Effects of aging and exercise training on leg hemodynamics and oxidative metabolism in the transition from rest to steady-state exercise: role of cGMP signaling

Abstract

Aging is associated with slower skeletal muscle O uptake (V̇o) kinetics; however, the mechanisms underlying this effect of age are unclear. Also, the effects of exercise training in elderly on the initial vascular and metabolic response to exercise remain to be elucidated. We measured leg hemodynamics and oxidative metabolism in the transition from rest to steady-state exercise engaging the knee-extensor muscles in young ( n = 15, 25 ± 1 yr) and older ( n = 15, 72 ± 1 yr) subjects before and after a period of aerobic high-intensity exercise training. To enhance cGMP signaling, pharmacological inhibition of phosphodiesterase 5 (PDE5) was performed. Before training, the older group had a slower ( P <0.05) increase in femoral arterial blood flow and leg vascular conductance in the transition from rest to steady-state exercise at low- and moderate-intensity compared with the young group. The rate of increase in leg V̇o was, however, similar in the two groups as a result of higher ( P < 0.05) arteriovenous O difference in the older group. Potentiation of cGMP signaling did not affect the rate of increase in blood flow or V̇o in either group. Exercise training augmented ( P < 0.05) the increase in leg vascular conductance and blood flow during the onset of moderate-intensity exercise in both groups without altering V̇o. These findings suggest that an age-related reduction in the initial vascular response to low- and moderate-intensity knee-extensor exercise is not limiting for V̇o in older individuals. A lower blood flow response in aging does not appear to be a result of reduced cGMP signaling.

A High Activity Level Is Required for Augmented Muscle Capillarization in Older Women

“…To our knowledge, this is the first study to evaluate matching of leg oxygen delivery and uptake in postmenopausal women. In men of similar age, matching of oxygen delivery and uptake is impaired compared with young subjects (31), and in line with our current observations, exercise training has been shown to improve matching of leg oxygen delivery and uptake in older men (32).…”

Matching of O2 Utilization and O2 Delivery in Contracting Skeletal Muscle in Health, Aging, and Heart Failure

“…In one group of older life-long sedentary individuals, skeletal muscle O 2 delivery and O 2 uptake were reported to be lower with no compensatory increase in a-vO 2 difference ( Mortensen et al, 2012b ; Nyberg et al, 2012 ), thus indicating impairments in convective and potentially diffusive O 2 transport. In line with this proposition, acute potentiation of cGMP signalling with phosphodiesterase 5 inhibition increases O 2 delivery and utilisation during low-to moderate-intensity exercise in older but not young subjects ( Nyberg et al, 2015b ; Piil et al, 2018 ).…”

“…In the setting of knee-extensor exercise, older individuals display a slower increase in skeletal muscle vascular conductance, blood flow, and O 2 delivery in the transition from rest to steady-state exercise at low- and moderate-intensity ( Piil et al, 2018 ). Notably, the rate of increase in O 2 uptake was similar in the group of young and older individuals because of higher a-vO 2 difference in the older group.…”

“…Hence, one obvious question is to what extent impairments in these systems are a consequence of aging, inactivity, or a combination of the two. One piece to this puzzle comes from the observation that training-induced potentiation of cGMP signaling leads to improvements in skeletal muscle blood flow and O 2 delivery in older subjects ( Piil et al, 2018 ). Furthermore, lifelong physical activity is associated with enhanced leg endothelial function, purinergic signalling, and ability for functional sympatholysis as well as preserved skeletal muscle oxidative metabolism during knee-extensor exercise ( Mortensen et al, 2012b ; Nyberg et al, 2012 ).…”