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

Abstract

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.

Combined Exercise and Insulin-Like Growth Factor-1 Supplementation Induces Neurogenesis in Old Rats, but Do Not Attenuate Age-Associated DNA Damage

“…The significant decrease of SIRT1 content was associated with a large change in lysine acetylation in the hippocampus, which could affect protein stability. 89 Acetylation of lysine residues could prevent the ubiquitination of the same residue, which would be important for the substrate recognition of proteasome-to-protein degradation. Therefore, overacetylation could impact protein stability and the half-life of proteins.…”

Redox-regulating sirtuins in aging, caloric restriction, and exercise

“…Exercise appears to increase SIRT1 levels in the hippocampus [153], but not in the cerebellum [100]. However, data from other studies have shown that age-associated decreases in brain function can be alleviated by regular exercise [82,154].…”

“…The activation of SIRT1 resulted in enhanced degradation of FOXO3 by the proteasome system. Aging results in a loss of the activity of SIRT1, which is associated with increased levels of lysine acetylation in rat brain and skeletal muscle [42,82,100]. The level of acetylated lysine residues correlated well with that of carbonylation, which may mean that acetylated lysine could not have been ubiquitinated and degraded by proteasomes.…”

Sirtuin-Dependent Metabolic Control and Its Role in the Aging Process

“…In heart, age-related in SIRT1, decline is accompanied by a higher level of oxidative stress and the decrease in the expression of endogenous antioxidant enzymes and their regulators (Ferrara et al, 2008). In central nervous system, aging results in decreased activity of SIRT1 in cerebellum that leads to the increase in acetylation of protein residues specially affecting motor function (Marton et al, 2010). In cell culture models, cellular senescence induced by ionizing radiation is accompanied by the decrease in the levels of SIRT1 (Hong et al, 2010).…”