Journal Mobile Options
Table of Contents
Vol. 55, No. 2, 2009
Issue release date: March 2009
Section title: Experimental Section
Free Access
Gerontology 2009;55:205–216
(DOI:10.1159/000200772)

The Evolutionary Theories of Aging Revisited – A Mini-Review

Ljubuncic P. · Reznick A.Z.
Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
email Corresponding Author

Abstract

This short review portrays the evolutionary theories of aging in the light of the existing discoveries from genomic and molecular genetic studies on aging and longevity. At the outset, an historical background for the development of the evolutionary theories of aging is presented through the works of August Weismann (programmed death and the germ plasm theories) including his exceptional theoretical postulation, later experimentally validated by the existence of cell division limits. Afterwards, the theory of mutation accumulation of Peter Medawar and the theory modification by Charlesworth (late-life mortality plateau) are presented as well as the antagonistic pleiotropy hypothesis of George Williams, and the disposable soma theory of Kirkwood and Holliday. These theories are discussed in the light of the different research studies, which include studies on insulin signaling and longevity, the possibility that nuclear factor kappa B may be a major mediator of aging, studies of anti-aging Sirtuins and studies on heat shock proteins and longevity and on gene sets as biomarkers of aging. Finally, the proposals for future research in biogerontology, such as studies on the control of protein synthesis, validation of biomarkers of aging, understanding the biochemistry of longevity and research in the field of gerontologic pathology are presented. Likewise, further attention is suggested regarding the work on telomere shortening, stem cells and studies on understanding the biochemical and molecular basis for longevity in centenarians.

© 2009 S. Karger AG, Basel


  

Key Words

  • Evolution
  • Aging
  • Longevity
  • Genomic studies
  • Nuclear factor kappa B

References

  1. Weismann A: Essays Upon Heredity. Oxford, Clarendon Press, 1891.
  2. Weismann A: Über die Dauer des Lebens. Fisher, Jena, 1882.
  3. Dyke B, Gage T, Alford P, Swenson B, Williams-Blangero S: Model life table for captive chimpanzees. Am J Primatol 1995;37:25–37.
  4. Hill K, Boesch C, Goodall J, Pusey A, Williams J, Wrangham R: Mortality rates among wild chimpanzees. J Hum Evol 2001;40:437–450.
  5. Austad SN: Retarded senescence in an insular population of opossums (Didelphis virginiana). J Zool 1993;229:695–708.

    External Resources

  6. Weismann A: Über Leben und Tod. Fisher, Jena, 1892.
  7. Hayflick L, Moorhead PS: The serial cultivation of human diploid cell strains. Exp Cell Res 1961;25:585–621.
  8. Hayflick L: The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965;37:614–636.
  9. Kerr JF, Wyllie AH, Currie AR: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972;26:239–257.
  10. Vicencio JM, Galluzzi L, Tajeddine N, Ortiz C, Criollo A, Tasdemir E, Morselli E, Ben Younes A, Maiuri MC, Lavandero S, Kroemer G: Senescence, apoptosis or autophagy? When a damaged cell must decide its path: a mini-review. Gerontology 2008;54:92–99.
  11. Weismann A: Essays Upon Heredity and Kindred Biological Problems. Oxford, Clarendon Press, 1889.
  12. Kirkwood TB: Evolution of ageing. Nature 1977;270:301–304.
  13. Medawar PB: An Unsolved Problem of Biology. London, HK Lewis, 1952.
  14. Charlesworth B: Fisher, Medawar, Hamilton and the evolution of aging. Genetics 2000;156:927–931.
  15. Charlesworth B: Evolution in Age-Structured Populations. Cambridge, Cambridge University Press, 1994.
  16. Gavrilova NS, Gavrilov LA, Evdokushkina GN, Semyonova VG, Gavrilova AL, Evdokushkina NN, Kushnareva YE, Kroutko VN, Andreyev AY: Evolution, mutation, and human longevity: European royal and noble families. Hum Biol 1998;70:799–804.
  17. Strehler BL: Origin and comparison of the effects of time and high energy radiations on living systems. Quart Rev Biol 1959;34:117–142.
  18. Kim SA: Common aging pathways in worms, flies, mice and humans. J Exp Biol 2007;210:1607–1612.
  19. Carey JR, Liedo P, Orozco D, Vaupel JW: Slowing of mortality-rates at older ages in large medfly cohorts. Science 1992;258:457–461.
  20. Curtsinger JW, Fukui HH, Townsend DR, Vaupel JW: Demography of genotypes: failure of the limited life-span paradigm in Drosophila melanogaster. Science 1992;258:461–463.
  21. Charlesworth B: Patterns of age-specific means and genetic variances of mortality rates predicted by the mutation-accumulation theory of ageing. J Theor Biol 2001;210:47–65.
  22. Reynolds RM, Temiyasathit S, Reedy MM, Ruedi EA, Drnevich JM, Leips J, Hughes KA: Age specificity of inbreeding load in Drosophila melanogaster and implications for the evolution of late-life mortality plateaus. Genetics 2007;177:587–595.
  23. Williams GC: Pleiotropy, natural selection, and the evolution of senescence. Evolution 1957;11:398–411.

