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
The FOXO3 gene, also called FOXO3A, helps regulate how cells respond to stress and changes in nutrient availability. It produces a transcription factor—a protein that controls the activity of other genes—involved in cell maintenance and metabolism [R].
FOXO3 is studied for its connection to human longevity. Researchers have found that certain variants, including rs9400239, occur more frequently in people who reach advanced ages. A Danish study comparing 1,089 very old adults with 736 middle-aged adults supported an association between this marker and longevity [R].
SNP ID | Your Genotype | Alt Allele | Interpretation |
|---|---|---|---|
rs9400239 | Analyze your DNA to see your genotype | T | Analyze your DNA to see a personalized result. |
rs9400239 — a longevity-associated FOXO3 variant
TT – Two longevity-associated alleles: You carry two copies of the T allele linked to increased odds of reaching advanced age in multiple populations (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). This does not imply impaired FOXO3 function or a shortened lifespan by itself.
These interpretations describe a population association rather than a guaranteed benefit for an individual (R).
What might this variant change?
A 2023 study identified a short form of FOXO3, called FOXO3A-Short, that is mainly expressed in skeletal muscle. In a Danish twin cohort, T-allele carriers cleared glucose from the blood more quickly during an insulin-infusion test. Experiments in human muscle cells also found allele-dependent differences in how this short form regulates glucose use (R).
Does this predict a longer life?
No specific number of extra years can be assigned from this result. Reaching advanced age and surviving longer once already very old are also different outcomes: one Danish study supported the first association but found no statistically significant FOXO3 SNP associations with subsequent survival after correcting for multiple testing (R).
For a related gene involved in lipid transport and age-related disease research, explore our APOE gene guide. You can also read how we build DNA reports for more about interpreting genetic associations.
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