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other·preclinical research, biomedical research, nutrition, research methods·PMC10464975

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

PLOS Biology · 8 authors, 2 centres

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TL;DR

This preclinical study in budding yeast found that an unrestricted early-life galactose diet, compared to glucose, minimizes age-related markers of senescence and gene expression dysregulation without extending lifespan, indicating that these outcomes are separable processes.

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Researchers compared replicative ageing trajectories under unrestricted glucose versus galactose diets. The central result was that an early-life galactose diet minimized age-associated changes, including senescence markers and gene expression dysregulation, while the average mother cell division rate was comparable to glucose and lifespan was actually shorter on galactose. This shows these senescence markers are not intrinsic to replicative ageing but are associated processes. Respiration on galactose was found to be critical. Forced respiration via Hap4 overexpression during glucose ageing had a similar effect but only in a fraction of cells, which maintained youthful profiles.

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other

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preclinical research

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ORIGINAL PAPER

PMC10464975

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

PLOS Biology

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ABSTRACT

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.

CITATION EXPORT

Dorottya Horkai, Hanane Hadj-Moussa, Alex J. Whale et al.. Dietary change without caloric restriction maintains a youthful profile in ageing yeast. PLOS Biology. (2023). https://doi.org/10.1371/journal.pbio.3002245

AUTHORS

8 · 2 CENTRES

Dorottya Horkai, Hanane Hadj-Moussa, Alex J. Whale, Jonathan Houseley, Roland G. Roberts, Roland G. Roberts, Roland G. Roberts, Roland G. Roberts

Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom
Stowers Institute for Medical Research, UNITED STATES

EDITOR / REVIEWER

Sarah E. Zanders