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Mécanismes et pathologies du vieillissement

Mechanisms and aging related diseases

  • Article de Synthèse / Review Article
  • Published:
Journal Africain du Cancer / African Journal of Cancer

Résumé

Le vieillissement est une perte progressive et inéluctable des capacités fonctionnelles de l’organisme. Des caractéristiques socio-économiques, des facteurs génétiques et le genre influent sur ce processus et en déterminent la complexité. Les mécanismes moléculaires et cellulaires, qui fondent la physiologie du vieillissement et de la longévité, commencent à être mieux élucidés. Souvent ambivalents, ils sont aussi impliqués dans la survenue de nombreuses pathologies liées à l’âge. Certains d’entre-eux (les principaux) sont décrits dans cet article (restriction calorique, séquences télomériques, klotho, Apolipoprotéine E, voie de signalisation mTOR, axe IGF-1/PI3 kinase/insuline, sirtuines, autophagie, radicaux libres, etc.). Une meilleure compréhension de ces mécanismes suscite beaucoup d’espoirs en termes de prévention et de perspectives thérapeutiques. Néanmoins, des dérives éthiques possibles sont redoutées. Le vieillissement est, ainsi, un enjeu sociétal et de santé publique aussi bien dans les pays développés que dans les pays en développement. Le problème de sa prise en charge se posera avec acuité devant l’augmentation de l’espérance de vie et du nombre de personnes âgées dans le monde.

Abstract

Aging is known as a process leading to a progressive and relentless decline of functional capacities. Social, economic, gender and genetic factors are key modulators of its complexity. A better understanding of cellular and molecular mechanisms that underlie aging and life span physiology is slowly but surely occurring. Here, we give a comprehensive synthesis of the main biological mechanisms controlling aging and aging related diseases (caloric restriction, telomeric sequences, Klotho, Apolipoproteine E, mTOR pathway, IGF-1/PI3 kinase/insulin axis, sirtuins, autophagy, free radicals...). Promising hopes in terms of aging prevention and therapeutic perspectives are made in the near future. Nevertheless, general public fear ethical excesses. At all events, aging is becoming a social and public health stake in developed and developing countries. The elderly care management will be a huge issue regarding the enhancement of life span and the growing number of seniors worldwide.

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Références

  1. Newman A, Newman C, Jane A (2012) The epidemiology of aging. Springer, 2012

  2. Martin GM (2011) The biology of aging: 1985–2010 and beyond. FASEB 25:3756–3762

    Article  CAS  Google Scholar 

  3. http://genomics.senescence.info/species/ (dernier accès le 18 mars 2013)

  4. Allard M, Lebre V, Robine JM, Calment J (1998) Jeanne Calment: from Van Gogh’s time to ours: 122 extraordinary years. New York: W.H. Freeman, 1998

    Google Scholar 

  5. Austad SN (2006) Why women live longer than men: sex differences in longevity. Gend Med 3:79–92

    Article  PubMed  Google Scholar 

  6. Guérin S (2011) La nouvelle société des seniors, Michalon, 2011, Paris

    Google Scholar 

  7. http://www.who.int/features/factfiles/ageing/fr/index.html (dernier accès le 18 mars 2013)

  8. http://www.who.int/features/factfiles/ageing/ageing_facts/fr/index.html (dernier accès le 18 mars 2013)

  9. http://www.who.int/features/factfiles/ageing/ageing_facts/fr/index4.html (dernier accès le 18 mars 2013)

  10. http://www.who.int/features/factfiles/ageing/ageing_facts/fr/index2.html (dernier accès le 18 mars 2013)

  11. Aboderin I (2012) Global poverty, inequalities and ageing in Sub-Saharan Africa: a focus for policy and scholarship. J Pop Ageing 5:87–90

    Article  Google Scholar 

  12. WHO (2012) Une bonne santé pour mieux vieillir. Geneva, WHO, 2012

    Google Scholar 

  13. Herrmann M (2012) Population aging and economic development: Anxieties and policy responses. J Pop Ageing 5:23–46

    Article  Google Scholar 

  14. de Magalhaes JP, Wuttke D, Wood SH, et al (2012) Genomeenvironment interactions that modulate aging: powerful targets for drug discovery. Pharmacol Rev 64:88–101

