A change in the lipoprotein profile is a metabolic hallmark of aging and has been the target for modern medical
developments. Although pharmaceutical interventions aimed at lipid lowering substantially decrease the risk of cardiovascular
disease, they have much less impact on mortality and longevity. Moreover, they have not affected death from other
age-related diseases. In this review we focus on high density lipoprotein (HDL) cholesterol, the levels of which are either
elevated or do not decrease as would be expected with aging in centenarians, and which are associated with lower prevalence
of numerous age-related diseases; thereby, suggesting a potential HDL-mediated mechanism for extended survival.
We also provide an update on the progress of identifying longevity-mediating lipid genes, describe approaches to discover
longevity genes, and discuss possible limitations. Implicating lipid genes in exceptional longevity may lead to drug therapies
that prevent several age-related diseases, with such efforts already on the way.
Keywords: Aging, APOC3, CETP, genetics, HDL, longevity.
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