The relationship between mitochondrial function and walking performance in older adults with a wide range of physical function

Abstract

Background Age related declines in walking performance may be partly attributable to skeletal muscle mitochondrial dysfunction as mitochondria produce over 90% of ATP needed for movement and the capacity for oxidative phosphorylation decreases with age. Methods Participants were from two studies: an ancillary to the Lifestyle Interventions and Independence for Elders (LIFE) Study (n = 33), which recruited lower functioning participants (Short Physical Performance Battery [SPPB], 7.8 ± 1.2), and the Study of Energy and Aging-Pilot (SEA, n = 29), which enrolled higher functioning (SPPB, 10.8 ± 1.4). Physical activity was measured objectively using the Actigraph accelerometer (LIFE) and SenseWear Pro armband (SEA). Phosphocreatine recovery following muscle contraction of the quadriceps was measured using 31P magnetic resonance spectroscopy and ATPmax (mM ATP/s) was calculated. Walking performance was defined as time (s) to walk 400 m at a usual-pace. The cross-sectional association between mitochondrial function and walking performance was assessed using multivariable linear regression. Results Participants were 77.6 ± 5.3 years, 64.2% female and 67.2% white. ATPmax was similar in LIFE vs. SEA (0.52 ± 0.14 vs. 0.55 ± 0.14, p = 0.31), despite different function and activity levels (1.6 ± 2.2 vs.77.4 ± 73.3 min of moderate activity/day, p < 0.01). Higher ATPmax was related to faster walk-time in SEA (r2 = 0.19, p = 0.02,); but not the LIFE (r2 < 0.01, p = 0.74) cohort. Conclusions Mitochondrial function was associated with walking performance in higher functioning, active older adults, but not lower functioning, sedentary older adults.

Skeletal muscle ex vivo mitochondrial respiration parallels decline in vivo oxidative capacity, cardiorespiratory fitness, and muscle strength: The Baltimore Longitudinal Study of Aging

“…However, this association was no longer statistically significant when the analysis was adjusted for age and BMI (β = −.025, p = .848 and β = .184, p = .192, respectively). P 31 MRI spectroscopy studies have reported a significant correlation between mitochondrial function and muscle strength, suggesting that muscle function mediates the association between mitochondrial function and mobility (Choi et al., ; Santanasto et al., ; Zane et al., ).…”

“…Again, our findings could be due to the heterogeneity of the effect in the analyzed samples. For example, it has been shown that the mitochondrial function is associated with walking performance in higher functioning active older adults, but not lower functioning sedentary adults (Santanasto et al., ). Interestingly, we found a significant negative correlation of respiration in State 4, Submaximal State 3, and State 3 with the 400‐m walk test, a proxy of mobility and fatigability.…”

Increased skeletal muscle mitochondrial free radical production in peripheral arterial disease despite preserved mitochondrial respiratory capacity

“…In this study, participants were carefully matched for physical activity using both accelerometry (Table 1) and questionnaires. Prior studies have associated a decline in mitochondrial function with walking performance in older adults (Coen et al, 2013;Santanasto et al, 2016) and in patients with PAD (Hou et al, 2002), while also demonstrating the beneficial effects of exercise to off-set this age-related decline in mitochondrial function (Joseph, Adhihetty, & Leeuwenburgh, 2015). Furthermore, the efficacy of physical activity to preserve mitochondrial function with age would most likely translate into preserved mitochondrial function with maintained physical activity in patients with PAD.…”

Skeletal muscle mitochondrial remodeling in exercise and diseases

“…176 ATPmax and mitochondrial respiration rates measured in permeabilized muscle fibers also correlate with walking speed in older adults. 177,178 Walking speed and function is a particularly relevant readout as this is directly related to functional independence in the elderly.…”