Translational Research on Aging and Chronic Disease Laboratory, Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, 80523-1582, USA.
J Physiol. 2017 Oct 15;595(20):6401-6407. doi: 10.1113/JP274335. Epub 2017 Aug 10.
Proteostasis is one of the seven "pillars of aging research" identified by the Trans-NIH Geroscience Initiative and loss of proteostasis is associated with aging and age-related chronic disease. Accumulated protein damage and resultant cellular dysfunction are consequences of limited protein repair systems and slowed protein turnover. When relatively high rates of protein turnover are maintained despite advancing age, damaged proteins are more quickly degraded and replaced, maintaining proteome fidelity. Therefore, maintenance of protein turnover represents an important proteostatic mechanism. However, measurement of protein synthesis without consideration for cell proliferation can result in an incomplete picture, devoid of information about how new proteins are being allocated. Simultaneous measurement of protein and DNA synthesis provides necessary mechanistic insight about proteins apportioned for newly proliferating cells versus for somatic maintenance. Using this approach with a number of murine models of slowed aging shows that, compared to controls, energetic resources are directed more toward somatic maintenance and proteostasis, and away from cell growth and proliferation. In particular, slowed aging models are associated with heightened mechanisms of mitochondrial proteostatic maintenance. Taking cell proliferation into account may explain the paradoxical findings that aging itself and slowed aging interventions can both be characterized by slower rates of protein synthesis.
蛋白质稳态是跨 NIH 衰老研究倡议确定的七大“衰老研究支柱”之一，蛋白质稳态的丧失与衰老和与年龄相关的慢性疾病有关。蛋白质损伤的积累和由此产生的细胞功能障碍是蛋白质修复系统有限和蛋白质周转率减慢的结果。当相对较高的蛋白质周转率在年龄增长的情况下得以维持时，受损的蛋白质会更快地降解和替换，从而保持蛋白质组的保真度。因此，维持蛋白质周转率是一种重要的蛋白质稳定机制。然而，如果不考虑细胞增殖来测量蛋白质合成，可能会导致对其了解不完整，缺乏有关新蛋白质如何分配的信息。同时测量蛋白质和 DNA 的合成可以提供有关新增殖细胞和体细胞维持中分配的蛋白质的必要机制见解。用许多减缓衰老的小鼠模型使用这种方法表明，与对照组相比，能量资源更多地用于体细胞维持和蛋白质稳定，而不是细胞生长和增殖。特别是，减缓衰老的模型与增强的线粒体蛋白质稳态维持机制有关。考虑细胞增殖可以解释一个矛盾的发现，即衰老本身和减缓衰老的干预措施都可以表现为蛋白质合成率较慢。
