在不限制热量的情况下改变饮食可以使老化酵母保持年轻状态。

IF 7.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY PLoS Biology Pub Date : 2023-08-29 eCollection Date: 2023-08-01 DOI:10.1371/journal.pbio.3002245
Dorottya Horkai, Hanane Hadj-Moussa, Alex J Whale, Jonathan Houseley
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引用次数: 2

摘要

热量限制可以延长寿命并改善衰老健康,但尚不清楚这些结果是否可以通过不那么严重的干预措施来分离或实现。在这里,我们发现,无论以后的饮食如何,早期不受限制的半乳糖饮食都能最大限度地减少萌芽酵母复制衰老过程中的变化。葡萄糖和半乳糖饮食的平均母细胞分裂率相当,半乳糖的寿命更短,但在葡萄糖上观察到的衰老和基因表达的进行性失调的标志物在半乳糖上是最小的,这表明这些不是复制衰老的内在方面,而是相关的过程。对半乳糖的呼吸对于最大限度地减少衰老特征至关重要,而在葡萄糖衰老过程中,通过线粒体生物发生因子Hap4的过度表达进行的强迫呼吸也具有相同的效果,尽管只是在一小部分细胞中。该部分保持Hap4活性至衰老晚期,具有低衰老和年轻的基因表达谱,而同一群体中的其他细胞失去Hap4活力,经历基因表达的显著失调,并积累与衰老密切相关的染色体XII(ChrXIIr)片段。我们的发现支持酵母中存在两个可分离的衰老轨迹。我们提出,在没有热量限制的情况下,通过在早期改变饮食,可以在野生型细胞中实现向健康衰老模式的完全转变。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Dietary change without caloric restriction maintains a youthful profile in ageing yeast.

Caloric restriction increases lifespan and improves ageing health, but it is unknown whether these outcomes can be separated or achieved through less severe interventions. Here, we show that an unrestricted galactose diet in early life minimises change during replicative ageing in budding yeast, irrespective of diet later in life. Average mother cell division rate is comparable between glucose and galactose diets, and lifespan is shorter on galactose, but markers of senescence and the progressive dysregulation of gene expression observed on glucose are minimal on galactose, showing that these are not intrinsic aspects of replicative ageing but rather associated processes. Respiration on galactose is critical for minimising hallmarks of ageing, and forced respiration during ageing on glucose by overexpression of the mitochondrial biogenesis factor Hap4 also has the same effect though only in a fraction of cells. This fraction maintains Hap4 activity to advanced age with low senescence and a youthful gene expression profile, whereas other cells in the same population lose Hap4 activity, undergo dramatic dysregulation of gene expression and accumulate fragments of chromosome XII (ChrXIIr), which are tightly associated with senescence. Our findings support the existence of two separable ageing trajectories in yeast. We propose that a complete shift to the healthy ageing mode can be achieved in wild-type cells through dietary change in early life without caloric restriction.

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来源期刊
PLoS Biology
PLoS Biology 生物-生化与分子生物学
CiteScore
14.40
自引率
2.00%
发文量
359
审稿时长
3 months
期刊介绍: PLOS Biology is an open-access, peer-reviewed general biology journal published by PLOS, a nonprofit organization of scientists and physicians dedicated to making the world's scientific and medical literature freely accessible. The journal publishes new articles online weekly, with issues compiled and published monthly. ISSN Numbers: eISSN: 1545-7885 ISSN: 1544-9173
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