Vascular mitochondrial respiratory function: the impact of advancing age.

Little is known about vascular mitochondrial respiratory function and the impact of age. Therefore, skeletal muscle feed arteries (SMFAs) were harvested from young (33±7yrs, n=10), middle (54±5yrs, n=10), and old (70±7yrs, n=10) subjects, and mitochondrial respiration as well as citrate synthase (CS) activity were assessed. Complex I (CI) and complex I+II (CI+II), state 3 respiration were greater in the young (CI: 10.4±0.8, CI+II: 12.4±0.8 pmol/s/mg, P<0.05) compared to both middle (CI: 7±0.6, CI+II: 8.3±0.5 pmol/s/mg) and old (CI: 7.2±0.4, CI+II: 7.6±0.5 pmol/s/mg) and, in addition to CII state 3, were inversely correlated with age (CI: r=-0.56, CI+II: r=-0.7, CII: r=0.4; P<0.05). In contrast, state 4 respiration and mitochondria-specific superoxide levels were not different across groups. The respiratory control ratio (RCR) was greater in the young (2.2±0.2, P<0.05) compared to the middle and old (1.4±0.1, 1.1±0.1) and inversely correlated with age (r=-0.71, P<0.05). As CS activity was inversely correlated with age (r=-0.54, P<0.05), when normalized for mitochondrial content, the age-related differences and relationships with state 3 were ablated. In contrast, mitochondrion-specific state 4 was now lower in the young (15±1.4 pmol/s/mg/U CS, P<0.05) than the middle and old (23.4±3.6, 27.9±3.4 pmol/s/mg/U CS), and correlated with age (r=0.46, P<0.05). Similarly, superoxide/CS levels were lower in the young (0.07±0.01) than the old (0.19±0.41), and correlated with age (r=0.44, P<0.05). Therefore, with aging vascular mitochondrial respiratory function declines, predominantly as a consequence of falling mitochondrial content. However, per mitochondrion, aging likely results in greater mitochondrial-derived oxidative stress, which may contribute to age-related vascular dysfunction.