Association of Mitochondrial <scp>DNA</scp> Levels in Peripheral Blood Leukocytes With Physical Performance in Older Adults

BACKGROUND: Mitochondrial DNA copy number (mtDNA-CN) in peripheral blood leukocytes has emerged as a surrogate marker of mitochondrial function. This study examined associations between leukocyte mtDNA-CN, physical performance, and lipid metabolism in community-dwelling older adults. METHODS: We conducted a cross-sectional analysis of 594 adults aged ≥ 50 years (median 71 years; 351 women, 243 men) who were independent in activities of daily living. Physical performance was assessed using handgrip strength and gait parameters measured with a triaxial accelerometer. Frailty status was evaluated using the Japanese version of the Cardiovascular Health Study (J-CHS) criteria. Blood samples were collected after fasting for mtDNA-CN and other blood chemical measurements. RESULTS: Median values of mtDNA-CN were 124 in women and 114 in men. According to the J-CHS criteria, 6.1% of women and 6.3% of men were classified as frail, while 48.9% of women and 53.6% of men were pre-frail. Participants with higher mtDNA-CN levels demonstrated superior physical performance. After multivariable adjustment, mtDNA-CN correlated positively with gate ability in women and handgrip strength in men. In addition, mtDNA-CN correlated positively with iron in women and high-density lipoprotein cholesterol (HDL-C) in men, and negatively with uric acid and C-reactive protein in men. In the multivariate regression analyses, mtDNA-CN still showed positive associations with handgrip strength and HDL-C, a negative association with uric acid in men, and a positive association with iron in women and men. CONCLUSION: Leukocyte mtDNA-CN was associated with physical performance, suggesting its potential utility as a biomarker for frailty assessment in older adults.