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Lipoprotein Genotype and Conserved Pathway for Exceptional Longevity in Humans

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 lon...

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Autores principales: Atzmon, Gil, Rincon, Marielisa, Schechter, Clyde B, Shuldiner, Alan R, Lipton, Richard B, Bergman, Aviv, Barzilai, Nir
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1413567/
https://www.ncbi.nlm.nih.gov/pubmed/16602826
http://dx.doi.org/10.1371/journal.pbio.0040113
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author Atzmon, Gil
Rincon, Marielisa
Schechter, Clyde B
Shuldiner, Alan R
Lipton, Richard B
Bergman, Aviv
Barzilai, Nir
author_facet Atzmon, Gil
Rincon, Marielisa
Schechter, Clyde B
Shuldiner, Alan R
Lipton, Richard B
Bergman, Aviv
Barzilai, Nir
author_sort Atzmon, Gil
collection PubMed
description 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.
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spelling pubmed-14135672006-04-04 Lipoprotein Genotype and Conserved Pathway for Exceptional Longevity in Humans Atzmon, Gil Rincon, Marielisa Schechter, Clyde B Shuldiner, Alan R Lipton, Richard B Bergman, Aviv Barzilai, Nir PLoS Biol Research Article 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. Public Library of Science 2006-04 2006-04-04 /pmc/articles/PMC1413567/ /pubmed/16602826 http://dx.doi.org/10.1371/journal.pbio.0040113 Text en Copyright: © 2006 Atzmon et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Atzmon, Gil
Rincon, Marielisa
Schechter, Clyde B
Shuldiner, Alan R
Lipton, Richard B
Bergman, Aviv
Barzilai, Nir
Lipoprotein Genotype and Conserved Pathway for Exceptional Longevity in Humans
title Lipoprotein Genotype and Conserved Pathway for Exceptional Longevity in Humans
title_full Lipoprotein Genotype and Conserved Pathway for Exceptional Longevity in Humans
title_fullStr Lipoprotein Genotype and Conserved Pathway for Exceptional Longevity in Humans
title_full_unstemmed Lipoprotein Genotype and Conserved Pathway for Exceptional Longevity in Humans
title_short Lipoprotein Genotype and Conserved Pathway for Exceptional Longevity in Humans
title_sort lipoprotein genotype and conserved pathway for exceptional longevity in humans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1413567/
https://www.ncbi.nlm.nih.gov/pubmed/16602826
http://dx.doi.org/10.1371/journal.pbio.0040113
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