Genetic and phenotypic factors associated with exceptional longevity

16 May 2005

A study of long-lived Ashkenazi Jewish men and women to investigate biological and genetic factors associated with unusual longevity has reported an association with significantly increased sizes of high and low-density lipoproteins [Barzilai, N. et al. (2003) JAMA 290, 2030-2040]. Previous studies have suggested that there is a genetic basis for exceptional longevity. Long-lived individuals (aged between 95 and 107, with a mean age of 98.2 years) and their offspring were found to have significantly larger high and low-density lipoprotein (HDL and LDL) particle sizes than controls, independent of total blood lipoprotein levels. This phenotype was associated with a lower prevalence of hypertension, CVD and metabolic syndrome in offspring compared with controls (matched for age and body mass index), and with an increased frequency of homozygosity for an allelic variant of the cholesteryl ester transfer protein (CETP) gene. Cholesteryl ester transfer protein is involved in regulation of levels and sizes of HDLs and LDLs. Whether the size of lipoproteins has a direct functional influence on survival has not been determined, but the authors propose that lipoprotein particle size may well have a causal effect, since smaller lipoproteins are associated with the development of CVD. They cite the reduced incidence of CVD in offspring (which was found to correlate with larger lipoprotein size) as further support for a link between lipoprotein sizes and age-related disease.

Comment: Identifying biological markers and genes that contribute to a prolonged lifespan is relevant to the study of ageing and mechanisms that protect people from common diseases. It is worth noting that the offspring of long-lived individuals will not necessarily prove to be long-lived themselves, but their inclusion in the study is important because it allowed comparison with an age and BMI matched control group (not feasible for the extremely old study participants).

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