Age-Linked Non-Transmissible Diseases

  • Bernard Swynghedauw
Part of the Practical Issues in Geriatrics book series (PIG)


Age-linked non-transmissible disease is becoming a new epidemiological category, which is likely to be mostly favored or even caused by the biological (in-) activity of senescent cells and their secretome.


Cancers Diabetes CV diseases Renal failure COPD Neurodegenerative diseases Alzheimer’s Parkinson’s Hypothalamus Atherosclerosis Emphysema 


  1. 1.
    Callahan D, et al. The Quagmire. How American medicine is destroying itself. The New Republic 2011 May 19.Google Scholar
  2. 2.
    Foreman KJ, et al. Forecasting life expectancy years of life lost, and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories. Lancet. 2018;392(10159):2052–90.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the GBDS 2016. Lancet. 2017;390:1211–59.CrossRefGoogle Scholar
  4. 4.
    GBD 2016 DALYS and HALE Collaborators. Global, regional, and national disability-adjusted life-years (DALYS) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: a systematic analysis for the GBDS 2016. Lancet. 2017;390:1260–344.CrossRefGoogle Scholar
  5. 5.
    Belmin J, et al., editors. Gériatrie. Paris: Elsevier/Masson; 2009. p. 835.Google Scholar
  6. 6.
    Naylor RM, et al. Senescent cells : a novel therapeutic target for aging and age-related diseases. Clin Pharmacol Ther. 2013;93:105–16.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Brondello JM, et al. La sénescence cellulaire.Un nouveau mythe de Janus? MédSci. 2012;28:288–94.Google Scholar
  8. 8.
    Rochefort H, et al. Endocrine disruptors (EDs) and hormone-dependent cancers: correlation or causal relationship? C R Biol. 2017;340:439–45.PubMedCrossRefGoogle Scholar
  9. 9.
    Michaloglou C, et al. BRAFE600-associated senescence-like cell cycle like arrest of human naevi. Nature. 2005;436:720–4.PubMedCrossRefGoogle Scholar
  10. 10.
    Jonna S, et al. Geriatric assessment factors are associated with mortality after hospitalization in older adults with cancer. Support Care Cancer. 2016;24:4807–13.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Falandry C, et al. Biology of cancer and aging: a complex association with cellular senescence. J Clin Oncol. 2014;32:2604–10.PubMedCrossRefGoogle Scholar
  12. 12.
    Finkel T, et al. The common biology of cancer and ageing. Nature. 2007;448:767–74.CrossRefGoogle Scholar
  13. 13.
    Aunan JR, et al. The biology of aging and cancer: a brief overview of shared and divergent molecuar hallmarks. Aging Dis. 2017;8:628–42.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Tomasetti C, et al. Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science. 2017;355:1330–4.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Lakatta EG. So! What’s aging? Is cardiovascular aging a disease? J Mol Cell Cardiol. 2015;83:1–13.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Swynghedauw B. Molecular mechanisms of myocardial remodeling. Physiol Rev. 1999;79:215–62.PubMedCrossRefGoogle Scholar
  17. 17.
    Willis MS, et al. Proteotoxicity and cardiac dysfunction- Alzheimer’s disease of the heart? N Engl J Med. 2013;368:454–64.CrossRefGoogle Scholar
  18. 18.
    Floor SL, et al. Hallmarks of cancer: of all cancer cells all the time. Trends Mol Med. 2012;18:509.PubMedCrossRefGoogle Scholar
  19. 19.
    Hanahan D, et al. Hallmarks of cancer: the next generation. Cell. 2011;144:647.CrossRefGoogle Scholar
  20. 20.
