Skip to main content
SpringerLink
Log in

Cell and Molecular Aging

  • Chapter
  • First Online:
Principles and Practice of Geriatric Surgery

  • 1761 Accesses

Abstract

Discussions of aging invariably begin by establishing a satisfactory definition for the term aging and the related word senescence. Although the term aging is commonly used to refer to postmaturational processes that lead to diminished homeostasis and increased organismic vulnerability, the more correct term for this is senescence (derived from the Latin word “senescere,” meaning to grow old or to diminish), which explicitly refers to the process of growing old and sustaining related deterioration. Aging on the other hand can refer to any time-related process. We will use senescence to refer to cellular phenomena and aging to refer to changes, as organisms grow old.

 Portions of this chapter are reprinted with permission from Troen BR (2003) The biology of aging. Mt Sinai J Med 70(1):3–22.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Cutler RG (1985) Evolutionary perspective of human longevity. In: Hazzard WR, Andres R, Bierman EL et al (eds) Principles of geriatric medicine and gerontology, 2nd edn. McGraw-Hill, New York, p 16

    Google Scholar 

  2. Kung HC, Hoyert DL, Xu JQ, Murphy SL (2008) Deaths: final data for 2005, vol 56. National Center for Health Statistics, Hyattsville, MD

    Google Scholar 

  3. He W, Sengupta M, Velkoff VA, DeBarros KA (2005) 65+ in the United States: 2005. Current Population Reports, P23-P209. U.S. Government Printing Office, Washington, DC

    Google Scholar 

  4. Perls TT, Alpert L, Fretts RC (1997) Middle-aged mothers live longer. Nature 389(6647):133

    Article  PubMed  CAS  Google Scholar 

  5. Snowden DA, Kane RL, Beeson WL (1989) Is early natural menopause a biological marker of health and ageing? Am J Public Health 79:709–714

    Article  Google Scholar 

  6. van der Schouw YT, van der Graaf Y, Steyerberg EW, Eijkemans JC, Banga JD (1996) Menopause as a risk factor for cardiovascular mortality. Lancet 347(9003):714–718

    Article  PubMed  Google Scholar 

  7. Helle S, Lummaa V, Jokela J (2005) Are reproductive and somatic senescence coupled in humans? Late, but not early, reproduction correlated with longevity in historical Sami women. Proc R Soc B Biol Sci 272(1558):29–37

    Article  Google Scholar 

  8. Morley JE, Haren MT, Kim MJ, Kevorkian R, Perry HM III (2005) Testosterone, aging and quality of life. J Endocrinol Invest 28(3 Suppl):76–80

    PubMed  CAS  Google Scholar 

  9. Yeap BB (2008) Are declining testosterone levels a major risk factor for ill-health in aging men? Int J Impot Res 21(1):24–36

    Article  PubMed  CAS  Google Scholar 

  10. Roush W (1996) Live long and prosper? [news]. Science 273(5271): 42–46

    PubMed  CAS  Google Scholar 

  11. Greville TN, Bayo F, Foster R (1975) United States life tables by causes of death: 1960-71, vol 1, Number 5, Technical Report

    Google Scholar 

  12. Sohal RS, Weindruch R (1996) Oxidative stress, caloric restriction, and aging. Science 273(5271):59–63

    Article  PubMed  CAS  Google Scholar 

  13. Mair W, Dillin A (2008) Aging and survival: the genetics of life span extension by dietary restriction. Annu Rev Biochem 77:727–754

    Article  PubMed  CAS  Google Scholar 

  14. Weindruch R, Walford RL (1982) Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence. Science 215(4538):1415–1418

    Article  PubMed  CAS  Google Scholar 

  15. Yu BP, Masoro EJ, McMahan CA (1985) Nutritional influences on aging of Fischer 344 rats: I. Physical, metabolic, and longevity characteristics. J Gerontol 40(6):657–670

    Article  PubMed  CAS  Google Scholar 

  16. Masoro EJ (1993) Dietary restriction and aging. J Am Geriatr Soc 41(9):994–999

    PubMed  CAS  Google Scholar 

  17. Weindruch R, Sohal RS (337) Seminars in medicine of the Beth Israel Deaconess Medical Center. Caloric intake and aging. N Engl J Med 14:986–994

    Google Scholar 

  18. Dulloo AG, Girardier L (1993) 24 hour energy expenditure several months after weight loss in the underfed rat: evidence for a chronic increase in whole-body metabolic efficiency. Int J Obes Relat Metab Disord 17(2):115–123

    PubMed  CAS  Google Scholar 

  19. Gonzales-Pacheco DM, Buss WC, Koehler KM, Woodside WF, Alpert SS (1993) Energy restriction reduces metabolic rate in adult male Fisher-344 rats. J Nutr 123(1):90–97

    PubMed  CAS  Google Scholar 

  20. McCarter R, Masoro EJ, Yu BP (1985) Does food restriction retard aging by reducing the metabolic rate? Am J Physiol 248(4 Pt 1):E488–E490

    PubMed  CAS  Google Scholar 

  21. Lane MA, Baer DJ, Rumpler WV et al (1996) Calorie restriction lowers body temperature in rhesus monkeys, consistent with a postulated anti-aging mechanism in rodents. Proc Natl Acad Sci USA 93(9):4159–4164

    Article  PubMed  CAS  Google Scholar 

  22. Ramsey JJ, Roecker EB, Weindruch R, Kemnitz JW (1997) Energy expenditure of adult male rhesus monkeys during the first 30 mo of dietary restriction. Am J Physiol 272(5 Pt 1):E901–E907

    PubMed  CAS  Google Scholar 

  23. Verdery RB, Ingram DK, Roth GS, Lane MA (1997) Caloric restriction increases HDL2 levels in rhesus monkeys (Macaca mulatta). Am J Physiol 273(4 Pt 1):E714–E719

    PubMed  CAS  Google Scholar 

  24. Mattison JA, Lane MA, Roth GS, Ingram DK (2003) Calorie restriction in rhesus monkeys. Exp Gerontol 38(1–2):35–46

    Article  PubMed  Google Scholar 

  25. Heilbronn LK, de Jonge L, Frisard MI et al (2006) Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial. JAMA 295(13):1539–1548

    Article  PubMed  CAS  Google Scholar 

  26. Lefevre M, Redman LM, Heilbronn LK et al (2009) Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals. Atherosclerosis 203(1):206–213

    Article  PubMed  CAS  Google Scholar 

  27. Gompertz B (1825) On the nature of the function expressive of the law of human mortality and on a new mode of determining life contingencies. Philos Trans R Soc Lond 115:513

    Article  Google Scholar 

  28. Kung HC, Hoyert DL, Xu JQ, Murphy SL (2008) Deaths: final data for 2005. National Vital Statistics Reports. Vol 56. National Center for Health Statistics, Hyattsville, MD

    Google Scholar 

  29. Shock NW, Greulich RC, Andres R et al (eds) (1984) Normal human aging: the baltimore longitudinal study of aging. U.S. Department of Health and Human Services, Washington, DC

    Google Scholar 

  30. Riggs BL, Melton LJ III (1986) Involutional osteoporosis. N Engl J Med 314(26):1676–1686

    Article  PubMed  CAS  Google Scholar 

  31. Florini JR (ed.) (1981) Composition and function of cells and tissues. In: Handbook of biolochemistry in aging. CRC Press, Boca Raton

    Google Scholar 

  32. Strehler BL (1977) Time, cells, and aging, 2nd edn. Academic Press, New York

    Google Scholar 

  33. Bjorksten J (1974) Cross linkage and the aging process. In: Rothstein M (ed) Theoretical aspects of aging. Academic Press, New York, p 43

    Google Scholar 

  34. Kohn RR (1978) Aging of animals: possible mechanisms. In: Principles of mammalian aging, 2nd edn. Prentice-Hall, Englewood Cliffs, NJ

    Google Scholar 

  35. Herbig U, Ferreira M, Condel L, Carey D, Sedivy JM (2006) Cellular senescence in aging primates. Science 311(5765):1257

    Article  PubMed  CAS  Google Scholar 

  36. Jeyapalan JC, Ferreira M, Sedivy JM, Herbig U (2007) Accumulation of senescent cells in mitotic tissue of aging primates. Mech Ageing Dev 128(1):36–44

    Article  PubMed  CAS  Google Scholar 

  37. Sedelnikova OA, Horikawa I, Zimonjic DB, Popescu NC, Bonner WM, Barrett JC (2004) Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks. Nat Cell Biol 6(2):168–170

    Article  PubMed  CAS  Google Scholar 

  38. Finch CE (1990) Introduction: gefinitions and concepts. In: Longevity, senescence, and the genome. University of Chicago Press, Chicago

    Google Scholar 

  39. Schneider EL, Rowe JW (eds) (1996) Handbook of the biology of aging, 4th edn. Academic Press, San Diego

    Google Scholar 

  40. Shock NW (1985) Longitudinal studies of aging in humans. In: Finch CE, Schneider EL (eds) Handbook of the biology of aging, 2nd edn. Van Nostrand Reinhold, New York, p 721

    Google Scholar 

  41. Lakatta EG (1990) Changes in cardiovascular function with aging. Eur Heart J 11(Suppl C):22–29

    Article  PubMed  Google Scholar 

  42. Lindeman RD, Tobin J, Shock NW (1985) Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 33(4):278–285

    PubMed  CAS  Google Scholar 

  43. Adelman RC, Britton GW, Rotenberg S (1978) Endocrine regulation of gene activity in aging animals of different genotypes. In: Bergsma D, Harrison DE (eds) Genetic effects on aging. Alan R. Liss, New York, p 355

    Google Scholar 

  44. Dorshkind K, Montecino-Rodriguez E, Signer RAJ et al (2009) The ageing immune system: is it ever too old to become young again? Nat Rev Immunol 9(1):57–62

    Article  PubMed  CAS  Google Scholar 

  45. Brody JA, Brock DB (1985) Epidemiological and statistical characteristics of the United States elderly population. In: Finch CE, Schneider EL (eds) Handbook of the biology of aging, 2nd edn. Van Nostrand Reinhold, New York, p 3

    Google Scholar 

  46. Rosenberg HM, Ventura SJ, Maurer JD et al (1996) Births and deaths: United States, 1995. Mon Vital Stat Rep 45(3 Suppl 2):31–33

    Google Scholar 

  47. Hitt R, Young-Xu Y, Silver M, Perls T (1999) Centenarians: the older you get, the healthier you have been. Lancet 354(9179):652

    Article  PubMed  CAS  Google Scholar 

  48. Niedernhofer LJ, Garinis GA, Raams A et al (2006) A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature 444(7122):1038–1043

    Article  PubMed  CAS  Google Scholar 

  49. Rose MR, Graves JL Jr (1989) What evolutionary biology can do for gerontology. J Gerontol 44(2):B27–B29

    Article  PubMed  CAS  Google Scholar 

  50. Kirkwood TB, Rose MR (1991) Evolution of senescence: late survival sacrificed for reproduction. Philos Trans R Soc Lond B Biol Sci 332(1262):15–24

    Article  PubMed  CAS  Google Scholar 

  51. Kirkwood TB (1996) Human senescence. Bioessays 18(12): 1009–1016

    Article  PubMed  CAS  Google Scholar 

  52. Finch CE, Tanzi RE (1997) Genetics of aging. Science 278:407–411

    Article  PubMed  CAS  Google Scholar 

  53. Jazwinski SM (1996) Longevity, genes, and aging. Science 273(5271):54–59

    Article  PubMed  CAS  Google Scholar 

  54. Murakami S, Johnson TE (1996) A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics 143(3):1207–1218

    PubMed  CAS  Google Scholar 

  55. Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G (1997) daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans [see comments]. Science 277(5328):942–946

