Level D· Scientific groundwork from lab and animal studiesAnimal StudyPubMedOpen access

Car4-positive adipocyte progenitor cells adapt to the aging environment and work as protection against ROS via glutathione metabolism.

Horino M., Ikeda K., Okazaki R., Nakano Y., Kaneda R., Ishii R.

Animal Study, published in Sci Rep (2025) — summary generated from the PubMed abstract.

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Level D· Scientific groundwork from lab and animal studiesEvidence level of this study

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

  • Level A · Stronger Clinical Evidence
  • Level B · Emerging clinical evidence with positive signals
  • Level C · Early human research exploring benefits
  • Level D · Scientific groundwork from lab and animal studies
  • Emerging · Emerging topic under active research
Read the A–D evidence level guide

This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.

Study type
Animal Study
Journal
Sci Rep (2025)
Country
England
Reported sample size
—
Source database
PubMed
PMID
40883493
PMCID
PMC12397281
DOI
10.1038/s41598-025-17231-7

Abstract (original English)

The induction of beige adipocytes is significantly reduced in aged mice due to the senescence of adipocyte progenitor cells (APCs). Recent studies have revealed the existence of beige adipocyte subtypes, suggesting that APCs comprise a heterogeneous population. Therefore, in this study, we aimed to elucidate the mechanism through which long-term cold exposure induces the production of beige adipocytes even in aged mice. Single-cell RNA sequencing identified carbonic anhydrase 4 (Car4)-positive APCs. The number of Car4-positive APCs increased with age and cold exposure. Car4 knockdown (KD) mitigated intracellular pH reduction and significantly suppressed beige adipocyte differentiation. Furthermore, Car4 KD cells demonstrated reduced expression of genes in the glutathione pathway and increased susceptibility to reactive oxygen species (ROS), which was alleviated by glutathione supplementation. Our findings suggest that ROS resistance is an adaptation to the cellular aging environment. Our study provides insights into the age-related decline in beige adipocyte induction and identifies Car4 as a potential therapeutic target for enhancing energy expenditure in elderly individuals. This may pave the way for the development of new strategies to combat age-related metabolic diseases and offer hope for improved health and longevity in an aging population.

What this study does not prove

  • • This study does not prove SVF is an approved treatment or a replacement for standard care.
  • • This is preclinical work; animal or laboratory results cannot be applied to humans.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

How we grade evidence
AnimalsReactive Oxygen SpeciesMiceGlutathioneAgingStem CellsCarbonic AnhydrasesAdipocytes, BeigeCellular SenescenceMice, Inbred C57BL

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