    Hanahan D, et al. The hallmarks of cancer. Cell. 2000;100:57–70.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Jesus BB, et al. Telomerase at the intersection of cancer and aging. Trends Genet. 2013;29:513–20.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Stratton MR, et al. The cancer genome. Nature. 2009;458:719–24.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Hou L, et al. Blood telomere length attrition and cancer development in the normative aging study cohort. EBioMedicine. 2015;2:591–6.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Krtolica A, et al. Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. PNAS. 2001;98:12072–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Campisi J, et al. Aging, cellular senescence, and cancer. Annu Rev Physiol. 2013;75:685–705.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Weilner S, et al. Secretion of microvesicular miRNAs in cellular and organismal aging and age-related diseases. Exp Gerontol. 2013;48:626–33.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Camici GG, et al. Molecular mechanism of endothelial and vascular aging: implications for cardiovascular disease. Eur Heart J. 2015;36:3392–403.PubMedCrossRefGoogle Scholar
  28. 28.
    Collado M, et al. Cellular senescence in cancer and aging. Cell. 2007;130:223–33.PubMedCrossRefGoogle Scholar
  29. 29.
    Kennedy AL, et al. Activation of the PIK3CA/AKT pathway suppresses senescence induced by an activated RAS oncogene to promote tumorigenesis. Mol Cell. 2011;42:36–49.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Schultz MB, et al. When stem cells grow old: phenotype and mechanisms of stem cell aging. Development. 2018;143:3–14.CrossRefGoogle Scholar
  31. 31.
    Davalos AR, et al. Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis Rev. 2010;29:273–83.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Jacob F. Evolution and tinkering. Science. 1977;196:1161–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Golde TE, et al. Proteinopathy-induced neuronal senescence: a hypothesis for brain failure in Alzheimer’s and other neurodegenerative diseases. Alzheimer’s Res Therap. 2009;1:5–17.CrossRefGoogle Scholar
  34. 34.
    Weller RO, et al. Cerebrovascular disease is a major factor in the failure of elimination of Abeta from the aging human brain. Ann NY Acad Sci. 2002;977:162–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Jacqmin-Gadda H, et al. 20-year prevalence projections for dementia and impact of preventive policy about risk factors. Eur J Epidemiol. 2013;28:493–502.PubMedCrossRefGoogle Scholar
  36. 36.
    Golde TE, et al. Thinking laterally about neurodegenerative proteinopathies. J Clin Invest. 2013;123:1847–55.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Weinstein G, et al. Risk estimations, risk factors, and genetic variants associated with Alzheimer’s disease in selected publications from the Framingham heart study. J Alzheimers Dis. 2013;33:S439–45.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Glass DJ, et al. Some evolutionary perspectives on Alzheimer’s disease pathogenesis and pathology. AlzheimersDement. 2012;8:343–51.Google Scholar
  39. 39.
    Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 2001;81:741–66.PubMedCrossRefGoogle Scholar
  40. 40.
    Venegas C, et al. Microglia-derived ASC specks cross-seed amyloid-beta in Alzheimer’s disease. Nature. 2017;552:355–61.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Godet O, et al. Association of white-matter lesions with brain atrophy markers: the three-city Dijon MRI study. Cerebrovasc Dis. 2009;28:177–84.CrossRefGoogle Scholar
  42. 42.
    Dubois B, et al. Research criteria fot the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6:734–46.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Hanon O, et al. Plasma amyloid levels within the Alzheimer’s process and correlations with central biomarkers. Alzheimers Dement. 2018;14(7):858–68.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Levy-Noqueira M, et al. Alzheimer’s disease diagnosis relies on a twofold clinical-biological algorithm: three memory clinic case report. J Alzheimers Dis. 2017;60:577–83.CrossRefGoogle Scholar
  45. 45.
    Nakamura A, et al. High performance plasma amyloid-beta biomarkers for Alzheimer disease. Nature. 2018;554:249–54.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Bousiges O, Blanc F. Diagnostic values of cerebro-spinal fluid biomarkers in dementia with lewy bodies. Clin Chim Acta. 2019;490:222–8.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Bussian TJ, et al. Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Nature. 2018;562:578–82.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Scheff SW, et al. Is synaptic loss a unique hallmark of Alzheimer’s diesase? Biochem Pharmacol. 2014;88:517–28.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    de Wilde MC, et al. Meta-analysis of synaptic pathology in Alzheimer’s disease reveals selective molecular vesicular machinery vulnerability. Alzheimers Dement. 2016;12:633–44.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Zhang Y, et al. Hypothalamic stem cells control ageing speed partly through exosomal miRNAs. Nature. 2017;548:52–7.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Fitzpatrick AWP, et al. Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature. 2017;547:185–90.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Alvergne A, et al. Evolutionary thinking in medicine. Berlin: Springer; 2015.Google Scholar
  53. 53.
