Programmed aging in yeast cells Following the fate of individual yeast cells has revealed aging to be more of a programmable decision process rather than a simple accumulation of deleterious events. Li et al. combined single-cell studies and mathematical modeling to show that yeast cells showed two different forms of aging: one with more ribosomal DNA silencing, in which nucleoli were degraded, and another with more heme accumulation and hemedependent transcription, in which mitochondria were more affected. Overexpression of the lysine deacetylase Sir2, which contributes to ribosomal DNA silencing, led to a third cell-aging fate in which the average life span was extended. If other cells age in similar ways, then this study may provide new ways to consider dynamics of aging and strategies to extend the health span. Science this issue p. 325 Clues to the aging process are derived from analysis of single yeast cells throughout their life span. 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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可编程的命运决定格局是酵母单细胞衰老的基础

酵母细胞中的程序性衰老 单个酵母细胞的命运表明衰老更多是一个程序化的决策过程，而不是有害事件的简单积累。李等人。结合单细胞研究和数学模型，表明酵母细胞表现出两种不同的衰老形式：一种具有更多的核糖体 DNA 沉默，其中核仁被降解，另一种具有更多的血红素积累和血红素依赖性转录，其中线粒体受到更多的影响。赖氨酸脱乙酰酶 Sir2 的过度表达有助于核糖体 DNA 沉默，导致第三次细胞衰老，平均寿命延长。如果其他细胞以类似的方式老化，那么这项研究可能会提供新的方法来考虑老化动态和延长健康跨度的策略。科学这个问题 p。325 条衰老过程的线索来自对单个酵母细胞整个生命周期的分析。染色质不稳定和线粒体衰退是导致细胞衰老的保守过程。尽管这两个过程都在其不同的信号通路背景下进行了单独探索，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酵母复制衰老的表观遗传景观，具有代表不同类型衰老终末状态的多种平衡状态。在衰老过程中，景观的结构驱动单细胞分化为这些状态之一，从而很早就确定了命运，并且对细胞内的噪音不敏感。