    External Resources

  24. Zahavi A: Mate selection: a selection for a handicap. J Theor Biol 1975;53:205-214.
  25. Krtolica A, Parrinello S, Lockett S, Desprez PY, Campisi J: Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc Natl Acad Sci USA 2001;98:12072–12077.
  26. Cutler RG, Semsei I: Development, cancer and aging: possible common mechanisms of action and regulation. J Gerontol 1989;44:25–34.
  27. Economos AC, Lints FA: Developmental temperature and life-span in Drosophila-melanogaster. 1. Constant developmental temperature: evidence for physiological adaptation in a wide temperature-range. Gerontology 1986;32:18–27.
  28. Johnson TE, Hutchinson EW: Absence of strong heterosis for life span and other life history traits in Caenorhabditis elegans. Genetics 1993;134:465–474.
  29. Walker DW, McColl G, Jenkins NL, Harris J, Lithgow GJ: Evolution of lifespan in C. elegans. Nature 2000;405:296–297.
  30. Wick G, Berger P, Jansen-Dürr P, Grubeck-Loebenstein B: A Darwinian-evolutionary concept of age-related diseases. Exp Gerontol 2003;38:13–25.
  31. Martin GM: Modalities of gene action predicted by the classical evolutionary biological theory of aging. Ann NY Acad Sci 2007;1100:14–20.
  32. Mannucci PM, Mari D, Merati G, Peyvandi F, Tagliabue L, Sacchi E, Taioli E, Sansoni P, Bertolini S, Franceschi C: Gene polymorphisms predicting high plasma levels of coagulation and fibrinolysis proteins: a study in centenarians. Arterioscler Thromb Vasc Biol 1997;17:755–759.
  33. Le Bourg É: A mini-review of the evolutionary theories of aging: is it the time to accept them? Demogr Res 2001;4:1–28.