    Taylor RC, et al. Aging as an event of proteostasis collapse. Cold Spring Harb Perspect Biol. 2011;3:a004440.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Golde TE, et al. Proteinopathy-induced neuronal senescence: a hypothesis for brain failure in Alzheimer’s and other neurodegenerative diseases. Alzheimers Res Ther. 2009;1:5–17.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Bhat R, et al. Astrocyte senescence as a component of Alzheimer’s disease. PLoS ONE. 2012;7:e45069.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Bellingham SA, et al. Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases. Front Physiol. 2012;3:124.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Leidinger P, et al. A blood-based 12-miRNA signature of Alzheimer disease patients. Genome Biol. 2013;14:R78.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Ransohoff RM. How neuro-inflammation contributes to neuro-degeneration. Science. 2016;353:777–84.CrossRefGoogle Scholar
  59. 59.
    Vermeij WP, et al. Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice. Nature. 2016;532:427–31.CrossRefGoogle Scholar
  60. 60.
    Jucker M, Walker LC. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature. 2013;501:45–51.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Itzhaki RF, et al. Microbes and Alzheiner’s disease. J Alzheimers Dis. 2016;51:979–84.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Abbott A. The red-hot debate about transmissible Alzheimer’s. Nature. 2016;531:294–7.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Leon LJ, et al. Staying young at heat: autophagy and adaptation to cardiac aging. J Mol Cell Cardiol. 2016;95:78–85.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Fox M, et al. Hygiene and the world distribution of Alzhzeimer’s disease. Evol Med Public Health. 2013;2013:173–86.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Elbaz A, et al. Professional exposure to pesticides and Parkinson disease. Ann Neurol. 2009;66:494–504.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Marano F, et al. Toxique ? Santé et environnement: de l’alerte la décision. Paris: Buchet-Chastel; 2015.Google Scholar
  67. 67.
    MacDade E, et al. Stop Alzheimer’s before it starts. Nature. 2017;547:153–5.CrossRefGoogle Scholar
  68. 68.
    Bredesen DE. Reversal of cognitive decline: a novel therapeutic program. Aging. 2014;6:707–17.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Aisen PS, et al. What we have learned from Expedition III and EPOCH trials? Perspective of the CTAD task force. J Prev Alzheimers Dis. 2018;5:171–4.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Fuchsberger C, et al. The genetic architecture of type 2 diabetes. Nature. 2016;536:41–7.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Chia CW, et al. Age-related changes in glucose metabolism, hyperglycemia, and cardiovascular risk. Circ Res. 2018;123:886–904.PubMedCrossRefGoogle Scholar
  72. 72.
    Lee PG, et al. The pathophysiology of hyperglycemia in older adults: clinical considerations. Diabetes Care. 2017;40:444–52.PubMedCrossRefGoogle Scholar
  73. 73.
    Poitout V, et al. Minireview: secondary beta-cell failure in type 2 diabetes: a convergence of glucotoxicity and lipotoxicity. Endocrinology. 2002;143:339–42.PubMedCrossRefGoogle Scholar
  74. 74.
    Swynghedauw B, et al. Effects of IV injection of glucose on blood triglycerides in normal and diabetic subjects. Rev Fr Etudes Clin Biol. 1965;10(4):427–30.Google Scholar
  75. 75.
