Clin Res Cardiol (2023). https://doi.org/10.1007/s00392-023-02180-w

Reduced lifespan in male rats with low intrinsic exercise capacity is associated with reduced complex IV threshold in aging
A. Spangnolo1, E. Heyne1, T. Doenst1, M. Schwarzer1
1Klinik für Herz- und Thoraxchirurgie, Universitätsklinikum Jena, Jena;

In a rat model of high (HCR) and low (LCR) intrinsic exercise capacity, LCR showed a shorter lifespan. There were no differences in cardiac mitochondrial respiration or cardiac function between adult HCR and LCR. Complex specific threshold further describes the relation between respiratory capacity and complex activity. The complex specific threshold refers to the percentage of inhibition of a mitochondrial complex activity above which mitochondrial respiration rapidly decreases. We thus determined the threshold effect of mitochondrial complexes.

We determined complex I and IV threshold in isolated cardiac interfibrillar mitochondria of male adult and old HCR and LCR by measuring complex activities and mitochondrial respiration with different concentrations of specific inhibitors.

Complexes I and IV showed threshold effects in adult and old mitochondria in both phenotypes. In adults, complex I and IV thresholds were comparable between HCR and LCR. Complex I threshold was not affected by phenotype or age. However, complex IV threshold tendentially decreased in LCR with age (complex IV threshold (%) adult LCR vs. old LCR 58 ±7 vs. 39 ± 4). In addition, complex IV threshold was lower in old LCR compared to old HCR (complex IV threshold (%) old LCR vs HCR 39 ± 4 vs. 65 ± 7).

Aging was associated with a selective decrease of complex IV threshold in rats with low exercise capacity which is associated with lower life expectancy.


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