    External Resources

  34. Gavrilov LA, Gavrilova NS: Evolutionary theories of aging and longevity. Scientific World Journal 2002;2:339–356.

    External Resources

  35. Kirkwood TB, Holliday R: The evolution of ageing and longevity. Proc R Soc Lond B Biol Sci 1979;205:531–546.
  36. Kirkwood TB, Austad SN: Why do we age? Nature 2000;408:233–238.
  37. Congdon JD, Nagle RD, Kinney OM, van Loben Sels RC, Quinter T, Tinkle DW: Testing hypotheses of aging in long-lived painted turtles (Chrysemys picta). Exp Gerontol 2003;38:765–772.
  38. Hamilton WD: The moulding of senescence by natural selection. J Theor Biol 1966;12:12–45.
  39. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang RA: C. elegans mutant that lives twice as long as wild type. Nature 1993;366:461–464.
  40. Kirkwood TB: Evolution of ageing. Mech Ageing Dev 2002;123:737–745.
  41. Gems D, Partridge L: Insulin/IGF signalling and ageing: seeing the bigger picture. Cur Opin Genet Dev 2001;11:287–292.
  42. Finch CE, Ruvkun G: The genetics of aging. Annu Rev Genomics Hum Genet 2001;2:435–462.
  43. Kenyon C: The plasticity of aging: insights from long-lived mutants. Cell 2005;120:449–460.
  44. Johnson T: Increased life-span of age-1 mutants in Caenorhabditis elegans and lower Gompertz rate of aging. Science 1990;249:908–912.
  45. Hertweck M, Gobel C, Baumeister R: C. elegans SGK-1 is the critical component in the Akt/PKB kinase complex to control stress response and life span. Dev Cell 2004;6:577–588.
  46. Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, Ruvkun G: The Forkhead transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 1997;389:994–999.
  47. Selman C, Lingard S, Choudhury AI, Batterham RL, Claret M, Clements M, Ramadani F, Okkenhaug K, Schuster E, Blanc E, Piper MD, Al-Qassab H, Speakman JR, Carmignac D, Robinson IC, Thornton JM, Gems D, Partridge L, Withers DJ: Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB J 2008;22:807–818.
  48. Adler AS, Sinha S, Kawahara TL, Zhang JY, Segal E, Chang HY: Motif module map reveals enforcement of aging by continual NF-κB activity. Genes Dev 2007;21:3244–3257.
  49. Adler AS, Kawahara TL, Segal E, Chang HY: Reversal of aging by NFκB blockade. Cell Cycle 2008;7:556–559.
  50. Cai D, Frantz JD, Tawa Jr NE, Melendez PA, Oh BC, Lidov HG, Hasselgren PO, Frontera WR, Lee J, Glass DJ, Shoelson SE: IKKβ/NF-κB activation causes severe muscle wasting in mice. Cell 2004;119:285–298.
  51. Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, Wynshaw-Boris A, Poli G, Olefsky J, Karin M: IKK-β links inflammation to obesity-induced insulin resistance. Nat Med 2005;11:191–198.
  52. Chen J, Zhou Y, Mueller-Steiner S, Chen LF, Kwon H, Yi S, Mucke L, Gan L: SIRT1 protects against microglia-dependent amyloid-β toxicity through inhibiting NF-κB signaling. J Biol Chem 2005;280:40364–40374.
  53. Bar-Shai M, Reznick AZ: Peroxynitrite induces an alternative NF-kappaB activation pathway in L8 rat myoblasts. Antioxid Redox Signal 2006;8:639–652.
  54. Bar-Shai M, Carmeli M, Coleman E, Rozen R, Perek N, Fuchs S, Reznick AZ: The effect of hindlimb immobilization on acid phosphatase, metalloproteinases and nuclear factor-kappaB in muscles of young and old rats. Mech Ageing Dev 2005;126:289–297.
  55. Bar-Shai M, Carmeli E, Ljubuncic P, Reznick AZ: Exercise and immobilization in aging animals: the involvement of oxidative stress and NFkB activation. Free Radic Biol Med 2007;44:202–214.
  56. Reed T, Dick DM, Uniacke SK, Foroud T, Nichols WC: Genome-wide scan for a healthy aging phenotype provides support for a locus near D4S1564 promoting healthy aging. J Gerontol A Biol Sci Med Sci 2004;59:227–232.
  57. Sengupta N, Seto E: Regulation of histone deacetylase activities. J Cell Biochem 2004;93:57–67.
  58. Lin SJ, Ford E, Haigis M, Liszt G, Guarente L: Calorie restriction extends yeast life span by lowering the level of NADH. Genes Dev 2004;18:12–16.
  59. Tissenbaum HA, Guarente L: Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 2001;410:227–230.
  60. Rogina B, Helfand SL: Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci USA 2004;101:15998–16003.
  61. Morrow G, Tanguay RM: Heat shock proteins and aging in Drosophila melanogaster. Semin Cell Develop Biol 2003;14:291–299.
  62. Yokoyama K: Extended longevity of Caenorhabditis elegans by knocking in extra copies of hsp70F, a homolog of mot-2 (mortalin)/mthsp70/Grp75. FEBS Lett 2002;516:53–57.
  63. Hsu AL, Murphy CT, Kenyon C: Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 2003;300:1142–1145.
  64. Longo VD: Search for methuselah genes heats up. Sci Aging Knowledge Environ 2004;6:pe6.
  65. Zahn JM, Sonu R, Vogel H, Crane E, Mazan-Mamczarz K, Rabkin R, Davis RW, Becker KG, Owen AB, Kim SK: Transcriptional profiling of aging in human muscle reveals a common aging signature. PLoS Genet 2006;2:e115.
  66. Golden TR, Hinerfeld DA, Melov S: Oxidative stress and aging: beyond correlation. Aging Cell 2002;1:117–123.
  67. Zahn JM, Poosala S, Owen AB, Ingram DK, Lustig A, Carter A, Weeraratna AT, Taub DD, Gorospe M, Mazan-Mamczarz K, Lakatta EG, Boheler KR, Xu X, Mattson MP, Falco G, Ko MSH, Schlessinger D, Firman J, Kummerfeld SK, Wood WH 3rd, Zonderman AB, Kim SK, Becke KG: AGEMAP: A Gene Expression Database for Aging in Mice. PLoS Genet 2007;3:e201.
  68. Simon AF, Shih C, Mack A, Benzer S: Steroid control of longevity in Drosophila melanogaster. Science 2003;299:1407–1410.
  69. Kirkwood TB: Understanding ageing from an evolutionary perspective. J Intern Med 2008;263:117–127.
  70. Lund J, Tedesco P, Duke K, Wang J, Kim SK, Johnson TE: Transcriptional profile of aging in C. elegans. Curr Biol 2002;12:1566–1573.
  71. Partridge L, Gems D: Beyond the evolutionary theory of ageing, from functional genomics to evo-gero. Trends Ecol Evol 2006;21:334–340.
  72. Campisi J: Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 2005;120:513–522.
  73. Driscoll M, Gerstbrein B: Dying for a cause: invertebrate genetics takes on human neurodegeneration. Nat Rev Genet 2003;4:181–194.
  74. Ruvalcaba RH, Churesigaew S, Myhre SA, Kelley VC, Martin GM: Children who age rapidly: progeroid syndromes: case report of a new variant. Clin Pediatr (Phila) 1997;16:248–252.