    Article  PubMed  CAS  Google Scholar 

  56. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type [see comments]. Nature 366(6454):461–464

    Article  PubMed  CAS  Google Scholar 

  57. Lin K, Dorman JB, Rodan A, Kenyon C (1997) daf-16: An HNF-3/forkhead family member that can function fo double the life-span of Caenorhabditis elegans. Science 278:1319–1322

    Article  PubMed  CAS  Google Scholar 

  58. Kaeberlein M, McVey M, Guarente L (2001) Using yeast to discover the fountain of youth. Science of aging and knowledge environment. http://sageke.sciencemag.org/cgi/content/full/sageke;2001/1/pe1: http://sageke.sciencemag.org/cgi/content/full/sageke;2001/1/pe1

  59. Guarente L (2007) Sirtuins in aging and disease. Cold Spring Harb Symp Quant Biol 72:483–488

    Article  PubMed  CAS  Google Scholar 

  60. Schwer B, Verdin E (2008) Conserved metabolic regulatory functions of sirtuins. Cell Metab 7(2):104–112

    Article  PubMed  CAS  Google Scholar 

  61. Lin YJ, Seroude L, Benzer S (1998) Extended life-span and stress resistance in the Drosophila mutant methuselah. Science 282(5390):943–946

    Article  PubMed  CAS  Google Scholar 

  62. Rogina B, Reenan RA, Nilsen SP, Helfand SL (2000) Extended life-span conferred by cotransporter gene mutations in Drosophila. Science 290(5499):2137–2140

    Article  PubMed  CAS  Google Scholar 

  63. Dudas SP, Arking R (1995) A coordinate upregulation of antioxidant gene activities is associated with the delayed onset of senescence in a long-lived strain of Drosophila. J Gerontol A Biol Sci Med Sci 50(3):B117–B127

    Article  PubMed  CAS  Google Scholar 

  64. Rose MR, Vu LN, Park SU, Graves JL Jr (1992) Selection on stress resistance increases longevity in Drosophila melanogaster. Exp Gerontol 27(2):241–250

    Article  PubMed  CAS  Google Scholar 

  65. Migliaccio E, Giorgio M, Mele S et al (1999) The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402(6759):309–313

    Article  PubMed  CAS  Google Scholar 

  66. Flurkey K, Papaconstantinou J, Harrison DE (2002) The Snell dwarf mutation Pit1(dw) can increase life span in mice. Mech Ageing Dev 123(2–3):121–130

    Article  PubMed  CAS  Google Scholar 

  67. De Benedictis G, Rose G, Carrieri G et al (1999) Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans. FASEB J 13(12):1532–1536

    PubMed  Google Scholar 

  68. Salvioli S, Capri M, Santoro A et al (2008) The impact of mitochondrial DNA on human lifespan: a view from studies on centenarians. Biotechnol J 3(6):740–749

    Article  PubMed  CAS  Google Scholar 

  69. Rose G, Passarino G, Carrieri G et al (2001) Paradoxes in longevity: sequence analysis of mtDNA haplogroup J in centenarians. Eur J Hum Genet 9(9):701–707

    Article  PubMed  CAS  Google Scholar 

  70. Ross OA, McCormack R, Curran MD et al (2001) Mitochondrial DNA polymorphism: its role in longevity of the Irish population. Exp Gerontol 36(7):1161–1178

    Article  PubMed  CAS  Google Scholar 

  71. Capri M, Salvioli S, Sevini F et al (2006) The genetics of human longevity. Ann NY Acad Sci 1067:252–263

    Article  PubMed  CAS  Google Scholar 

  72. Glatt SJ, Chayavichitsilp P, Depp C, Schork NJ, Jeste DV (2007) Successful aging: from phenotype to genotype. Biol Psychiatry 62(4):282–293

    Article  PubMed  CAS  Google Scholar 

  73. Barzilai N, Atzmon G, Schechter C et al (2003) Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA 290(15):2030–2040

    Article  PubMed  CAS  Google Scholar 

  74. Willcox BJ, Donlon TA, He Q et al (2008) FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci USA 105(37):13987–13992

    Article  PubMed  CAS  Google Scholar 

  75. Flachsbart F, Caliebe A, Kleindorp R et al (2009) Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc Natl Acad Sci USA 106(8):2700–2705

    Article  PubMed  CAS  Google Scholar 

  76. Lunetta KL, D’Agostino RB Sr, Karasik D 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(Suppl 1):S13

    Article  PubMed  CAS  Google Scholar 

  77. Bellizzi D, Rose G, Cavalcante P et al (2005) A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages. Genomics 85(2):258–263

    Article  PubMed  CAS  Google Scholar 

  78. Rose G, Dato S, Altomare K et al (2003) Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly. Exp Gerontol 38(10):1065–1070

    Article  PubMed  CAS  Google Scholar 

  79. Suh Y, Atzmon G, Cho MO et al (2008) Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci USA 105(9):3438–3442

    Article  PubMed  CAS  Google Scholar 

  80. Hong MG, Reynolds C, Gatz M et al (2008) Evidence that the gene encoding insulin degrading enzyme influences human lifespan. Hum Mol Genet 17(15):2370–2378

    Article  PubMed  CAS  Google Scholar 

  81. Hurme M, Lehtimaki T, Jylha M, Karhunen PJ, Hervonen A (2005) Interleukin-6–174G/C polymorphism and longevity: a follow-up study. Mech Ageing Dev 126(3):417–418

    Article  PubMed  CAS  Google Scholar 

  82. Di Bona D, Vasto S, Capurso C et al (2009) Effect of interleukin-6 polymorphisms on human longevity: a systematic review and meta-analysis. Ageing Res Rev 8(1):36–42

    Article  PubMed  Google Scholar 

  83. Scola L, Candore G, Colonna-Romano G et al (2005) Study of the association with -330T/G IL-2 in a population of centenarians from centre and south Italy. Biogerontology 6(6):425–429

    Article  PubMed  CAS  Google Scholar 

  84. Hurme M, Kivimaki M, Pertovaara M et al (2007) CRP gene is involved in the regulation of human longevity: a follow-up study in Finnish nonagenarians. Mech Ageing Dev 128(10):574–576

    Article  PubMed  CAS  Google Scholar 

  85. Hindorff LA, Rice KM, Lange LA et al (2008) Common variants in the CRP gene in relation to longevity and cause-specific mortality in older adults: the Cardiovascular Health Study. Atherosclerosis 197(2):922–930

    Article  PubMed  CAS  Google Scholar 

  86. Cardelli M, Cavallone L, Marchegiani F et al (2008) A genetic-demographic approach reveals male-specific association between survival and tumor necrosis factor (A/G)-308 polymorphism. J Gerontol A Biol Sci Med Sci 63(5):454–460

    Article  PubMed  Google Scholar 

  87. Schachter F, Faure-Delanef L, Guenot F et al (1994) Genetic associations with human longevity at the APOE and ACE loci. Nat Genet 6(1):29–32

    Article  PubMed  CAS  Google Scholar 

  88. Perls T, Levenson R, Regan M, Puca A (2002) What does it take to live to 100? Mech Ageing Dev 123(2–3):231–242

    Article  PubMed  Google Scholar 

  89. Adams ER, Nolan VG, Andersen SL, Perls TT, Terry DF (2008) Centenarian offspring: start healthier and stay healthier. J Am Geriatr Soc 56(11):2089–2092

    Article  PubMed  Google Scholar 

  90. Lee CK, Klopp RG, Weindruch R, Prolla TA (1999) Gene expression profile of aging and its retardation by caloric restriction. Science 285(5432):1390–1393

    Article  PubMed  CAS  Google Scholar 

  91. Lee CK, Weindruch R, Prolla TA (2000) Gene-expression profile of the ageing brain in mice. Nat Genet 25(3):294–297

    Article  PubMed  CAS  Google Scholar 

  92. Kayo T, Allison DB, Weindruch R, Prolla TA (2001) Influences of aging and caloric restriction on the transcriptional profile of skeletal muscle from rhesus monkeys. Proc Natl Acad Sci USA 98(9): 5093–5098

    Article  PubMed  CAS  Google Scholar 

  93. Weindruch R, Kayo T, Lee CK, Prolla TA (2001) Microarray ­profiling of gene expression in aging and its alteration by caloric restriction in mice. J Nutr 131(3):918S–923S

    PubMed  CAS  Google Scholar 

  94. Kirkwood TB, Holliday R (1979) The evolution of ageing and ­longevity. Proc R Soc Lond B Biol Sci 205(1161):531–546

    Article  PubMed  CAS  Google Scholar 

  95. Westendorp RGJ, Kirkwood TBL (1998) Human longevity at the cost of reproductive success. Nature 396(6713):743–746

    Article  PubMed  CAS  Google Scholar 

  96. Mobbs CV (1996) Nueroendocrinology of aging. In: Schneider EL, Rowe JW (eds) Handbook of the biology of aging, 4th edn. Academic Press, San Diego, pp 234–282

    Google Scholar 

  97. Wise PM, Krajnak KM, Kashon ML (1996) Menopause: the aging of multiple pacemakers. Science 273(5271):67–70

    Article  PubMed  CAS  Google Scholar 

  98. Denckla WD (1975) A time to die. Life Sci 16(1):31–44

    Article  PubMed  CAS  Google Scholar 

  99. Gilad GM, Gilad VH (1987) Age-related reductions in brain cholinergic and dopaminergic indices in two rat strains differing in longevity. Brain Res 408(1–2):247–250

    Article  PubMed  CAS  Google Scholar 

  100. Cotzias GC, Miller ST, Tang LC, Papavasiliou PS (1977) Levodopa, fertility, and longevity. Science 196(4289):549–551

    Article  PubMed  CAS  Google Scholar 

  101. Knoll J (1992) (-)Deprenyl-medication: a strategy to modulate the age-related decline of the striatal dopaminergic system. J Am Geriatr Soc 40(8):839–847

    PubMed  CAS  Google Scholar 

  102. Kitani K, Kanai S, Sato Y, Ohta M, Ivy GO, Carrillo MC (1993) Chronic treatment of (−)deprenyl prolongs the life span of male Fischer 344 rats. Further evidence. Life Sci 52(3):281–288

    Article  PubMed  CAS  Google Scholar 

  103. Milgram NW, Racine RJ, Nellis P, Mendonca A, Ivy GO (1990) Maintenance on L-deprenyl prolongs life in aged male rats. Life Sci 47(5):415–420

    Article  PubMed  CAS  Google Scholar 

  104. Kappeler L, De Magalhaes Filho CM, Dupont J et al (2008) Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism. PLoS Biol 6(10):e254

    Article  PubMed  CAS  Google Scholar 

  105. Walford RL (1974) Immunologic theory of aging: current status. Fed Proc 33(9):2020–2027

    PubMed  CAS  Google Scholar 

  106. Miller RA (1996) The aging immune system: primer and prospectus. Science 273(5271):70–74

    Article  PubMed  CAS  Google Scholar 

  107. Yunis EJ, Salazar M (1993) Genetics of life span in mice. Genetica 91(1–3):211–223

    Article  PubMed  CAS  Google Scholar 

  108. Caruso C, Candore G, Romano GC et al (2001) Immunogenetics of longevity. Is major histocompatibility complex polymorphism relevant to the control of human longevity? A review of literature data. Mech Ageing Dev 122(5):445–462

