It is known that the activation of FOXO transcription factors promote extreme longevity, which has been demonstrated in research animals as well as in animals such as the multi-cell animal hydra. In human longevity, those with gene variants which activate higher levels of FOXO are also the longest lived with least amounts of illness and disease.
Despite years of research declaring that antioxidants, such as vitamins C and E, promoted longevity, none have been shown to activate the longevity factors FOXO or Nrf2. Rather, potent longevity factor activation has been shown by many plant based flavonoids. (1) Flavonoids are yellow in nature, and the word is derived from the latin flavus, which means yellow.
Other FOXO Activators and Longevity Pathways:
(1) Pallauf K, et al. Flavonoids as Putative Inducers of the Transcription Factors Nrf2, FoxO, and PPARγ. Oxid Med Cell Longev. 2017
(2) Paredes-Gonzales X, et al. Induction of NRF2-mediated gene expression by dietary phytochemical flavones apigenin and luteolin. Biopharm Drug Dispos. 2015 Oct
(3) Zhang L, et al. Significant longevity-extending effects of EGCG on Caenorhabditis elegans under stress Free Radic Biol Med.
(4) Wai-Jiao Cai, et al. Icariin and its Derivative Icariside II Extend Healthspan via Insulin/IGF-1 Pathway in C. elegans. PLoS One, 2011
(5) Zhang SQ, et al. Icariin, a natural flavonol glycoside, extends healthspan in mice. Exp Gerontol. 2015 Sep;
(6) Jung HY, et al. Myricetin improves endurance capacity and mitochondrial density by activating SIRT1 and PGC-1α. Sci Rep. 2017 Jul 24
(7) Tang BL. Sirt1 and the Mitochondria. Mol Cells. 2016 Feb
(8) 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 Nov
(9) Shen LR, et al. Curcumin-supplemented diets increase superoxide dismutase activity and mean lifespan in Drosophila. Age (Dordr) 2013 Aug;
Aging is suppressed through the ability of the body to regenerate more youthful cells and tissues. Extreme longevity is closely coupled to the ability of the body to replace aging cells, which lead to disease and aging, with youthful healthy cells. The capacity to regenerate cells depends on the ability of the body to maintain a healthy functioning pool of stem cells. Stem cells are the precursor cells which generate new replacement cells. For example, neural stem cells (NSC) can rejuvenate the brain by creating new brain cells.
However, aging stem cells progressively lose the ability to generate replacement cells. More precisely, aging stem cells lose the ability to segregate damaged molecules during cellular replication, thereby diminishing the ability of stem cells to proliferate into new replacement cells. Sulforaphane has been shown to partially reverse detrimental cellular changes in stem cells, which may be able to restore stem cell function and cellular rejuvenation.
In addition to extreme longevity, healthy stem cells may also support stem cell therapy, which depends on the proliferation ability of stem cells to heal damaged tissue.
(1) Mendelsohn AR, et al. Aging Stem Cells Lose the Capability to Distribute Damaged Proteins Asymmetrically. Rejuvenation Res. 2015 Dec