    External Resources

  75. Martin GM, Oshima J: Lessons from human progeroid syndromes. Nature 2000;408:263–266.
  76. Campisi J: Cancer, aging and cellular senescence. In Vivo 2000;14:183–188.
  77. Bagnara GP, Bonsi L, Strippoli P, Bonifazi F, Tonelli R, D’Addato S, Paganelli R, Scala E, Fagiolo U, Monti D, Cossarizza A, Bonafé M, Franceschi C: Hemopoiesis in healthy old people and centenarians: well-maintained responsiveness of CD34+ cells to hemopoietic growth factors and remodeling of cytokine network. J Gerontol A Biol Sci Med Sci 2000;55:B61–B66; commentary B69–B70.
  78. Sharpless NE, Depinho RA: How stem sells age and why this makes us grow old. Nat Rev Mol Cell Biol 2007;8:703–713.
  79. Rosi DJ, Jamieson CH, Weissman IL: Stems cells and the pathways to aging and cancer. Cell 2008;132:681–696.
  80. Atzmon G, Rincon M, Rabizadeh P, Barzilai N: Biological evidence for inheritance of exceptional longevity. Mech Ageing Dev 2005;126:341–345.
  81. Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ, Barzilai N, Cohen P: Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci USA 2008;105:3438–3442.
  82. Bergman A, Atzmon G, Ye K, MacCarthy T, Barzilai N: Buffering mechanisms in aging: a systems approach toward uncovering the genetic component of aging. PLoS Comput Biol 2007;3:e170.

  

Author Contacts

A.Z. Reznick
Department of Anatomy and Cell Biology, Faculty of Medicine
Technion – Israel Institute of Technology
Haifa 31096 (Israel)
Tel. +972 4 829 5388, Fax +972 4 829 5403, E-Mail reznick@tx.technion.ac.il

  

Article Information

Received: July 21, 2008
Accepted: December 22, 2008
Published online: February 7, 2009
Number of Print Pages : 12
Number of Figures : 0, Number of Tables : 0, Number of References : 82

  

Publication Details

Gerontology (International Journal of Experimental, Clinical, Behavioural and Technological Gerontology)

Vol. 55, No. 2, Year 2009 (Cover Date: March 2009)

Journal Editor: Wick G. (Innsbruck)
ISSN: 0304-324X (Print), eISSN: 1423-0003 (Online)