    Article  PubMed  CAS  Google Scholar 

  109. Holehan AM, Merry BJ (1985) Lifetime breeding studies in fully fed and dietary restricted female CFY Sprague–Dawley rats. 1. Effect of age, housing conditions and diet on fecundity. Mech Ageing Dev 33(1):19–28

    Article  PubMed  CAS  Google Scholar 

  110. Merry BJ, Holehan AM (1979) Onset of puberty and duration of fertility in rats fed a restricted diet. J Reprod Fertil 57(2):253–259

    Article  PubMed  CAS  Google Scholar 

  111. Partridge L, Gems D, Withers DJ (2005) Sex and death: what is the connection? Cell 120(4):461–472

    Article  PubMed  CAS  Google Scholar 

  112. Selesniemi K, Lee H-J, Tilly JL (2008) Moderate caloric restriction initiated in rodents during adulthood sustains function of the female reproductive axis into advanced chronological age. Aging Cell 7(5):622–629

    Article  PubMed  CAS  Google Scholar 

  113. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:298

    Article  PubMed  CAS  Google Scholar 

  114. Harman D (1981) The aging process. Proc Natl Acad Sci USA 78(11):7124–7128

    Article  PubMed  CAS  Google Scholar 

  115. Fridovich I (1989) Superoxide dismutases. An adaptation to a paramagnetic gas. J Biol Chem 264(14):7761–7764

    PubMed  CAS  Google Scholar 

  116. Sen CK, Packer L (1996) Antioxidant and redox regulation of gene transcription [see comments]. FASEB J 10(7):709–720

    PubMed  CAS  Google Scholar 

  117. Suzuki YJ, Forman HJ, Sevanian A (1997) Oxidants as stimulators of signal transduction. Free Radic Biol Med 22(1–2):269–285

    Article  PubMed  CAS  Google Scholar 

  118. Finkel T (2003) Oxidant signals and oxidative stress. Curr Opin Cell Biol 15(2):247–254

    Article  PubMed  CAS  Google Scholar 

  119. Valko M, Morris H, Cronin TD (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12(10):1161–1208

    Article  PubMed  CAS  Google Scholar 

  120. Sun J, Folk D, Bradley TJ, Tower J (2002) Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster. Genetics 161(2):661–672

    PubMed  CAS  Google Scholar 

  121. Mockett RJ, Orr WC, Rahmandar JJ et al (1999) Overexpression of Mn-containing superoxide dismutase in transgenic Drosophila melanogaster. Arch Biochem Biophys 371(2):260–269

    Article  PubMed  CAS  Google Scholar 

  122. Paul A, Belton A, Nag S, Martin I, Grotewiel MS, Duttaroy A (2007) Reduced mitochondrial SOD displays mortality characteristics reminiscent of natural aging. Mech Ageing Dev 128(11–12):706–716

    Article  PubMed  CAS  Google Scholar 

  123. Parkes TL, Elia AJ, Dickinson D, Hilliker AJ, Phillips JP, Boulianne GL (1998) Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat Genet 19(2):171–174

    Article  PubMed  CAS  Google Scholar 

  124. Sun J, Tower J (1999) FLP Recombinase-mediated induction of Cu/Zn-superoxide dismutase transgene expression can extend the life span of adult Drosophila melanogaster flies. Mol Cell Biol 19(1):216–228

    PubMed  CAS  Google Scholar 

  125. Parker JD, Parker KM, Sohal BH, Sohal RS, Keller L (2004) Decreased expression of Cu-Zn superoxide dismutase 1 in ants with extreme lifespan. Proc Natl Acad Sci USA 101(10):3486–3489

    Article  PubMed  CAS  Google Scholar 

  126. Orr WC, Sohal RS (1994) Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263(5150):1128–1130

    Article  PubMed  CAS  Google Scholar 

  127. Orr WC, Mockett RJ, Benes JJ, Sohal RS (2003) Effects of overexpression of copper-zinc and manganese superoxide dismutases, catalase, and thioredoxin reductase genes on longevity in Drosophila melanogaster. J Biol Chem 278(29):26418–26422

    Article  PubMed  CAS  Google Scholar 

  128. Mockett RJ, Sohal RS, Orr WC (1999) Overexpression of glutathione reductase extends survival in transgenic Drosophila melanogaster under hyperoxia but not normoxia. FASEB J 13(13): 1733–1742

    PubMed  CAS  Google Scholar 

  129. Brys K, Vanfleteren JR, Braeckman BP (2007) Testing the rate-of-living/oxidative damage theory of aging in the nematode model Caenorhabditis elegans. Exp Gerontol 42(9):845–851

    Article  PubMed  CAS  Google Scholar 

  130. Halaschek-Wiener J, Khattra JS, McKay S et al (2005) Analysis of long-lived C. elegans daf-2 mutants using serial analysis of gene expression. Genome Res 15(5):603–615

    Article  PubMed  CAS  Google Scholar 

  131. Murphy CT, McCarroll SA, Bargmann CI et al (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424(6946):277–283

    Article  PubMed  CAS  Google Scholar 

  132. Keaney M, Matthijssens F, Sharpe M, Vanfleteren J, Gems D (2004) Superoxide dismutase mimetics elevate superoxide dismutase activity in vivo but do not retard aging in the nematode Caenorhabditis elegans. Free Radic Biol Med 37(2):239–250

    Article  PubMed  CAS  Google Scholar 

  133. Adachi H, Fujiwara Y, Ishii N (1998) Effects of oxygen on protein carbonyl and aging in Caenorhabditis elegans mutants with long (age-1) and short (mev-1) life spans. J Gerontol A Biol Sci Med Sci 53(4):B240–B244

    Article  PubMed  CAS  Google Scholar 

  134. Sohal RS, Svensson I, Sohal BH, Brunk UT (1989) Superoxide anion radical production in different animal species. Mech Ageing Dev 49(2):129–135

    Article  PubMed  CAS  Google Scholar 

  135. Schriner SE, Linford NJ, Martin GM et al (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308(5730):1909–1911

    Article  PubMed  CAS  Google Scholar 

  136. Mitsui A, Hamuro J, Nakamura H et al (2002) Overexpression of human thioredoxin in transgenic mice controls oxidative stress and life span. Antioxid Redox Signal 4(4):693–696

    Article  PubMed  CAS  Google Scholar 

  137. Salmon AB, Murakami S, Bartke A, Kopchick J, Yasumura K, Miller RA (2005) Fibroblast cell lines from young adult mice of long-lived mutant strains are resistant to multiple forms of stress. Am J Physiol Endocrinol Metab 289(1):E23–E29

    Article  PubMed  CAS  Google Scholar 

  138. Harper JM, Salmon AB, Leiser SF, Galecki AT, Miller RA (2007) Skin-derived fibroblasts from long-lived species are resistant to some, but not all, lethal stresses and to the mitochondrial inhibitor rotenone. Aging Cell 6(1):1–13

    Article  PubMed  CAS  Google Scholar 

  139. Maynard SP, Miller RA (2006) Fibroblasts from long-lived Snell dwarf mice are resistant to oxygen-induced in vitro growth arrest. Aging Cell 5(1):89–96

    Article  PubMed  CAS  Google Scholar 

  140. Linnane AW, Zhang C, Baumer A, Nagley P (1992) Mitochondrial DNA mutation and the ageing process: bioenergy and pharmacological intervention. Mutat Res 275(3–6):195–208

    PubMed  CAS  Google Scholar 

  141. Fleming JE, Miquel J, Cottrell SF, Yengoyan LS, Economos AC (1982) Is cell aging caused by respiration-dependent injury to the mitochondrial genome? Gerontology 28(1):44–53

    Article  PubMed  CAS  Google Scholar 

  142. Wallace DC (1992) Mitochondrial genetics: a paradigm for aging and degenerative diseases? Science 256(5057):628–632

    Article  PubMed  CAS  Google Scholar 

  143. Ozawa T (1997) Genetic and functional changes in mitochondria associated with aging. Physiol Rev 77(2):425–464

    PubMed  CAS  Google Scholar 

  144. Katayama M, Tanaka M, Yamamoto H, Ohbayashi T, Nimura Y, Ozawa T (1991) Deleted mitochondrial DNA in the skeletal muscle of aged individuals. Biochem Int 25(1):47–56

    PubMed  CAS  Google Scholar 

  145. Lee CM, Chung SS, Kaczkowski JM, Weindruch R, Aiken JM (1993) Multiple mitochondrial DNA deletions associated with age in skeletal muscle of rhesus monkeys. J Gerontol 48(6):B201–B205

    Article  PubMed  CAS  Google Scholar 

  146. Melov S, Shoffner JM, Kaufman A, Wallace DC (1995) Marked increase in the number and variety of mitochondrial DNA rearrangements in aging human skeletal muscle [published erratum appears in Nucleic Acids Res 1995 Dec 11;23(23):4938]. Nucleic Acids Res 23(20):4122–4126

    Article  PubMed  CAS  Google Scholar 

  147. Torii K, Sugiyama S, Tanaka M et al (1992) Aging-associated deletions of human diaphragmatic mitochondrial DNA. Am J Respir Cell Mol Biol 6(5):543–549

    PubMed  CAS  Google Scholar 

  148. Hayakawa M, Torii K, Sugiyama S, Tanaka M, Ozawa T (1991) Age-associated accumulation of 8-hydroxydeoxyguanosine in mitochondrial DNA of human diaphragm. Biochem Biophys Res Commun 179(2):1023–1029

    Article  PubMed  CAS  Google Scholar 

  149. Sugiyama S, Hattori K, Hayakawa M, Ozawa T (1991) Quantitative analysis of age-associated accumulation of mitochondrial DNA with deletion in human hearts. Biochem Biophys Res Commun 180(2):894–899

    Article  PubMed  CAS  Google Scholar 

  150. Hayakawa M, Katsumata K, Yoneda M, Tanaka M, Sugiyama S, Ozawa T (1996) Age-related extensive fragmentation of mitochondrial DNA into minicircles [published erratum appears in Biochem Biophys Res Commun 1997 Mar 27;232(3):832]. Biochem Biophys Res Commun 226(2):369–377

    Article  PubMed  CAS  Google Scholar 

  151. Hayakawa M, Hattori K, Sugiyama S, Ozawa T (1992) Age-associated oxygen damage and mutations in mitochondrial DNA in human hearts. Biochem Biophys Res Commun 189(2): 979–985

    Article  PubMed  CAS  Google Scholar 

  152. Hayakawa M, Sugiyama S, Hattori K, Takasawa M, Ozawa T (1993) Age-associated damage in mitochondrial DNA in human hearts. Mol Cell Biochem 119(1–2):95–103

    Article  PubMed  CAS  Google Scholar 

  153. Ikebe S, Tanaka M, Ohno K et al (1990) Increase of deleted mitochondrial DNA in the striatum in Parkinson’s disease and senescence. Biochem Biophys Res Commun 170(3):1044–1048

    Article  PubMed  CAS  Google Scholar 

  154. Corral-Debrinski M, Horton T, Lott MT, Shoffner JM, Beal MF, Wallace DC (1992) Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age. Nat Genet 2(4):324–329

    Article  PubMed  CAS  Google Scholar 

  155. Trounce I, Byrne E, Marzuki S (1989) Decline in skeletal muscle mitochondrial respiratory chain function: possible factor in ageing [see comments]. Lancet 1(8639):637–639

