Anabolic signaling and response in sarcopenia as a model for microgravity induced muscle deconditioning: A systematic review

Abstract Purpose Muscle mass, sustained through buildup exceeding constant parallel breakdown, is mainly regulated through amino acid availability and mechanic stimulation and conveyed through the key mediator mTORC1. Sarcopenia, as age- and immobilization related loss of muscle mass, strength and function, may serve as an analog to muscle deconditioning in space travel. Optimal countermeasures to muscle deconditioning syndromes may be impacted by impaired anabolic response. This review assesses the pathophysiological contribution of anabolic resistance to muscle deconditioning, and its influence on adequate interventions applied in aging and immobilization as an analog for detrimental effects of space travel. Methods A systematic search of the MEDLINE database identified relevant publications. Selection criteria included clinical trials assessing markers of anabolic resistance in aged or disused muscle, as well as modulation of synthetic activity through adequate interventions. Results Increased protein intake and resistance training, especially combined, show the greatest potential for counteracting sarcopenia as an analog for microgravity-induced muscle deconditioning. However, elderly display partly attenuated responses to anabolic stimulation, which is reflected in decreased synthetic activity and muscle mass gain or absence of beneficial effects at all. Amongst other targets and dysregulations in anabolic signaling, there is an emerging role of REDD1 as a downstream inhibitor of mTORC1. Conclusion Findings on anabolic resistance and underlying effectors, such as REDD1, are partly controversial regarding its exclusively inhibitory role. Further detailed investigation on the exact mechanisms, the extent of occurrence, and subsequent impact of anabolic resistance on therapeutic approaches in analogs for microgravity-induced muscle deconditioning is needed.