FOXO3 in Cardiovascular Disease
FOXO3 is one of the few genes in which variants correlate with human longevity in multiple study populations. Effect sizes are still small of course, meaning a modest adjustment to the odds of reaching very old age, but one can at least look into the role of FOXO3 and say something about processes likely to be important in human late life mortality. Evidence suggests that FOXO3, while influencing very general cell behaviors such as stress responses, is involved in vascular aging. Cardiovascular disease is the largest cause of human mortality. That said, it seems unlikely that there is any basis for effective therapy in a deeper examination of FOXO3; the effect of variants on human longevity just isn't large enough.
Forkhead box O3 (FOXO3) has been proposed as a homeostasis regulator, capable of integrating multiple upstream signaling pathways that are sensitive to environmental changes and counteracting their adverse effects due to external changes, such as oxidative stress, metabolic stress, and growth factor deprivation. FOXO3 polymorphisms are associated with extreme human longevity. Intriguingly, longevity-associated single nucleotide polymorphisms (SNPs) in human FOXO3 correlate with lower-than-average morbidity from cardiovascular diseases in long-lived people.
Healthy aging is critical for addressing the increasing severity of global population aging. The unique role of FOXO3 in the vasculature provides promising avenues for therapeutics against aging-related vascular diseases. Post-translational modifications that regulate FOXO3 activity may be potential therapeutic targets. It is expected that research into strategies for delaying the occurrence and development of vascular aging by targeting the FOXO3 will uncover novel perspectives for the development of new drugs.
Despite advances in our understanding of FOXO3's function in retarding vascular senescence, the particular processes remain poorly known, and other issues remain unresolved. For instance, FOXO3 activation promotes vascular smooth muscle cell apoptosis, which may result in atherosclerotic plaque instability and rupture, causing myocardial infarction, and cerebral infarction. In some cases, FOXO3 promotes extracellular matrix degradation which may accelerate the progression of atherosclerosis. While therapies targeting FOXO3 seem appealing, we need to understand all the details to maximize its effectiveness. Despite these challenges, in-depth research into FOXO3 functions may pave the way for future therapeutic approaches.