    Article  PubMed  CAS  Google Scholar 

  156. Schapira AH, Mann VM, Cooper JM et al (1990) Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson’s disease. J Neurochem 55(6):2142–2145

    Article  PubMed  CAS  Google Scholar 

  157. Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 54(3):823–827

    Article  PubMed  CAS  Google Scholar 

  158. Hoyer S (1986) Senile dementia and Alzheimer’s disease. Brain blood flow and metabolism. Prog Neuropsychopharmacol Biol Psychiatry 10(3–5):447–478

    Article  PubMed  CAS  Google Scholar 

  159. Sims NR, Finegan JM, Blass JP, Bowen DM, Neary D (1987) Mitochondrial function in brain tissue in primary degenerative dementia. Brain Res 436(1):30–38

    Article  PubMed  CAS  Google Scholar 

  160. Beal MF (1994) Neurochemistry and toxin models in Huntington’s disease. Curr Opin Neurol 7(6):542–547

    Article  PubMed  CAS  Google Scholar 

  161. Schulz JB, Beal MF (1996) Mitochondrial dysfunction in movement disorders. Mech Dev 57(1):3–20

    Article  Google Scholar 

  162. Lin FH, Lin R, Wisniewski HM et al (1992) Detection of point mutations in codon 331 of mitochondrial NADH dehydrogenase subunit 2 in Alzheimer’s brains. Biochem Biophys Res Commun 182(1):238–246

    Article  PubMed  CAS  Google Scholar 

  163. Shoffner JM, Brown MD, Torroni A et al (1993) Mitochondrial DNA variants observed in Alzheimer disease and Parkinson disease patients. Genomics 17(1):171–184

    Article  PubMed  CAS  Google Scholar 

  164. Ozawa T, Tanaka M, Ino H et al (1991) Distinct clustering of point mutations in mitochondrial DNA among patients with mitochondrial encephalomyopathies and with Parkinson’s disease. Biochem Biophys Res Commun 176(2):938–946

    Article  PubMed  CAS  Google Scholar 

  165. Ozawa T, Tanaka M, Ikebe S, Ohno K, Kondo T, Mizuno Y (1990) Quantitative determination of deleted mitochondrial DNA relative to normal DNA in parkinsonian striatum by a kinetic PCR analysis. Biochem Biophys Res Commun 172(2):483–489

    Article  PubMed  CAS  Google Scholar 

  166. Ikebe S, Tanaka M, Ozawa T (1995) Point mutations of mitochondrial genome in Parkinson’s disease. Brain Res Mol Brain Res 28(2):281–295

    Article  PubMed  CAS  Google Scholar 

  167. Poulton J, Deadman ME, Ramacharan S, Gardiner RM (1991) Germ-line deletions of mtDNA in mitochondrial myopathy. Am J Hum Genet 48(4):649–653

    PubMed  CAS  Google Scholar 

  168. Ionasescu VV, Hart M, DiMauro S, Moraes CT (1994) Clinical and morphologic features of a myopathy associated with a point mutation in the mitochondrial tRNA(Pro) gene. Neurology 44(5):975–977

    Article  PubMed  CAS  Google Scholar 

  169. Ozawa T, Tanaka M, Sugiyama S et al (1991) Patients with idiopathic cardiomyopathy belong to the same mitochondrial DNA gene family of Parkinson’s disease and mitochondrial encephalomyopathy. Biochem Biophys Res Commun 177(1):518–525

    Article  PubMed  CAS  Google Scholar 

  170. Katsumata K, Hayakawa M, Tanaka M, Sugiyama S, Ozawa T (1994) Fragmentation of human heart mitochondrial DNA associated with premature aging. Biochem Biophys Res Commun 202(1):102–110

    Article  PubMed  CAS  Google Scholar 

  171. Ozawa T (1994) Mitochondrial cardiomyopathy. Herz 19(2):105–118, 125

    PubMed  CAS  Google Scholar 

  172. Yoneda M, Katsumata K, Hayakawa M, Tanaka M, Ozawa T (1995) Oxygen stress induces an apoptotic cell death associated with fragmentation of mitochondrial genome. Biochem Biophys Res Commun 209(2):723–729

    Article  PubMed  CAS  Google Scholar 

  173. Trifunovic A, Wredenberg A, Falkenberg M et al (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429(6990):417–423

    Article  PubMed  CAS  Google Scholar 

  174. Trifunovic A, Hansson A, Wredenberg A et al (2005) Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci USA 102(50):17993–17998

    Article  PubMed  CAS  Google Scholar 

  175. Maisonneuve E, Ezraty B, Dukan S (2008) Protein aggregates: an aging factor involved in cell death. J Bacteriol 190(18): 6070–6075

    Article  PubMed  CAS  Google Scholar 

  176. Melov S, Hinerfeld D, Esposito L, Wallace DC (1997) Multi-organ characterization of mitochondrial genomic rearrangements in ad libitum and caloric restricted mice show striking somatic mitochondrial DNA rearrangements with age. Nucleic Acids Res 25(5):974–982

    Article  PubMed  CAS  Google Scholar 

  177. Larsen PL, Clarke CF (2002) Extension of life-span in Caenorhabditis elegans by a diet lacking coenzyme Q. Science 295(5552):120–123

    Article  PubMed  CAS  Google Scholar 

  178. Zainal TA, Oberley TD, Allison DB, Szweda LI, Weindruch R (2000) Caloric restriction of rhesus monkeys lowers oxidative damage in skeletal muscle. FASEB J 14(12):1825–1836

    Article  PubMed  CAS  Google Scholar 

  179. Meydani M (2001) Nutrition interventions in aging and age-associated disease. Ann NY Acad Sci 928:226–235

    Article  PubMed  CAS  Google Scholar 

  180. Lopez-Lluch G, Irusta PM, Navas P, de Cabo R (2008) Mitochondrial biogenesis and healthy aging. Exp Gerontol 43(9): 813–819

    Article  PubMed  CAS  Google Scholar 

  181. Civitarese AE, Carling S, Heilbronn LK et al (2007) Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med 4(3):e76

    Article  PubMed  CAS  Google Scholar 

  182. Lanza IR, Short DK, Short KR et al (2008) Endurance exercise as a countermeasure for aging. Diabetes 57(11):2933–2942

    Article  PubMed  CAS  Google Scholar 

  183. Melov S, Tarnopolsky MA, Beckman K, Felkey K, Hubbard A (2007) Resistance exercise reverses aging in human skeletal muscle. PLoS ONE 2(5):e465

    Article  PubMed  CAS  Google Scholar 

  184. Failla G (1958) The aging process and carcinogenesis. Ann NY Acad Sci 71:1124

    Article  PubMed  CAS  Google Scholar 

  185. Szilard L (1959) On the nature of the aging process. Proc Natl Acad Sci USA 45:30

    Article  PubMed  CAS  Google Scholar 

  186. Casarett GW (1963) Concept and criteria of radiologic ageing. In: Harris RJ (ed) Cellular basis and aetiology of late somatic effects of ionizing radiation. Academic Press, New York, p 189

    Google Scholar 

  187. Walburg HE (1975) Radiation-induced life-shortening and premature aging. Adv Radiat Biol 5:145

    Google Scholar 

  188. Sacher CA (1977) Life table modification and life prolongation. In: Finch CE, Hayflick L (eds) Handbook of the biology of aging. Van Nostrand Reinhold, New York, p 582

    Google Scholar 

  189. Lindop PJ, Rotblat J (1961) Long-term effect of a single whoe-body exposure of mice to ionizing radiations. Proc R Soc Lond 154:350

    Article  Google Scholar 

  190. Garinis GA, van der Horst GT, Vijg J, Hoeijmakers JH (2008) DNA damage and ageing: new-age ideas for an age-old problem. Nat Cell Biol 10(11):1241–1247

    Article  PubMed  CAS  Google Scholar 

  191. Hart RW, Setlow RB (1974) Correlation between deoxyribonucleic acid excision-repair and life-span in a number of mammalian species. Proc Natl Acad Sci USA 71(6):2169–2173

    Article  PubMed  CAS  Google Scholar 

  192. Cabelof DC, Raffoul JJ, Yanamadala S, Ganir C, Guo Z, Heydari AR (2002) Attenuation of DNA polymerase [beta]-dependent base excision repair and increased DMS-induced mutagenicity in aged mice. Mutat Res 500(1–2):135–145

    PubMed  CAS  Google Scholar 

  193. Intano GW, Cho EJ, McMahan CA, Walter CA (2003) Age-related base excision repair activity in mouse brain and liver nuclear extracts. J Gerontol A Biol Sci Med Sci 58(3):B205–B211

    Article  Google Scholar 

  194. Cabelof DC, Yanamadala S, Raffoul JJ, Guo Z, Soofi A, Heydari AR (2003) Caloric restriction promotes genomic stability by induction of base excision repair and reversal of its age-related decline. DNA Repair 2(3):295–307

    Article  PubMed  CAS  Google Scholar 

  195. Seluanov A, Mittelman D, Pereira-Smith OM, Wilson JH, Gorbunova V (2004) DNA end joining becomes less efficient and more error-prone during cellular senescence. Proc Natl Acad Sci USA 101(20):7624–7629

    Article  PubMed  CAS  Google Scholar 

  196. Sedelnikova OA, Horikawa I, Redon C et al (2008) Delayed kinetics of DNA double-strand break processing in normal and pathological aging. Aging Cell 7(1):89–100

    Article  PubMed  CAS  Google Scholar 

  197. Hanawalt PC, Gee P, Ho L (1990) DNA repair in differentiating cells in relation to aging. In: Finch CE, Johnson TE (eds) Molecular biology of aging. UCLA symposia on molecular and cellular biology, vol 123. Alan R. Liss, New York, p 45

    Google Scholar 

  198. Henle ES, Han Z, Tang N, Rai P, Luo Y, Linn S (1999) Sequence-specific DNA Cleavage by Fe2+-mediated Fenton reactions has possible biological implications. J Biol Chem 274(2):962–971

    Article  PubMed  CAS  Google Scholar 

  199. Lu T, Pan Y, Kao S-Y et al (2004) Gene regulation and DNA damage in the ageing human brain. Nature 429(6994):883–891

    Article  PubMed  CAS  Google Scholar 

  200. Orgel LE (1963) The maintenance of the accuracy of protein synthesis and its relevance to aging. Proc Natl Acad Sci USA 49:517

    Article  PubMed  CAS  Google Scholar 

  201. Kristal BS, Yu BP (1992) An emerging hypothesis: synergistic induction of aging by free radicals and Maillard reactions. J Gerontol 47(4):B107–B114

    Article  PubMed  CAS  Google Scholar 

  202. Levine RL, Stadtman ER (1996) Protein Modifications with Aging. In: Schneider EL, Rowe JW (eds) Handbook of the biology of aging, 4th edn. Academic Press, San Diego, pp 184–197

    Google Scholar 

  203. Gracy RW, Yuksel KU, Chapman MD et al (1985) Impaired protein degradation may account for the accumulation of “abnormal” proteins in aging cells. In: Adelman RC, Dekker EE (ed) Modern aging research, modification of proteins during aging. Alan R. Liss, New York, p 1

    Google Scholar 

  204. Brown WT (1990) Genetic diseases of premature aging as models of senescence. Annu Rev Gerontol Geriatr 10:23–42

    PubMed  CAS  Google Scholar 

  205. Meshorer E, Gruenbaum Y (2008) Gone with the Wnt/Notch: stem cells in laminopathies, progeria, and aging. J Cell Biol 181(1):9–13

