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What Is FOXO And How Does It Relate to Aging And Disease?


FOXO, short for Forkhead Box O, is a key regulator of pathways of aging. From controlling autophagy, a cellular recycling process, to managing the production of antioxidants and inflammation, FOXO is a key component in our understanding of aging.

FOXO: A Key to Understanding Aging

Aging is a natural process that affects us all. Understanding the mechanisms behind aging can help scientists develop treatments to slow or reverse the effects of aging. One molecule that has been found to play a key role in aging is FOXO (Forkhead box protein O). This transcription factor is involved in many cellular processes and is essential for regulating longevity in both invertebrates and mammals. (Learn about many other longevity molecules and how FOXO relates in this article.

FOXO is a family of proteins that are widely distributed in different tissues throughout the body. It regulates genes involved in cell cycle control, apoptosis, metabolism, stress resistance, and lifespan extension. Its activity is regulated by multiple signaling pathways, including growth factors, oxidative stress, nutrient sensing, and metabolic pathways.

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FOXO’s Influence on Aging and Lifespan

Studies have shown that FOXO plays an important role in the aging process. In mice, a deficiency of FOXO decreased insulin sensitivity and increased mortality (Garcia Whitlock et al., 2021). In humans, individuals with mutations in FOXO had shorter lifespans (Willcox et al., 2008). Furthermore, FOXO has been shown to be involved in age-related diseases such as diabetes (O’Neill et al., 2019), cancer (Jiramongkol & Lam, 2020), and neurodegenerative diseases (Oli et al., 2021).

The exact mechanism by which FOXO influences aging remains unknown. However, it is known that FOXO affects many cellular processes related to aging. For example, FOXO regulates autophagy, which helps to clear out damaged cells and prevents them from accumulating and causing age-related diseases (Cheng et al., 2019). It also modulates the production of antioxidant enzymes, which protect against oxidative damage caused by free radicals (Barnes, 2020). Additionally, FOXO may play a role in reducing inflammation, which is one of the major causes of aging (Murtaza et al., 2017).

The Link to Prolonged Lifespan

In summary, FOXO is a critical molecule in the aging process. Its activity is regulated by various pathways and its deficiency can lead to shorter lifespans and age-related diseases. Understanding how FOXO functions may provide insight into how to slow down the aging process and prevent age-related diseases.

Did you know that NOVOS Core contains ingredients that are shown to support FOXO? Pterostilbene, fisetin, and ginger each have evidence pointing to possible improvements to FOXO levels.


  1. Barnes P. J. (2020). Oxidative stress-based therapeutics in COPD. Redox biology, 33, 101544.
  2. Cheng Z. (2019). The FoxO-Autophagy Axis in Health and Disease. Trends in endocrinology and metabolism: TEM, 30(9), 658–671.
  3. Garcia Whitlock, A. E., Sostre-Colón, J., Gavin, M., Martin, N. D., Baur, J. A., Sims, C. A., & Titchenell, P. M. (2021). Loss of FOXO transcription factors in the liver mitigates stress-induced hyperglycemia. Molecular metabolism, 51, 101246.
  4. Jiramongkol, Y., & Lam, E. W. (2020). FOXO transcription factor family in cancer and metastasis. Cancer metastasis reviews, 39(3), 681–709.
  5. Murtaza, G., Khan, A. K., Rashid, R., Muneer, S., Hasan, S. M. F., & Chen, J. (2017). FOXO Transcriptional Factors and Long-Term Living. Oxidative medicine and cellular longevity, 2017, 3494289.
  6. Oli, V., Gupta, R., & Kumar, P. (2021). FOXO and related transcription factors binding elements in the regulation of neurodegenerative disorders. Journal of chemical neuroanatomy, 116, 102012.
  7. O’Neill, B. T., Bhardwaj, G., Penniman, C. M., Krumpoch, M. T., Suarez Beltran, P. A., Klaus, K., Poro, K., Li, M., Pan, H., Dreyfuss, J. M., Nair, K. S., & Kahn, C. R. (2019). FoxO Transcription Factors Are Critical Regulators of Diabetes-Related Muscle Atrophy. Diabetes, 68(3), 556–570.
  8. Willcox, B. J., Donlon, T. A., He, Q., Chen, R., Grove, J. S., Yano, K., Masaki, K. H., Willcox, D. C., Rodriguez, B., & 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.

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