Muscle-brain crosstalk in sarcopenia and cognitive impairment: endocrine signaling, metabolic regulation, and exercise modulation

Abstract

Aging is accompanied by progressive changes in endocrine signaling, metabolic regulation, and inter-organ communication that may contribute to functional decline. Sarcopenia and cognitive impairment frequently coexist in older adults, raising the possibility that their association involves disruption of communication between skeletal muscle and the brain in addition to shared age-related processes. This narrative review synthesizes clinical and mechanistic evidence on muscle–brain crosstalk in sarcopenia and cognitive impairment, with emphasis on endocrine and metabolic mechanisms and their modulation by exercise. Clinical evidence consistently links sarcopenia with cognitive impairment, while muscle strength and physical performance appear more closely related to cognitive function than muscle mass alone. Potential mechanisms include myokine and exerkine signaling, inflammaging and immune–endocrine dysregulation, mitochondrial dysfunction and oxidative stress, insulin resistance and glucose dysregulation, and lactate-mediated metabolic signaling. Exercise provides a dynamic physiological context in which several components of muscle–brain communication can be modified, including inflammatory, metabolic, neurotrophic, and lactate-related responses. However, direct evidence establishing complete signaling pathways in humans remains limited. Future studies integrating muscle and cognitive phenotypes with circulating biomarkers, metabolic measures, and neuroimaging are needed to clarify the clinical relevance of muscle–brain crosstalk in individuals with coexisting sarcopenia and cognitive impairment.