Metabolic Perturbations from Step Reduction in Older Persons at Risk for Sarcopenia: Plasma Biomarkers of Abrupt Changes in Physical Activity.

Sarcopenia is the age-related loss of skeletal muscle mass, strength and function, which may be accelerated during periods of physical inactivity. Declines in skeletal muscle and functionality not only impacts mobility but also increases chronic disease risk, such as type 2 diabetes. The aim of this study was to measure adaptive metabolic responses to acute changes in habitual activity in a cohort of overweight, pre-diabetic older adults (age = 69 ± 4 years; BMI = 27 ± 4 kg/m2, n = 17) when using non-targeted metabolite profiling by multisegment injection-capillary electrophoresis-mass spectrometry. Participants completed two weeks of step reduction (<1000 steps/day) followed by a two week recovery period, where fasting plasma samples were collected at three time intervals at baseline, after step reduction and following recovery. Two weeks of step reduction elicited increases in circulatory metabolites associated with a decline in muscle energy metabolism and protein degradation, including glutamine, carnitine and creatine (q < 0.05; effect size > 0.30), as well as methionine and deoxycarnitine (p < 0.05; effect size ≈ 0.20) as compared to baseline. Similarly, decreases in uremic toxins in plasma that promote muscle inflammation, indoxyl sulfate and hippuric acid, as well as oxoproline, a precursor used for intramuscular glutathione recycling, were also associated with physical inactivity (p < 0.05; effect size > 0.20). Our results indicate that older persons are susceptible to metabolic perturbations due to short-term step reduction that were not fully reversible with resumption of normal ambulatory activity over the same time period. These plasma biomarkers may enable early detection of inactivity-induced metabolic dysregulation in older persons at risk for sarcopenia not readily measured by current imaging techniques or muscle function tests, which is required for the design of therapeutic interventions to counter these deleterious changes in support of healthy ageing.

Failed Recovery of Glycemic Control and Myofibrillar Protein Synthesis With 2 wk of Physical Inactivity in Overweight, Prediabetic Older Adults.

Background: Physical inactivity impairs insulin sensitivity, which is exacerbated with aging. We examined the impact of 2 wk of acute inactivity and recovery on glycemic control, and integrated rates of muscle protein synthesis in older men and women. Methods: Twenty-two overweight, prediabetic older adults (12 men, 10 women, 69 ± 4 y) undertook 7 d of habitual activity (baseline; BL), step reduction (SR; <1,000 steps.d-1 for 14 d), followed by 14 d of recovery (RC). An oral glucose tolerance test was used to assess glycemic control and deuterated water ingestion to measure integrated rates of muscle protein synthesis. Results: Daily step count was reduced (all p < .05) from BL at SR (7362 ± 3294 to 991 ± 97) and returned to BL levels at RC (7117 ± 3819). Homeostasis model assessment-insulin resistance increased from BL to SR and Matsuda insulin sensitivity index decreased and did not return to BL in RC. Glucose and insulin area under the curve were elevated from BL to SR and did not recover in RC. Integrated muscle protein synthesis was reduced during SR and did not return to BL in RC. Conclusions: Our findings demonstrate that 2 wk of SR leads to lowered rates of muscle protein synthesis and a worsening of glycemic control that unlike younger adults is not recovered during return to normal activity in overweight, prediabetic elderly humans. Clinical Trials Registration: ClinicalTrials.gov identifier: NCT03039556.

Low-load resistance training during step-reduction attenuates declines in muscle mass and strength and enhances anabolic sensitivity in older men.

Step-reduction (SR) in older adults results in muscle atrophy and an attenuated rise in postprandial muscle protein synthesis (MPS): anabolic resistance. Knowing that resistance exercise (RT) can enhance MPS, we examined whether RT could enhance MPS following 2 weeks of SR. In addition, as we postulated that SR may impair feeding-induced vasodilation limiting nutrient delivery to muscle, we also examined whether citrulline (CIT), as an arginine and nitric oxide precursor, could attenuate muscle anabolic resistance accompanying SR. We used a unilateral leg model to compare older subjects' who had undergone SR to a loaded condition of SR plus RT (SR + RT). Thirty older men (70 ± 1 years) underwent 14 days of SR (<1500 steps/day) with supplementation of either 5 g/day CIT or glycine placebo. Throughout SR, subjects performed unilateral low-load RT thrice weekly. We assessed muscle protein synthesis in the postabsorptive and postprandial state (20 g whey isolate plus 15 g glycine or as micellar-whey with 5 g CIT or 15 g glycine, n = 10/group). As MPS was similar after ingestion of either whey isolate, micellar-whey, or micellar-whey + CIT data related to different dietary groups were collapsed to compare SR and SR + RT legs. Subjects' daily steps were reduced by 80 ± 2% during SR (P < 0.001) compared with baseline. Leg fat-free mass decreased with SR (-124 ± 61 g) and increased in the SR + RT (+126 ± 68 g; P = 0.003). Myofibrillar FSR was lower (P < 0.0001) in the SR as compared with the SR + RT leg in the postabsorptive (0.026 ± 0.001%/h vs. 0.045 ± 0.001%/h) and postprandial states (0.055 ± 0.002%/h vs. 0.115 ± 0.003%/h). We conclude that low-load RT, but not supplementation with CIT, can attenuate the deleterious effects of SR in aging muscle.

Whey protein supplementation preserves postprandial myofibrillar protein synthesis during short-term energy restriction in overweight and obese adults.

BACKGROUND: Higher dietary energy as protein during weight loss results in a greater loss of fat mass and retention of muscle mass; however, the impact of protein quality on the rates of myofibrillar protein synthesis (MPS) and lipolysis, processes that are important in the maintenance of muscle and loss of fat, respectively, are unknown. OBJECTIVE: We aimed to determine how the consumption of different sources of proteins (soy or whey) during a controlled short-term (14-d) hypoenergetic diet affected MPS and lipolysis. METHODS: Men (n = 19) and women (n = 21) (age 35-65 y; body mass index 28-50 kg/m(2)) completed a 14-d controlled hypoenergetic diet (-750 kcal/d). Participants were randomly assigned, double blind, to receive twice-daily supplements of isolated whey (27 g/supplement) or soy (26 g/supplement), providing a total protein intake of 1.3 ± 0.1 g/(kg · d), or isoenergetic carbohydrate (25 g maltodextrin/supplement) resulting in a total protein intake of 0.7 ± 0.1 g/(kg · d). Before and after the dietary intervention, primed continuous infusions of L-[ring-(13)C6] phenylalanine and [(2)H5]-glycerol were used to measure postabsorptive and postprandial rates of MPS and lipolysis. RESULTS: Preintervention, MPS was stimulated more (P < 0.05) with ingestion of whey than with soy or carbohydrate. Postintervention, postabsorptive MPS decreased similarly in all groups (all P < 0.05). Postprandial MPS was reduced by 9 ± 1% in the whey group, which was less (P < 0.05) than the reduction in soy and carbohydrate groups (28 ± 5% and 31 ± 5%, respectively; both P < 0.05) after the intervention. Lipolysis was suppressed during the postprandial period (P < 0.05), but more so with ingestion of carbohydrate (P < 0.05) than soy or whey. CONCLUSION: We conclude that whey protein supplementation attenuated the decline in postprandial rates of MPS after weight loss, which may be of importance in the preservation of lean mass during longer-term weight loss interventions. This trial was registered at clinicaltrials.gov as NCT01530646.