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Published on: December 9, 2022
Effects of FOXO genotypes on longevity: a biodemographic analysis
Yi Zeng1, Lingguo Cheng, Huashuai Chen
1Center for the Study of Aging and Human Development, Medical School of Duke University, Durham, NC 27710, USA. zengyi68@gmail.com
Summary
FOXO gene variants influence longevity, with FOXO3A positively impacting survival and FOXO1A having a negative effect. Interactions between these genes and exercise also affect lifespan in older adults.
Area of Science:
- Genetics
- Longevity research
- Biodemography
Background:
- The FOXO gene family plays a crucial role in cellular stress response and aging.
- Understanding the genetic underpinnings of extreme longevity is vital for public health.
- Centenarians represent a unique population for studying factors contributing to a long lifespan.
Purpose of the Study:
- To investigate the biodemographic effects of FOXO genotypes on longevity.
- To analyze the independent and joint effects of FOXO1A and FOXO3A gene variants on long-term survival.
- To explore gene-gene (G×G) and gene-environment (G×E) interactions related to longevity.
Main Methods:
- Analysis of genetic data from 760 Han Chinese centenarians and 1060 middle-aged controls.
- Longitudinal cohort analysis over ten years, focusing on individuals aged 92-110.
- Statistical modeling to assess independent and joint effects of FOXO1A and FOXO3A genotypes, including interactions with single-nucleotide polymorphisms and regular exercise.
Main Results:
- Significant gender differences observed in the effects of FOXO genotypes on longevity.
- FOXO3A demonstrated a positive effect on survival, while FOXO1A showed a negative effect; these effects largely compensated when both genotypes were present, with FOXO3A having a stronger influence.
- G×G interactions between specific FOXO1A and FOXO3A variants decreased survival likelihood (32%-36%), while G×E interactions between FOXO1A and regular exercise increased survival likelihood (31%-32%).
Conclusions:
- FOXO3A is a significant positive predictor of survival at advanced ages.
- Interactions between FOXO genes and lifestyle factors like exercise can modulate longevity.
- Genetic variations in FOXO1A and FOXO3A, along with their interactions, contribute to understanding the complex mechanisms of human aging and survival.
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