Treadmill exercise induces selective changes in hippocampal histone acetylation during the aging process in rats

Physical exercise and the aging process have been shown to induce opposite effects on epigenetic marks, such as histone acetylation. The impact of exercise on hippocampal histone acetylation on specific lysine residues, especially during the aging process, is rarely studied. The aim of this study was to investigate the effect of treadmill exercise (20 min/day during 2 weeks) on H3K9, H4K5 and H4K12 acetylation levels in hippocampi of young adult and aged rats. Male Wistar rats aged 3 or 20-21 months were assigned to sedentary and exercise groups. Single-trial step-down inhibitory avoidance conditioning was employed as an aversive memory paradigm. Hippocampal H3K9, H4K5 and H4K12 acetylation was determined by Western blotting. The daily moderate exercise protocol improved the aversive memory performance and increased hipocampal H4K12 acetylation levels in both tested ages. Exercise was also able to increase H3K9 acetylation levels in aged rats. An age-related decline in memory performance was observed, without any effect of the aging process on histone acetylation state. Our data suggest that treadmill exercise can impact hippocampal the histone acetylation profile in an age- and lysine-dependent manner. In addition, higher hippocampal H4K12 acetylation levels at both ages may be related to improvement of aversive memory performance.