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FOXO3 longevity genotype mitigates the increased mortality risk in men with a cardiometabolic disease

Randi Chen1, Brian J Morris1,2,3, Timothy A Donlon1,4,5

  • 1Department of Research, Kuakini Medical Center, Honolulu, HI 96817, USA.

Aging
|December 1, 2020
PubMed

Insights

The longevity gene FOXO3 extends lifespan in individuals with cardiometabolic diseases (CMD). This FOXO3 longevity genotype offers protection against cardiometabolic stress, improving survival in at-risk populations.

Area of Science:

  • Genetics
  • Longevity research
  • Cardiovascular health

Background:

  • The gene FOXO3 is recognized as a significant longevity gene.
  • Previous research has not clarified if FOXO3 variants protect against mortality in all individuals or only those with age-related diseases.

Purpose of the Study:

  • To investigate whether longevity-associated FOXO3 genetic variants are associated with mortality protection in individuals with and without cardiometabolic disease (CMD).

Main Methods:

  • Examined longevity-associated FOXO3 single nucleotide polymorphisms in a haplotype block.
  • Analyzed mortality data in 3,584 elderly American men of Japanese ancestry (2,512 with CMD, 1,072 without).
  • Assessed baseline CMD conditions including diabetes, hypertension, and coronary heart disease (CHD).

Main Results:

  • In individuals with CMD, longevity-associated FOXO3 alleles were linked to significantly longer lifespan (hazard ratio 0.81).
  • Men with CMD and the FOXO3 longevity genotype exhibited survival rates similar to men without CMD.
  • No association between FOXO3 longevity alleles and lifespan was observed in men without CMD.

Conclusions:

  • The FOXO3 longevity genotype appears to increase lifespan specifically in individuals at risk due to cardiometabolic stress.
  • This study provides new insights into the role of FOXO3 in longevity, particularly its protective effects against mortality in the context of aging-related diseases.

Keywords:
FOXO3geneticslongevitymortalityresilience

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