    Einstein FH, et al. Enhanced activation of a “nutrient sensing” pathways with age contributes to insulin-resistance. FASEB J. 2008;22:3450–7.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Dirks AJ, et al. Mitochondrial DNA mutations, energy metabolism and apoptosis in aging muscle. Ageing Res Rev. 2006;5:179–96.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Barzilai N, et al. The critical role of metabolic pathways in aging. Diabetes. 2012;61:1315–22.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Sone H, et al. Pancreatic beat cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice. Diabetologia. 2005;48:58–67.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017;542:177–85.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Childs BG, et al. Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science. 2016;354:472–7.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Bartling B. Cellular senescence in normal and premature lung aging. Z Gerontol Geriatr. 2013;46:613–22.PubMedCrossRefGoogle Scholar
  82. 82.
    Chilosi M, et al. The pathogenesis of COPD and IPF: distinct horns for the same devil? Respir Res. 2012;13:3.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Hashimoto M, et al. Elimination of p19ARF-expressing cells enhances pulmonary function in mice. JCI Insight. 2016;1:e87732.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Schafer MJ, et al. Cellular senescence mediates fibrotic pulmonary disease. Nat Commun. 2017;8:1–11.CrossRefGoogle Scholar
  85. 85.
    Sturmlechner I, et al. Cellular senescence in renal ageing and disease. Nat Rev Nephrol. 2017;13:77–89.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Schmitt R, Melk A. Molecular mechanisms of renal aging. Kidney Int. 2017;92(3):569–79.PubMedCrossRefGoogle Scholar
  87. 87.
    Krizhanovsky V, et al. Senescence of activated stellate cells limits fibrosis. Cell. 2008;134:657–67.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Lakatta EG, et al. Perspectives on mammalian cardiovascular aging: human to molecules. Comp Biochem Physiol A Mol Integr Physiol. 2002;132:699–721.PubMedCrossRefGoogle Scholar
  89. 89.
    Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises. Part I: aging arteries: a “set up” for vascular disease. Circulation. 2003;107:139–46.PubMedCrossRefGoogle Scholar
  90. 90.
    Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises. Part II: the aging heart in health: links to heart disease. Circulation. 2003;107:346–54.PubMedCrossRefGoogle Scholar
  91. 91.
    Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises. Part III: cellular and molecular clues to heart and arterial aging. Circulation. 2003;107:490–7.PubMedCrossRefGoogle Scholar
  92. 92.
    Rozenberg S, et al. Severe impairment of ventricular compliance accounts for advanced age-associated hemodynamic dysfunction in rats. Exp Gerontol. 2006;41:289–95.PubMedCrossRefGoogle Scholar
  93. 93.
    Swynghedauw B, editor. Hypertrophy and heart failure. Paris Londres: INSERM/J. LIBBEY pub; 1990.Google Scholar
  94. 94.
    Swynghedauw B. Les racines dixneuviémistes de la révolution biologique contemporaine. Hist Sci Med. 2006;40:141–50.PubMedGoogle Scholar
  95. 95.
    Levy B, et al. Biology of the arterial wall. Boston: Kluwer Academic Pub; 1999.CrossRefGoogle Scholar
  96. 96.
    Burton DGA, et al. Pathophysiology of vascular calcification: pivotal role of cellular senescence in vascular smooth cells. Exp Gerontol. 2010;45:819–24.PubMedCrossRefGoogle Scholar
  97. 97.
    Ieda M, et al. Cardiac fibroblasts regulate myocardial proliferation through beta 1 integrin signaling. Dev Cell. 2009;16:233–44.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Raggi P, et al. Coronary artery calcium to predict mortality in elderly men and women. J Am Coll Cardiol. 2008;52:17–23.PubMedCrossRefGoogle Scholar
  99. 99.
    Anderson R, et al. Mechanisms driving the ageing heart. Exp Gerontol. 2018;109:5–15.PubMedCrossRefGoogle Scholar
  100. 100.
    Rodeheffer RJ, et al. Exercise cardiac output is maintained with advancing age in healthy human subjects: cardiac dilatation and increased stroke volume compensate for diminished heart rate. Circulation. 1984;69:203–13.PubMedCrossRefGoogle Scholar
  101. 101.
