Myokines as Molecular Mediators of the Muscle-Brain Axis: Mechanisms Linking Sarcopenia to Cognitive Decline and Implications for Preventive Strategies in Aging

This narrative review aims to synthesize evidence on the biological mechanisms through which myokines mediate cross-talk between skeletal muscle and the brain (muscle-brain axis) in the context of aging. We will characterize the role of key myokines — including irisin/FNDC5, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), and Cathepsin B — in linking age-related sarcopenia to cognitive decline and dementia. The review will integrate evidence from pre-clinical models and human studies, address mitochondrial dysfunction(definition) and neuromuscular junction impairment as shared pathophysiological mechanisms, and propose myokine-based preventive strategies applicable to aging populations.