For additional information: http://www.karger.com/GER


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

This short review portrays the evolutionary theories of aging in the light of the existing discoveries from genomic and molecular genetic studies on aging and longevity. At the outset, an historical background for the development of the evolutionary theories of aging is presented through the works of August Weismann (programmed death and the germ plasm theories) including his exceptional theoretical postulation, later experimentally validated by the existence of cell division limits. Afterwards, the theory of mutation accumulation of Peter Medawar and the theory modification by Charlesworth (late-life mortality plateau) are presented as well as the antagonistic pleiotropy hypothesis of George Williams, and the disposable soma theory of Kirkwood and Holliday. These theories are discussed in the light of the different research studies, which include studies on insulin signaling and longevity, the possibility that nuclear factor kappa B may be a major mediator of aging, studies of anti-aging Sirtuins and studies on heat shock proteins and longevity and on gene sets as biomarkers of aging. Finally, the proposals for future research in biogerontology, such as studies on the control of protein synthesis, validation of biomarkers of aging, understanding the biochemistry of longevity and research in the field of gerontologic pathology are presented. Likewise, further attention is suggested regarding the work on telomere shortening, stem cells and studies on understanding the biochemical and molecular basis for longevity in centenarians.

© 2009 S. Karger AG, Basel


  

Author Contacts

A.Z. Reznick
Department of Anatomy and Cell Biology, Faculty of Medicine
Technion – Israel Institute of Technology
Haifa 31096 (Israel)
Tel. +972 4 829 5388, Fax +972 4 829 5403, E-Mail reznick@tx.technion.ac.il

  

Article Information

Received: July 21, 2008
Accepted: December 22, 2008
Published online: February 7, 2009
Number of Print Pages : 12
Number of Figures : 0, Number of Tables : 0, Number of References : 82

  

Publication Details

Gerontology (International Journal of Experimental, Clinical, Behavioural and Technological Gerontology)

Vol. 55, No. 2, Year 2009 (Cover Date: March 2009)

Journal Editor: Wick G. (Innsbruck)
ISSN: 0304-324X (Print), eISSN: 1423-0003 (Online)

For additional information: http://www.karger.com/GER


Article / Publication Details

First-Page Preview
Abstract of Experimental Section

Received: 7/21/2008
Accepted: 12/22/2008
Published online: 2/7/2009
Issue release date: March 2009

Number of Print Pages: 12
Number of Figures: 0
Number of Tables: 0

ISSN: 0304-324X (Print)
eISSN: 1423-0003 (Online)

For additional information: http://www.karger.com/GER


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Weismann A: Essays Upon Heredity. Oxford, Clarendon Press, 1891.
  2. Weismann A: Über die Dauer des Lebens. Fisher, Jena, 1882.
  3. Dyke B, Gage T, Alford P, Swenson B, Williams-Blangero S: Model life table for captive chimpanzees. Am J Primatol 1995;37:25–37.
  4. Hill K, Boesch C, Goodall J, Pusey A, Williams J, Wrangham R: Mortality rates among wild chimpanzees. J Hum Evol 2001;40:437–450.
  5. Austad SN: Retarded senescence in an insular population of opossums (Didelphis virginiana). J Zool 1993;229:695–708.

