可编程的命运决策景观是酵母单细胞衰老的基础。
A programmable fate decision landscape underlies single-cell aging in yeast.
机构信息
Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.
Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.
出版信息
Science. 2020 Jul 17;369(6501):325-329. doi: 10.1126/science.aax9552.
Abstract
Chromatin instability and mitochondrial decline are conserved processes that contribute to cellular aging. Although both processes have been explored individually in the context of their distinct signaling pathways, the mechanism that determines which process dominates during aging of individual cells is unknown. We show that interactions between the chromatin silencing and mitochondrial pathways lead to an epigenetic landscape of yeast replicative aging with multiple equilibrium states that represent different types of terminal states of aging. The structure of the landscape drives single-cell differentiation toward one of these states during aging, whereby the fate is determined quite early and is insensitive to intracellular noise. Guided by a quantitative model of the aging landscape, we genetically engineered a long-lived equilibrium state characterized by an extended life span.
摘要
染色质不稳定和线粒体衰退是保守的过程，它们共同导致细胞衰老。虽然这两个过程在其独特的信号通路背景下都得到了探索，但决定哪个过程在单个细胞衰老过程中占主导地位的机制尚不清楚。我们表明，染色质沉默和线粒体途径之间的相互作用导致了酵母复制衰老的表观遗传景观，其中存在多个平衡状态，代表了衰老的不同类型的终态。景观的结构在衰老过程中驱动单细胞向其中一个状态分化，在这个过程中，命运很早就被决定，并且对细胞内噪声不敏感。在衰老景观的定量模型的指导下，我们通过基因工程设计了一个具有延长寿命的长寿命平衡状态。
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