Resting plasma irisin shows lower levels in older adults independently of muscle mass and physical activity and is not associated with cognitive performance

Although exercise-induced irisin has been associated with improvements in cognitive and metabolic health, the determinants and functional relevance of resting plasma irisin (RPI) remain unclear. We investigated age-related differences in RPI and its association with cognitive performance in a population-based cross-sectional sample of 186 middle-aged (mean age 42.1 years; 48% female) and 178 older adults (mean age 71.5 years; 64% female). RPI was measured by ELISA and examined in relation to body composition (muscle mass, fat mass, and basal metabolic rate), habitual physical activity, and cognitive performance. Multivariable regression analyses demonstrated a significant inverse association between chronological age and RPI (β = − 4.57 pg/mL/year; [95% CI, − 5.90, − 3.24]), independent of sex, body composition, physical activity, and basal metabolic rate. No significant sex differences in RPI concentrations were observed within either age group. RPI was not associated with any cognitive outcome in either age group, even after adjustment for body composition and physical activity. These findings indicate that RPI is lower in older compared to middle-aged adults, independently of body composition and physical activity, and is not associated with cognitive performance. The cognitive benefits attributed to irisin in exercise and animal studies may therefore not extend to resting physiological concentrations, pointing to potentially distinct biological roles for exercise-induced and resting irisin during aging.