Impaired Muscle Efficiency but Preserved Peripheral Hemodynamics and Mitochondrial Function With Advancing Age: Evidence From Exercise in the Young, Old, and Oldest-Old

Abstract

Muscle weakness in the elderly has been linked to recurrent falls and morbidity; therefore, elucidating the mechanisms contributing to the loss of muscle function and mobility with advancing age is critical. To this aim, we comprehensively examined skeletal muscle metabolic function and hemodynamics in 11 young (23 ± 2 years), 11 old (68 ± 2 years), and 10 oldest-old (84 ± 2 years) physical activity-matched participants. Specifically, oxidative stress markers, mitochondrial function, and the ATP cost of contraction as well as peripheral hemodynamics were assessed during dynamic plantar flexion exercise at 40 per cent of maximal work rate (WRmax). Both the PCr recovery time constant and the peak rate of mitochondrial ATP synthesis were not significantly different between groups. In contrast, the ATP cost of dynamic contractions (young: 1.5 ± 1.0, old: 3.4 ± 2.1, oldest-old: 6.1 ± 3.6 mM min-1 W-1) and systemic markers of oxidative stress were signficantly increased with age, with the ATP cost of contraction being negatively correlated with WRmax (r = .59, p < .05). End-of-exercise blood flow per Watt rose significantly with increasing age (young: 37 ± 20, old: 82 ± 68, oldest-old: 154 ± 93 mL min-1 W-1). These findings suggest that the progressive deterioration of muscle contractile efficiency with advancing age may play an important role in the decline in skeletal muscle functional capacity in the elderly.

Figure 1.

Changes in phosphocreatine (PCr) (A), intracellular pH (B), inorganic phosphate (Pi) (C), and adenosine diphosphate (ADP) (B) with respect to time at the onset of plantar flexion exercise in young (empty circles, female = 6; male = 5; n = 11), old (gray circles, female = 6; male = 5; n = 11), and oldest-old (black circles, female = 4; male = 6; n = 10). Values are presented as means ± SEM. *Significantly different from young at the same time point (p < .05).

Figure 2.

(A) ATP cost of contraction during submaximal plantar flexion exercise in the young, old, and oldest-old participants, (B) the relationship between the maximal work rate reached during an incremental plantar flexion exercise and the ATP cost of contraction during submaximal plantar flexion exercise [young (empty circles, female = 6; male = 5; n = 11), old (gray circles, female = 6; male = 5; n = 11), and oldest old (black circles, female = 4; male = 6; n = 10)]. Values are presented as mean ± SEM. *p < .05, significantly different from the old and young.

Figure 3.

PCr changes with respect to time at the offset of plantar flexion exercise in the young (empty circles, female = 6; male = 5; n = 11), old (gray circles, female = 6; male = 5; n = 11), and oldest-old (black circles, female = 4; male = 6; n = 10). Values are presented as mean ± SEM. The figure inset provides the mean of the estimated peak rate of mitochondrial ATP synthesis. There was no significant difference between groups (p > 0.05).

Figure 4.

(A) Mean of the initial blood flow per watt; (B) blood flow changes with respect to time at the offset of plantar flexion exercise in the young (empty circles, female = 6; male = 5; n = 11), old (gray circles, female = 6; male = 5; n = 11), and oldest-old (black circles, female = 4; male = 6; n = 10). *p < .05, significantly different from both the young and old. Values are presented as mean ± SEM.

Figure 5.

The relationship between the level of free radicals measured by electron paramagnetic resonance spectroscopy (EPR) and the ATP cost of contraction during submaximal plantar flexion exercise [young (empty circles, female = 5; male = 3; n = 9), old (gray circles, female = 5; male = 5; n = 10), and oldest-old (black circles, female = 4; male = 5; n = 9)].