# Anabolic resistance

Anabolic resistance is the age-related blunting of muscle protein synthesis (MPS) in response to protein and resistance exercise. In young adults, roughly 20 to 25 g of protein per meal maxes out the post-meal MPS. But older muscle needs much more leucine, with thresholds estimated at 35 to 40 g per sitting. Several defects underlie this. The mTORC1 effectors p70S6K1 and 4E-BP1 get less activation. Your gut and liver hold back more of the dietary amino acids. Amino-acid transport is impaired. Chronic low-grade inflammation is present. And satellite cells respond less. Cuthbertson et al. (2005, FASEB Journal) showed these nodes were significantly less activated in older versus younger muscle, after a matched amino-acid infusion. Wall et al. (2015, PLOS ONE) found MPS was 16% lower in older men (about 75) than young men (about 22), with more than threefold less relative response to dietary protein. Anabolic resistance is a primary driver of sarcopenia, and of the drop in muscle quality that predicts falls and all-cause death. Stable-isotope tracer studies support a protein intake of at least 1.2 g/kg a day in older adults, spread across meals and paired with resistance exercise. Whether these strategies fully reverse the deficit is still under study.

## Sources

- Wall BT, Gorissen SH, Pennings B, Koopman R, Groen BBL, Verdijk LB, et al.. (2015). Aging Is Accompanied by a Blunted Muscle Protein Synthetic Response to Protein Ingestion. PLOS ONE. https://doi.org/10.1371/journal.pone.0140903
- Cuthbertson D, Smith K, Babraj J, Leese G, Waddell T, Atherton P, et al.. (2005). Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. The FASEB Journal. https://doi.org/10.1096/fj.04-2640fje
- Prokopidis K, Chambers E, Ni Lochlainn M, Witard OC. (2021). Mechanisms Linking the Gut-Muscle Axis With Muscle Protein Metabolism and Anabolic Resistance: Implications for Older Adults at Risk of Sarcopenia. Frontiers in Physiology. https://doi.org/10.3389/fphys.2021.770455

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_Canonical: https://longevity-switzerland.com/en/glossary/anabolic-resistance · Part of Longevity Cities · Updated 2026-06-22_