Lazaro-Pena Maria I, Ward Zachary C, Yang Sifan, Strohm Alexandra, Merrill Alyssa K, Soto Celia A, Samuelson Andrew V
Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, United States.
Department of Biology, University of Rochester, Rochester, NY, United States.
Front Aging. 2022 Jul 8;3:861686. doi: 10.3389/fragi.2022.861686. eCollection 2022.
Discoveries made in the nematode revealed that aging is under genetic control. Since these transformative initial studies, has become a premier model system for aging research. Critically, the genes, pathways, and processes that have fundamental roles in organismal aging are deeply conserved throughout evolution. This conservation has led to a wealth of knowledge regarding both the processes that influence aging and the identification of molecular and cellular hallmarks that play a causative role in the physiological decline of organisms. One key feature of age-associated decline is the failure of mechanisms that maintain proper function of the proteome (proteostasis). Here we highlight components of the proteostatic network that act to maintain the proteome and how this network integrates into major longevity signaling pathways. We focus in depth on the heat shock transcription factor 1 (HSF1), the central regulator of gene expression for proteins that maintain the cytosolic and nuclear proteomes, and a key effector of longevity signals.
在线虫中的发现揭示衰老受基因控制。自这些具有变革性的初步研究以来，线虫已成为衰老研究的首要模型系统。至关重要的是，在生物体衰老中起基本作用的基因、信号通路和过程在整个进化过程中都高度保守。这种保守性带来了关于影响衰老的过程以及在生物体生理衰退中起因果作用的分子和细胞特征识别的丰富知识。与衰老相关的衰退的一个关键特征是维持蛋白质组正常功能的机制（蛋白质稳态）失效。在这里，我们重点介绍维持蛋白质组的蛋白质稳态网络的组成部分，以及该网络如何整合到主要的长寿信号通路中。我们深入关注热休克转录因子1（HSF1），它是维持细胞质和细胞核蛋白质组的蛋白质基因表达的核心调节因子，也是长寿信号的关键效应器。
