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

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-(13)C(6)]-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 (r(2) = 0.33; P = 0.015) and leg fat mass (r(2) = 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.