X-Message-Number: 27942
Date: Tue, 16 May 2006 18:12:02 -0400
From: Keith Henson <>
Subject: Lipoprotein Genotype and Conserved Pathway for Exceptional

Lipoprotein Genotype and Conserved Pathway for Exceptional Longevity in Humans

Gil Atzmon, Marielisa Rincon, Clyde B. Schechter, Alan R. Shuldiner, 
Richard B. Lipton, Aviv Bergman, Nir Barzilai

Alteration of single genes involved in nutrient and lipoprotein metabolism 
increases longevity in several animal models. Because exceptional longevity 
in humans is familial, it is likely that polymorphisms in genes favorably 
influence certain phenotypes and increase the likelihood of exceptional 
longevity. A group of Ashkenazi Jewish centenarians (n = 213), their 
offspring (n = 216), and an age-matched Ashkenazi control group (n = 258) 
were genotyped for 66 polymorphisms in 36 candidate genes related to 
cardiovascular disease (CVD). These genes were tested for association with 
serum lipoprotein levels and particle sizes, apolipoprotein A1, B, and C-3 
levels and with outcomes of hypertension, insulin resistance, and 
mortality. The prevalence of homozygosity for the ?641C allele in the APOC3 
promoter (rs2542052) was higher in centenarians (25%) and their offspring 
(20%) than in controls (10%) (p = 0.0001 and p = 0.001, respectively). This 
genotype was associated with significantly lower serum levels of APOC3 and 
a favorable pattern of lipoprotein levels and sizes. We found a lower 
prevalence of hypertension and greater insulin sensitivity in the ?641C 
homozygotes, suggesting a protective effect against CVD and the metabolic 
syndrome. Finally, in a prospectively studied cohort, a significant 
survival advantage was demonstrated in those with the favorable ?641C 
homozygote (p < 0.0001). Homozygosity for the APOC3 ?641C allele is 
associated with a favorable lipoprotein profile, cardiovascular health, 
insulin sensitivity, and longevity. Because modulation of lipoproteins is 
also seen in genetically altered longevity models, it may be a common 
pathway influencing lifespan from nematodes to humans.

Full Text at PLoS (Free)


Keith Henson

PS.  Two speakers and at least 37 Alcor members at the Singularity conference.

Independently, nobody recognizes me in an Elvis wig.

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