    Article  PubMed  Google Scholar 

  15. Austad SN (2004) Is aging programed? Aging Cell 3:249–251

    Article  PubMed  CAS  Google Scholar 

  16. Revollo JR, Li X (2013) The ways and means that fine tune Sirt1 activity. Trends Biochem Sci 38:160–167

    Article  PubMed  CAS  Google Scholar 

  17. Haigis MC, Guarente L (2006) Mammalian sirtuins-emerging roles in physiology, aging, and calorie restriction. Genes Dev 20:2913–2921

    Article  PubMed  CAS  Google Scholar 

  18. Hutchison CJ (2011) The role of DNA damage in laminopathy progeroid syndromes. Biochem Soc Trans 39:1715–1718

    Article  PubMed  CAS  Google Scholar 

  19. Varela I, Pereira S, Ugalde AP, et al (2008) Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. Nature Medicine 14:767–772

    Article  PubMed  CAS  Google Scholar 

  20. Faragher RG, Kill IR, Hunter JA, et al (1993) The gene responsible for Werner syndrome may be a cell division bcountingQ gene. PNAS 90:12030–12034

    Article  PubMed  CAS  Google Scholar 

  21. Gire V (2005) La sénescence. Une barrière télomérique à l’immortalité ou une réponse cellulaire aux stress physiologiques ? Médecine/Sciences 21:491–497

    Article  Google Scholar 

  22. Mikhelson VM, Gamaley IA (2012) Telomere shortening is a sole mechanism of aging in mammals. Curr Aging Sci 5:203–208

    Article  PubMed  Google Scholar 

  23. Gomez DE, Armando RG, Farina HG, et al (2012) Telomere structure and telomerase in health and disease (review). Int J Oncol 41:1561–1569

    PubMed  CAS  Google Scholar 

  24. Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25:585–621

    Article  PubMed  CAS  Google Scholar 

  25. Olovnikov AM (1973) A theory of marginotomy: the incomplete copying of template margin in enzymatic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol 41:181–190

    Article  PubMed  CAS  Google Scholar 

  26. Sanders [REMOVED HYPERLINK FIELD] JL, Newman AB (2013) Telomere length in epidemiology: a biomarker of aging, age-related disease, both, or neither? Epidemiol Rev 35:112–131

    Article  Google Scholar 

  27. Sanz A, Stefanatos RK (2008) The mitochondrial free radical theory of aging: a critical view. Curr Aging Sci 1:10–21

    Article  PubMed  CAS  Google Scholar 

  28. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontology 11:298–300

    Article  CAS  Google Scholar 

  29. Gomez-Cabrera MC, Sanchis-Gomar F, et al (2012) Mitochondria as sources and targets of damage in cellular aging. Clin Chem Lab Med 50:1287–1295

    Article  PubMed  CAS  Google Scholar 

  30. Barouki R (2006) Stress oxydant et vieillissement. Médecine/Sciences 22:266–272

    Article  Google Scholar 

  31. Legallet JY, Ardaillou R (2009) Biologie du vieillissement. Bull Acad Natle Méd, Tome 193, No 2, p. 365–404

    Google Scholar 

  32. Every AE, Russu IM (2013) Opening dynamics of 8-oxoguanine in DNA. J Mol Recognit 26:175–180

    Article  PubMed  CAS  Google Scholar 

  33. Baraibar MA, Friguet B (2012) Changes of the proteasomal system during the aging process. Prog Mol Biol Transl Sci 109: 249–275

    Article  PubMed  CAS  Google Scholar 

  34. Rubinsztein DC, Marino G, Kroemer G (2011) Autophagy and aging. Cell 146:682–695

    Article  PubMed  CAS  Google Scholar 

  35. Brieger K, Schiavone S, Miller FJ Jr, Krause KH (2012) Reactive oxygen species: from health to disease. Swiss Med Wkly 142:w13659

