| Description |
In the first study, skeletal muscle feed arteries (SMFAs) were harvested from young, middle aged, and old 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 compared to both middle aged and old and, in addition to CII state 3, were inversely correlated with age. 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 compared to the middle aged and old and inversely correlated with age. As CS activity was inversely correlated with age, 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 than the middle aged and old and correlated with age. Similarly, superoxide/CS levels were lower in the young than the old and correlated with age. 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. The second study sought to examine the link between vascular and mitochondrial respiratory function in the vasculature with aging. SMFAs were harvested from young and old subjects. Using pressure myography, vasodilation in SMFAs was assessed in iv response to flow-induced shear stress, acetylcholine (ACh), and sodium nitroprusside (SNP) and mitochondrial and respiration were measured, by respirometry, in permeabilized smooth muscle fibers. Endothelium-dependent vasodilation was significantly attenuated in the old, induced by flow or ACh, while endotheliumindependent vasodilation was not altered by age. CI+II, state 3 respiration was significantly lower in the old. Although state 4 respiration and mitochondrial-specific free radical production, assessed by electron paramagnetic resonance spectroscopy, were not different between groups, both tended to be higher in the old. RCR was also significantly attenuated in the old. State 3 and 4 respiration as well as RCR exhibited significant correlations with endothelium dependent but not endothelium-independent capacity. Free radical levels were also significantly correlated with advancing age. Therefore, the agerelated decline in vasodilatory capacity in humans is related to a concomitant attenuation in mitochondrial respiratory capacity and may be a consequence of augmented free radical production. |
