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FOXO3

Forkhead box O3

Gene Number: 2309

Location: 6q21

Key Functions: Transcription factor activity, regulation of oxidative stress response, modulation of apoptosis, promotion of autophagy, lifespan regulation


FOXO3 encodes Forkhead box O3, a member of the FOXO subfamily of transcription factors that act downstream of the insulin/IGF-1 signaling pathway.


FOXO3 regulates the expression of genes involved in:

  • Cellular stress resistance

  • Apoptosis

  • Metabolism

  • DNA repair


FOXO3 plays a pivotal role in longevity and healthy aging, with genetic variants repeatedly associated with exceptional lifespan in human populations. In addition to aging, FOXO3 activity influences immune regulation, cancer suppression, cardiovascular health, and neuroprotection.

SNP ID
Your Genotype
Alternative Alleles
Interpretation
rs9400239
No matching variant or no valid DNA data
T
No interpretation available
rs2802292
No matching variant or no valid DNA data
G
No interpretation available
rs9400239

  • TT – Longevity-associated genotype; carriers show increased odds of reaching advanced age and healthier stress-response regulation (R).

  • CT – Heterozygous; partial longevity benefit, moderate protection compared to C/C (R).

  • CC – Common genotype; not associated with enhanced lifespan in current studies (R).

Functional effect: The T allele has been linked to exceptional longevity in several cohorts, often in strong linkage with other FOXO3 SNPs (rs2802292, rs2764264). It is thought to promote better cellular stress resistance and metabolic regulation.


rs2802292

  • TT – Reference genotype; less likely to reach extreme old age compared to carriers of the G allele (R).

  • TG – Heterozygous; moderate longevity benefit with one copy of the protective allele (R).

  • GG – Strongly longevity-associated genotype; up to ~2.7× higher odds of living to 100; improved insulin sensitivity and stress resilience (R).

Functional effect: The G allele of rs2802292 is the most robust FOXO3 longevity variant replicated across multiple populations (Japanese, German, Italian centenarians, etc.). It enhances FOXO3 expression in skeletal muscle and liver, boosting oxidative stress defense, autophagy, and metabolic homeostasis. The T allele is more common globally and represents the baseline lifespan trajectory.


Learn more about what you can do to mitigate risks, and other factors involved by becoming a member of GenesUnveiled today!

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