Leucine and Mammalian Target of Rapamycin-Dependent Activation of Muscle Protein Synthesis in Aging.
Level 5 - mechanism / opinion, no new human data
Narrative review of mechanistic pathways without systematic review methodology or original empirical data.
PubMed 27934653 · doi:10.3945/jn.116.234518
What was done
This narrative review examined the molecular mechanisms underlying age-related muscle anabolic resistance, focusing on the role of leucine in stimulating muscle protein synthesis through mechanistic/mammalian target of rapamycin complex 1 (mTORC1) signaling, and considered the therapeutic potential and safety of leucine supplementation.
What was found
The abstract reports no numerical data or quantitative outcomes. It notes that aged muscle demonstrates impaired mTORC1 activation and reduced sensitivity of muscle protein synthesis to amino acids, alongside paradoxically higher basal phosphorylation of certain pathway intermediates. It describes leucine supplementation as an effective strategy to stimulate cap-dependent translation initiation and counter anabolic resistance, while highlighting unresolved concerns regarding long-term, high-dose leucine exposure and potential risks of insulin resistance and tumorigenesis.
Why it matters
It outlines the mechanistic rationale for targeted amino acid supplementation to counter age-related sarcopenia and muscle anabolic resistance. It also flags potential metabolic and oncologic safety concerns that require evaluation before recommending chronic high-dose regimens.
Limits
As a narrative review, it lacks a systematic literature search, meta-analytic pooling, and primary clinical data. The review notes that observed mTORC1 impairments in aging are heavily confounded by physical inactivity, systemic inflammation, insulin resistance, and inadequate baseline nutrition, leaving it unclear whether signaling defects are intrinsic to aging itself. No optimal dose or safety thresholds are quantified.
Cited by
- supports Leucine stimulates the mTOR pathway to initiate the anabolic muscle protein synthesis signaling cascade.