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A Suppressor Screen for the Characterization of Genetic Links Regulating Chronological Lifespan in Saccharomyces cerevisiae
Published on: September 17, 2020
Lipoprotein genotype and conserved pathway for exceptional longevity in humans
Gil Atzmon1, Marielisa Rincon, Clyde B Schechter
1Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Plos Biology
|April 11, 2006
Summary
A specific gene variant, APOC3 -641C homozygosity, is linked to longevity. This genetic trait promotes a healthier lipoprotein profile, cardiovascular health, and insulin sensitivity, contributing to a longer lifespan.
Area of Science:
- Genetics and Aging Research
- Cardiovascular Disease Epidemiology
- Metabolic Syndrome Studies
Background:
- Exceptional human longevity is familial, suggesting genetic influences on favorable phenotypes.
- Nutrient and lipoprotein metabolism genes impact longevity in animal models.
- Candidate genes related to cardiovascular disease (CVD) are crucial for understanding human lifespan.
Purpose of the Study:
- To investigate the association between genetic polymorphisms and exceptional longevity in Ashkenazi Jewish centenarians.
- To examine the relationship between candidate gene polymorphisms and cardiovascular risk factors, including lipoprotein levels, hypertension, and insulin resistance.
- To identify genetic factors contributing to increased lifespan and reduced CVD risk.
Main Methods:
- Genotyping of 66 polymorphisms in 36 candidate genes in centenarians, their offspring, and controls.
- Association analysis of genotypes with serum lipoprotein levels, particle sizes, and apolipoprotein levels.
- Evaluation of associations with hypertension, insulin resistance, and mortality outcomes.
- Prospective survival analysis in a cohort with the identified genetic variant.
Main Results:
- Homozygosity for the APOC3 promoter -641C allele (rs2542052) was significantly more prevalent in centenarians (25%) and offspring (20%) than controls (10%).
- This genotype correlated with lower serum APOC3 levels, favorable lipoprotein profiles, reduced hypertension, and enhanced insulin sensitivity.
- The APOC3 -641C homozygote demonstrated a significant survival advantage in prospective analysis.
Conclusions:
- Homozygosity for the APOC3 -641C allele is a significant genetic factor associated with longevity.
- This genetic variant confers benefits including improved lipoprotein metabolism, cardiovascular health, and insulin sensitivity.
- Modulation of lipoprotein metabolism may represent a conserved pathway influencing lifespan across species.
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