Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina (IBUB), Universitat de Barcelona, Nucli Universitari de Pedralbes, 08028 Barcelona, Spain.
Exp Gerontol. 2010 Sep;45(9):702-10. doi: 10.1016/j.exger.2010.04.010. Epub 2010 May 9.
Dietary interventions have been proposed as a way to increase lifespan and improve health. The senescence-accelerated prone 8 (SAMP8) mice have a shorter lifespan and show alterations in the central nervous system. Moreover, this mouse strain shows decreased sirtuin 1 protein expression and elevated expression of the acetylated targets NFkappaB and FoxO1, which are implicated in transcriptional control of key genes in cell proliferation and cell survival, in reference to control strain, SAMR1. After eight weeks of intermittent fasting, sirtuin 1 protein expression was recovered in SAMP8. This recovery was accompanied by a reduction in the two acetylated targets. Furthermore, SAMP8 showed a lower protein expression of BDNF and HSP70 while intermittent fasting re-established normal values. The activation of JNK and FoxO1 was also reduced in SAMP8 mice subjected to an IF regimen, compared with control SAMP8. Our findings provide new insights into the participation of sirtuin 1 in ageing and point to a potential novel application of this enzyme to prevent frailty due to ageing processes in the brain.
饮食干预被提出作为一种延长寿命和改善健康的方法。衰老加速敏感 8 号（SAMP8）小鼠的寿命更短，并显示中枢神经系统的改变。此外，这种小鼠品系显示出沉默信息调节因子 1 （Sirtuin 1）蛋白表达降低，乙酰化靶标 NFkappaB 和 FoxO1 的表达升高，这与关键基因的转录控制有关，这些基因涉及细胞增殖和细胞存活，与对照品系 SAMR1 相比。间歇性禁食 8 周后，SAMP8 中的 Sirtuin 1 蛋白表达得到恢复。这种恢复伴随着两个乙酰化靶标的减少。此外，SAMP8 显示出 BDNF 和 HSP70 的蛋白表达降低，而间歇性禁食则恢复了正常水平。与对照 SAMP8 相比，接受 IF 方案的 SAMP8 小鼠中 JNK 和 FoxO1 的激活也减少。我们的研究结果为 Sirtuin 1 参与衰老提供了新的见解，并指出这种酶在预防因大脑衰老过程而导致的虚弱方面有潜在的新应用。
