Department of Biology, Concordia University, Montreal, Quebec H4B 1R6, Canada.
Oncotarget. 2022 Jul 28;13:918-943. doi: 10.18632/oncotarget.28256. eCollection 2022.
We propose a hypothesis of a mechanism linking cellular aging to cellular quiescence in chronologically aging budding yeast. Our hypothesis posits that this mechanism integrates four different processes, all of which are initiated after yeast cells cultured in a medium initially containing glucose consume it. Quiescent cells that develop in these cultures can be separated into the high- and low-density sub-populations of different buoyant densities. Process 1 of the proposed mechanism consists of a cell-cycle arrest in the G phase and leads to the formation of high-density quiescent cells. Process 2 results in converting high-density quiescent cells into low-density quiescent cells. Processes 3 and 4 cause a fast or slow decline in the quiescence of low- or high-density quiescent cells, respectively. Here, we tested our hypothesis by assessing how four different geroprotectors influence the four processes that could link cellular aging to cellular quiescence. We found that these geroprotectors differently affect processes 1 and 2 and decelerate processes 3 and 4. We also found that a rise in trehalose within quiescent yeast contributes to chronological aging and quiescence maintenance. These data collectively provide conclusive evidence for a mechanistic link between cellular aging and cellular quiescence.
我们提出了一个假说，即细胞衰老与酵母细胞在有丝分裂过程中的衰老之间存在一种机制联系。我们的假说是，这个机制整合了四个不同的过程，所有这些过程都是在酵母细胞在最初含有葡萄糖的培养基中消耗完葡萄糖后开始的。在这些培养物中发育的静止细胞可以分为不同浮力密度的高密度和低密度亚群。所提出的机制的第 1 个过程是在 G 期的细胞周期停滞，导致高密度静止细胞的形成。第 2 个过程导致高密度静止细胞转化为低密度静止细胞。第 3 和第 4 个过程分别导致低或高密度静止细胞的静止迅速或缓慢下降。在这里，我们通过评估四种不同的长寿保护剂如何影响可能将细胞衰老与细胞静止联系起来的四个过程来检验我们的假说。我们发现，这些长寿保护剂对过程 1 和 2 有不同的影响，并减缓了过程 3 和 4 的速度。我们还发现，静止酵母中海藻糖的增加有助于有丝分裂衰老和静止维持。这些数据共同为细胞衰老和细胞静止之间的机制联系提供了确凿的证据。
