Targeting the molecular & cellular pillars of human aging with exercise

Biological aging is the main driver of age‐associated chronic diseases. In 2014, the United States National Institute of Aging (NIA) sponsored a meeting between several investigators in the field of aging biology, who identified seven biological pillars of aging and a consensus review, “Geroscience: Linking Aging to Chronic Disease,” was published. The pillars of aging demonstrated the conservation of aging pathways in diverse model organisms and thus represent a useful framework with which to study human aging. In this present review, we revisit the seven pillars of aging from the perspective of exercise and discuss how regular physical exercise can modulate these pillars to stave off age‐related chronic diseases and maintain functional capacity. The seven cellular and molecular pillars that drive human aging include macromolecular damage, dysregulated stress response, disrupted proteostasis, metabolic dysregulation, epigenetic drift, inflammaging, and stem cell exhaustion. The rate of biological aging is coupled to the age‐dependent disruption of these homeostatic networks. Exercise training positively influences multiple pillars of aging and offers broad‐range benefits to delay aging, maintain functional capacity, and delay the onset of chronic diseases of old age.