Pathophysiological Mechanisms Explaining the Association Between Low Skeletal Muscle Mass and Cognitive Function.

Area of Science:

• Gerontology
• Neuroscience
• Muscle Physiology

Background:

• Low skeletal muscle mass is a growing concern in aging populations.
• This condition is increasingly associated with cognitive impairment and dementia.
• Understanding the molecular links between muscle and brain health is crucial for developing interventions.

Purpose of the Study:

• To review the pathophysiological mechanisms connecting low skeletal muscle mass and cognitive impairment in older adults.
• To explore the role of myokines and physical activity in this relationship.
• To propose a working model for the interplay between muscle health, inflammation, metabolism, and brain function.

Main Methods:

• Literature review of studies on skeletal muscle mass, cognitive function, and related molecular pathways.
• Analysis of proposed mechanisms including systemic inflammation, insulin and protein metabolism, and mitochondrial function.
• Examination of the role of myokines (e.g., irisin, cathepsin B) and neurotrophins (e.g., BDNF).

Main Results:

• Physical inactivity leads to dysfunctional myokine secretion, impacting brain-derived neurotrophic factor (BDNF) and neuroprotection.
• Impaired muscle glucose metabolism and altered insulin transport across the blood-brain barrier are implicated.
• Age-related decline in muscle mass contributes to mitochondrial dysfunction, oxidative stress, and cellular senescence in both muscle and brain.

Conclusions:

• Restoring myokine balance through physical activity is a potential targeted approach to address the pathophysiology of low muscle mass and cognitive decline.
• Myokines released by active muscle play a critical role in neuroprotection and cognitive function.
• A multi-faceted approach considering inflammation, metabolism, and mitochondrial health is necessary to combat age-related cognitive impairment linked to sarcopenia.