In vivo mitochondrial function in aging skeletal muscle: capacity, flux, and patterns of use

Abstract

Because of the fundamental dependence of mammalian life on adequate mitochondrial function, the question of how and why mitochondria change in old age is the target of intense study. Given the importance of skeletal muscle for the support of mobility and health, this question extends to the need to understand mitochondrial changes in the muscle of older adults, as well. We and others have focused on clarifying the age-related changes in human skeletal muscle mitochondrial function in vivo. These changes include both the maximal capacity for oxidative production of energy (ATP), as well as the relative use of mitochondrial ATP production for powering muscular activity. It has been known for nearly 50 yr that muscle mitochondrial content is highly plastic; exercise training can induce an ∼2-fold increase in mitochondrial content, while disuse has the opposite effect. Here, we suggest that a portion of the age-related changes in mitochondrial function that have been reported are likely the result of behavioral effects, as physical activity influences have not always been accounted for. Further, there is emerging evidence that various muscles may be affected differently by age-related changes in physical activity and movement patterns. In this review, we will focus on age-related changes in oxidative capacity and flux measured in vivo in human skeletal muscle.

Bioenergetic basis for the increased fatigability with ageing

“…; Homma et al . ), may play a more prominent role in altering muscle oxidative capacity rather than ageing per se (Kent & Fitzgerald, ).…”

“…), which are all muscle groups with similar or greater muscle oxidative capacity in old compared to young adults (Fitzgerald et al . ; Kent & Fitzgerald, ). By contrast, there is evidence from the ankle plantarflexors that old adults have an increased ATP cost of contraction during dynamic exercise compared to young adults, which is independent of the ability of the cardiovascular system to perfuse the working muscle (Layec et al .…”

Measuring biological aging in humans: A quest

“…Based on information in the section above, developing a proxy measure of biological aging for humans still requires work but is a very dynamic and promising area of investigation with strong potential for translation. Some of the measures described-namely mitochondrial function, DNA methylation, and, to a lesser extent, cellular senescence and autophagy-are ready to be implemented based on several epidemiological studies, although refinements are always possible Choi et al, 2016;Cohen, Morissette-Thomas, Ferrucci, & Fried, 2016;Jylhävä, Pedersen, & Hägg, 2017;Jylhävä et al, 2014;Kananen et al, 2016;Kent & Fitzgerald, 2016;Kim & Jazwinski, 2015;Levine et al, 2018;Li et al, 2018;Marioni et al, 2019;Marttila et al, 2015;Putin et al, 2017;Sillanpää et al, 2018). Measures of telomere length are hampered by noise and wide longitudinal variations that cannot be explained by health events and at this stage are not useful for measuring biological age (Arai et al, 2015;Jodczyk, Fergusson, Horwood, Pearson, & Kennedy, 2014;Tomaska & Nosek, 2009).…”

Low plasma lysophosphatidylcholines are associated with impaired mitochondrial oxidative capacity in adults in the Baltimore Longitudinal Study of Aging

“…Progressive mitochondrial dysfunction is an important hallmark of aging (López‐Otín, Blasco, Partridge, Serrano, & Kroemer, ). A variety of changes in mitochondria have been described in aging skeletal muscle, including a reduction of number, morphological changes, reduced oxidative phosphorylation efficiency that impairs ATP production, and excess release of reactive oxygen species that cause oxidative damage and possibly accumulation of mitochondrial DNA mutations (Gonzalez‐Freire et al, ; Kent & Fitzgerald, ). The decline of skeletal muscle mitochondrial oxidative capacity has been associated with lower gait speed, especially in task that require endurance (Choi et al, ).…”

“…The decline of skeletal muscle mitochondrial oxidative capacity has been associated with lower gait speed, especially in task that require endurance (Choi et al, ). Higher physical activity has been associated with higher mitochondrial mass and function (Kent & Fitzgerald, ). Insulin resistance is associated with lower mitochondrial function, although the direction of this association is still a matter of discussion (Fabbri et al, ).…”