    Article  PubMed  CAS  Google Scholar 

  206. De Sandre-Giovannoli A, Bernard R, Cau P et al (2003) Lamin A truncation in Hutchinson–Gilford progeria. Science 300(5628):2055

    Article  PubMed  Google Scholar 

  207. Eriksson M, Brown WT, Gordon LB et al (2003) Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome. Nature 423(6937):293–298

    Article  PubMed  CAS  Google Scholar 

  208. Scaffidi P, Misteli T (2005) Reversal of the cellular phenotype in the premature aging disease Hutchinson–Gilford progeria syndrome. Nat Med 11(4):440–445

    Article  PubMed  CAS  Google Scholar 

  209. Cao K, Capell BC, Erdos MR, Djabali K, Collins FS (2007) A lamin A protein isoform overexpressed in Hutchinson–Gilford progeria syndrome interferes with mitosis in progeria and normal cells. Proc Natl Acad Sci USA 104(12):4949–4954

    Article  PubMed  CAS  Google Scholar 

  210. Dahl KN, Scaffidi P, Islam MF, Yodh AG, Wilson KL, Misteli T (2006) Distinct structural and mechanical properties of the nuclear lamina in Hutchinson–Gilford progeria syndrome. Proc Natl Acad Sci USA 103(27):10271–10276

    Article  PubMed  CAS  Google Scholar 

  211. Dechat T, Shimi T, Adam SA et al (2007) Alterations in mitosis and cell cycle progression caused by a mutant lamin A known to accelerate human aging. Proc Natl Acad Sci USA 104(12): 4955–4960

    Article  PubMed  CAS  Google Scholar 

  212. Liu B, Wang J, Chan KM et al (2005) Genomic instability in laminopathy-based premature aging. Nat Med 11(7):780–785

    Article  PubMed  CAS  Google Scholar 

  213. Muftuoglu M, Oshima J, von Kobbe C, Cheng W-H, Leistritz D, Bohr V (2008) The clinical characteristics of Werner syndrome: molecular and biochemical diagnosis. Hum Genet 124(4): 369–377

    Article  PubMed  CAS  Google Scholar 

  214. Epstein CJ, Martin GM, Schultz AL, Motulsky AG (1966) Werner’s syndrome a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine (Baltimore) 45(3):177–221

    CAS  Google Scholar 

  215. Goto M (1997) Hierarchical deterioration of body systems in Werner’s syndrome: implications for normal ageing. Mech Ageing Dev 98(3):239–254

    Article  PubMed  CAS  Google Scholar 

  216. Goto M, Rubenstein M, Weber J, Woods K, Drayna D (1992) Genetic linkage of Werner’s syndrome to five markers on chromosome 8. Nature 355(6362):735–738

    Article  PubMed  CAS  Google Scholar 

  217. Yu CE, Oshima J, Fu YH et al (1996) Positional cloning of the Werner’s syndrome gene [see comments]. Science 272(5259): 258–262

    Article  PubMed  CAS  Google Scholar 

  218. Brosh RM Jr, Bohr VA (2002) Roles of the Werner syndrome protein in pathways required for maintenance of genome stability. Exp Gerontol 37(4):491–506

    Article  PubMed  CAS  Google Scholar 

  219. Ogburn CE, Oshima J, Poot M et al (1997) An apoptosis-inducing genotoxin differentiates heterozygotic carriers for Werner helicase mutations from wild-type and homozygous mutants. Hum Genet 101(2):121–125

    Article  PubMed  CAS  Google Scholar 

  220. Poot M, Gollahon KA, Emond MJ, Silber JR, Rabinovitch PS (2002) Werner syndrome diploid fibroblasts are sensitive to 4-nitroquinoline-N-oxide and 8-methoxypsoralen: implications for the disease phenotype. FASEB J 16(7):757–758

    PubMed  CAS  Google Scholar 

  221. Poot M, Yom JS, Whang SH, Kato JT, Gollahon KA, Rabinovitch PS (2001) Werner syndrome cells are sensitive to DNA cross-linking drugs. FASEB J 15(7):1224–1226

    PubMed  CAS  Google Scholar 

  222. Pichierri P, Franchitto A, Mosesso P, Palitti F (2000) Werner’s syndrome cell lines are hypersensitive to camptothecin-induced chromosomal damage. Mutat Res 456(1–2):45–57

    PubMed  CAS  Google Scholar 

  223. Poot M, Gollahon KA, Rabinovitch PS (1999) Werner syndrome lymphoblastoid cells are sensitive to camptothecin-induced apoptosis in S-phase. Hum Genet 104(1):10–14

    Article  PubMed  CAS  Google Scholar 

  224. Stevnsner T, Muftuoglu M, Aamann MD, Bohr VA (2008) The role of Cockayne Syndrome group B (CSB) protein in base excision repair and aging. Mech Ageing Dev 129(7–8):441–448

    Article  PubMed  CAS  Google Scholar 

  225. Henning KA, Li L, Iyer N et al (1995) The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH. Cell 82(4):555–564

    Article  PubMed  CAS  Google Scholar 

  226. Groisman R, Polanowska J, Kuraoka I et al (2003) The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell 113(3):357–367

    Article  PubMed  CAS  Google Scholar 

  227. Troelstra C, van Gool A, de Wit J, Vermeulen W, Bootsma D, Hoeijmakers JH (1992) ERCC6, a member of a subfamily of putative helicases, is involved in Cockayne’s syndrome and preferential repair of active genes. Cell 71(6):939–953

    Article  PubMed  CAS  Google Scholar 

  228. Horibata K, Iwamoto Y, Kuraoka I et al (2004) Complete absence of Cockayne syndrome group B gene product gives rise to UV-sensitive syndrome but not Cockayne syndrome. Proc Natl Acad Sci USA 101(43):15410–15415

    Article  PubMed  CAS  Google Scholar 

  229. Martin GM, Turker MS (1990) Genetic of human disease, longevity, and aging. In: Hazzard WR, Andres R, Bierman EL et al (eds) Principles of geriatric medicine and gerontology, 2nd edn. McGraw-Hill, New York, p 22

    Google Scholar 

  230. Fanconi G (1967) Familial constitutional panmyelocytopathy, Fanconi’s anemia (F.A.). I. Clinical aspects. Semin Hematol 4(3): 233–240

    PubMed  CAS  Google Scholar 

  231. Neveling K, Bechtold A, Hoehn H (2007) Genetic instability syndromes with progeroid features. Z Gerontol Geriatr 40(5): 339–348

    Article  PubMed  CAS  Google Scholar 

  232. Joenje H, Arwert F, Eriksson AW, de Koning H, Oostra AB (1981) Oxygen-dependence of chromosomal aberrations in Fanconi’s anaemia. Nature 290(5802):142–143

    Article  PubMed  CAS  Google Scholar 

  233. Zhang X, Li J, Sejas DP, Pang Q (2005) Hypoxia-reoxygenation induces premature senescence in FA bone marrow hematopoietic cells. Blood 106(1):75–85

    Article  PubMed  CAS  Google Scholar 

  234. Park SJ, Ciccone SL, Beck BD et al (2004) Oxidative stress/damage induces multimerization and interaction of Fanconi anemia proteins. J Biol Chem 279(29):30053–30059

    Article  PubMed  CAS  Google Scholar 

  235. Drachtman RA, Alter BP (1992) Dyskeratosis congenita: clinical and genetic heterogeneity. Report of a new case and review of the literature. Am J Pediatr Hematol Oncol 14(4):297–304

    Article  PubMed  CAS  Google Scholar 

  236. Vulliamy T, Dokal I (2006) Dyskeratosis congenita. Semin Hematol 43(3):157–166

    Article  PubMed  CAS  Google Scholar 

  237. Marrone A, Dokal I (2004) Dyskeratosis congenita: molecular insights into telomerase function, ageing and cancer. Expert Rev Mol Med 6(26):1–23

    Article  PubMed  Google Scholar 

  238. Chang S, Multani AS, Cabrera NG et al (2004) Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat Genet 36(8):877–882

    Article  PubMed  CAS  Google Scholar 

  239. Wong KK, Maser RS, Bachoo RM et al (2003) Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Nature 421(6923):643–648

    Article  PubMed  CAS  Google Scholar 

  240. Elchuri S, Oberley TD, Qi W et al (2005) CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene 24(3):367–380

    Article  PubMed  CAS  Google Scholar 

  241. Hashizume K, Hirasawa M, Imamura Y et al (2008) Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice. Am J Pathol 172(5):1325–1331

    Article  PubMed  Google Scholar 

  242. Van Remmen H, Ikeno Y, Hamilton M et al (2003) Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics 16(1):29–37

    Article  PubMed  CAS  Google Scholar 

  243. Ho YS, Xiong Y, Ma W, Spector A, Ho DS (2004) Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury. J Biol Chem 279(31):32804–32812

    Article  PubMed  CAS  Google Scholar 

  244. Ho YS, Magnenat JL, Bronson RT et al (1997) Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia. J Biol Chem 272(26): 16644–16651

    Article  PubMed  CAS  Google Scholar 

  245. Van Remmen H, Qi W, Sabia M et al (2004) Multiple deficiencies in antioxidant enzymes in mice result in a compound increase in sensitivity to oxidative stress. Free Radic Biol Med 36(12):1625–1634

    Article  PubMed  CAS  Google Scholar 

  246. Hayflick L, Moorhead PS (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636

    Article  PubMed  CAS  Google Scholar 

  247. Wang E (1995) Senescent human fibroblasts resist programmed cell death, and failure to suppress bcl2 is involved. Cancer Res 55(11):2284–2292

    PubMed  CAS  Google Scholar 

  248. Marcotte R, Lacelle C, Wang E (2004) Senescent fibroblasts resist apoptosis by downregulating caspase-3. Mech Ageing Dev 125(10–11):777–783

    Article  PubMed  CAS  Google Scholar 

  249. Hampel B, Malisan F, Niederegger H, Testi R, Jansen-Dürr P (2004) Differential regulation of apoptotic cell death in senescent human cells. Exp Gerontol 39(11-12):1713–1721

    Article  PubMed  CAS  Google Scholar 

  250. Bayreuther K, Rodemann HP, Hommel R, Dittmann K, Albiez M, Francz PI (1988) Human skin fibroblasts in vitro differentiate along a terminal cell lineage. Proc Natl Acad Sci USA 85(14):5112–5116

    Article  PubMed  CAS  Google Scholar 

  251. Pignolo RJ, Rotenberg MO, Cristofalo VJ (1994) Alterations in contact and density-dependent arrest state in senescent WI-38 cells. In Vitro Cell Dev Biol Anim 30A(7):471–476

    Article  PubMed  CAS  Google Scholar 

  252. Matsumura T, Zerrudo Z, Hayflick L (1979) Senescent human ­diploid cells in culture: survival, DNA synthesis and morphology. J Gerontol 34(3):328–334

    Article  PubMed  CAS  Google Scholar 

  253. Ponten J (1973) Aging properties of glia. In: Bourliere F, Courtois Y, Macieira-Coelho A et al (eds) Molecular and cellular mechanisms of aging. INSERM, Paris, p 53

    Google Scholar 

  254. Rheinwald JG, Green H (1975) Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell 6(3):331–343

    Article  PubMed  CAS  Google Scholar 

  255. Bierman EL (1978) The effect of donor age on the in vitro life span of cultured human arterial smooth-muscle cells. In Vitro 14(11):951–955

    Article  PubMed  CAS  Google Scholar 

  256. Tassin J, Malaise E, Courtois Y (1979) Human lens cells have an in vitro proliferative capacity inversely proportional to the donor age. Exp Cell Res 123(2):388–392

