Over the past 150 years, there has been a significant increase in life expectancy. However, this also means that most people today experience numerous age-related ailments for longer periods of time. As a result, one of the main goals of current aging research is to prevent age-related functional decline and increase healthspan, the number of years that active older people can live without experiencing illness or impairment. Geroprotectors, or drugs that target aging-related processes, are becoming more widely acknowledged as a technique to prolong life expectancy in older people. The FOXO3 gene has been identified as a geroprotective gene that is closely linked to aging and lifespan.
Human longevity, lowered disease risks, and even self-reported health have all been associated with FOXO3 genetic variations. Therefore, one of the most direct candidate approaches to prolonging health-span in aging individuals is the identification of FOXO3-activating chemicals. Dr. McIntyre and a team of scientists from the USA and the Netherlands reviewed many substances that either activate FOXO3 or affect lifespan or health in a FOXO3-dependent manner, in a recent scientific paper. Th various substances were categorized as either pharmaceuticals (including PI3K/AKT inhibitors and AMPK activators, antidepressants and antipsychotics, muscle relaxants, and HDAC inhibitors) or nutraceuticals (including extracts, polyphenols, terpenoids, and other purified natural compounds), including primary and secondary metabolites involved in cell growth and sustenance. The substances described in the study can serve as a foundation and resource for more studies and development, with the ultimate objective of fostering a long and healthy life span.
McIntyre RL, Liu YJ, Hu M, Morris BJ, Willcox BJ, Donlon TA, Houtkooper RH, Janssens GE. Pharmaceutical and nutraceutical activation of FOXO3 for healthy longevity. Ageing Res Rev. 2022 Jun;78:101621. doi: 10.1016/j.arr.2022.101621. Epub 2022 Apr 11. PMID: 35421606.