    PubMed  CAS  Google Scholar 

  36. Vellai T, Takács-Vellai K, Sass M, Klionsky DJ (2009) The regulation of aging: does autophagy underlie longevity? Trends Cell Biol 19:487–494

    Article  PubMed  CAS  Google Scholar 

  37. Song E, Jaishankar GB, Saleh H, et al (2011) Chronic granulomatous disease: a review of the infectious and inflammatory complications. Clin Mol Allergy 9:10

    Article  PubMed  CAS  Google Scholar 

  38. Kappeler L, Magalhaes Filho C, Le Bouc Y, Holzenberger M (2006) Durée de vie, génétique et axe somatotrope. Médecine/Ssciences 22:259–265

    Article  Google Scholar 

  39. Berryman DE, Christiansen JS, Johannsson G, et al (2008) Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models. Growth Horm IGF Res 18:455–471

    Article  PubMed  CAS  Google Scholar 

  40. Froesch ER, Schmid C, Schwander J, Zapf J (1985) Actions of insulin like growth factors. Annu Rev Physiol 47:443–67

    Article  PubMed  CAS  Google Scholar 

  41. Trojan J, Cloix JF, Ardourel M, et al (2007) IGF-I biology and targeting in malignant glioma. Neuroscience 145:795–811

    Article  PubMed  CAS  Google Scholar 

  42. Le Roith D (2003) The insulin-like growth factor system. Exp Diabesity Res 4:205–212

    Article  PubMed  Google Scholar 

  43. Boccitto M, Lamitina T, Kalb RG (2012) Daf-2 signaling modifies mutant SOD1 toxicity in C. elegans. PLoS One 7:e33494

    Article  CAS  Google Scholar 

  44. Honda Y, Tanaka M, Honda S (2008) Modulation of longevity and diapause by redox regulation mechanisms under the insulinlike signaling control in Caenorhabditis elegans. Exp Gerontol 43:520–529

    Article  PubMed  CAS  Google Scholar 

  45. Broughton S, Alic N, Slack C, et al (2008) Reduction of DILP2 in Drosophila triages a metabolic phenotype from lifespan revealing redundancy and compensation among DILPs. PLoS One. 3:e3721

    Article  PubMed  Google Scholar 

  46. Tazearslan Miook C, Cho1, Suh Y (2012) Discovery of functional gene variants associated with human longevity: opportunities and challenges. J Gerontol A Biol Sci Med Sci 67A:376–383

    Article  Google Scholar 

  47. Obrepalska-Steplowska A, Kedzia A, Trojan J, Gozdzicka-Jozefiak A (2003) Analysis of coding and promoter sequences of the IGF-I gene in children with growth disorders presenting with normal level of growth hormone. J Pediatr Endocrinol Metab 16:1267–1275

    PubMed  CAS  Google Scholar 

  48. Harrela M, Koistinen H, Kaprio J, et al (1996) Genetic and environmental components of interindividual variation in circulating levels of IGF-I, IGF-II, IGFBP-1, and IGFBP-3. J Clin Invest 98:2612–2615

    Article  PubMed  CAS  Google Scholar 

  49. Puche JE, Castilla-Cortázar I (2012) Human conditions of insulin-like growth factor-I (IGF-I) deficiency. J Transl Med 10:224

    Article  PubMed  CAS  Google Scholar 

  50. Ly A, Duc HT, Kalamarides M, et al (2001) Human glioma cells transformed by IGF-I triple helix technology show immune and apoptotic characteristics determining cell selection for gene therapy of glioblastoma. Mol Pathol 54:230–239

    Article  PubMed  CAS  Google Scholar 

  51. Trojan J, Pan YX, Wei MX, Ly A, et al (2012) Methodology for Anti-Gene Anti-IGF-I Therapy of Malignant Tumours. Chemother Res Pract. 2012:721873

    Google Scholar 

  52. Baulieu EE (1995) Studies on dehydroepiandrosterone (DHEA) and its sulphate during aging. C R Acad Sci III 318:7–11

    PubMed  CAS  Google Scholar 

  53. Martin A, David V, Quarles LD (2012) Regulation and function of the FGF23/klotho endocrine pathways. Physiol Rev 92:131–155

