Oxidative capacity and ageing in human muscle

Abstract

This study determined the decline in oxidative capacity per volume of human vastus lateralis muscle between nine adult (mean age 38.8 years) and 40 elderly (mean age 68.8 years) human subjects (age range 25‐80 years). We based our oxidative capacity estimates on the kinetics of changes in creatine phosphate content ([PCr]) during recovery from exercise as measured by 31P magnetic resonance (MR) spectroscopy. A matched muscle biopsy sample permitted determination of mitochondrial volume density and the contribution of the loss of mitochondrial content to the decline in oxidative capacity with age. The maximal oxidative phosphorylation rate or oxidative capacity was estimated from the PCr recovery rate constant (kPCr) and the [PCr] in accordance with a simple electrical circuit model of mitochondrial respiratory control. Oxidative capacity was 50 % lower in the elderly vs. the adult group (0.61 ± 0.04 vs. 1.16 ± 0.147 mM ATP s−1). Mitochondrial volume density was significantly lower in elderly compared with adult muscle (2.9 ± 0.15 vs. 3.6 ± 0.11 %). In addition, the oxidative capacity per mitochondrial volume (0.22 ± 0.042 vs. 0.32 ± 0.015 mM ATP (s %)−1) was reduced in elderly vs. adult subjects. This study showed that elderly subjects had nearly 50 % lower oxidative capacity per volume of muscle than adult subjects. The cellular basis of this drop was a reduction in mitochondrial content, as well as a lower oxidative capacity of the mitochondria with age.

Changes in mitochondrial energy utilization in young and old worker honeybees (Apis mellifera)

“…Notably, ATP concentration in trophocytes and fat cells have also been shown to decrease with advancing age in worker bees reared in a thermostatic chamber at 34°C (Hsu and Chan 2011a), providing further support for the idea that young and old workers reared in a field hive can be used for studying aging. This decrease in ATP concentration in trophocytes and fat cells of older workers is also consistent with previous studies showing that ATP levels decrease with advancing age in the gastric mucosa and muscle of humans (Kawano et al 1991;Conley et al 2000;Petersen et al 2003;Gurd et al 2008), the blood and brains of mice (Jayachandran et al 2005;Joo et al 1999), the erythrocytes of rabbits (Subasinghe and Spence 2008) and cows (Bartosz et al 1982), and the hearts of rats (Guerrieri et al 1996). This finding is also consistent with the results of ΔΨm measurements reported in this study; as was the case for NAD + , a decrease in ΔΨm can result in a decrease in ATP concentration.…”

Lower Mitochondrial Energy Production of the Thigh Muscles in Patients With Low‐Normal Ankle‐Brachial Index

“…This is taken as an index of in vivo muscle oxidative phosphorylation capacity, as there are minimal other energy demands during this resting period. k PCr resynthesis is primarily considered a function of maximum mitochondrial ATP production with no or minimal contribution of anaerobic metabolism 15, 16, 17, 18, 19, 20. The percentage of PCr depletion was calculated as the decrease in the PCr peak area from pre‐exercise PCrbaseline to PCr0 21, 22.…”

Muscle strength mediates the relationship between mitochondrial energetics and walking performance

“…Studies conducted in animal models and in humans have shown that skeletal muscle mitochondrial oxidative capacity declines with age (Conley et al ., 2000; Short et al ., 2005; Fleischman et al ., 2010; Peterson et al ., 2012), likely due to a decline in both total mitochondrial mass and decreased intrinsic mitochondrial functional capacity (Conley et al ., 2000). This steady decline of mitochondrial function with aging is believed to contribute to the progressive deterioration of muscle strength and quality (Metter et al ., 1999), as diminished energy production may constrain muscle performance, and dysfunctional mitochondria create oxidative stress that can damage proteins and mitochondrial DNA (Peterson et al ., 2012).…”

“…This method is reproducible (McCully et al ., 2009), can be focused to a specific, single muscle (McCully et al ., 1993), is not affected by postural or balance impairments, and has been validated against in vitro techniques (McCully et al ., 1993; Conley et al ., 2000). Muscular oxidative capacity is indexed by the postexercise PCr resynthesis rate constant, or k PCr , which is determined by monitoring the mono‐exponential recovery of PCr (Meyer, 1988) in the rest period following an exercise‐induced depletion.…”