Department of Pharmacology and Physiology, University of Zaragoza, c) Domingo Miral s/n, 50009 Zaragoza, Spain.
Neurobiol Aging. 2011 Nov;32(11):2045-54. doi: 10.1016/j.neurobiolaging.2009.12.013. Epub 2010 Jan 22.
We evaluated the autophagy-lysosomal pathway and membrane fluidity in brain cells and mitochondrial membranes obtained from senescence-accelerated (SAMP(8)) and senescence-resistant (SAMR(1)) mice at 5 and 10 months of age. Moreover, we studied whether chronic treatment from age 1 to 10 months with melatonin stabilizes membrane fluidity. Fluidity was measured by polarization changes of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene-p-toluene sulfonate. Results showed that in untreated animals at 5 months of age, synaptosomal and mitochondrial fluidity was decreased in SAMP(8) compared to SAMR(1), as was the cathepsin D/B ratio, indicating dysfunction of the autophagy-lysosomal pathway. Moreover, we detected synaptosomal rigidity and programmed cell death capability in both groups at 10 months of age. Mitochondrial fluidity, however, did not show a significant age-dependent change but was lower in SAMP(8) than in SAMR(1) at the 5- and 10-month time points. Melatonin administration prevented rigidity in the mitochondrial membrane and seemed to decrease age-related autophagy-lysosomal alterations. These data suggest that melatonin may act to slow down the aging process because of its ability to enhance membrane fluidity and maintain structural pathways.
我们评估了来自快速老化（SAMP(8))和抗快速老化（SAMR(1))小鼠 5 个月和 10 个月龄时脑细胞和线粒体膜中的自噬溶酶体途径和膜流动性。此外，我们研究了从 1 个月龄到 10 个月龄的慢性褪黑素处理是否能稳定膜流动性。通过 1-(4-三甲铵苯基)-6-苯基-1,3,5-己三烯-p-甲苯磺酸盐的偏振变化来测量流动性。结果表明，在未经处理的 5 月龄动物中，与 SAMR(1)相比，SAMP(8)中的突触小体和线粒体流动性降低，组织蛋白酶 D/B 比值也降低，表明自噬溶酶体途径功能障碍。此外，我们在两组动物 10 月龄时检测到突触小体刚性和程序性细胞死亡能力。然而，线粒体流动性并没有随年龄的变化而显著变化，但在 5 个月和 10 个月时，SAMP(8)中的线粒体流动性均低于 SAMR(1)。褪黑素的给药可防止线粒体膜的刚性，并似乎可减少与年龄相关的自噬溶酶体改变。这些数据表明，褪黑素可能通过增强膜流动性和维持结构途径来减缓衰老过程，从而发挥作用。
