Abstract Muscle fatty infiltration is associated with impaired physical performance. However, the association between ectopic fat, such as lower extremity fat distribution, and sex-specific differences among older adults remains to be determined. This study aimed to examine sex-specific differences in calf muscle fat infiltration and their association with physical performance among healthy older adults aged 76 to 80 years. The pilot study comprised 40 subjects (20 men; 20 women) matched by age and body mass index. The participants underwent dual-energy X-ray absorptiometry, magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopy (1H-MRS) to assess body composition and lower extremity fat distribution. The tibialis anterior intramyocellular lipid (IMCL) as assessed by 1H-MRS was negatively associated with the five-times sit-to-stand test scores (rs=0.518, p=0.023) in men, while the soleus IMCL content was negatively associated with the timed up-and-go test scores (rs=0.472, p=0.048) in women. However, the soleus extramyocellular lipid (EMCL) content was positively associated with the five-times sit-to-stand test scores (rs=−0.488, p=0.040) in women, but this association was not statistically significant in men. Regarding the calf cross-sectional area (CSA) parameters assessed by MRI, calf subcutaneous fat CSA was positively associated with the usual gait speed (rs=0.447, p=0.048) in women only. To conclude, this study showed an inverse correlation between IMCL content and physical performance in healthy older individuals and calf muscle-specific IMCL based on sex differences. Furthermore, our results suggest that greater EMCL content in the soleus and calf subcutaneous fat might affect physical performance positively in older women but not older men.
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