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  55. Kuro-o M (2009) Klotho and aging. Biochim Biophys Acta 1790:1049–1058

    Article  PubMed  CAS  Google Scholar 

  56. Kuro-o M (2012) Klotho in health and disease. Curr Opin Nephrol Hypertens 21:362–368

    Article  PubMed  CAS  Google Scholar 

  57. Wolff S, Ma H, Burch D, et al (2006) SMK-1, an Essential Regulator of DAF-16-Mediated Longevity. Cell 124:1039–1053

    Article  PubMed  CAS  Google Scholar 

  58. Panowski SH, Wolff S, Aguilaniu H, et al (2007) PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans. Nature 447:550–555

    Article  CAS  Google Scholar 

  59. Andrysik Z, Bernstein WZ, Deng L, et al (2010) The novel mouse Polo-like kinase 5 responds to DNA damage and localizes in the nucleolus. Nucleic Acids Res 38: 2931–2943

    Article  PubMed  CAS  Google Scholar 

  60. Morris BJ (2013) Seven sirtuins for seven deadly diseases of aging. Free Radic Biol Med 56:133–171

    Article  PubMed  CAS  Google Scholar 

  61. Ghosh S, Liu B, Zhou Z (2013) Resveratrol activates SIRT1 in a Lamin A-dependent manner. Cell Cycle 12:872–876

    Article  PubMed  CAS  Google Scholar 

  62. Tiraby C, Langin D (2005) PGC-1α, un co-activateur transcriptionnel impliqué dans le métabolisme. Médecine/Sciences 21:49–54

    Article  Google Scholar 

  63. Canto C, Auwerx J (2009) PGC-1a, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Current Opinion in Lipidology 20:98–105

    Article  PubMed  CAS  Google Scholar 

  64. Milne JC, Lambert PD, Schenk S, et al (2007) Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 450:712–715

    Article  PubMed  CAS  Google Scholar 

  65. Walford RL, Mock D, et al (2002) Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. J Gerontol A Biol Sci Med Sci 57:B211–B224

    Article  PubMed  Google Scholar 

  66. U.S. National Institute on Aging. National Institutes of Health (2002) Panel on the characterization of participants in the studies of exceptional survival in humans. www.nia.nih.gov/ResearchInformation/ConferencesAndMeetings/NIAPanel.html (dernier accès le 18 mars 2013)

    Google Scholar 

  67. http://www.okicent.org/study.html (dernier accès le 18 mars 2013)

  68. Chan YC, Suzuki M, Yamamoto S (1997) Dietary, anthropometric, hematological and biochemical assessment of the nutritional status of centenarians and elderly people in Okinawa, Japan. J Am Coll Nutr 16:229–235

    PubMed  CAS  Google Scholar 

  69. Takata H, Suzuki M, Ishii T, Sekiguchi S, Iri H (2006) Influence of major histocompatibility complex region genes on human longevity among Okinawan-Japanese centenarians and nonagenarians. Lancet 2:824–826

    Google Scholar 

  70. Willcox BJ, Willcox DC, He Q et al (2006) Siblings of Okinawan (2006) centenarians exhibit lifelong mortality advantages. J Gerontol A Biol Sci Med Sci. 61:345–354

    Article  PubMed  Google Scholar 

  71. McKay GJ, Silvestri G, Chakravarthy U, et al (2011) Variations in apolipoprotein e frequency with age in a pooled analysis of a large group of older people. [REMOVED HYPERLINK FIELD] Am J Epidemiol 173:1357–1364

    Article  Google Scholar 

  72. Bonomini F, Filippini F, Hayek T, et al (2010) Apolipoprotein E and its role in aging and survival. Exp Gerontol 45:149–157

    Article  PubMed  CAS  Google Scholar 

  73. Koffie RM, Hashimoto T, Tai HC, et al (2012) Apolipoprotein E4 effects in Alzheimer’s disease are mediated by synaptotoxic oligomeric amyloid-β. Brain 135(Pt 7):2155–2168

