title: Bone mechanotransduction may require augmentation in order to strengthen the senescent skeleton.
abstract: Physical exercise is thought to hold promise as a non-invasive countermeasure against skeletal fragility arising from post-menopausal and age-related osteoporosis. Importantly, mechanical loading and exercise are capable of increasing bone size via periosteal expansion, which by far, is the most effective means of strengthening the structure of a given bone. The focus of this review was to therefore explore whether exercise has the potential to increase periosteal modeling and bone size in the senescent skeleton. A survey of exercise trials in humans suggests that exercise interventions that enhance periosteal modeling in the young skeleton fail to do the same in the elderly skeleton. Underlying this ineffectiveness, in vitro studies indicate that aging lowers basal levels of cell function and degrades bone mechanotransduction at a variety of levels from altered second messenger signaling to gene expression driving proliferation and/or differentiation. Given these age-related alterations, the ultimate efficacy of an exercise intervention may depend upon concurrent supplementation that directly address deficits in signaling and/or cell function. In this context, in vivo animal models of mechanical loading that simulate the muted periosteal adaptation in the elderly hold potential to examine the efficacy of countermeasures. Preliminary in vivo experiments suggest that pharmacologically counteracting age-related deficits in cellular function can restore exercise induced periosteal modeling in the senescent skeleton to levels observed in young animals. If the safety and efficacy of this strategy were to be confirmed for human use, it would enable the utilization of exercise as a viable countermeasure against skeletal fragility at senescence.
authors.affiliation: Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, WA 98104-4240, USA. sundars@u.washington.edu
authors.forename: Sundar
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Ted S
authors.initials: TS
authors.lastname: Gross
authors.forename: Steven D
authors.initials: SD
authors.lastname: Bain
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D016723:Bone Remodeling / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D010024:Osteoporosis / Q000503:physiopathology / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic / Q000379:methods