Vittorini S, Paradiso C, Donati A, Cavallini G, Masini M, Gori Z, Pollera M, Bergamini E
Istituto di Patologia Generale, University of Pisa, Italy.
J Gerontol A Biol Sci Med Sci. 1999 Aug;54(8):B318-23. doi: 10.1093/gerona/54.8.b318.
Increases of protein carbonyl in animal tissues have been associated with the aging process. So far, the accumulation of oxidized proteins, highly susceptible to proteolysis, has been attributed to age-related changes in proteasomal alkaline proteases. Carbonyl in protein was monitored in six different tissues of male Sprague-Dawley rats fed ad libitum up to the age of 27 months, and of 24 and 27-month-old rats subjected to anti-aging diet restriction (every-other-day feeding ad libitum). Alkaline protease activities and liver lysosomal proteolysis were studied. The levels of protein carbonyl were significantly different in different tissues, and quite stable throughout life; accumulation was restricted to liver tissue very late in life, between ages 24 and 27 months; was fully prevented by diet restriction; was not accompanied by any diet-restriction-sensitive decline of alkaline protease activity; and was accompanied by a dramatic age-related decline in lysosomal proteolysis that was partially prevented by anti-aging diet restriction. No correlation was found between levels of alkaline protease activity and levels of protein carbonyl in the different tissues from younger animals. It is concluded that the process of autophagy, a well-known mechanism for cell maintenance, may deserve more interest in aging studies.
动物组织中蛋白质羰基的增加与衰老过程相关。到目前为止，极易被蛋白酶解的氧化蛋白质的积累，被归因于蛋白酶体碱性蛋白酶的年龄相关变化。对自由采食直至27月龄的雄性斯普拉格-道利大鼠的六种不同组织，以及24和27月龄接受抗衰老饮食限制（隔日自由采食）的大鼠的组织，监测了蛋白质中的羰基。研究了碱性蛋白酶活性和肝脏溶酶体蛋白水解作用。蛋白质羰基水平在不同组织中存在显著差异，并且在整个生命过程中相当稳定；羰基积累仅限于生命后期（24至27月龄）的肝脏组织；饮食限制可完全预防羰基积累；羰基积累并未伴随碱性蛋白酶活性出现任何对饮食限制敏感的下降；并且羰基积累伴随着溶酶体蛋白水解作用显著的年龄相关下降，而抗衰老饮食限制可部分预防这种下降。在较年轻动物的不同组织中，未发现碱性蛋白酶活性水平与蛋白质羰基水平之间存在相关性。得出的结论是，自噬过程作为一种众所周知的细胞维持机制，可能在衰老研究中值得更多关注。
