FOXO3 longevity variant
DEFOXO3-Langlebigkeitsvariante
FOXO3 is a gene for a transcription factor. It sits at a crossroads of longevity pathways. It integrates signals from the insulin/IGF-1 and AMPK pathways. With those, it controls stress resistance, autophagy, cell death, and antioxidant genes. A cluster of variants in its introns, most prominently rs2802292, was first linked to exceptional longevity. That was in Hawaiian men of Japanese ancestry (Willcox et al., 2008). It has since been replicated across many independent cohorts, in Europe, East Asia, and Ashkenazi populations. The protective version is thought to keep FOXO3 in the nucleus longer. That boosts its downstream targets, like GADD45, SOD2, and autophagy regulators. Because FOXO3 sits where several conserved longevity pathways converge, it remains one of the most consistently replicated genetic links to how long you live.
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Sources
- Willcox BJ, Donlon TA, He Q, et al.. (2008). FOXO3A genotype is strongly associated with human longevity. *Proceedings of the National Academy of Sciences*doi:10.1073/pnas.0801030105
- Orea-Soufi A, Paik J, Bragança J, Donlon TA, Willcox BJ, Link W. (2022). FOXO transcription factors as therapeutic targets in human diseases. *Trends in Pharmacological Sciences*doi:10.1016/j.tips.2022.09.010
- Flachsbart F, Caliebe A, Kleindorp R, Blanché H, von Eller-Eberstein H, Nikolaus S, Schreiber S, Nebel A. (2009). Association of FOXO3A variation with human longevity confirmed in German centenarians. *Proceedings of the National Academy of Sciences*doi:10.1073/pnas.0809594106