Improving sarcopenia by targeting mitochondria

Sarcopenia, the age-related loss of skeletal muscle mass and function, predicts for morbidity, mortality and excessive healthcare costs. Other than exercise, lifestyle therapies for slowing the progression of sarcopenia in older men and women remain elusive. Mitochondrial dysfunction is a common mechanistic link between aging and many pathological factors contributing to sarcopenia. We propose to test whether supplementing the diet with an oil rich linoleic acid (LA; 18:2n6), the preferred fatty acyl constituent of cardiolipin, improves muscle strength and physical mobility. In mice, dietary LA-rich oil increases LA-rich cardiolipin (e.g., 4-LA- cardiolipin) and mitochondrial respiration. Therefore, the effect of LA-rich oil to increase 4-LA-cardiolipin and mitochondrial respiration in older people with sarcopenia will be measured evaluated. Because LA is a required nutrient for humans, e.g., an essential fatty acid that must be attained in the diet, dietary sources are the sole method to replenish LA for cardiolipin, the signature phospholipid of inner mitochondrial membranes. In a phase II double-blinded, randomized controlled trial, this study will test the effect of LA-oil supplementation to change muscle strength, physical mobility, 4-LA-cardiolipin and mitochondrial function. Identifying a mechanistic link between LA and mitochondrial capacity could aid in the development of mechanistically targeted therapies to slow or stop the progression of sarcopenia as well as other mitochondrial-related conditions that develop in older adults.