Skeletal Muscle Mitochondrial Energetics Are Associated With Maximal Aerobic Capacity and Walking Speed in Older Adults

Aging is associated with reduced mitochondrial capa city (1,2) and loss of muscle mass and strength (3,4), which could potentially predispose individuals to frailty and a slower preferential walking speed (5,6). Preferred walking speed is slower in older adults (7,8), and is a strong, independent predictor of disability, health care utilization, nursing home admission, and mortality (9–11). A number of studies have found a close relationship between VO2 peak and walking speed in older adults (12,13), which suggests that the decline in aerobic capacity contributes to, and may be predictive of, slower walking speed with age. A reduced efficiency of locomotion is also apparent in older adults, which leads to an increased metabolic cost of walking (14). Aging is also associated with declines in both the capacity and efficiency of energy supply in muscle. Several studies using a variety of techniques have reported reduced capacity to generate ATP with age (1,15,16). The age-related changes in skeletal muscle mitochondrial function apparent in these studies are consistent with their likely role in the parallel loss of aerobic capacity (1,16). In addition, reduced mitochondrial efficiency (energy conversion of O2 uptake into ATP generation) has been reported in a variety of tissues in vitro and in vivo (17–19). The importance of mitochondrial efficiency is that it could affect the ability to generate ATP during ambulation (16) as well as movement efficiency (20–22). One study found that walking speed in patients with peripheral arterial disease was related to their capacity for ATP generation assessed by phosphorus magnetic resonance spectroscopy (31P MRS) (23). Although the loss of muscle mitochondrial function has been widely hypothesized to contribute to the decline in VO2 max and slowing of locomotion with age, there currently is insufficient published evidence to show that reductions in available energy results in a decline in customary walking speed with aging and disease (11). Furthermore, the potential role of mitochondrial efficiencey in energy availablity for walking has not been examined. The goal of this study was to test the hypothesis that reduced mitochondrial capacity and efficiency are associated with slower walking speed in older adults. In vitro (respirometry) and in vivo (31P MRS) measurements of mitochondrial function were combined and related to whole-body aerobic capacity (VO2 peak) and preferred walking speed in a group of older men and women. High-resolution respirometry of permeabilized fibers isolated from muscle biopsy specimens yielded mitochondrial oxidative capacity (State 3 or St3 respiration). These measures of mitochondrial capacity at cellular level were extended to the muscle tissue level by assessing quadriceps muscle volume with magnetic resonance imaging (MRI). 31P MRS was used to determine the maximum mitochondrial ATP production (ATPmax) in vivo, which was combined with St3 respiration to yield an index of mitochondrial efficiency (ATPmax/St3). This study tested the paradigm that muscle mitochondrial properties affect walking speed and that mitochondria capacity and efficiency may be associated with the decline in mobility with age (Figure 1). Figure 1. Concept map illustrating age-related changes in muscle physiology and how they contribute to reduced walking speed in older adults. This study examined the relationships between muscle mitochondrial capacity/efficiency, aerobic capacity, and walking speed ...