Key pointsr Five days of bed rest resulted in a reduction in leg lean mass and strength in older adults. r After bed rest, older (but not younger) adults had reduced amino acid-induced anabolic sensitivity (blunted muscle protein synthesis; MPS) and enhanced markers associated with the ubiquitin proteasome and autophagy-lysosomal systems (increase in molecular markers related to muscle proteolysis).r Younger adults did not lose leg lean mass (via DXA) after 5 days of bed rest despite blunted amino acid-induced mTORC1 signalling and increased skeletal muscle REDD1, REDD2 and MURF1 mRNA expression.r Exercise rehabilitation restored bed rest-induced deficits in lean mass, strength, nutrient-induced protein anabolism (protein synthesis and mTORC1 signalling) and select muscle proteolytic markers in older adults.Abstract Bed rest-induced muscle loss and impaired muscle recovery may contribute to age-related sarcopenia. It is unknown if there are age-related differences in muscle mass and muscle anabolic and catabolic responses to bed rest. A secondary objective was to determine if rehabilitation could reverse bed rest responses. Nine older and fourteen young adults participated in a 5-day bed rest challenge (BED REST). This was followed by 8 weeks of high intensity resistance exercise (REHAB). Leg lean mass (via dual-energy X-ray absorptiometry; DXA) and strength were determined. Muscle biopsies were collected during a constant stable isotope infusion in the postabsorptive state and after essential amino acid (EAA) ingestion on three occasions: before (PRE), after bed rest and after rehabilitation. Samples were assessed for protein synthesis, mTORC1 signalling, REDD1/2 expression and molecular markers related to muscle proteolysis (MURF1, MAFBX, AMPKα, LC3II/I, Beclin1). We found that leg lean mass and strength decreased in older but not younger adults after bedrest (P < 0.05) and was restored after rehabilitation. EAA-induced mTORC1 signalling and protein synthesis increased before bed rest in both age groups (P < 0.05). Although both groups had blunted mTORC1 signalling, increased REDD2 and MURF1 mRNA after bedrest, only older adults had reduced EAA-induced protein synthesis rates and increased MAFBX mRNA, p-AMPKα and the LC3II/I ratio (P < 0.05). We conclude that older adults are more susceptible than young persons to muscle loss after short-term bed rest. This may be partially explained by a combined suppression of protein synthesis and a marginal increase in proteolytic markers. Finally, rehabilitation restored bed rest-induced deficits in lean mass and strength in older adults.

We conclude that physical inactivity in frail older women is associated with a downregulation of ubiquitin-mediated and autophagic lysosomal skeletal muscle gene expression, perhaps related to low muscle mass and poor physical function.

Inactivity‐induced skeletal muscle loss coupled with impaired recovery may contribute to sarcopenia in older adults. We have previously observed in older adults after bed rest that essential amino acid (EAA)‐induced mTORC1 signaling was suppressed along with a loss in lean mass. It is unknown if exercise rehabilitation can reverse nutrient impairments and whether there are age‐related differences. We also investigated muscle proteolysis as measured by markers of autophagy. Nine healthy older and 14 young adults participated in a 5‐day bed rest experiment at the local Center for Clinical and Translational Sciences. After bed rest, subjects engaged in an 8‐week eccentric resistance exercise intervention (3x/week) with a protein supplement (4.5g Leu) provided after each session. Thigh muscle biopsies were collected before and after acute EAA ingestion at 3‐time points: before (PRE) and after bed rest and after exercise rehabilitation (REHAB). Leg lean mass decreased (4%) only in older adults after bed rest (P<0.05). Lean mass was restored in older adults after REHAB and increased above PRE in young adults (P<0.05). mTORC1 nutrient signaling was blunted after bed rest in older and younger adults (P<0.05) but returned to PRE levels after REHAB in both groups. p‐AMPKα, LC3II/I, and beclin1 modestly increased in older but not younger adults after bed rest (P<0.05). These data support that exercise rehabilitation can restore bed rest‐induced decrements in mTORC1 nutrient signaling and lean mass. Alterations in mTORC1 nutrient signaling and autophagy may contribute to age‐related differences in muscle loss with bed rest. K01AG038556, AFAR, UL1TR000105

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