Sedentary behavior and the biological hallmarks of aging

While the benefits of physical exercise for a healthy aging are well-recognized, a growing body of evidence shows that sedentary behavior has deleterious health effects independently, to some extent, of physical activity levels. Yet, the increasing prevalence of sedentariness constitutes a major public health issue that contributes to premature aging but the potential cellular mechanisms through which prolonged immobilization may accelerate biological aging remain unestablished. This narrative review summarizes the impact of sedentary behavior using different models of extreme sedentary behaviors including bedrest, unilateral limb suspension and space travel studies, on the hallmarks of aging such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. We further highlight the remaining knowledge gaps that need more research in order to promote healthspan extension and to provide future contributions to the field of geroscience.