Ferrara Nicola, Rinaldi Barbara, Corbi Graziamaria, Conti Valeria, Stiuso Paola, Boccuti Silvia, Rengo Giuseppe, Rossi Francesco, Filippelli Amelia
Department of Health Sciences, Faculty of Medicine, University of Molise, Campobasso, Italy.
Rejuvenation Res. 2008 Feb;11(1):139-50. doi: 10.1089/rej.2007.0576.
The objective of this study was to determine the effects of aging and exercise training on SIRT1 activity and to identify a pathway linking SIRT1 to antioxidant response and cell cycle regulation in rats. SIRT1 is a NAD(+)-dependent deacetylase involved in the oxidative stress response and aging. The effects of aging and of moderate and prolonged exercise training in rats are unknown. We measured SIRT1 activity in heart and adipose tissue of young (6 months old), sedentary old (24 months), and trained old (24 months) rats using an assay kit. Peroxidative damage was determined by measuring levels of thiobarbituric reactive substances (TBARS) and the protein-aldehyde adduct 4-hydroxynonenal (4-HNE). MnSOD, catalase, and FOXO3a levels were evaluated by Western blot, and GADD45a, cyclin D(2), and FOXO3a mRNA by RT-PCR. Aging significantly reduced SIRT1 activity in heart, but not in adipose tissue, increased TBARS and 4-HNE and decreased Mn-SOD and catalase expression in both heart and adipose tissue. Aging did not affect FOXO3a protein expression in the heart or FOXO3a mRNA in adipose tissue. Exercise training significantly increased FOXO3a protein in the heart and FOXO3a mRNA in adipose tissue of aged rats. It also significantly increased Mn-SOD and catalase levels in both heart and adipose tissue. The exercise-induced increase in SIRT1 activity in the heart caused a decrease in cyclin D(2) and an increase in GADD45a mRNA expression. There was a similar decrease in cyclin D(2), and no changes in GADD45a mRNA expression in adipose tissue. We concluded that exercise training, which significantly increases SIRT1 activity, could counteract age-related systems impairment.
本研究的目的是确定衰老和运动训练对SIRT1活性的影响，并确定一条将SIRT1与大鼠抗氧化反应和细胞周期调控联系起来的途径。SIRT1是一种参与氧化应激反应和衰老的NAD(+)依赖性脱乙酰酶。衰老以及适度和长期运动训练对大鼠的影响尚不清楚。我们使用检测试剂盒测量了年轻（6个月大）、久坐不动的老年（24个月）和经过训练的老年（24个月）大鼠心脏和脂肪组织中的SIRT1活性。通过测量硫代巴比妥酸反应性物质（TBARS）和蛋白质-醛加合物4-羟基壬烯醛（4-HNE）的水平来确定氧化损伤。通过蛋白质印迹法评估锰超氧化物歧化酶（MnSOD）、过氧化氢酶和FOXO3a的水平，通过逆转录聚合酶链反应（RT-PCR）评估生长停滞和DNA损伤诱导蛋白45α（GADD45a）、细胞周期蛋白D(2)和FOXO3a的mRNA水平。衰老显著降低了心脏中的SIRT1活性，但脂肪组织中未降低，同时增加了心脏和脂肪组织中的TBARS和4-HNE，并降低了Mn-SOD和过氧化氢酶的表达。衰老并未影响心脏中FOXO3a蛋白的表达或脂肪组织中FOXO3a的mRNA表达。运动训练显著增加了老年大鼠心脏中的FOXO3a蛋白和脂肪组织中的FOXO3a mRNA。它还显著增加了心脏和脂肪组织中Mn-SOD和过氧化氢酶的水平。运动诱导的心脏中SIRT1活性增加导致细胞周期蛋白D(2)减少和GADD45a mRNA表达增加。脂肪组织中细胞周期蛋白D(2)也有类似的减少，而GADD45a mRNA表达没有变化。我们得出结论，显著增加SIRT1活性的运动训练可以抵消与年龄相关的系统损伤。
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