Schilling Jan M, Patel Hemal H
VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA, 92161, USA.
Department of Anesthesiology, University of California, San Diego, La Jolla, CA, 92093, USA.
J Physiol. 2016 Aug 15;594(16):4581-9. doi: 10.1113/JP270591. Epub 2015 Oct 14.
Many different theories of ageing have been proposed but none has served the unifying purpose of defining a molecular target that can limit the structural and functional decline associated with age that ultimately leads to the demise of the organism. We propose that the search for a molecule with these unique properties must account for regulation of the signalling efficiency of multiple cellular functions that degrade with age due to a loss of a particular protein. We suggest caveolin as one such molecule that serves as a regulator of key processes in signal transduction. We define a particular distinction between cellular senescence and ageing and propose that caveolin plays a distinct role in each of these processes. Caveolin is traditionally thought of as a membrane-localized protein regulating signal transduction via membrane enrichment of specific signalling molecules. Ultimately we focus on two non-canonical roles for caveolin - membrane repair and regulation of mitochondrial function - which may be novel features of stress adaptation, especially in the setting of ageing. The end result of preserving membrane structure and mitochondrial function is maintenance of homeostatic signalling, preserving barrier function, and regulating energy production for cell survival and resilient ageing.
人们已经提出了许多不同的衰老理论，但没有一个理论能起到统一的作用，即定义一个分子靶点来限制与衰老相关的结构和功能衰退，而这种衰退最终会导致生物体死亡。我们认为，寻找具有这些独特性质的分子必须考虑到对多种细胞功能信号传导效率的调节，这些功能会因特定蛋白质的缺失而随着年龄增长而退化。我们提出小窝蛋白就是这样一种分子，它作为信号转导关键过程的调节因子。我们定义了细胞衰老和衰老之间的一个特殊区别，并提出小窝蛋白在这些过程中的每一个中都发挥着独特的作用。传统上，小窝蛋白被认为是一种膜定位蛋白，通过特定信号分子的膜富集来调节信号转导。最终，我们关注小窝蛋白的两个非经典作用——膜修复和线粒体功能调节——这可能是应激适应的新特征，尤其是在衰老的情况下。保持膜结构和线粒体功能的最终结果是维持稳态信号传导、保持屏障功能以及调节能量产生以促进细胞存活和弹性衰老。
