Donati A, Cavallini G, Paradiso C, Vittorini S, Pollera M, Gori Z, Bergamini E
Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Infettivologia ed Epidemiologia--University of Pisa, Italy.
J Gerontol A Biol Sci Med Sci. 2001 Jul;56(7):B288-93. doi: 10.1093/gerona/56.7.b288.
During intervals between meals, autophagy is a major source of nutrients and may remove damaged organelles and membranes. Age-related changes in the regulation of autophagic proteolysis were studied by monitoring the rate of valine release from liver cells of 2-, 6-, 12-, 18-, and 24-month-old male Sprague-Dawley rats fed ad libitum, and incubated in vitro with added amino acids and 10(-7) M of insulin or glucagon. The maximum rate of proteolysis and its maximum inhibition by amino acids were reached at 6 months and declined thereafter. In contrast, the rate of protein degradation in the presence of high concentrations of amino acids was not affected by aging. The inhibitor effect of insulin was additive to that of amino acids and was not altered significantly by age. The conclusion is that altered regulation of autophagic proteolysis decreases susceptibility of older cells to lysosomal degradation, and it may lead to the accumulation of altered organelles and membranes.
在两餐之间的间隔期，自噬是营养物质的主要来源，并且可能清除受损的细胞器和膜。通过监测自由采食的2、6、12、18和24月龄雄性Sprague-Dawley大鼠肝细胞中缬氨酸的释放速率，并在体外与添加的氨基酸以及10⁻⁷ M胰岛素或胰高血糖素一起孵育，研究了自噬性蛋白水解调节的年龄相关变化。蛋白水解的最大速率及其被氨基酸的最大抑制作用在6个月时达到，此后下降。相反，在高浓度氨基酸存在下的蛋白质降解速率不受衰老影响。胰岛素的抑制作用与氨基酸的抑制作用相加，且不受年龄显著改变。结论是自噬性蛋白水解调节的改变降低了老年细胞对溶酶体降解的敏感性，并且可能导致改变的细胞器和膜的积累。
