Is There a Link between Mitochondrial Reserve Respiratory Capacity and Aging?

Abstract

Oxidative phosphorylation is an indispensable resource of ATP in tissues with high requirement of energy. If the ATP demand is not met, studies suggest that this will lead to senescence and cell death in the affected tissue. The term reserve respiratory capacity or spare respiratory capacity is used to describe the amount of extra ATP that can be produced by oxidative phosphorylation in case of a sudden increase in energy demand. Depletion of the reserve respiratory capacity has been related to a range of pathologies affecting high energy requiring tissues. During aging of an organism, and as a result of mitochondrial dysfunctions, the efficiency of oxidative phosphorylation declines. Based on examples from the energy requiring tissues such as brain, heart, and skeletal muscle, we propose that the age-related decline of oxidative phosphorylation decreases the reserve respiratory capacity of the affected tissue, sensitizes the cells to surges in ATP demand, and increases the risk of resulting pathologies.

Rotenone-induced energy stress decompensated in ventral mesocerebrum is associated with Parkinsonism progression in rats

“…Energy stress has been demonstrated to burden mitochondria via energy metabolism compensation, which favors the production of reactive oxygen species (23,24). Furthermore, energy stress may induce dysfunction in energy production and anti-oxidation systems (20,21), which exacerbates the energy crisis and further damages the cells, particularly during energy decompensation. Therefore, in some energy sensitive cells, repeated energy stress may damage the energy producing ability of cells, which may accumulate and result in the cells being more sensitive to energy disturbances.…”

“…In the aged organisms, oxidative damage may accumulate more readily, leading to weakened energy producing capabilities (20), which favors the induction of energy crisis by rotenone treatment.…”

“…Since rotenone treatment made some rats very weak and unable to stay on the bar until 24 to 48 h later, the rota-rod tests were performed 48 h post-treatment, once every 4 weeks. The results demonstrated that, in control group, the time that rats remained on the bar initially increased between weeks 4-12, (45.0±21.4, 63.0±25.8 and 85.1±31.5 sec, respectively), then was maintained at 91.4±30.7 sec for weeks [16][17][18][19][20][21][22][23][24] ( Fig. 2A).…”

“…With energy stress, cells respond by enhancing their energy metabolism activity, therefore the levels of lactic acid, ND1 mRNA and LDHB mRNA increase; however, if energy stress is severe and the cells maximum energy producing capabilities are insufficient, cell dysfunction occurs with subsequent inhibition of energy producing activity (20,21). These results suggested that, in VM tissue following rotenone treatment for 24 weeks, the energy producing capability of cells may have been attenuated, thus the energy disturbance induced by rotenone treatment could not be withstood.…”

Differential expression of seven mitochondrion enzymes in osteoarthritis cartilages and normal cartilages

“…Electrons that are donated from the Krebs cycle are passed through the electron transport chain (ETC) eventually reducing oxygen and producing water. This potential created by the flux of electrons between the intermembrane space and the matrix is utilized by the ATP synthase to phosphorylate ADP producing ATP (5).…”