    Article  PubMed  CAS  Google Scholar 

  257. Mueller SN, Rosen EM, Levine EM (1980) Cellular senescence in a cloned strain of bovine fetal aortic endothelial cells. Science 207(4433):889–891

    Article  PubMed  CAS  Google Scholar 

  258. Tice RR, Schneider EL, Kram D, Thorne P (1979) Cytokinetic analysis of the impaired proliferative response of peripheral lymphocytes from aged humans to phytohemagglutinin. J Exp Med 149(5):1029–1041

    Article  PubMed  CAS  Google Scholar 

  259. Stampfer MR (1985) Isolation and growth of human mammary epithelial cells. J Tissue Culture Methods 9:107–115

    Article  Google Scholar 

  260. Yaswen P, Stampfer MR (2002) Molecular changes accompanying senescence and immortalization of cultured human mammary epithelial cells. Int J Biochem Cell Biol 34(11):1382–1394

    Article  PubMed  CAS  Google Scholar 

  261. Harrison DE (1985) Cell and tissue transplantation: a means of studying the aging process. In: Finch CE, Schneider EL (eds) Handbook of the biology of Aging, 2nd edn. Van Nostrand Reinhold, New York, p 332

    Google Scholar 

  262. Olsson L, Ebbesen P (1977) Ageing decreases the activity of epidermal G1 and G2 inhibitors in mouse skin independent of grafting on old or young recipients. Exp Gerontol 12(1–2):59–62

    Article  PubMed  CAS  Google Scholar 

  263. Rohme D (1981) Evidence for a relationship between longevity of mammalian species and life spans of normal fibroblasts in vitro and erythrocytes in vivo. Proc Natl Acad Sci USA 78(8): 5009–5013

    Article  PubMed  CAS  Google Scholar 

  264. Martin GM, Sprague CA, Epstein CJ (1970) Replicative life-span of cultivated human cells. Effects of donor’s age, tissue, and genotype. Lab Invest 23(1):86–92

    PubMed  CAS  Google Scholar 

  265. Pignolo RJ, Masoro EJ, Nichols WW, Bradt CI, Cristofalo VJ (1992) Skin fibroblasts from aged Fischer 344 rats undergo similar changes in replicative life span but not immortalization with caloric restriction of donors. Exp Cell Res 201(1):16–22

    Article  PubMed  CAS  Google Scholar 

  266. Schneider EL, Mitsui Y (1976) The relationship between in vitro cellular aging and in vivo human age. Proc Natl Acad Sci USA 73(10):3584–3588

    Article  PubMed  CAS  Google Scholar 

  267. Goldstein S, Littlefield JW, Soeldner JS (1969) Diabetes mellitus and aging: diminished planting efficiency of cultured human fibroblasts. Proc Natl Acad Sci USA 64(1):155–160

    Article  PubMed  CAS  Google Scholar 

  268. Le Guilly Y, Simon M, Lenoir P, Bourel M (1973) Long-term culture of human adult liver cells: morphological changes related to in vitro senescence and effect of donor’s age on growth potential. Gerontologia 19(5):303–313

    Article  PubMed  Google Scholar 

  269. Wille JJ Jr, Pittelkow MR, Shipley GD, Scott RE (1984) Integrated control of growth and differentiation of normal human prokeratinocytes cultured in serum-free medium: clonal analyses, growth kinetics, and cell cycle studies. J Cell Physiol 121(1):31–44

    Article  PubMed  CAS  Google Scholar 

  270. Effros RB, Boucher N, Porter V et al (1994) Decline in CD28+ T cells in centenarians and in long-term T cell cultures: a possible cause for both in vivo and in vitro immunosenescence. Exp Gerontol 29(6):601–609

    Article  PubMed  CAS  Google Scholar 

  271. Cristofalo VJ, Allen RG, Pignolo RJ, Martin BG, Beck JC (1998) Relationship between donor age and the replicative lifespan of human cells in culture: a reevaluation. Proc Natl Acad Sci USA 95(18):10614–10619

    Article  PubMed  CAS  Google Scholar 

  272. Dimri G, Lee X, Basile G et al (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 92(20):9363–9367

    Article  PubMed  CAS  Google Scholar 

  273. Ressler S, Bartkova J, Niederegger H et al (2006) p16INK4A is a robust in vivo biomarker of cellular aging in human skin. Aging Cell 5(5):379–389

    Article  PubMed  CAS  Google Scholar 

  274. Clark AJ, Ferrier P, Aslam S et al (2003) Proliferative lifespan is conserved after nuclear transfer. Nat Cell Biol 5(6):535–538

    Article  PubMed  CAS  Google Scholar 

  275. Cristofalo VJ, Palaxxo R, Charpentier RL (1980) Limited lifespan of human fibroblasts in vitro: metabolic time or replications? In: Adelman RC, Roberts J, Baker GT et al (eds) Neural regulatory mechanisms during aging. Alan R. Liss, New York, p 203

    Google Scholar 

  276. Campisi J, D’Adda di Fagagna F (2007) Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 8(9):729–740

    Article  PubMed  CAS  Google Scholar 

  277. Toussaint O, Medrano EE, von Zglinicki T (2000) Cellular and molecular mechanisms of stress-induced premature senescence (SIPS) of human diploid fibroblasts and melanocytes. Exp Gerontol 35(8):927–945

    Article  PubMed  CAS  Google Scholar 

  278. Toussaint O, Remacle J, Dierick JF et al (2002) Stress-induced premature senescence: from biomarkers to likeliness of in vivo occurrence. Biogerontology 3(1–2):13–17

    Article  PubMed  CAS  Google Scholar 

  279. d’Adda di Fagagna F, Reaper PM, Clay-Farrace L et al (2003) A DNA damage checkpoint response in telomere-initiated senescence. Nature 426(6963):194–198

    Article  PubMed  CAS  Google Scholar 

  280. Hemann MT, Narita M (2007) Oncogenes and senescence: breaking down in the fast lane. Genes Dev 21(1):1–5

    Article  PubMed  CAS  Google Scholar 

  281. Takahashi A, Ohtani N, Yamakoshi K et al (2006) Mitogenic signalling and the p16INK4a-Rb pathway cooperate to enforce irreversible cellular senescence. Nat Cell Biol 8(11):1291–1297

    Article  PubMed  CAS  Google Scholar 

  282. Campisi J (1997) Aging and cancer: the double-edged sword of replicative senescence. J Am Geriatr Soc 45(4):482–488

    PubMed  CAS  Google Scholar 

  283. Shay JW, Wright WE, Werbin H (1993) Toward a molecular understanding of human breast cancer: a hypothesis. Breast Cancer Res Treat 25(1):83–94

    Article  PubMed  CAS  Google Scholar 

  284. Stein GH, Beeson M, Gordon L (1990) Failure to phosphorylate the retinoblastoma gene product in senescent human fibroblasts. Science 249(4969):666–669

    Article  PubMed  CAS  Google Scholar 

  285. Ozer HL, Banga SS, Dasgupta T et al (1996) SV40-mediated immortalization of human fibroblasts. Exp Gerontol 31(1–2):303–310

    Article  PubMed  CAS  Google Scholar 

  286. Shay JW, Pereira-Smith OM, Wright WE (1991) A role for both RB and p53 in the regulation of human cellular senescence. Exp Cell Res 196(1):33–39

    Article  PubMed  CAS  Google Scholar 

  287. Hara E, Tsurui H, Shinozaki A, Nakada S, Oda K (1991) Cooperative effect of antisense-Rb and antisense-p53 oligomers on the extension of life span in human diploid fibroblasts, TIG-1. Biochem Biophys Res Commun 179(1):528–534

    Article  PubMed  CAS  Google Scholar 

  288. Afshari CA, Nichols MA, Xiong Y, Mudryj M (1996) A role for a p21-E2F interaction during senescence arrest of normal human fibroblasts. Cell Growth Differ 7(8):979–988

    PubMed  CAS  Google Scholar 

  289. Noda A, Ning Y, Venable SF, Pereira-Smith OM, Smith JR (1994) Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp Cell Res 211(1):90–98

    Article  PubMed  CAS  Google Scholar 

  290. Tahara H, Sato E, Noda A, Ide T (1995) Increase in expression level of p21sdi1/cip1/waf1 with increasing division age in both normal and SV40-transformed human fibroblasts. Oncogene 10(5):835–840

    PubMed  CAS  Google Scholar 

  291. Alcorta DA, Xiong Y, Phelps D, Hannon G, Beach D, Barrett JC (1996) Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc Natl Acad Sci USA 93(24):13742–13747

    Article  PubMed  CAS  Google Scholar 

  292. Palmero I, McConnell B, Parry D et al (1997) Accumulation of p16INK4a in mouse fibroblasts as a function of replicative senescence and not of retinoblastoma gene status. Oncogene 15(5):495–503

    Article  PubMed  CAS  Google Scholar 

  293. Reznikoff CA, Yeager TR, Belair CD, Savelieva E, Puthenveettil JA, Stadler WM (1996) Elevated p16 at senescence and loss of p16 at immortalization in human papillomavirus 16 E6, but not E7, transformed human uroepithelial cells. Cancer Res 56(13):2886–2890

    PubMed  CAS  Google Scholar 

  294. Brown JP, Wei W, Sedivy JM (1997) Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. Science 277(5327):831–834

    Article  PubMed  CAS  Google Scholar 

  295. Yang L, Didenko VV, Noda A et al (1995) Increased expression of p21Sdi1 in adrenocortical cells when they are placed in culture. Exp Cell Res 221(1):126–131

    Article  PubMed  CAS  Google Scholar 

  296. Medcalf AS, Klein-Szanto AJ, Cristofalo VJ (1996) Expression of p21 is not required for senescence of human fibroblasts. Cancer Res 56(20):4582–4585

    PubMed  CAS  Google Scholar 

  297. Vogt M, Haggblom C, Yeargin J, Christiansen-Weber T, Haas M (1998) Independent induction of senescence by p16INK4a and p21CIP1 in spontaneously immortalized human fibroblasts. Cell Growth Differ 9(2):139–146

    PubMed  CAS  Google Scholar 

  298. Afshari CA, Vojta PJ, Annab LA, Futreal PA, Willard TB, Barrett JC (1993) Investigation of the role of G1/S cell cycle mediators in cellular senescence. Exp Cell Res 209(2):231–237

    Article  PubMed  CAS  Google Scholar 

  299. Tyner SD, Venkatachalam S, Choi J et al (2002) p53 mutant mice that display early ageing-associated phenotypes. Nature 415(6867):45–53

    Article  PubMed  CAS  Google Scholar 

  300. Beausejour CM, Krtolica A, Galimi F et al (2003) Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J 22(16):4212–4222

    Article  PubMed  CAS  Google Scholar 

  301. Itahana K, Zou Y, Itahana Y et al (2003) Control of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1. Mol Cell Biol 23(1):389–401

    Article  PubMed  CAS  Google Scholar 

  302. Herbig U, Jobling WA, Chen BP, Chen DJ, Sedivy JM (2004) Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell 14(4):501–513

    Article  PubMed  CAS  Google Scholar 

  303. Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88(5):593–602

    Article  PubMed  CAS  Google Scholar 

  304. Benanti JA, Galloway DA (2004) Normal human fibroblasts are resistant to RAS-induced senescence. Mol Cell Biol 24(7):2842–2852

