High Genetically Determined Exercise Capacity Prevents the Loss of Mitochondrial Function in Advanced Age

High exercise capacity is associated with greater life expectancy. In advanced age, exercise capacity declines. This decline has been linked to impaired mitochondrial function and associated with higher risk for cardiovascular disease as well as impaired surgical outcome. In the rat model of genetically determined differences in exercise capacity, high exercise capacity (HCR) is associated with a mean survival of 34 month compared with a mean survival of 24 month with low exercise capacity (LCR). We hypothesized that toward the end of LCRs lifespan cardiac mitochondrial respiratory capacity is reduced compared with HCR.

HCR and LCR rats were assessed at 24 months of age. We characterized weights, glucose tolerance, citrate synthase activity, mitochondrial morphology, respiratory capacity and ATP/O ratios in cardiac interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria, isolated with differential centrifugation.

LCR has significantly higher body weight and lower glucose tolerance than HCR (HCR vs. LCR AUC 1115 ± 203 vs. 1417 ± 41). Cardiac citrate synthase activity as a mitochondrial marker was not different between HCR and LCR (12.4 ± 1.2 vs. 12.9 ± 2.5). Both, IFM and SSM were not different in size and internal complexity between HCR and LCR. However, respiratory capacity of both mitochondrial subpopulations was lower in LCR compared with HCR (HCR-IFM vs. LCR-IFM vs. HCR-SSM vs. LCR-SSM 226 ± 29 vs. 193 ± 21 vs. 206 ± 14 vs. 157 ± 20 natoms O/min/mg protein). There was no difference in ADP limited respiration and ADP/O ratios between strains (state 4 36,2 ± 1,8, ADP/O2,56 ± 0,06). These findings were identical in males and females.

High exercise capacity seems to be associated with preserved cardiac mitochondrial respiratory capacity in aged animals. One may speculate that increased life expectancy may be linked to preserved cardiac mitochondrial respiratory capacity.

No conflict of interest has been declared by the author(s).