Related Experiment Video

Updated: Sep 19, 2025

The Replica Set Method: A High-throughput Approach to Quantitatively Measure Caenorhabditis elegans Lifespan
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Metformin modulates the unfolded protein responses, altering lifespan and health-promoting effects in UPR-activated

Jerald Tan1, Chutipong Chiamkunakorn1, Kanpapat Boonchuay1

  • 1Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Plos One
|June 16, 2025
PubMed

Insights

Metformin extends lifespan in worms, but its effects on the unfolded protein response (UPR) and stress resistance are complex and vary depending on the specific UPR pathway involved.

Area of Science:

  • Cellular Biology
  • Aging Research
  • Genetics

Background:

  • Metformin is known to extend lifespan in model organisms.
  • Its molecular mechanisms involve cytoplasm and organelles like mitochondria.
  • The relationship between metformin, unfolded protein response (UPR), stress resistance, and locomotion is not fully understood.

Purpose of the Study:

  • To investigate metformin's impact on the unfolded protein response (UPRmt and UPRer).
  • To determine the correlation between metformin's lifespan-extending effects and its interaction with UPR pathways.
  • To assess metformin's influence on stress resistance and locomotion in UPR-activated worms.

Main Methods:

  • Utilized Caenorhabditis elegans (C. elegans) as a model organism.
  • Examined metformin's effects on wild-type and UPR-activated (tomm-22, cco-1, mdt-15, tmem-131 RNAi) worms.
  • Assessed UPRmt and UPRer activation, lifespan, thermotolerance, oxidative stress resistance, and locomotion.

Main Results:

  • Metformin showed differential effects on UPRmt and UPRer.
  • Lifespan extension was observed in wild-type, tomm-22, and cco-1 RNAi worms, with metformin suppressing UPRmt in tomm-22 worms but not affecting UPRmt in cco-1 worms.
  • Metformin had inconsistent effects on UPRer, slightly increasing it in mdt-15 RNAi worms (without lifespan extension) and suppressing it in tmem-131 RNAi worms (with lifespan extension).
  • Stress resistance and locomotion were inconsistently correlated with metformin's lifespan effects.

Conclusions:

  • Metformin's interaction with UPR pathways is complex and context-dependent.
  • Metformin can extend lifespan independently of or in conjunction with modulating UPR pathways.
  • The study highlights the intricate relationship between metformin, UPR, aging, and stress response.

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