    External Resources

  6. Weismann A: Über Leben und Tod. Fisher, Jena, 1892.
  7. Hayflick L, Moorhead PS: The serial cultivation of human diploid cell strains. Exp Cell Res 1961;25:585–621.
  8. Hayflick L: The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965;37:614–636.
  9. Kerr JF, Wyllie AH, Currie AR: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972;26:239–257.
  10. Vicencio JM, Galluzzi L, Tajeddine N, Ortiz C, Criollo A, Tasdemir E, Morselli E, Ben Younes A, Maiuri MC, Lavandero S, Kroemer G: Senescence, apoptosis or autophagy? When a damaged cell must decide its path: a mini-review. Gerontology 2008;54:92–99.
  11. Weismann A: Essays Upon Heredity and Kindred Biological Problems. Oxford, Clarendon Press, 1889.
  12. Kirkwood TB: Evolution of ageing. Nature 1977;270:301–304.
  13. Medawar PB: An Unsolved Problem of Biology. London, HK Lewis, 1952.
  14. Charlesworth B: Fisher, Medawar, Hamilton and the evolution of aging. Genetics 2000;156:927–931.
  15. Charlesworth B: Evolution in Age-Structured Populations. Cambridge, Cambridge University Press, 1994.
  16. Gavrilova NS, Gavrilov LA, Evdokushkina GN, Semyonova VG, Gavrilova AL, Evdokushkina NN, Kushnareva YE, Kroutko VN, Andreyev AY: Evolution, mutation, and human longevity: European royal and noble families. Hum Biol 1998;70:799–804.
  17. Strehler BL: Origin and comparison of the effects of time and high energy radiations on living systems. Quart Rev Biol 1959;34:117–142.
  18. Kim SA: Common aging pathways in worms, flies, mice and humans. J Exp Biol 2007;210:1607–1612.
  19. Carey JR, Liedo P, Orozco D, Vaupel JW: Slowing of mortality-rates at older ages in large medfly cohorts. Science 1992;258:457–461.
  20. Curtsinger JW, Fukui HH, Townsend DR, Vaupel JW: Demography of genotypes: failure of the limited life-span paradigm in Drosophila melanogaster. Science 1992;258:461–463.
  21. Charlesworth B: Patterns of age-specific means and genetic variances of mortality rates predicted by the mutation-accumulation theory of ageing. J Theor Biol 2001;210:47–65.
  22. Reynolds RM, Temiyasathit S, Reedy MM, Ruedi EA, Drnevich JM, Leips J, Hughes KA: Age specificity of inbreeding load in Drosophila melanogaster and implications for the evolution of late-life mortality plateaus. Genetics 2007;177:587–595.
  23. Williams GC: Pleiotropy, natural selection, and the evolution of senescence. Evolution 1957;11:398–411.

    External Resources

  24. Zahavi A: Mate selection: a selection for a handicap. J Theor Biol 1975;53:205-214.
  25. Krtolica A, Parrinello S, Lockett S, Desprez PY, Campisi J: Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc Natl Acad Sci USA 2001;98:12072–12077.
  26. Cutler RG, Semsei I: Development, cancer and aging: possible common mechanisms of action and regulation. J Gerontol 1989;44:25–34.
  27. Economos AC, Lints FA: Developmental temperature and life-span in Drosophila-melanogaster. 1. Constant developmental temperature: evidence for physiological adaptation in a wide temperature-range. Gerontology 1986;32:18–27.
  28. Johnson TE, Hutchinson EW: Absence of strong heterosis for life span and other life history traits in Caenorhabditis elegans. Genetics 1993;134:465–474.
  29. Walker DW, McColl G, Jenkins NL, Harris J, Lithgow GJ: Evolution of lifespan in C. elegans. Nature 2000;405:296–297.
  30. Wick G, Berger P, Jansen-Dürr P, Grubeck-Loebenstein B: A Darwinian-evolutionary concept of age-related diseases. Exp Gerontol 2003;38:13–25.
  31. Martin GM: Modalities of gene action predicted by the classical evolutionary biological theory of aging. Ann NY Acad Sci 2007;1100:14–20.
  32. Mannucci PM, Mari D, Merati G, Peyvandi F, Tagliabue L, Sacchi E, Taioli E, Sansoni P, Bertolini S, Franceschi C: Gene polymorphisms predicting high plasma levels of coagulation and fibrinolysis proteins: a study in centenarians. Arterioscler Thromb Vasc Biol 1997;17:755–759.
  33. Le Bourg É: A mini-review of the evolutionary theories of aging: is it the time to accept them? Demogr Res 2001;4:1–28.