    Assayag P, et al. Effects of low-flow ischemia on myocardial function and calcium-regulating proteins in adult and senescent rat hearts. Cardiovasc Res. 1998;38:169–80.PubMedCrossRefGoogle Scholar
  102. 102.
    Boluyt MO, et al. Echocardiographic assessment of age-associated changes in systolic and diastolic function of the female F344 rat heart. J Appl Physiol. 2004;96:822–8.PubMedCrossRefGoogle Scholar
  103. 103.
    Pacher P, et al. Left ventricular pressure-volume relationship in a rat model of advanced aging-associated heart failure. Am J Phys. 2004;287:H2132–7.Google Scholar
  104. 104.
    Bergmann O, et al. Evidence for cardiomyocyte renewal in adults. Science. 2009;324:98–102.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Corman B, et al. Aminoguanidine prevents age-related arterial stiffening and cardiac hypertrophy. Proc Natl Acad Sci U S A. 1998;95:1301–6.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Gude NA, et al. Cardiac ageing: extrinsic and intrinsic factors in cellular renewal and senescence. Nat Rev Cardiol. 2018;15:523–42.PubMedCrossRefGoogle Scholar
  107. 107.
    Kajstura J, et al. Cardiomyogenesis in the aging and failing human heart. Circulation. 2012;126:1869–81.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Malliaras K, et al. Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart. EMBO Mol Med. 2013;5:191–209.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Senyo SE, et al. Cardiac regeneration based on mechanisms of cardiomyocyte proliferation and differentiation. Stem Cell Res. 2014;13:532–41.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Besse S, et al. Nonsynchronous changes in myocardial collagen mRNA and protein during aging: effect of Doca-salt hypertension. Am J Phys. 1994;267:H2237–44.Google Scholar
  111. 111.
    Besse S, et al. Is the senescent heart overloaded and already failing ?A review. Cardiovasc Drug Ther (Invit Editor). 1994;8:581–7.CrossRefGoogle Scholar
  112. 112.
    Lompré AM, et al. Myosin isoenzyme redistribution in chronic heart overloading. Nature. 1979;282:105–7.PubMedCrossRefGoogle Scholar
  113. 113.
    Benetos A, et al. Short telomeres are associated with increased carotid atherosclerosis in hypertensive subjects. Hypertension. 2004;43:182–5.PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Calado RT, Young NS. Telomere diseases. N Engl J Med. 2009;361:2353–65.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Benetos A, et al. Short leukocyte telomere length precedes clinical expression of atherosclerosis. The blood-and-muscle model. Circ Res. 2018;122:616–23.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Swynghedauw B, et al. Le pourquoi du vieillissement. In: Artigou JY, et al., editors. Traité de cardiologie.SFC. Paris: Elsevier Masson; 2007. p. 1201–3.Google Scholar
  117. 117.
    Swynghedauw B. Phenotypic plasticity of adult myocardium: molecular mechanisms. J Exp Biol. 2009;209(Pt 12):2320–7.Google Scholar
  118. 118.
    Swynghedauw B. Developmental and functional adaptation of contractile proteins in cardiac and skeletal muscle. Physiol Rev. 1986;66:710–71.PubMedCrossRefGoogle Scholar
  119. 119.
    Assayag P, et al. Senescent heart as compared to pressure overload induced hypertrophy. Hypertension. 1997;29:15–21.PubMedCrossRefGoogle Scholar
  120. 120.
    Weber KT. Wound healing in cardiovascular disease. Armonk: Futura Publishing Cy; 1995.Google Scholar
  121. 121.
    Weber KT, et al. Myofibroblast-mediated mechanisms of pathological remodelling of the heart. Nat Rev Cardiol. 2013;10:15–26.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Buckberg GD, et al. Left ventricular form and function.Scientific priorities and strategic planning for development of new views of the disease. Circulation. 2004;110:e333–6.PubMedCrossRefGoogle Scholar
  123. 123.
