Differential Effect of Endurance Training on Mitochondrial Protein Damage, Degradation, and Acetylation in the Context of Aging

Abstract

Acute aerobic exercise increases reactive oxygen species and could potentially damage proteins, but exercise training (ET) enhances mitochondrial respiration irrespective of age. Here, we report a differential impact of ET on protein quality in young and older participants. Using mass spectrometry we measured oxidative damage to skeletal muscle proteins before and after 8 weeks of ET and find that young but not older participants reduced oxidative damage to both total skeletal muscle and mitochondrial proteins. Young participants showed higher total and mitochondrial derived semitryptic peptides and 26S proteasome activity indicating increased protein degradation. ET however, increased the activity of the endogenous antioxidants in older participants. ET also increased skeletal muscle content of the mitochondrial deacetylase SIRT3 in both groups. A reduction in the acetylation of isocitrate dehydrogenase 2 was observed following ET that may counteract the effect of acute oxidative stress. In conclusion aging is associated with an inability to improve skeletal muscle and mitochondrial protein quality in response to ET by increasing degradation of damaged proteins. ET does however increase muscle and mitochondrial antioxidant capacity in older individuals, which provides increased buffering from the acute oxidative effects of exercise.

Radical Oxygen Species, Exercise and Aging: An Update

“…Future studies should focus on the relationship between exercise intensity and oxidative stress in the elderly, and the relationship between different types of exercise (aerobic, anaerobic or mixed) and oxidative stress in this population. [25,26,113]. These studies found that endurance training attenuated resting and exerciseinduced oxidative stress, and increased protection against oxidative stress by increasing the efficiency of enzymatic and non-enzymatic antioxidant defence systems, suggesting training-induced adaptations of oxidative stress.…”

Release of skeletal muscle peptide fragments identifies individual proteins degraded during insulin deprivation in type 1 diabetic humans and mice

“…Detected PTMs were attested following previously published guidelines (11). Relative expression of protein PTMs (at sample level) between two groups was performed using peptide intensities as described previously (24) and then displayed as percent difference between study days.…”

The ageing neuromuscular system and sarcopenia: a mitochondrial perspective

“…An acute endurance exercise programme up‐regulated proteins involved in activation of the electron transport chain components such as mitochondrial SIRT3, as well as mitochondrial antioxidant capacity, in older adults (>65 years) (Johnson et al . ). Nevertheless, elevated protein degradation and reduced oxidative damage were only observed in the young, suggesting age‐specific effects (Johnson et al .…”

“…Nevertheless, elevated protein degradation and reduced oxidative damage were only observed in the young, suggesting age‐specific effects (Johnson et al . ). In contrast, 12 weeks of aerobic exercise intervention in 20‐ and 70‐year‐old participants resulted in increased aerobic capacity, skeletal muscle size and markers of mitochondrial biogenesis and dynamics in both groups (Konopka et al .…”