FOXO Gene Transcription Factors
- the basis for Extreme Levels of Aging
FOXO is a family of powerful anti-aging transcription factors. Transcription factors are proteins which activate specific genes. When the genes are activated, they produce proteins which play a role in the body. FOXO transcription factors play a uniquerole, whereby they target genes which promote cellular and tissue renewal and rejuvenation. Furthermore, they also have a role of tumor suppression, which suppresses the formation of cancer. An important role of FOXO is the maintenance of stem cells. Stem cells in adults are a continued source of regenerated cells and replacement tissue.(1)
• Extreme aging in humans (living beyond 100 years)
is associated with genetic variations which increase levels of FOXO. These genes affect the
insulin-FOXO signaling pathway.(2, 6)
• Immortality is not only possible but has been solved.
Aging is common in all animals, but one multi-cellular animal seems to resist aging. This animal is
the hydra, which has the ability to continuously renew components of its body.Essentially, the hydra
does not age! Therefore, immortality is possible in the hydra. Studies indicate that continuous
regeneration and renewal of body parts are achieved by stem cells.Furthermore, FOXO plays the
critical role in ensuring an indefinite, self-renewing supply of stem cells. An endless supply of stem
cells ensures that the hydra will never age. The hydra has very high levels of FOXO gene expression.
FOXO also maintains the stem cells in humans and other animals.(3)
• FOXO levels can be elevated by supplementation.
In animal longevity studies, FOXO (or daf-16 equivalent) increased gene activity occurred by adding
tetrahydrocurcumin(4) and purple anthocyanins(5) (including C3G) to the diet. Tetrahydrocurcumin
and purple anthocyanin supplementation resulted in significant increases in lifespan. Studies also
indicate significant longevity gene effects of tyrosol (Cañuelo A, 2012) also attributed to FOXO/daf16
insulin-signaling modulation. SIRT1activation can also indirectly raise FOXO levels (via pterostilbene or resveratrol).
1. Calnan DR, et al. Methylation by Set9 modulates FoxO3 stability and transcriptional activity. Aging (Albany NY). 2012 Jul 21.
2. Brunet A. Aging and the control of the insulin-FOXO signaling pathway. Med Sci (Paris). 2012 Mar;28(3):316-20.
3. Boehm AM, et al. FoxO is a critical regulator of stem cell maintenance in immortal Hydra. Proc Natl Acad Sci USA 2012 Nov 12.
4. Xiang L, et al. Tetrahydrocurcumin extends life span and inhibits the oxidative stress response by regulating the FOXO forkhead transcription factor. Aging (Albany NY). 2011 November; 3(11): 1098–1109.
5. Chen W, et al. Anthocyanin-rich purple wheat prolongs the life span of Caenorhabditis elegans probably by activating the DAF-16/FOXO transcription factor. J Agric Food Chem. 2013 Mar 27;61(12):3047-53.
6. Morris BJ, et al. FOXO3: A major Gene for Human Longevity - A Mini-Review. Gerontology 2015 March.