Aging and exercise affect the level of protein acetylation and SIRT1 activity in cerebellum of male rats.

Aging is associated with a gradual decline in cognitive and motor functions, the result of complex biochemical processes including pre- and posttranslational modifications of proteins. Sirtuins are NAD(+) dependent protein deacetylases. These enzymes modulate the aging process by lysine deacetylation, which alters the activity and stability of proteins. Exercise can increase mean life-span and improve quality of life. Data from our laboratories revealed that 4 weeks of treadmill running improves performance in the Morris Maze test for young (4 months, old) but not old (30 months, old) male rats, and the exercise could not prevent the age-associated loss in muscle strength assessed by a gripping test. The positive correlation between protein acetylation and the gripping test suggests that the age-dependent decrease in relative activity of SIRT1 in the cerebellum impairs motor function. Similarly to the acetylation level of total proteins, the acetylation of ά -tubulin is also increased with aging, while the effect of exercise training was not found to be significant. Moreover, the protein content of nicotinamide phosphoribosyltransferase, one of the key enzymes of NAD biosynthesis, decreased in the young exercise group. These data suggest that aging results in decreased specific activity of SIRT1 in cerebellum, which could lead to increased acetylation of protein residues, including ά-tubulin, that interfere with motor function.

High altitude and free radicals.

High altitude exposure results in decreased oxygen pressure and an increased formation of reactive oxygen and nitrogen species (RONS), which is often associated with increases in oxidative damage to lipids, proteins and DNA. Exposure to high altitude appears to decrease the activity and effectiveness of antioxidant enzymes system. Moreover, during high altitude exposure several RONS generating source are activated, including mitochondrial electron transport chain, xanthine oxidase, and nitric oxide synthase (NO). Physical exercise at high altitude can further enhance the oxidative stress. The available information suggests that RONS are involved and are even a causative factor of acute mountain sickness. Supplementation of antioxidant seems to be a necessary step to prevent or decrease to high altitude exposure associated oxidative stress. Key PointsReactive oxygen and nitrogen speciesHigh altitude-induced oxidative stressAntioxidant down regulation by altitudeExercise and altitude associated oxidative stress.