    Article  PubMed  CAS  Google Scholar 

  305. Rai P, Onder TT, Young JJ et al (2009) Continuous elimination of oxidized nucleotides is necessary to prevent rapid onset of cellular senescence. Proc Natl Acad Sci USA 106(1):169–174

    Article  PubMed  Google Scholar 

  306. Romanov SR, Kozakiewicz BK, Holst CR, Stampfer MR, Haupt LM, Tlsty TD (2001) Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes. Nature 409(6820):633–637

    Article  PubMed  CAS  Google Scholar 

  307. Rheinwald JG, Hahn WC, Ramsey MR et al (2002) A two-stage, p16(INK4A)- and p53-dependent keratinocyte senescence mechanism that limits replicative potential independent of telomere status. Mol Cell Biol 22(14):5157–5172

    Article  PubMed  CAS  Google Scholar 

  308. Muller M (2009) Cellular senescence: molecular mechanisms, in vivo significance, and redox considerations. Antioxid Redox Signal 11(1):59–98

    Article  PubMed  CAS  Google Scholar 

  309. Sohal RS, Brunk UT (1989) Lipofuscin as an indicator of oxidative stress and aging. Adv Exp Med Biol 266:17–26; discussion 27–19

    PubMed  CAS  Google Scholar 

  310. Narita M, Nunez S, Heard E et al (2003) Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113(6):703–716

    Article  PubMed  CAS  Google Scholar 

  311. Severino J, Allen RG, Balin S, Balin A, Cristofalo VJ (2000) Is beta-galactosidase staining a marker of senescence in vitro and in vivo? Exp Cell Res 257(1):162–171

    Article  PubMed  CAS  Google Scholar 

  312. Litaker JR, Pan J, Cheung Y et al (1998) Expression profile of senescence-associated beta-galactosidase and activation of telomerase in human ovarian surface epithelial cells undergoing immortalization. Int J Oncol 13(5):951–956

    PubMed  CAS  Google Scholar 

  313. Untergasser G, Gander R, Rumpold H, Heinrich E, Plas E, Berger P (2003) TGF-beta cytokines increase senescence-associated beta-galactosidase activity in human prostate basal cells by supporting differentiation processes, but not cellular senescence. Exp Gerontol 38(10):1179–1188

    Article  PubMed  CAS  Google Scholar 

  314. Kurz DJ, Decary S, Hong Y, Erusalimsky JD (2000) Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J Cell Sci 113(Pt 20):3613–3622

    PubMed  CAS  Google Scholar 

  315. Yang NC, Hu ML (2005) The limitations and validities of senescence associated-beta-galactosidase activity as an aging marker for human foreskin fibroblast Hs68 cells. Exp Gerontol 40(10): 813–819

    Article  PubMed  CAS  Google Scholar 

  316. Lee BY, Han JA, Im JS et al (2006) Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging Cell 5(2):187–195

    Article  PubMed  CAS  Google Scholar 

  317. Matthews C, Gorenne I, Scott S et al (2006) Vascular smooth muscle cells undergo telomere-based senescence in human atherosclerosis: effects of telomerase and oxidative stress. Circ Res 99(2): 156–164

    Article  PubMed  CAS  Google Scholar 

  318. Krishnamurthy J, Ramsey MR, Ligon KL et al (2006) p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443(7110):453–457

    Article  PubMed  CAS  Google Scholar 

  319. Krishnamurthy J, Torrice C, Ramsey MR et al (2004) Ink4a/ARF expression is a biomarker of aging. J Clin Invest 114(9):1299–1307

    PubMed  CAS  Google Scholar 

  320. Collado M, Gil J, Efeyan A et al (2005) Tumour biology: senescence in premalignant tumours. Nature 436(7051):642

    Article  PubMed  CAS  Google Scholar 

  321. Harley CB (1991) Telomere loss: mitotic clock or genetic time bomb? Mutat Res 256(2–6):271–282

    PubMed  CAS  Google Scholar 

  322. Greider CW (1990) Telomeres, telomerase and senescence. Bioessays 12(8):363–369

    Article  PubMed  CAS  Google Scholar 

  323. Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345(6274):458–460

    Article  PubMed  CAS  Google Scholar 

  324. Allsopp RC, Vaziri H, Patterson C et al (1992) Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA 89(21):10114–10118

    Article  PubMed  CAS  Google Scholar 

  325. Chang E, Harley CB (1995) Telomere length and replicative aging in human vascular tissues. Proc Natl Acad Sci USA 92(24):11190–11194

    Article  PubMed  CAS  Google Scholar 

  326. Lindsey J, McGill NI, Lindsey LA, Green DK, Cooke HJ (1991) In vivo loss of telomeric repeats with age in humans. Mutat Res 256(1):45–48

    Article  PubMed  CAS  Google Scholar 

  327. Vaziri H, Schachter F, Uchida I et al (1993) Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am J Hum Genet 52(4):661–667

    PubMed  CAS  Google Scholar 

  328. Frenck RW Jr, Blackburn EH, Shannon KM (1998) The rate of telomere sequence loss in human leukocytes varies with age. Proc Natl Acad Sci USA 95(10):5607–5610

    Article  PubMed  CAS  Google Scholar 

  329. Counter CM, Hirte HW, Bacchetti S, Harley CB (1994) Telomerase activity in human ovarian carcinoma [see comments]. Proc Natl Acad Sci USA 91(8):2900–2904

    Article  PubMed  CAS  Google Scholar 

  330. Sugihara S, Mihara K, Marunouchi T, Inoue H, Namba M (1996) Telomere elongation observed in immortalized human fibroblasts by treatment with 60Co gamma rays or 4-nitroquinoline 1-oxide. Hum Genet 97(1):1–6

    Article  PubMed  CAS  Google Scholar 

  331. Bryan TM, Englezou A, Gupta J, Bacchetti S, Reddel RR (1995) Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J 14(17):4240–4248

    PubMed  CAS  Google Scholar 

  332. Chiu CP, Dragowska W, Kim NW et al (1996) Differential expression of telomerase activity in hematopoietic progenitors from adult human bone marrow. Stem Cells 14(2):239–248

    Article  PubMed  CAS  Google Scholar 

  333. Broccoli D, Young JW, de Lange T (1995) Telomerase activity in normal and malignant hematopoietic cells. Proc Natl Acad Sci USA 92(20):9082–9086

    Article  PubMed  CAS  Google Scholar 

  334. Counter CM, Gupta J, Harley CB, Leber B, Bacchetti S (1995) Telomerase activity in normal leukocytes and in hematologic malignancies. Blood 85(9):2315–2320

    PubMed  CAS  Google Scholar 

  335. Terry DF, Nolan VG, Andersen SL, Perls TT, Cawthon R (2008) Association of longer telomeres with better health in centenarians. J Gerontol A Biol Sci Med Sci 63(8):809–812

    Article  PubMed  Google Scholar 

  336. Ludlow AT, Zimmerman JB, Witkowski S, Hearn JW, Hatfield BD, Roth SM (2008) Relationship between physical activity level, telomere length, and telomerase activity. Med Sci Sports Exerc 40(10):1764–1771

    Article  PubMed  CAS  Google Scholar 

  337. Woo J, Tang NL, Suen E, Leung JC, Leung PC (2008) Telomeres and frailty. Mech Ageing Dev 129(11):642–648

    Article  PubMed  CAS  Google Scholar 

  338. Hofer AC, Tran RT, Aziz OZ et al (2005) Shared phenotypes among segmental progeroid syndromes suggest underlying pathways of aging. J Gerontol A Biol Sci Med Sci 60(1):10–20

    Article  PubMed  Google Scholar 

  339. Rudolph KL, Chang S, Lee HW et al (1999) Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96(5):701–712

    Article  PubMed  CAS  Google Scholar 

  340. Wright WE, Brasiskyte D, Piatyszek MA, Shay JW (1996) Experimental elongation of telomeres extends the lifespan of immortal × normal cell hybrids. EMBO J 15(7):1734–1741

    PubMed  CAS  Google Scholar 

  341. Bodnar AG, Ouellette M, Frolkis M et al (1998) Extension of life-span by introduction of telomerase into normal human cells [see comments]. Science 279(5349):349–352

    Article  PubMed  CAS  Google Scholar 

  342. Gorbunova V, Seluanov A, Pereira-Smith OM (2002) Expression of human telomerase (hTERT) Does not prevent stress-induced senescence in normal human fibroblasts but protects the cells from stress-induced apoptosis and necrosis. J Biol Chem 277(41): 38540–38549

    Article  PubMed  CAS  Google Scholar 

  343. Naka K, Tachibana A, Ikeda K, Motoyama N (2004) Stress-induced premature senescence in htert-expressing ataxia telangiectasia fibroblasts. J Biol Chem 279(3):2030–2037

    Article  PubMed  CAS  Google Scholar 

  344. Forsyth NR, Evans AP, Shay JW, Wright WE (2003) Developmental differences in the immortalization of lung fibroblasts by telomerase. Aging Cell 2(5):235–243

    Article  PubMed  CAS  Google Scholar 

  345. Petersen S, Saretzki G, Zglinicki Tv (1998) Preferential accumulation of single-stranded regions in telomeres of human fibroblasts. Exp Cell Res 239(1):152–160

    Article  PubMed  CAS  Google Scholar 

  346. Passos JF, Saretzki G, von Zglinicki T (2007) DNA damage in telomeres and mitochondria during cellular senescence: is there a connection? Nucleic Acids Res 35(22):7505–7513

    Article  PubMed  CAS  Google Scholar 

  347. Janzen V, Forkert R, Fleming HE et al (2006) Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443(7110):421–426

    PubMed  CAS  Google Scholar 

  348. de Haan G, Van Zant G (1999) Dynamic changes in mouse hematopoietic stem cell numbers during aging. Blood 93(10): 3294–3301

    PubMed  Google Scholar 

  349. Geiger H, Van Zant G (2002) The aging of lympho-hematopoietic stem cells. Nat Immunol 3(4):329–333

    Article  PubMed  CAS  Google Scholar 

  350. Molofsky AV, Slutsky SG, Joseph NM et al (2006) Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443(7110):448–452

    Article  PubMed  CAS  Google Scholar 

  351. Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA (1999) Creation of human tumour cells with defined genetic elements. Nature 400(6743):464–468

    Article  PubMed  CAS  Google Scholar 

  352. Vaziri H, Benchimol S (1999) Alternative pathways for the extension of cellular life span: inactivation of p53/pRb and expression of telomerase. Oncogene 18(53):7676–7680

    Article  PubMed  CAS  Google Scholar 

  353. Elenbaas B, Spirio L, Koerner F et al (2001) Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells. Genes Dev 15(1):50–65

    Article  PubMed  CAS  Google Scholar 

  354. Kendall SD, Linardic CM, Adam SJ, Counter CM (2005) A network of genetic events sufficient to convert normal human cells to a tumorigenic state. Cancer Res 65(21):9824–9828

    Article  PubMed  CAS  Google Scholar 

  355. Lundberg AS, Randell SH, Stewart SA et al (2002) Immortalization and transformation of primary airway epithelial cells by gene transfer. Oncogene 21(29):4577–4586

    Article  PubMed  CAS  Google Scholar 

  356. Bartkova J, Horejsi Z, Koed K et al (2005) DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434(7035):864–870

    Article  PubMed  CAS  Google Scholar 

  357. Michaloglou C, Vredeveld LCW, Soengas MS et al (2005) BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436(7051):720–724

    Article  PubMed  CAS  Google Scholar 

  358. Castro P, Giri D, Lamb D, Ittmann M (2003) Cellular senescence in the pathogenesis of benign prostatic hyperplasia. Prostate 55(1):30–38

