Written by: Jamie October 4, 2019
What is FOXO3?
Forkhead box O3 protein (FOXO3) helps regulate genes involved in DNA repair, tumor suppression, immune function, and resistance to oxidative stress, among other things. Some variants of FOXO3 are associated with a longer and healthier life. [1,2]
What does FOXO3 have to do with longevity?
Oxidative stress occurs when there is an imbalance between free radical and antioxidant activity. Normally, free radicals help fight off pathogens and infection. When there are not enough antioxidants to balance the free radicals, damage to your DNA and fatty tissue occurs. This can lead to diseases such as diabetes, high blood pressure, heart disease, and cancer. The FOXO3 gene helps protect against oxidative stress reducing the risk of some diseases that can decrease longevity. 
How do genes play a role?
Everyone has a FOXO3A gene, but it is the variation in single sections of that gene (single nucleotide polymorphisms) which are important. Three variants associated with longevity have been studied:
- If you have two copies of the G variant of the genotype rs2802292, it is associated with a 1.5-2.7% more likely chance of living to be 100.  This variant is the most studied.
- The A variant of the genotype rs2802288 is associated with an increased lifespan 
- The T variant of the genotype rs9400239 is associated with an increased lifespan 
What can you do about it?
- Review your genetic predispositions.
- If you have done genetic testing, you can search your raw data for the genotypes listed above.
- Get your genes tested with Secret Sequence if you need testing!
- If you have the FOXO3 gene variants known to prolong life, you want to make sure the gene is “on”. Things like calorie restriction, intermittent fasting, heat stress like in sauna use, and EGCG which is found in green tea, can help do this. [7,8,9]
- If you don’t have the gene variants, it is even more important to make good lifestyle choices like eating a diet rich in vegetables, exercising, and getting enough sleep to give you a better chance at a healthier life.
- Discussing you results with your doctor can help you make educated decisions on any dietary changes you wish to make in your life regardless if you have the variants or not.
What Comes Next?
New research on the topic is being done all the time. You have the ability to learn more about your DNA, so why wouldn’t you want to learn what changes can make you a healthier you?
One more important reminder: you need to be in control of who you share that information with. Secret Sequence will never sell your data—we never even ask for your name! Safely learn more about yourself and your health: order our reports today to learn more about your body’s individual responses!
*Disclaimer: All information, content, and material of this website is for information purposes only and are not intended to serve as a substitute for the consultation, diagnosis, and/or medical treatment of a qualified physician or healthcare provider.
 Willcox, B. J., Donlon, T. A., He, Q., Chen, R., Grove, J. S., Yano, K., … Curb, J. D. (2008). FOXO3A genotype is strongly associated with human longevity. Proceedings of the National Academy of Sciences of the United States of America, 105(37), 13987–13992. doi:10.1073/pnas.0801030105
 Flachsbart, F., Caliebe, A., Kleindorp, R., Blanché, H., von Eller-Eberstein, H., Nikolaus, S., … Nebel, A. (2009). Association of FOXO3A variation with human longevity confirmed in German centenarians. Proceedings of the National Academy of Sciences of the United States of America, 106(8), 2700–2705. doi:10.1073/pnas.0809594106
 Akasaki, Y., Alvarez-Garcia, O., Saito, M., Caramés, B., Iwamoto, Y., & Lotz, M. K. (2014). FoxO transcription factors support oxidative stress resistance in human chondrocytes. Arthritis & rheumatology (Hoboken, N.J.), 66(12), 3349–3358. doi:10.1002/art.38868
 Kim, M.-S., Pak, Y. K., Jang, P.-G., Namkoong, C., Choi, Y.-S., Won, J.-C., … Lee, K.-U. (2006). Role of hypothalamic Foxo1 in the regulation of food intake and energy homeostasis. Nature Neuroscience, 9(7), 901–906. doi:10.1038/nn1731
 Kim, D. H., Park, M. H., Lee, E. K., Choi, Y. J., Chung, K. W., Moon, K. M., … Chung, H. Y. (2014). The roles of FoxOs in modulation of aging by calorie restriction. Biogerontology, 16(1), 1–14. doi:10.1007/s10522-014-9519-y
 Belguise, K., Guo, S., & Sonenshein, G. E. (2007). Activation of FOXO3a by the Green Tea Polyphenol Epigallocatechin-3-Gallate Induces Estrogen Receptor Expression Reversing Invasive Phenotype of Breast Cancer Cells. Cancer Research, 67(12), 5763–5770. doi:10.1158/0008-5472.can-06-4327