Skeletal muscle mitochondrial oxidative capacity predicts cognitive decline over a decade, with markedly different pathways between sexes: glucose metabolism in men, hematologic-inflammatory signaling in women. This sex-differentiated mechanism reveals that identical biomarkers may reflect distinct physiological processes depending on biological sex.
Key Points
- Higher muscle mitochondrial capacity predicts slower cognitive decline in men, not women
- Men's cognition linked via glucose and metabolic efficiency; women's via inflammation and blood comp
- Executive function and processing speed show strongest male protection from mitochondrial fitness
Longevity Analysis
Mitochondrial function in skeletal muscle acts as a measurable proxy for cognitive resilience, but the mechanisms connecting muscle energetics to brain preservation diverge by sex. In men, the pathway runs through metabolic regulation—how efficiently the body manages glucose and sustains energy homeostasis—while in women, the connection operates through hematologic and inflammatory markers. This suggests that sex-specific interventions targeting muscle mitochondrial capacity may need different entry points: metabolic optimization in men, inflammatory modulation in women. Understanding these divergent pathways is essential for designing longevity protocols that account for biological sex rather than applying uniform strategies.
Original published by Wiley Aging Cell, by Qu Tian, Anjay Ambegaonkar, Luigi Ferrucci .