Inhibiting Cellular Senescence: A New Therapeutic Paradigm for Age-Related Osteoporosis.

Inhibiting Cellular Senescence: A New Therapeutic Paradigm for Age-Related Osteoporosis.

J Clin Endocrinol Metab. 2018 Feb 07;:

Authors: Khosla S, Farr JN, Kirkland JL

Abstract
Context: With the aging of the population and projected increase in osteoporotic fractures, coupled with the declining use of osteoporosis medications, there is a compelling need for new approaches to treat osteoporosis. Given that age-related osteoporosis generally co-exists with multiple other co-morbidities (e.g., atherosclerosis, diabetes, frailty), all sharing aging itself as the leading risk factor, there is growing interest in the "Geroscience Hypothesis", which posits that manipulation of fundamental aging mechanisms will delay the appearance or severity of multiple chronic diseases because these diseases share the same underlying risk factor - age. In this context, one fundamental aging mechanism that has received considerable attention recently as contributing to multiple age-related morbidities is cellular senescence. This mini-review provides an overview on cellular senescence with a particular focus on its role in mediating age-related bone loss.
Methods: This summary is based on the authors' knowledge of the field supplemented by a PubMed search using the terms "senescence", "aging", and "bone".
Results: There is now compelling evidence from pre-clinical models and supportive human data demonstrating an increase in senescent cells in the bone microenvironment with aging. These cells produce a pro-inflammatory secretome that leads to increased bone resorption and decreased bone formation, and approaches that either eliminate senescent cells or impair the production of their pro-inflammatory secretome have been shown to prevent age-related bone loss in mice.
Conclusions: Targeting cellular senescence represents a novel therapeutic strategy to prevent not only bone loss but potentially multiple age-related diseases simultaneously.

PMID: 29425296 [PubMed - as supplied by publisher]

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