Abstract
Epidemiological studies have shown that age is the chief risk factor for atherosclerotic cardiovascular diseases, but the molecular mechanisms that underlie the increase in risk conferred by aging remain unclear. Evidence suggests that the cardiovascular repair system is impaired with advancing age, thereby inducing age-associated cardiovascular dysfunction. Such impairment could be attributable to senescence of cardiovascular tissues at the cellular level as a result of telomere shortening, DNA damage, and genomic instability. In fact, the replicative ability of cardiovascular cells, particularly stem cells and/or progenitor cells, has been shown to decline with age. Recently, considerable progress has been made in understanding the pathogenesis of human progeroid syndromes that feature cardiovascular aging. Most of the genes responsible have a role in DNA metabolism, and mutated forms of these genes result in alterations of the response to DNA damage and in decreased cell proliferation, which might be common features of a phenotype of aging. Here we review the cardiovascular research on cellular senescence, stem cell aging, and progeroid syndromes and discuss the potential role of cellular senescence in the mechanisms underlying both normal aging and premature aging syndromes.
Key Points
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Cellular senescence probably contributes to the pathogenesis of cardiovascular disease
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Telomere integrity is impaired with advancing age, which leads to vascular dysfunction
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The number and function of cardiovascular stem cells and/or progenitor cells shows a progressive decline with age
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Telomere attrition, DNA damage, and genomic instability might be common features of both normal aging and progeroid syndromes
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Acknowledgements
T Minamino was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by grants from the Suzuken Memorial Foundation, the Japan Diabetes Foundation, the Ichiro Kanehara Foundation, the Tokyo Biochemical Research Foundation, and the Takeda Science Foundation. I Komuro was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture and by Health and Labor Sciences Research grants.
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Minamino, T., Komuro, I. Vascular aging: insights from studies on cellular senescence, stem cell aging, and progeroid syndromes. Nat Rev Cardiol 5, 637–648 (2008). https://doi.org/10.1038/ncpcardio1324
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DOI: https://doi.org/10.1038/ncpcardio1324
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