Sirtuin activation of brain during aging process

Aging increases the production of radicals in various tissues and this increase goes hand by hand with neurodegenerative diseases. Melatonin, which is a powerful scavenger of radicals, significantly decreases in the aging process. Curcumin has antiproliferative, antioxidant and antinflammatory features.Sirtuins are family of NAD-dependent deasetylase (class III histon deasetylase). Several studies indicated that SIRT2 is related to neurodegeneration and treatment of salermide, i.e. an inhibitor of SIRT2, has positive impact on neurodegenerative diseases.Following approval of the ethical committee, Wistar rats were divided in the groups of control (1% ethanol-PBS, sc at 17:00 for 30 days), Melatonin (MLT) (10mg\kg+ethanol-PBS, sc at 17:00pm for 30 days), dimethylsulfoxide (DMSO 100µl/bw, ip at 17:00pm for 30 days), Curcumin (CUR) (30mg/kg+DMSO, ip at 17:00pm for 30 days), SLM (100µmol/1µl+DMSO, ip at 17:00pm for 30 days), MLT+CUR and MLT+SLM in the laboratory under condition of equal period light and dark,12 hours of light/12hours dark cycle. The aim of the present study was to investigate the relation between levels of lipid peroxidation and SIRT2 in cerebral cortex of middle-aged rats (13 months, n=42).Comparing to the control groups, treatment of MLT and CUR significantly decreased MDA levels in cerebral cortex of the rats (4,77±0,14nmol/g tissue, 4,90±0,46nmol/g tissue; 6,33±0,71nmol/g tissue, 5,80±0,52nmol/g tissue, respectively, p<0,05). Furthermore, treatment of MLT alone and its combination with CUR or SLM significantly increased the level of GSH in cerebral cortex more than the control groups (2,54±0,03mol/g tissue, 2,82±0,03 mol/g tissue, 2,70±0,03mol/g tissue; 2,53±0,05 mol/g tissue, 2,48±0,06 mol/g tissue, respectively, p<0,05). Treatment of CUR and MLT+SLM increased the level of NO (25,80±2,15mol/g tissue, 28,20±2,14 mol/g tissue; 20,63±0,26 mol/g tissue, respectively p<0,05). The level of cortex NO in the group of MLT+SLM was higher than the groups of MLT, MLT+CUR, and SLM (28,20±2,14 mol/g tissue; 23,13±1,74 mol/g tissue, 21,86±0,99mol/g tissue, 22,75±0,9528, 20±2,14 mol/g tissue, respectively, p<0,05). Treatment of CUR significantly increased the level of SIRT2 in compared to the other groups (228,85±10,41 SIRT2/beta-aktin; 99,99±9,02 SIRT2/beta-aktin, 123,92±17,4 SIRT2/beta-aktin, 88,10±3,48 SIRT2/beta-aktin, 86,32±8,97 SIRT2/beta-aktin, 116,59±11,35 SIRT2/beta-aktin, 106,52±13,60 SIRT2/beta-aktin, respectively p<0,05).In sum, it was found that (1) free radicals in cerebral cortex were increased by aging, (2) treatment of MLT and CUR decreased levels of free radicals, and increased antioxidant defense, (3) treatment of MLT+SLM and CUR increased the levels of NO. However, alone CUR increased SIRT2 level. Finally, it was concluded that SIRT gene expression could be modulated by various agents in aging, and this modulation would have impact on the process of aging. Key words: Aging, melatonin,sirt2, curcumin, salermide, oxidative stress, glutathion, NO