Targeting Anabolic Impairment in Response to Resistance Exercise in Older Adults with Mobility Impairments: Potential Mechanisms and Rehabilitation Approaches

Muscle atrophy is associated with healthy aging (i.e., sarcopenia) and may be compounded by comorbidities, injury, surgery, illness, and physical inactivity. While a bout of resistance exercise increases protein synthesis rates in healthy young skeletal muscle, the effectiveness of resistance exercise to mount a protein synthetic response is less pronounced in older adults. Improving anabolic sensitivity to resistance exercise, thereby enhancing physical function, is most critical in needy older adults with clinical conditions that render them “low responders”. In this paper, we discuss potential mechanisms contributing to anabolic impairment to resistance exercise and highlight the need to improve anabolic responsiveness in low responders. This is followed with evidence suggesting that the recovery period of resistance exercise provides an opportunity to amplify the exercise-induced anabolic response using protein/essential amino acid ingestion. This anabolic strategy, if repeated chronically, may improve lean muscle gains, decrease time to recovery of function during periods of rehabilitation, and overall, maintain/improve physical independence and reduce mortality rates in older adults. 1. Aging, Muscle Atrophy, and the Clinical Significance Preserving physical function, mobility, and ultimately the physical wellbeing of older adults is a high priority given the rapid rise in the number of older adults (>65？y) expected in the ensuing decades [1]. A common feature of aging that contributes in part to physical dysfunction is a slow but significant decline in muscle mass, especially high-quality force-contracting muscle fibers, beginning as early as the 4th or 5th decade of life [2, 3]. Older adults are particularly susceptible to accelerated muscle loss, following an acute catabolic event, such as physical inactivity [4–6] or surgery [7] and is followed by a less than optimal muscle recovery [5, 8]. For that matter, interventions geared toward older adults with various clinical pathologies that are on a progressive downward decline toward frailty (e.g., hip fracture, postoperative, pneumonia) are needed, especially when muscle mass reserves and quality are low, mobility impairments are high, and physical independence is dwindling. Although pharmacologic approaches are being investigated as alternative methods to increase or attenuate declines in muscle mass [9] few, if any, countermeasures are superior to resistance exercise. 2. Exercise Is Good, But Is It Optimal? Resistance exercise is considered an efficacious, cost effective treatment to promote