    Hung C-L, et al. Age- and sex-related influences on left ventricular mechanics in elderly individuals free of prevalent heart failure. The ARIC Study (atherosclerosis risk in communities). Circ Cardiovasc Imaging. 2017;10:e004510.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Torrent-Guasp F, et al. The structure and function of the helical heart and its buttress wrapping. I. The normal macroscopic structure of the heart. Semin Thorac Cardiovasc Surg. 2001;13:301–19.PubMedCrossRefGoogle Scholar
  125. 125.
    McLendon PM, Robbins J. Proteotoxicity and cardiac disfunction. Circ Res. 2015;116:1863–82.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Nakayama H, et al. Macromolecular degradation systems and cardiovascular aging. Circ Res. 2016;118:1577–92.PubMedCrossRefGoogle Scholar
  127. 127.
    Henning RH, et al. Proteostasis in cardiac health and disease. Nat Rev Cardiol. 2017;14:637–53.CrossRefGoogle Scholar
  128. 128.
    Mizushima W, et al. BAG3 plays a central role in proteostasis in the heart. J Clin Invest. 2017;127:2900–3.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Blice-Baum AC, et al. Modest overexpression of FOXO maintains cardiac proteostasis and ameliorate age-associated functional decline. Aging Cell. 2017;16:93–103.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Sanbe A, et al. Desmin-related cardiomyopathy in transgenic mice.: a cardiac amyloidosis. Proc Natl Acad Sci U S A. 2004;101:10132–6.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Logeart D, et al. Evidence of cardiac myolysis in severe nonischemic heart failure and the potential role of increased wall strain. Am Heart J. 2001;141:247–53.PubMedCrossRefPubMedCentralGoogle Scholar
  132. 132.
    Kostin S, et al. Myocytes die by multiple mechanisms in failing human hearts. Circ Res. 2003;92:715–24.PubMedCrossRefPubMedCentralGoogle Scholar
  133. 133.
    Baker DJ, et al. Clearance of p16Ink4a-positive cells delays ageing-associated disorders. Nature. 2011;479:232–6.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Barral JM, et al. Role of the myosin assembly protein UNC-45 as a molecular chaperone for myosin. Science. 2002;295:665–71.CrossRefGoogle Scholar
  135. 135.
    Tanskanen M, et al. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based autopsy study. Ann Med. 2009;40:232–9.CrossRefGoogle Scholar
  136. 136.
    Donato AJ, et al. Mechanisms of dysfunction in the aging vasculature and the role in age-related disease. Circ Res. 2018;123:825–48.PubMedCrossRefPubMedCentralGoogle Scholar
  137. 137.
    Umemura T, et al. Aging and hypertension are independent risk factors for reduced number of circulating endothelial progenitor cells. Am J Hypertens. 2008;21:1203–9.PubMedCrossRefPubMedCentralGoogle Scholar
  138. 138.
    Plouin PF, et al. L’hypertension artérielle du sujet âgé. Bull Acad Natl Méd. 2006;190:793–806.PubMedGoogle Scholar
  139. 139.
    Safar M. Ageing and its effects on the cardiovascular system. Drugs. 1990;39(suppl I):1–8.PubMedCrossRefPubMedCentralGoogle Scholar
  140. 140.
    Minamino T, et al. Vascular senescence and vascular aging. J Mol Cell Cardiol. 2004;36:175–83.PubMedCrossRefPubMedCentralGoogle Scholar
  141. 141.
    Levy B, et al., editors. Role of the micro and macrocirculation in target organ damage in diabetes and hypertension. Hoboken: Wiley; 2009.Google Scholar
  142. 142.
    Scioli MG, et al. Ageing and microvasculature. Vasc Cell. 2014;6:19.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Klotz C, et al. Evidence for new forms of cardiac myosin heavy chains in mechanical heart overloading and in ageing. Eur J Biochem. 1981;115:415–21.PubMedCrossRefPubMedCentralGoogle Scholar
  144. 144.
