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. 2015 Sep 15;593(18):4259-73.
doi: 10.1113/JP270699. Epub 2015 Jul 31.

Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation

Ruth E Tanner  1 , Lucille B Brunker  2 , Jakob Agergaard  3 , Katherine M Barrows  2 , Robert A Briggs  2 , Oh Sung Kwon  2 , Laura M Young  4 , Paul N Hopkins  5 , Elena Volpi  6 , Robin L Marcus  2 , Paul C LaStayo  2   4 , Micah J Drummond  2   1
Affiliations

Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation

Ruth E Tanner et al. J Physiol. .

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.

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Figures

Figure 1
Figure 1
Study timeline and metabolic study See Methods for details. Note: of the 14 young subjects that completed BED REST, only half (n = 7) of these subjects were randomized to complete the REHAB intervention.
Figure 2
Figure 2
Changes in lean mass and strength with bed rest and rehabilitation Data (means ± SEM) in figure represents the percentage change in leg lean mass and strength (compared to pre-bed rest levels) in young and older adults after bed rest and after exercise rehabilitation. Leg lean mass determined by dual-energy X-ray absorptiometry and strength was determined by peak isometric knee extension.*Significantly different from pre-bed rest (P < 0.05);#significantly different from Young (P < 0.05);§significantly different from BED REST (P < 0.05).
Figure 3
Figure 3
Muscle mTORC1 Nutrient Signalling and REDD gene expression Data (means ± SEM) represents protein expression for: mTOR (Ser2448; A), S6K1 (Thr389; B), 4EBP1 (Thr37/46; C), and rpS6 (Ser240/244; D) at basal and 1 and 3 h after acute EAA ingestion repeated before bed rest (PRE, white bar), after 5 days bed rest (BED REST, light grey bar) and after 8 weeks exercise rehabilitation (REHAB, dark grey bar). Panels E and F are basal mRNA expression for REDD1 and REDD2, respectively, at PRE, BED REST and REHAB study time points. Western blot data are reported as fold change from fasting levels (basal), and therefore were set to 1. Data for mRNA are reported as fold change from basal calculated from 2−ΔΔCt.*Significantly different from Basal at corresponding time point or PRE (P < 0.05);§significantly different from BED REST at corresponding time point (P < 0.05);#significantly different from Young.
Figure 4
Figure 4
Muscle proteolytic markers and AMPKα Data (means ± SEM) in Young (white bar) and Older (grey bar) adults represents: MURF1(A) and MAFBX(B) mRNA expression and protein expression for AMPKα (Thr172; C), LC3II/I ratio(D) and Beclin1(E) sampled in the fasted state before bed rest (PRE), after 5 days bed rest (BED REST) and after 8 weeks exercise rehabilitation (REHAB). Western blot data are reported as fold change from fasting levels and therefore were set to 1. Data for mRNA are reported as fold change from basal calculated from2−ΔΔCt.*Significantly different from PRE (P < 0.05);#significantly different from Young at corresponding time point (P < 0.05).
Figure 5
Figure 5
Representative Western Blot Images A, Western blot images are EAA-induced mTORC1 nutrient signalling markers in Young (Y) and Older (O) adults skeletal muscle before bed rest (PRE), after 5 days bed rest (BED REST) and after 8 weeks of exercise rehabilitation (REHAB). Images (in replicate) are representative of fasted (basal) and 1 and 3 h EAA skeletal muscle responses following each intervention. B,representative western blot images (in replicate) for AMPKα and select proteolytic markers in Young (Y) and Older (O) adult skeletal muscle in the fasted state before (PRE), after bed rest (BED REST) and after exercise rehabilitation (REHAB).
Figure 6
Figure 6
Muscle protein synthesis Mixed muscle protein synthesis (means ± SEM) in skeletal muscle of young and older adults in the postabsorptive state (basal) and following essential amino acid (EAA) ingestion (0–3 h post EAA) at PRE (white bar), after BED REST (light grey bar) and after REHAB (dark grey bar).*Significantly different from respective postabsorptive value (P < 0.05);§significantly different from BED REST in response to EAA (P < 0.05);#significantly different from Young at BED REST.
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