Related Experiment Video

Updated: Jul 21, 2025

Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans
09:18

Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans

Published on: September 7, 2021

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Modulating p38 MAPK signaling by proteostasis mechanisms supports tissue integrity during growth and aging

Wang Yuan1, Yi M Weaver1, Svetlana Earnest1

  • 1Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX, USA.

Nature Communications
|July 28, 2023
PubMed

Insights

p38 MAPK signaling, specifically PMK-1 in C. elegans, dynamically supports tissue homeostasis during aging by modulating non-phosphorylated PMK-1 levels, promoting longevity and neuronal integrity.

Area of Science:

  • Cellular Biology
  • Aging Research
  • Molecular Signaling

Background:

  • The p38 MAPK pathway is crucial for stress responses, with PMK-1 in C. elegans regulating immunity and development.
  • Hyperactivation of PMK-1 can negatively impact organismal health.
  • Aging is associated with cellular stress and decline in tissue function.

Purpose of the Study:

  • To investigate the role of PMK-1 signaling in aging and its impact on tissue integrity and longevity.
  • To elucidate the mechanisms by which PMK-1 signaling is modulated during aging.
  • To determine if enhancing PMK-1 signaling can mitigate age-related decline.

Main Methods:

  • Utilized C. elegans as a model organism.
  • Investigated PMK-1 phosphorylation and non-phosphorylated forms during aging.
  • Employed genetic manipulation, including creating caspase cleavage-resistant PMK-1 mutants.
  • Assessed neuronal integrity, lysosome function, and lifespan.

Main Results:

  • PMK-1 signaling is enhanced during early aging by altering the stoichiometry of non-phospho-PMK-1, promoting tissue integrity and longevity.
  • Loss of pmk-1 function accelerates neuronal and lysosomal decline, reducing lifespan.
  • CED-3 caspase cleavage limits phosphorylated PMK-1.
  • Enhancing p38 signaling via cleavage-resistant PMK-1 preserves lysosomal and neuronal health, extending youthful function.
  • PMK-1 regulates lysosome formation through a transcriptional program.

Conclusions:

  • Modulating the stoichiometry of non-phospho-PMK-1 dynamically supports tissue homeostasis during aging without triggering hyperactivation of stress responses.
  • PMK-1 signaling plays a critical role in maintaining neuronal and lysosomal integrity, thereby influencing longevity.
  • Targeting PMK-1 stoichiometry offers a potential strategy to promote healthy aging.

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