    Article  PubMed  CAS  Google Scholar 

  359. Chen Z, Trotman LC, Shaffer D et al (2005) Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436(7051):725–730

    Article  PubMed  CAS  Google Scholar 

  360. Bartkova J, Rezaei N, Liontos M et al (2006) Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 444(7119):633–637

    Article  PubMed  CAS  Google Scholar 

  361. Di Micco R, Fumagalli M, Cicalese A et al (2006) Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444(7119):638–642

    Article  PubMed  CAS  Google Scholar 

  362. Mallette FA, Gaumont-Leclerc M-F, Ferbeyre G (2007) The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence. Genes Dev 21(1):43–48

    Article  PubMed  CAS  Google Scholar 

  363. Feldser DM, Greider CW (2007) Short telomeres limit tumor progression in vivo by inducing senescence. Cell 11(5):461–469

    CAS  Google Scholar 

  364. Xue W, Zender L, Miething C et al (2007) Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445(7128):656–660

    Article  PubMed  CAS  Google Scholar 

  365. Wu C-H, van Riggelen J, Yetil A, Fan AC, Bachireddy P, Felsher DW (2007) Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation. Proc Natl Acad Sci USA 104(32):13028–13033

    Article  PubMed  CAS  Google Scholar 

  366. Martins CP, Brown-Swigart L, Evan GI (2006) Modeling the ­therapeutic efficacy of p53 restoration in tumors. Cell 127(7): 1323–1334

    Article  PubMed  CAS  Google Scholar 

  367. Gorgoulis VG, Vassiliou L-VF, Karakaidos P et al (2005) Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 434(7035):907–913

    Article  PubMed  CAS  Google Scholar 

  368. Eyler CE, Rich JN (2008) Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol 26(17):2839–2845

    Article  PubMed  CAS  Google Scholar 

  369. Wajapeyee N, Serra RW, Zhu X, Mahalingam M, Green MR (2008) Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell 132(3):363–374

    Article  PubMed  CAS  Google Scholar 

  370. Acosta JC, O’Loghlen A, Banito A et al (2008) Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133(6): 1006–1018

    Article  PubMed  CAS  Google Scholar 

  371. Kuilman T, Michaloglou C, Vredeveld LCW et al (2008) Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133(6):1019–1031

    Article  PubMed  CAS  Google Scholar 

  372. Coppe J-P, Patil CK, Rodier F et al (2008) Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 6(12):e301

    Article  CAS  Google Scholar 

  373. Ries LAG, Melbert D, Krapcho M, Stinchcomb DG, Howlader N, Horner MJ, Mariotto A, Miller BA, Feuer EJ, Altekruse SF, Lewis DR, Clegg L, Eisner MP, Reichman M, Edwards BK (eds) (2008) SEER cancer statistics review, 1975-2005, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2005/, based on November 2007 SEER data submission, posted to the SEER web site

  374. Krtolica A, Parrinello S, Lockett S, Desprez PY, Campisi J (2001) Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc Natl Acad Sci USA 98(21):12072–12077

    Article  PubMed  CAS  Google Scholar 

  375. Liu D, Hornsby PJ (2007) Senescent human fibroblasts increase the early growth of xenograft tumors via matrix metalloproteinase secretion. Cancer Res 67(7):3117–3126

    Article  PubMed  CAS  Google Scholar 

  376. Maier B, Gluba W, Bernier B et al (2004) Modulation of mammalian life span by the short isoform of p53. Genes Dev 18(3):306–319

    Article  PubMed  CAS  Google Scholar 

  377. Garcia-Cao I, Garcia-Cao M, Martin-Caballero J et al (2002) ‘Super p53’ mice exhibit enhanced DNA damage response, are tumor resistant and age normally. EMBO J 21(22):6225–6235

    Article  PubMed  CAS  Google Scholar 

  378. Matheu A, Pantoja C, Efeyan A et al (2004) Increased gene dosage of Ink4a/Arf results in cancer resistance and normal aging. Genes Dev 18(22):2736–2746

    Article  PubMed  CAS  Google Scholar 

  379. Mendrysa SM, O’Leary KA, McElwee MK et al (2006) Tumor suppression and normal aging in mice with constitutively high p53 activity. Genes Dev 20(1):16–21

    Article  PubMed  CAS  Google Scholar 

  380. Matheu A, Maraver A, Klatt P et al (2007) Delayed ageing through damage protection by the Arf/p53 pathway. Nature 448(7151): 375–379

    Article  PubMed  CAS  Google Scholar 

  381. Partridge L, Gems D (2007) Benchmarks for ageing studies. Nature 450(7167):165–167

    Article  PubMed  CAS  Google Scholar 

  382. Lane MA, Ingram DK, Ball SS, Roth GS (1997) Dehydroepiandrosterone sulfate: a biomarker of primate aging slowed by calorie restriction. J Clin Endocrinol Metab 82(7): 2093–2096

    Article  PubMed  CAS  Google Scholar 

  383. Larson-Meyer DE, Newcomer BR, Heilbronn LK et al (2008) Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function. Obesity 16(6):1355–1362

    Article  PubMed  CAS  Google Scholar 

  384. Trichopoulou A, Vasilopoulou E (2000) Mediterranean diet and longevity. Br J Nutr 84(Suppl 2):S205–S209

    Article  PubMed  CAS  Google Scholar 

  385. Corder R, Mullen W, Khan NQ et al (2006) Oenology: red wine procyanidins and vascular health. Nature 444(7119):566

    Article  PubMed  CAS  Google Scholar 

  386. Allard JS, Perez E, Zou S, de Cabo R (2009) Dietary activators of Sirt1. Mol Cell Endocrinol 299(1):58–63

    Article  PubMed  CAS  Google Scholar 

  387. Baur JA, Pearson KJ, Price NL et al (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444(7117):337–342

    Article  PubMed  CAS  Google Scholar 

  388. Lagouge M, Argmann C, Gerhart-Hines Z et al (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127(6):1109–1122

    Article  PubMed  CAS  Google Scholar 

  389. Pearson KJ, Baur JA, Lewis KN et al (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 8(2):157–168

    Article  PubMed  CAS  Google Scholar 

  390. Barger JL, Kayo T, Vann JM et al (2008) A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS ONE 3(6):e2264

    Article  PubMed  CAS  Google Scholar 

  391. Schumacher B, van der Pluijm I, Moorhouse MJ et al (2008) Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genet 4(8):e1000161

    Article  PubMed  CAS  Google Scholar 

  392. Keyes WM, Wu Y, Vogel H, Guo X, Lowe SW, Mills AA (2005) p63 deficiency activates a program of cellular senescence and leads to accelerated aging. Genes Dev 19(17): 1986–1999

    Article  PubMed  CAS  Google Scholar 

  393. Mostoslavsky R, Chua KF, Lombard DB et al (2006) Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124(2):315–329

    Article  PubMed  CAS  Google Scholar 

  394. Kuro-o M, Matsumura Y, Aizawa H et al (1997) Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390(6655):45–51

    Article  PubMed  CAS  Google Scholar 

  395. Takeda T, Hosokawa M, Higuchi K (1997) Senescence-accelerated mouse (SAM): a novel murine model of senescence. Exp Gerontol 32(1–2):105–109

    Article  PubMed  CAS  Google Scholar 

  396. Lebel M, Leder P (1998) A deletion within the murine Werner syndrome helicase induces sensitivity to inhibitors of topoisomerase and loss of cellular proliferative capacity. Proc Natl Acad Sci USA 95(22):13097–13102

    Article  PubMed  CAS  Google Scholar 

  397. van der Horst GT, Meira L, Gorgels TG et al (2002) UVB ­radiation-induced cancer predisposition in Cockayne syndrome group A (Csa) mutant mice. DNA Repair (Amst) 1(2): 143–157

    Article  Google Scholar 

  398. Barlow C, Hirotsune S, Paylor R et al (1996) Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell 86(1):159–171

    Article  PubMed  CAS  Google Scholar 

  399. Ruzankina Y, Pinzon-Guzman C, Asare A et al (2007) Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss. Cell Stem Cell 1(1): 113–126

    Article  PubMed  CAS  Google Scholar 

  400. Bartke A, Brown-Borg HM, Bode AM, Carlson J, Hunter WS, Bronson RT (1998) Does growth hormone prevent or accelerate aging? Exp Gerontol 33(7–8):675–687

    Article  PubMed  CAS  Google Scholar 

  401. Mounkes LC, Kozlov S, Hernandez L, Sullivan T, Stewart CL (2003) A progeroid syndrome in mice is caused by defects in A-type lamins. Nature 423(6937):298–301

    Article  PubMed  CAS  Google Scholar 

  402. Liu X, Jiang N, Hughes B, Bigras E, Shoubridge E, Hekimi S (2005) Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice. Genes Dev 19(20):2424–2434

    Article  PubMed  CAS  Google Scholar 

  403. Holzenberger M, Dupont J, Ducos B et al (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421(6919):182–187

    Article  PubMed  CAS  Google Scholar 

  404. Bluher M, Kahn BB, Kahn CR (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299(5606): 572–574

    Article  PubMed  CAS  Google Scholar 

  405. Miskin R, Masos T (1997) Transgenic mice overexpressing urokinase-type plasminogen activator in the brain exhibit reduced food consumption, body weight and size, and increased longevity. J Gerontol A Biol Sci Med Sci 52(2):B118–B124

    Article  PubMed  CAS  Google Scholar 

  406. Chiu CH, Lin WD, Huang SY, Lee YH (2004) Effect of a C/EBP gene replacement on mitochondrial biogenesis in fat cells. Genes Dev 18(16):1970–1975

    Article  PubMed  CAS  Google Scholar 

  407. Yan L, Vatner DE, O’Connor JP et al (2007) Type 5 adenylyl cyclase disruption increases longevity and protects against stress. Cell 130(2):247–258

    Article  PubMed  CAS  Google Scholar 

  408. Flurkey K, Papaconstantinou J, Miller RA, Harrison DE (2001) Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc Natl Acad Sci USA 98(12):6736–6741

    Article  PubMed  CAS  Google Scholar 

  409. Brown-Borg HM, Borg KE, Meliska CJ, Bartke A (1996) Dwarf mice and the ageing process. Nature 384(6604):33

    Article  PubMed  CAS  Google Scholar 

  410. Coschigano KT, Clemmons D, Bellush LL, Kopchick JJ (2000) Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology 141(7):2608–2613

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Gerontology and Geriatric Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami VA GRECC, Miami, FL, USA

    Priyamvada Rai & Bruce R. Troen

Authors
  1. Priyamvada Rai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bruce R. Troen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Priyamvada Rai or Bruce R. Troen .

Editor information

Editors and Affiliations

  1. School of Medicine, Department of Surgery, Yale University, New Haven, 06520, Connecticut, USA

    Ronnie Ann Rosenthal

  2. Downstate Medical Center, State University of New York, Clarkson Ave. 450, Brooklyn, 11203, New York, USA

    Michael E. Zenilman

  3. , Chairman, Department of Surgery, Sinai Hospital, 2401 West Belvedere Avenue, Baltimore, 21215, Maryland, USA

    Mark R. Katlic

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Rai, P., Troen, B.R. (2011). Cell and Molecular Aging. In: Rosenthal, R., Zenilman, M., Katlic, M. (eds) Principles and Practice of Geriatric Surgery. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6999-6_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-6999-6_2

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-6998-9

  • Online ISBN: 978-1-4419-6999-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation