Dietary Supplements May Increase Longevity by Up-regulation of Daf-16/FoxO Gene
Scripps Center for Integrative Medicine
Deborah H. Lin MD, Thomas S.-H. Chiou PhD, Susanna Cunningham-Rundles PhD
Gene modification of daf-16 (the equivalent of mammalian FoxOs) in nematode C. elegans has been shown to double the expected lifespan. Mammals have four isoforms of the FoxO transcription factor family, FoxO1, FoxO3, FoxO4 and FoxO6. Research data from nested, case-control Hawaii life span study provided support for a genetic basis in the aging process, mainly a role of FoxO3A in longevity. This observation has been confirmed in other populations as well, including Japanese, German, American, Italian, and Chinese. It is now known that insulin and growth factor inhibit FoxO factors, while stress stimuli such as DNA damage, nutrient deprivation, cytokines and hypoxia up-regulate FoxO factors. FoxO-dependent transcription plays an important role in glucose metabolism, angiogenesis, detoxification of reactive oxygen species (ROS), repair of damaged DNA, apoptosis, stem cell maintenance, stress resistance, as well as immune, muscular and neuronal functions. Even though aging is a fundamental process with great innate diversity, we now know that aging, like many other biological process, is subject to regulation by pathways that have been conserved during evolution[4,5]. Recent advances in genetic and biochemical studies have made elucidation of these complex biological pathways and processes possible.