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semmelweis university - Faculty of Physical Education and Sport ...

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Orsolya Marton<br />

Semmelweis University, <strong>Faculty</strong> <strong>of</strong> P. E. <strong>and</strong> <strong>Sport</strong> Sciences (TF), Budapest, Hungary<br />

Supervisor: Dr. Zsolt Radák, pr<strong>of</strong>essor<br />

Consultant: Erika Koltai, PhD student<br />

The Effect <strong>of</strong> Aging <strong>and</strong> Exercise on Acetylation <strong>of</strong> Proteins in Cerebellum <strong>of</strong> Rats: Role<br />

<strong>of</strong> Sirtuins<br />

Introduction: Aging is an unavoidable process, in which sirtuins are playing important role.<br />

Sirtuins have got seven classes in mammals <strong>and</strong> are NAD + dependent protein deacetylases.<br />

Moreover, sirtuins suggested regulators <strong>of</strong> fat <strong>and</strong> sugar metabolisms, brain function, DNA<br />

repair, mitochondrial biogenesis, inflammation, apoptosis <strong>and</strong> fiber type differentiation <strong>of</strong><br />

skeletal muscle. In the present study the effects <strong>of</strong> sirtuins on proteins in cerebellum by aging<br />

<strong>and</strong> mild exercise were tested.<br />

Hypothesis: Our hypothesis is that exercise training prevents the age-associated decrease in<br />

the level <strong>and</strong> activity <strong>of</strong> SIRT1 in the cerebellum. Furthermore, we suggested that NAMPT<br />

level also decreasing with aging, since this enzyme plays a crucial role in the biosynthesis <strong>of</strong><br />

NAD + . Aging is associated with decreases in protein turnover <strong>and</strong> increases the half-life <strong>of</strong><br />

proteins. We hypothesized that acetylation <strong>of</strong> lysine residues could curb the ubiquitination,<br />

hence aging increases the level <strong>of</strong> acetylation, which results in increases in the half life <strong>of</strong><br />

proteins.<br />

Methods: Twelwe young (6 mo) <strong>and</strong> ten old (30 mo) male Wistar rats were selected for the<br />

study <strong>and</strong> divided into young control (YC), young exercised (YE), old control (OC) <strong>and</strong> old<br />

exercise (OE) groups. The exercise program was moderate running on treadmill for four<br />

weeks, four time a week with the gradually increasing duration with the starting from 20 min<br />

on the first week <strong>and</strong> 40 min on the last week. The running intensity was set at 60% <strong>of</strong> the<br />

VO2 max (ranged between 10-20 m/min). The brain function was evaluated by Morris-maze<br />

test. The strength <strong>of</strong> forelimb <strong>of</strong> the animals was assessed by gripping test on pole. The<br />

biochemical analysis was assessed by Western-blot <strong>and</strong> fluorometric methods. Statistical<br />

significance was assessed by one-way ANOVA, followed by Tukey‘s post hoc test <strong>and</strong><br />

correlation. The significance level was set at p

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