    Article  PubMed  Google Scholar 

  74. Siest G, Bertrand P, Herbeth B, et al (2000) Apolipoprotein E polymorphisms and concentration in chronic diseases and drug responses. Clin Chem Lab Med 38:841–852

    PubMed  CAS  Google Scholar 

  75. Kuhlmann I, Minihane AM, Huebbe P, et al (2010) Apolipoprotein E genotype and hepatitis C, HIV and herpes simplex disease risk: a literature review. Lipids in Health and Disease 9:1–14

    Article  Google Scholar 

  76. Edrey YH, Hanes M, Pinto M, et al (2011) Successful aging and sustained good health in the naked mole rat: a long-lived mammalian model for biogerontology and biomedical research. ILAR J 52:41–53

    Article  PubMed  CAS  Google Scholar 

  77. Gorbunova V, Hine C, Tian X, et al (2012) Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism. Acad Sci USA 109:19392–19396

    Article  CAS  Google Scholar 

  78. Harrison DE, Strong R, Sharp ZD, et al (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392–395

    PubMed  CAS  Google Scholar 

  79. Johnson SC, Rabinovitch PS, Kaeberlein M (2013) mTOR is a key modulator of ageing and age-related disease. Nature 493: 338–345

    Article  PubMed  CAS  Google Scholar 

  80. Vignot S, Faivre S, Aguirre D, Raymond E (2005) mTORtargeted therapy of cancer with rapamycin derivatives. Ann Oncol 16:525–537

    Article  PubMed  CAS  Google Scholar 

  81. Yu K, Shi C, Toral-Barza L (2010) Beyond rapalog therapy: preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2. Cancer Res 70:621–631

    Article  PubMed  CAS  Google Scholar 

  82. Holliday R (2009) The extreme arrogance of anti-aging medicine. Biogerontology 10: 223–228

    Article  PubMed  Google Scholar 

  83. Partridge B, Lucke J, Bartlett H (2009) Ethical, social, and personal implications of extended human lifespan identified by members of the public. Rejuvenation Res 12:351–357

    Article  PubMed  Google Scholar 

  84. Sebastiani P, Solovieff N, Dewan AT, et al (2012) Genetic signatures of exceptional longevity in humans. PLoS One 7:e29848

    Article  PubMed  CAS  Google Scholar 

  85. Fonds des Nations Unies pour la population (2011) État de la population mondiale 2011 rapport ISBN 978-0-89714-991-4, New York, UNFPA http://foweb.unfpa.org/SWP2011/reports/FR-SWOP2011.pdf (dernier accès le 18 mars 2013)

    Google Scholar 

  86. Dancey J (2010) mTOR signaling and drug development in cancer Nature Reviews Clinical Oncology 7:209–219

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Afrocancer, BP 60751, F-75827, Paris cedex 17, France

    A. Ly

  2. Inserm U602, hôpital Paul-Brousse, Université Paris XI, Villejuif, France

    A. Ly & J. Trojan

  3. Laboratory of Cell Engineering, Cardiology Institute, Moscow University, Cherepkowskaya Street, Moscow, 12 1552, Russia

    A. Shevelev

  4. INSERM U930, hôpital Bretonneau, Université de Tours, boulevard Tonnelle, F-37044, Tours, France

    C. Andres

  5. Department of General Medical Sciences, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH, 44106, USA

    X. Y. Pan

  6. Faculty of Medecine, El Bosque University, Bogota, Colombia

    J. Trojan

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  1. A. Ly
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  2. A. Shevelev
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  3. C. Andres
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  4. X. Y. Pan
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  5. J. Trojan
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Correspondence to A. Ly.

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Ly, A., Shevelev, A., Andres, C. et al. Mécanismes et pathologies du vieillissement. J Afr Cancer 5, 103–113 (2013). https://doi.org/10.1007/s12558-013-0270-4

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  • DOI: https://doi.org/10.1007/s12558-013-0270-4

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