Lipoproteins, Vascular-Related Genetic Factors, and Human Longevity

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Abstract
The relationships among lipoprotein metabolism, genetic vascular factors, vascular disease, and Alzheimer's disease suggest that the examination of centenarian populations in relation to certain genes or lipoprotein metabolism provide insights into human longevity. The findings on the higher frequency of the apolipoprotein E ɛ4 allele in middle-aged subjects than in centenarians were substantially confirmed. On the contrary, recent findings did not confirm previous data on increased prevalence of the high-risk angiotensin I converting enzyme D allele in French centenarians. The variability in the strength of association between angiotensin I converting enzyme polymorphism and longevity could be related to regional differences in angiotensin I converting enzyme D allele frequency in Europe recently showed, as also recently reported for apolipoprotein Eɛ2 and ɛ4 allele in centenarians. Indeed some studies of lipoprotein profiles in centenarians have also had contradictory outcomes, with evidence of lower serum levels of high-density lipoprotein cholesterol, with higher high-density lipoprotein 2 cholesterol subfraction, larger high-density lipoprotein and low-density lipoprotein particle sizes, and higher lipoprotein(a) concentration in centenarians, which is apparently disadvantageous for human longevity. Elevated lipoprotein(a) serum levels, increasing the risk for cerebrovascular disease, may play a role in determining clinical Alzheimer's disease, but lipoprotein(a) elevation in centenarians, in the absence of other coronary artery disease risk factors, appears as a positive survival factor. In different populations, there are significant trends in the reduction of serum apolipoprotein E levels from apolipoprotein E ɛ2- to ɛ4-carriers and significant differences in serum apolipoprotein E levels with respect to age in ɛ4-carriers but only after adjustment for high-density lipoprotein cholesterol. While further studies are needed to confirm the possible role of apolipoprotein E concentration as putative longevity factor this paper provides an overview of many of the investigated vascular factors with respect to longevity.