Frontiers in Physiology · Jun 5, 2026

Age-related anabolic resistance and post-absorptive muscle protein synthesis: integrative evidence from a systematic review and meta-analysis

By Kristiansen JB, Vissing K, Nielsen JL

INTRODUCTION: Age-related declines in skeletal muscle mass and function are partly attributed to anabolic resistance, a diminished stimulation of muscle protein synthesis (MPS) following nutrient intake or exercise. However, the magnitude and physiological specificity of this phenomenon remain incompletely defined. This systematic review and meta-analysis examined age-related differences in MPS across post-absorptive, post-prandial, post-exercise, and combined post-prandial/-exercise states in healthy adults. METHODS: A systematic literature search was conducted in November 2025 across major databases. Eligible studies compared MPS between young (18-35 years) and older (≥60 years) adults using stable isotope tracer techniques under controlled conditions. Random-effects meta-analyses were conducted for post-absorptive and post-prandial conditions, while post-exercise and combined post-prandial/-exercise findings were synthesized qualitatively due to substantial methodological heterogeneity. Meta-regression explored potential moderators, and risk of bias was assessed using the ROBINS-I tool. RESULTS: Forty-six studies including 1,280 participants (700 older adults, 580 young) met the inclusion criteria. Post-absorptive MPS was significantly lower in older compared with younger adults (SMD = -0.167; 95% CI: -0.313 to -0.021; p = 0.025; I² = 18.4%). Post-prandial MPS was also reduced in older adults (SMD = -0.348; 95% CI: -0.627 to -0.070; p = 0.014; I² = 83.4%), with consistent directionality across sensitivity analyses. Post-exercise (5/8) and combined post-prandial/-exercise (7/9) studies reported no significant age-related difference. Overall risk of bias was low to moderate. DISCUSSION: These findings demonstrate modest but significant reductions in both post-absorptive and post-prandial MPS with aging, consistent with basal and nutrient-related anabolic resistance. However, the preserved MPS response to exercise suggests maintained anabolic potential when appropriate stimuli are provided. Evidence for combined post-exercise MPS remains mixed, with evidence leaning toward a similar response in young and older adults. Standardization of tracer protocols and sex-specific analyses are warranted to refine mechanistic understanding of age-related anabolic heterogeneity.

doi.org/10.3389/fphys.2026.1740284 Open access PubMed 42326998 Mechanisms