New Horizons in the Treatment of Age-Associated Obesity, Sarcopenia and Osteoporosis.

The rapid increase in both the lifespan and proportion of older adults in developed countries is accompanied by the dramatic growth of age-associated chronic diseases, including obesity, sarcopenia, and osteoporosis. Hence, prevention and treatment of age-associated chronic diseases has become increasingly urgent. The key to achieving this goal is a better understanding of the mechanisms underlying their pathophysiology, some aspects of which, despite extensive investigation, are still not fully understood. Aging, obesity, sarcopenia, and osteoporosis are characterized by the creation of a systemic, chronic, low-grade inflammation (SCLGI). The common mechanisms that govern the development of these chronic conditions include a failed resolution of inflammation. Physiologically, the process of inflammation resolution is provided mainly by specialized pro-resolving mediators (SPMs) acting via cognate G protein-coupled receptors (GPCRs). Noteworthy, SPM levels and the expression of their receptors are significantly reduced in aging and the associated chronic disorders. In preclinical studies, supplementation of SPMs or their stable, small-molecule SPM mimetics and receptor agonists reveals clear beneficial effects in inflammation-related obesity and sarcopenic and osteoporotic conditions, suggesting a translational potential. Age-associated chronic disorders are also characterized by gut dysbiosis and the accumulation of senescent cells in the adipose tissue, skeletal muscle, and bones. Based on these findings, we propose SCLGI resolution as a novel strategy for the prevention/treatment of age-associated obesity, sarcopenia, and osteoporosis. Our approach entails the enhancement of inflammation resolution by SPM mimetics and receptor agonists in concert with probiotics/prebiotics and compounds that eliminate senescent cells and their pro-inflammatory activity.