest 123: 966–72.