Flewwelling · American journal of physiology. Cell physiology 2025 · narrative review · n=?

What are the potential mechanisms of fatigue-induced skeletal muscle hypertrophy with low-load resistance exercise training?

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing theoretical and mechanistic evidence without systematic search methodology

PubMed 39726254 · doi:10.1152/ajpcell.00266.2024 · record verified 2026-08-26

What was done

This narrative review synthesized the existing literature to evaluate potential direct and indirect physiological mechanisms through which muscle fatigue mediates skeletal muscle hypertrophy during low-load resistance exercise training (≤60% of 1-repetition maximum) performed near or to task failure.

What was found

The abstract reports no numerical data. It outlines theoretical direct mechanisms (metabolic by-product accumulation such as lactate, inflammation, oxidative stress) and indirect mechanisms (enhanced muscle fiber recruitment, mechanical tension, ultrastructural muscle damage, anabolic hormone secretion, and alterations in regulatory proteins like myostatin) by which fatigue may stimulate hypertrophy.

Why it matters

Understanding the physiological drivers of fatigue-mediated adaptation helps explain how low-load training can produce hypertrophy comparable to high-load protocols, guiding future mechanistic and exercise prescription research.

Limits

As a narrative review, it lacks a systematic search protocol, meta-analytic pooling, and risk of bias assessment. The abstract reports no original human data, sample sizes, or quantitative effect estimates.