Lipoprotein genotype and conserved pathway for exceptional longevity in humans |
| |
| Authors: | Atzmon Gil Rincon Marielisa Schechter Clyde B Shuldiner Alan R Lipton Richard B Bergman Aviv Barzilai Nir |
| |
| Affiliation: | 1Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York, United States of America;2Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York, United States of America;3Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, United States of America;4Department of Family and Social Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America;5Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, United States of America;6Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, United States of America;7Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, United States of America;8University of Maryland School of Medicine, and the Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, Maryland, United States of America;Buck InstituteUnited States of America |
| |
| Abstract: | 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. |
| |
| Keywords: | |
| 本文献已被 PubMed 等数据库收录！ |
| 点击此处可从《PLoS biology》浏览原始摘要信息 |
|
点击此处可从《PLoS biology》下载免费的PDF全文 |
|
