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

Research output: Contribution to journalArticle

147 Citations (Scopus)

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.

Original languageEnglish (US)
JournalPLoS Biology
Volume4
Issue number4
DOIs
StatePublished - Apr 2006

Fingerprint

lipoproteins
Lipoproteins
Genotype
homozygosity
Genes
genotype
Insulin Resistance
insulin resistance
Homozygote
Insulin
Polymorphism
Cardiovascular Diseases
hypertension
cardiovascular diseases
Alleles
Apolipoproteins C
Hypertension
genes
genetic polymorphism
Apolipoprotein A-I

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

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.

In: PLoS Biology, Vol. 4, No. 4, 04.2006.

Research output: Contribution to journalArticle

@article{120f472dd35d475292173d987aa4b5ff,
title = "Lipoprotein genotype and conserved pathway for exceptional longevity in humans.",
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.",
author = "Gil Atzmon and Marielisa Rincon and Schechter, {Clyde B.} and Shuldiner, {Alan R.} and Lipton, {Richard B.} and Aviv Bergman and Nir Barzilai",
year = "2006",
month = "4",
doi = "10.1371/journal.pbio.0040113",
language = "English (US)",
volume = "4",
journal = "PLoS Biology",
issn = "1544-9173",
publisher = "Public Library of Science",
number = "4",

}

TY - JOUR

T1 - Lipoprotein genotype and conserved pathway for exceptional longevity in humans.

AU - Atzmon, Gil

AU - Rincon, Marielisa

AU - Schechter, Clyde B.

AU - Shuldiner, Alan R.

AU - Lipton, Richard B.

AU - Bergman, Aviv

AU - Barzilai, Nir

PY - 2006/4

Y1 - 2006/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33750872801&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750872801&partnerID=8YFLogxK

U2 - 10.1371/journal.pbio.0040113

DO - 10.1371/journal.pbio.0040113

M3 - Article

C2 - 16602826

AN - SCOPUS:33646251112

VL - 4

JO - PLoS Biology

JF - PLoS Biology

SN - 1544-9173

IS - 4

ER -