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 (31)P 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 (k(PCr)) 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.

Figure 1. Stack plot of every third ³¹P NMR spectrum during rest, stimulation and recovery in an elderly individual

The abscissal scale references PCr to a chemical shift (δ) of -2.54 p.p.m. P_i, inorganic phosphate.

Figure 2. Metabolite levels as a function of time during the stimulation and recovery experiment

Symbols indicate means and error bars indicate s.e.m. Double-headed arrows indicate the duration of stimulation. □, adult subjects; ▪, elderly subjects.

Figure 3. [PCr] recovery following stimulation

Continuous lines are monoexponential fits to the data for an adult (□) and an elderly (▪) subject. The vertical dashed lines denote the time constant for each recovery.

Figure 4. [PCr] recovery rate constant (k_PCr) as a function of age

The line represents the regression equation: y = -0.0005x = 0.057 (r² = 0.35). Symbols as in Fig. 2.

Figure 5. Oxidative capacity as a function of age

The line represents the regression equation: y = -0.017x = 1.777 (r² = 0.34). Symbols as in Fig. 2.

Figure 6. Oxidative capacity, mitochondrial volume density (V_V(mt,f)) and oxidative capacity/V_V(mt,f) in the adult and elderly groups

Values are means ±s.e.m. and asterisks denote significant difference from the adult values. □, adult subjects; ▪, elderly subjects.