Cellular senescence and other aging mechanisms in bone and muscle

The worldwide older population is growing, which will produce an enormous socioeconomic burden as these individuals are at high risk for developing several age-related co-morbidities, such as osteoporosis and sarcopenia. Aging is driven by fundamental mechanisms that include: telomere shortening, genomic instability, loss of proteostasis, epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing, stem cell exhaustion, altered intercellular communication, and cellular senescence. Much excitement has emerged from several studies, predominantly in mice, demonstrating that each of these fundamental aging mechanisms can be manipulated to extend healthspan (i.e., the period of life free of chronic disease). Because these hallmarks of aging are interconnected and overlap, interventions that therapeutically target one should prevent or delay multiple co-morbidities, which is uniquely different than the current paradigm of treating individual diseases. One such hallmark of aging that appears to be particularly amendable to therapeutic targeting to prevent multiple co-morbidities, including osteosarcopenia, is cellular senescence.