    External Resources

  34. Gavrilov LA, Gavrilova NS: Evolutionary theories of aging and longevity. Scientific World Journal 2002;2:339–356.

    External Resources

  35. Kirkwood TB, Holliday R: The evolution of ageing and longevity. Proc R Soc Lond B Biol Sci 1979;205:531–546.
  36. Kirkwood TB, Austad SN: Why do we age? Nature 2000;408:233–238.
  37. Congdon JD, Nagle RD, Kinney OM, van Loben Sels RC, Quinter T, Tinkle DW: Testing hypotheses of aging in long-lived painted turtles (Chrysemys picta). Exp Gerontol 2003;38:765–772.
  38. Hamilton WD: The moulding of senescence by natural selection. J Theor Biol 1966;12:12–45.
  39. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang RA: C. elegans mutant that lives twice as long as wild type. Nature 1993;366:461–464.
  40. Kirkwood TB: Evolution of ageing. Mech Ageing Dev 2002;123:737–745.
  41. Gems D, Partridge L: Insulin/IGF signalling and ageing: seeing the bigger picture. Cur Opin Genet Dev 2001;11:287–292.
  42. Finch CE, Ruvkun G: The genetics of aging. Annu Rev Genomics Hum Genet 2001;2:435–462.
  43. Kenyon C: The plasticity of aging: insights from long-lived mutants. Cell 2005;120:449–460.
  44. Johnson T: Increased life-span of age-1 mutants in Caenorhabditis elegans and lower Gompertz rate of aging. Science 1990;249:908–912.
  45. Hertweck M, Gobel C, Baumeister R: C. elegans SGK-1 is the critical component in the Akt/PKB kinase complex to control stress response and life span. Dev Cell 2004;6:577–588.
  46. Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, Ruvkun G: The Forkhead transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 1997;389:994–999.
  47. Selman C, Lingard S, Choudhury AI, Batterham RL, Claret M, Clements M, Ramadani F, Okkenhaug K, Schuster E, Blanc E, Piper MD, Al-Qassab H, Speakman JR, Carmignac D, Robinson IC, Thornton JM, Gems D, Partridge L, Withers DJ: Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB J 2008;22:807–818.
  48. Adler AS, Sinha S, Kawahara TL, Zhang JY, Segal E, Chang HY: Motif module map reveals enforcement of aging by continual NF-κB activity. Genes Dev 2007;21:3244–3257.
  49. Adler AS, Kawahara TL, Segal E, Chang HY: Reversal of aging by NFκB blockade. Cell Cycle 2008;7:556–559.
  50. Cai D, Frantz JD, Tawa Jr NE, Melendez PA, Oh BC, Lidov HG, Hasselgren PO, Frontera WR, Lee J, Glass DJ, Shoelson SE: IKKβ/NF-κB activation causes severe muscle wasting in mice. Cell 2004;119:285–298.
  51. Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, Wynshaw-Boris A, Poli G, Olefsky J, Karin M: IKK-β links inflammation to obesity-induced insulin resistance. Nat Med 2005;11:191–198.
  52. Chen J, Zhou Y, Mueller-Steiner S, Chen LF, Kwon H, Yi S, Mucke L, Gan L: SIRT1 protects against microglia-dependent amyloid-β toxicity through inhibiting NF-κB signaling. J Biol Chem 2005;280:40364–40374.
  53. Bar-Shai M, Reznick AZ: Peroxynitrite induces an alternative NF-kappaB activation pathway in L8 rat myoblasts. Antioxid Redox Signal 2006;8:639–652.
  54. Bar-Shai M, Carmeli M, Coleman E, Rozen R, Perek N, Fuchs S, Reznick AZ: The effect of hindlimb immobilization on acid phosphatase, metalloproteinases and nuclear factor-kappaB in muscles of young and old rats. Mech Ageing Dev 2005;126:289–297.
  55. Bar-Shai M, Carmeli E, Ljubuncic P, Reznick AZ: Exercise and immobilization in aging animals: the involvement of oxidative stress and NFkB activation. Free Radic Biol Med 2007;44:202–214.
  56. Reed T, Dick DM, Uniacke SK, Foroud T, Nichols WC: Genome-wide scan for a healthy aging phenotype provides support for a locus near D4S1564 promoting healthy aging. J Gerontol A Biol Sci Med Sci 2004;59:227–232.
  57. Sengupta N, Seto E: Regulation of histone deacetylase activities. J Cell Biochem 2004;93:57–67.
  58. Lin SJ, Ford E, Haigis M, Liszt G, Guarente L: Calorie restriction extends yeast life span by lowering the level of NADH. Genes Dev 2004;18:12–16.
  59. Tissenbaum HA, Guarente L: Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 2001;410:227–230.
  60. Rogina B, Helfand SL: Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci USA 2004;101:15998–16003.
  61. Morrow G, Tanguay RM: Heat shock proteins and aging in Drosophila melanogaster. Semin Cell Develop Biol 2003;14:291–299.
  62. Yokoyama K: Extended longevity of Caenorhabditis elegans by knocking in extra copies of hsp70F, a homolog of mot-2 (mortalin)/mthsp70/Grp75. FEBS Lett 2002;516:53–57.
  63. Hsu AL, Murphy CT, Kenyon C: Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 2003;300:1142–1145.
  64. Longo VD: Search for methuselah genes heats up. Sci Aging Knowledge Environ 2004;6:pe6.
  65. Zahn JM, Sonu R, Vogel H, Crane E, Mazan-Mamczarz K, Rabkin R, Davis RW, Becker KG, Owen AB, Kim SK: Transcriptional profiling of aging in human muscle reveals a common aging signature. PLoS Genet 2006;2:e115.
  66. Golden TR, Hinerfeld DA, Melov S: Oxidative stress and aging: beyond correlation. Aging Cell 2002;1:117–123.
  67. Zahn JM, Poosala S, Owen AB, Ingram DK, Lustig A, Carter A, Weeraratna AT, Taub DD, Gorospe M, Mazan-Mamczarz K, Lakatta EG, Boheler KR, Xu X, Mattson MP, Falco G, Ko MSH, Schlessinger D, Firman J, Kummerfeld SK, Wood WH 3rd, Zonderman AB, Kim SK, Becke KG: AGEMAP: A Gene Expression Database for Aging in Mice. PLoS Genet 2007;3:e201.
  68. Simon AF, Shih C, Mack A, Benzer S: Steroid control of longevity in Drosophila melanogaster. Science 2003;299:1407–1410.
  69. Kirkwood TB: Understanding ageing from an evolutionary perspective. J Intern Med 2008;263:117–127.
  70. Lund J, Tedesco P, Duke K, Wang J, Kim SK, Johnson TE: Transcriptional profile of aging in C. elegans. Curr Biol 2002;12:1566–1573.
  71. Partridge L, Gems D: Beyond the evolutionary theory of ageing, from functional genomics to evo-gero. Trends Ecol Evol 2006;21:334–340.
  72. Campisi J: Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 2005;120:513–522.
  73. Driscoll M, Gerstbrein B: Dying for a cause: invertebrate genetics takes on human neurodegeneration. Nat Rev Genet 2003;4:181–194.
  74. Ruvalcaba RH, Churesigaew S, Myhre SA, Kelley VC, Martin GM: Children who age rapidly: progeroid syndromes: case report of a new variant. Clin Pediatr (Phila) 1997;16:248–252.

