Heat stress promotes longevity in budding yeast by relaxing the confinement of age-promoting factors in the mother cell

  1. Sandro Baldi
  2. Alessio Bolognesi
  3. Anne Cornelis Meinema
  4. Yves Barral  Is a corresponding author
  1. Ludwig-Maximilians-University, Germany
  2. Eidgenössische Technische Hochschule Zürich, Switzerland

Abstract

Although individuals of many species inexorably age, a number of observations established that the rate of ageing is modulated in response to a variety of mild stresses. Here, we investigated how heat stress promotes longevity in yeast. We show that upon growth at higher temperature, yeast cells relax the retention of DNA circles, which act as ageing factors in the mother cell. The enhanced frequency at which circles redistribute to daughter cells was not due to changes of anaphase duration or nuclear shape but solely to the downregulation of the diffusion barrier in the nuclear envelope. This effect depended on the PKA and Tor1 pathways, downstream of stress-response kinase Pkc1. Inhibition of these responses restored barrier function and circle retention and abrogated the effect of heat stress on longevity. Our data indicate that redistribution of ageing factors from aged cells to their progeny can be a mechanism for modulating longevity.

Article and author information

Author details

  1. Sandro Baldi

    Biomedical Center Munich, Ludwig-Maximilians-University, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Alessio Bolognesi

    Institute of Biochemistry, Department of Biology, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7268-4577
  3. Anne Cornelis Meinema

    Institute of Biochemistry, Department of Biology, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Yves Barral

    Institute of Biochemistry, Department of Biology, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland
    For correspondence
    yves.barral@bc.biol.ethz.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0989-3373

Funding

Eidgenössische Technische Hochschule Zürich

  • Yves Barral

H2020 European Research Council

  • Yves Barral

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2017, Baldi et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 4,018
    views
  • 497
    downloads
  • 30
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Sandro Baldi
  2. Alessio Bolognesi
  3. Anne Cornelis Meinema
  4. Yves Barral
(2017)
Heat stress promotes longevity in budding yeast by relaxing the confinement of age-promoting factors in the mother cell
eLife 6:e28329.
https://doi.org/10.7554/eLife.28329

Share this article

https://doi.org/10.7554/eLife.28329

Further reading

    1. Cell Biology
    2. Genetics and Genomics
    Keva Li, Nicholas Tolman ... UK Biobank Eye and Vision Consortium
    Research Article

    A glaucoma polygenic risk score (PRS) can effectively identify disease risk, but some individuals with high PRS do not develop glaucoma. Factors contributing to this resilience remain unclear. Using 4,658 glaucoma cases and 113,040 controls in a cross-sectional study of the UK Biobank, we investigated whether plasma metabolites enhanced glaucoma prediction and if a metabolomic signature of resilience in high-genetic-risk individuals existed. Logistic regression models incorporating 168 NMR-based metabolites into PRS-based glaucoma assessments were developed, with multiple comparison corrections applied. While metabolites weakly predicted glaucoma (Area Under the Curve = 0.579), they offered marginal prediction improvement in PRS-only-based models (p=0.004). We identified a metabolomic signature associated with resilience in the top glaucoma PRS decile, with elevated glycolysis-related metabolites—lactate (p=8.8E-12), pyruvate (p=1.9E-10), and citrate (p=0.02)—linked to reduced glaucoma prevalence. These metabolites combined significantly modified the PRS-glaucoma relationship (Pinteraction = 0.011). Higher total resilience metabolite levels within the highest PRS quartile corresponded to lower glaucoma prevalence (Odds Ratiohighest vs. lowest total resilience metabolite quartile=0.71, 95% Confidence Interval = 0.64–0.80). As pyruvate is a foundational metabolite linking glycolysis to tricarboxylic acid cycle metabolism and ATP generation, we pursued experimental validation for this putative resilience biomarker in a human-relevant Mus musculus glaucoma model. Dietary pyruvate mitigated elevated intraocular pressure (p=0.002) and optic nerve damage (p<0.0003) in Lmx1bV265D mice. These findings highlight the protective role of pyruvate-related metabolism against glaucoma and suggest potential avenues for therapeutic intervention.

    1. Cell Biology
    2. Immunology and Inflammation
    Alejandro Rosell, Agata Adelajda Krygowska ... Esther Castellano Sanchez
    Research Article

    Macrophages are crucial in the body’s inflammatory response, with tightly regulated functions for optimal immune system performance. Our study reveals that the RAS–p110α signalling pathway, known for its involvement in various biological processes and tumourigenesis, regulates two vital aspects of the inflammatory response in macrophages: the initial monocyte movement and later-stage lysosomal function. Disrupting this pathway, either in a mouse model or through drug intervention, hampers the inflammatory response, leading to delayed resolution and the development of more severe acute inflammatory reactions in live models. This discovery uncovers a previously unknown role of the p110α isoform in immune regulation within macrophages, offering insight into the complex mechanisms governing their function during inflammation and opening new avenues for modulating inflammatory responses.