Age-Related Anabolic Resistance of Myofibrillar Protein Synthesis Is Exacerbated in Obese Inactive Individuals

Abstract

Context: A diminished muscle anabolic response to protein nutrition may underpin age-associated muscle loss.

Objective: To determine how chronological and biological aging influence myofibrillar protein synthesis (MyoPS).

Design: Cross-sectional comparison.

Setting: Clinical research facility.

Participants: Ten older lean [OL: 71.7 ± 6 years; body mass index (BMI) ≤25 kg ⋅ m-2], 7 older obese (OO: 69.1 ± 2 years; BMI ≥30 kg ⋅ m-2), and 18 young lean (YL) individuals (25.5 ± 4 years; BMI ≤25 kg ⋅ m-2).

Intervention: Skeletal muscle biopsies obtained during a primed-continuous infusion of l-[ring-13C6]-phenylalanine.

Main outcome measures: Anthropometrics, insulin resistance, inflammatory markers, habitual diet, physical activity, MyoPS rates, and fiber-type characteristics.

Results: Fat mass, insulin resistance, inflammation, and type II fiber intramyocellular lipid were greater, and daily step count lower, in OO compared with YL and OL. Postprandial MyoPS rates rose above postabsorptive values by ∼81% in YL (P < 0.001), ∼38% in OL (P = 0.002, not different from YL), and ∼9% in OO (P = 0.11). Delta change in postprandial MyoPS from postabsorptive values was greater in YL compared with OL (P = 0.032) and OO (P < 0.001). Absolute postprandial MyoPS rates and delta postprandial MyoPS change were associated with step count (r2 = 0.33; P = 0.015) and leg fat mass (r2 = 0.4; P = 0.006), respectively, in older individuals. Paradoxically, lean mass was similar between groups, and muscle fiber area was greater in OO vs OL (P = 0.002).

Conclusion: Age-related muscle anabolic resistance is exacerbated in obese inactive individuals, with no apparent detriment to muscle mass.

Trial registration: ClinicalTrials.gov NCT03113279.

Figure 1.

(a) Plasma leucine concentration, (b) phenylalanine concentration, (c) serum insulin concentration, and (d) plasma ¹³C₆ phenylalanine enrichment in experimental trials. At t = 0, a 15-g bolus of milk protein isolate was consumed. Values are means ± standard error of the mean. Significance was set at P < 0.05. *Significantly greater than fasting values (−180 min); ^†significantly greater in OO compared with other groups.

Figure 2.

(a) Myofibrillar fractional synthesis rate (FSR) in rested postabsorptive and 4-h postprandial state following ingestion of 15 g of milk protein (dashed line at 0 min), with values presented as means ± standard error of the mean. (b) Net postprandial change in myofibrillar FSR from postabsorptive values, showing the median (central horizontal line), 25th and 75th percentiles (box), minimum and maximum values (vertical lines), and mean (cross). Significance was set at P < 0.05. *Significantly greater than corresponding postabsorptive values; ^†significantly greater than OO; ^‡significantly greater than OL.

Figure 3.

Correlations between (a) absolute postprandial myofibrillar fractional synthesis rate (FSR) and leg fat mass and (b) average daily step count in OL and OO combined. Correlations between (c) the delta change in postprandial myofibrillar FSR from postabsorptive values and leg fat mass and (d) average daily step count in OL and OO combined.