# The Muscle–Brain Axis in Aging: Mechanistic and Clinical Perspectives on Resistance Training and Cognitive Function

## TL;DR

This review explores how resistance training might improve brain health in older adults by stimulating muscle-derived signals that support cognitive function.

## Contribution

The paper integrates clinical and mechanistic evidence to propose the muscle–brain axis as a novel pathway linking resistance training to cognitive benefits.

## Key findings

- Resistance training may release myokines like irisin and IL-6 that could support neuronal health and synaptic plasticity.
- Clinical studies show mixed results, with some cognitive domains like memory and executive function potentially benefiting from resistance training.
- Optimal training parameters remain unclear due to variability in study design and lack of dose–response analyses.

## Abstract

This review examines the potential benefits of resistance training on cognitive function in older adults. We synthesize evidence from clinical and mechanistic studies to investigate possible biological pathways underlying these benefits. Current evidence from intervention studies, typically involving 2–3 sessions per week, suggests that resistance training may stimulate the release of myokines into circulation. These myokines are hypothesized to reach the brain, where they could support neuronal health, promote synaptic plasticity, and modulate neuroinflammation. While the muscle–brain axis represents a promising mechanism, causality remains to be fully established, and further research is needed to confirm these pathways and optimize exercise prescriptions. Understanding these processes could inform non-pharmacological strategies to support brain health during the aging process.

The global aging population has led to a rising prevalence of cognitive impairment, posing a significant public health challenge. Resistance training (RT) is a non-pharmacological intervention that has been increasingly investigated for its potential to support cognitive function in older adults. Clinical evidence suggests that RT may be associated with benefits in certain cognitive domains, including memory, executive function, processing speed, and visuospatial ability. However, findings across studies remain heterogeneous, with several trials reporting neutral outcomes. Most intervention studies involve structured RT programs conducted at moderate to high intensity and performed multiple times per week. However, optimal training parameters have not yet been clearly established due to variability in study design and the absence of formal dose–response analyses. Emerging evidence suggests that the cognitive effects of RT may be mediated, at least in part, through muscle–brain axis signaling involving exercise-induced myokines. Factors such as irisin, brain-derived neurotrophic factor, interleukin-6, interleukin-15, and insulin-like growth factor-1 have been implicated in processes related to neuroplasticity, neuroinflammatory regulation, and neurovascular function, primarily based on preclinical and translational research. This review synthesizes current evidence on RT-related molecular mechanisms and clinical findings to provide an integrative perspective on the potential role of resistance training in mitigating age-related cognitive decline.