    Mercadier JJ, et al. Myosin heavy chain and atrial size in patients with various types of mitral valve dysfunction: a quantitative study. J Am Coll Cardiol. 1987;9:1024–30.PubMedCrossRefPubMedCentralGoogle Scholar
  145. 145.
    Swynghedauw B, et al. Species-specificity of the isomyosin shift in cardiac overload. J Appl Cardiol. 1988;3:133–43.Google Scholar
  146. 146.
    Boutouyrie P, et al. Common carotid artery stiffness patterns of left ventricular hypertrophy in hypertensive patients. Hypertension. 1995;25:651–9.PubMedCrossRefPubMedCentralGoogle Scholar
  147. 147.
    Staessen JA, et al. Essential hypertension. Lancet. 2003;361:1629–41.PubMedCrossRefPubMedCentralGoogle Scholar
  148. 148.
    Minamino T, et al. Endothelial senescence in human atherosclerosis: role oftelomer in endothelial dysfunction. Circulation. 2002;105:1541–4.PubMedCrossRefPubMedCentralGoogle Scholar
  149. 149.
    Gardner SE, et al. Senescent vascular smooth muscle cells drive inflammation through an interleukin-1alpha dependent senescent-associated secretory phenotype. Arterioscler Thromb Vasc Biol. 2015;35:1963–074.PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Boddaert J, et al. Ch. 20 L’athérosclérose et ses interactions avec le vieillissement. In: Assayag P, et al., editors. Traité de médecine CV du sujet âge. Paris: Flammarion; 2007.Google Scholar
  151. 151.
    Rodier F, Campisi J. Four faces of cellular senescence. J Cell Biol. 2011;192:547–56.PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Upadhya B, et al. Evolution of a geriatric syndrome: pathophysiology and treatment of heart failure with preserved ejection function. J Am Ger Soc. 2017;65:2431–40.CrossRefGoogle Scholar
  153. 153.
    De Keulenaer GW, et al. Are systolic and diastolic heart failure overlapping or distinct phenotypes within the heart failure spectrum? Circulation. 2011;123:1996–2005.PubMedCrossRefPubMedCentralGoogle Scholar
  154. 154.
    Lewis GA, et al. Biological phenotypes of heart failure with preserved ejection fraction. J Am Coll Cardiol. 2017;70:2186–200.PubMedCrossRefPubMedCentralGoogle Scholar
  155. 155.
    Loffredo FS, et al. Heart failure with preserved ejection fraction: molecular pathways of the aged myocardium. Circ Res. 2014;115:97–107.PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    Owan TE, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355:251–9.PubMedCrossRefPubMedCentralGoogle Scholar
  157. 157.
    Shah AM, et al. Contemporary assessment of left ventricular diastolic function in older adults. The atherosclerosis risk in communities study. Circulation. 2017;135:426–39.PubMedCrossRefPubMedCentralGoogle Scholar
  158. 158.
    Shah SJ, et al. Phenomapping for novel classification of heart failure with preserved ejection function. Circulation. 2015;131:269–79.PubMedCrossRefPubMedCentralGoogle Scholar
  159. 159.
    Sharma K, et al. Heart failure with preserved ejection function: mechanisms, clinical features, and therapies. Circ Res. 2014;115:79–96.PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Boon RA, et al. MicroRNA-34a regulates cardiac ageing and function. Nature. 2013;495:107–10.PubMedCrossRefGoogle Scholar
  161. 161.
    Borlaug BA, et al. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J. 2011;32:670–9.PubMedCrossRefGoogle Scholar
  162. 162.
    Kaku K, et al. Age-related normal range of left ventricular strain and torsion using three-dimensional speckle-tracking echocardioagraphy. J Am Soc Echocardiogr. 2014;27:55–64.PubMedCrossRefGoogle Scholar
  163. 163.
    Lin YK, et al. Aging modulates the substrate and triggers remodeling in atrial fibrillation. Circ J. 2018;82(5):1237–44.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Bernard Swynghedauw
    • 1
  1. 1.French Institute of Health and Medical ResearchParisFrance

Personalised recommendations