A programmable fate decision landscape underlies single-cell aging in yeast.

Science
Yang LiNan Hao

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.

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Citations

Jan 5, 2021·Frontiers in Bioengineering and Biotechnology·Naia Risager WrightNikolaus Sonnenschein
Jan 30, 2021·Seminars in Cell & Developmental Biology·Albert T Higgins-ChenMorgan E Levine
Oct 28, 2020·Nature Cell Biology·Laura García-PratPura Muñoz-Cánoves
Feb 8, 2021·Current Opinion in Cell Biology·Yanfei Jiang, Nan Hao
Mar 9, 2021·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Ido Pen, Thomas Flatt
Apr 1, 2021·Scientific Reports·Hao-Bo GuoHong Qin
Apr 15, 2021·Journal of Translational Internal Medicine·Yumin QiuJun Tao
Jun 18, 2021·Cell Systems·Mojca Mattiazzi UsajBrenda J Andrews
Jul 18, 2021·Mechanisms of Ageing and Development·Morgan W Feng, Peter D Adams
Sep 29, 2021·Experimental Gerontology·Emerson SantiagoMurat Acar
Oct 6, 2021·Journal of Extracellular Vesicles·Yujia YinXipeng Wang

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