    External Resources

  75. Martin GM, Oshima J: Lessons from human progeroid syndromes. Nature 2000;408:263–266.
  76. Campisi J: Cancer, aging and cellular senescence. In Vivo 2000;14:183–188.
  77. Bagnara GP, Bonsi L, Strippoli P, Bonifazi F, Tonelli R, D’Addato S, Paganelli R, Scala E, Fagiolo U, Monti D, Cossarizza A, Bonafé M, Franceschi C: Hemopoiesis in healthy old people and centenarians: well-maintained responsiveness of CD34+ cells to hemopoietic growth factors and remodeling of cytokine network. J Gerontol A Biol Sci Med Sci 2000;55:B61–B66; commentary B69–B70.
  78. Sharpless NE, Depinho RA: How stem sells age and why this makes us grow old. Nat Rev Mol Cell Biol 2007;8:703–713.
  79. Rosi DJ, Jamieson CH, Weissman IL: Stems cells and the pathways to aging and cancer. Cell 2008;132:681–696.
  80. Atzmon G, Rincon M, Rabizadeh P, Barzilai N: Biological evidence for inheritance of exceptional longevity. Mech Ageing Dev 2005;126:341–345.
  81. Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ, Barzilai N, Cohen P: Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci USA 2008;105:3438–3442.
  82. Bergman A, Atzmon G, Ye K, MacCarthy T, Barzilai N: Buffering mechanisms in aging: a systems approach toward uncovering the genetic component of aging. PLoS Comput Biol 2007;3:e170.