Related Experiment Video

Updated: May 29, 2025

Assessing Lysosomal Alkalinization in the Intestine of Live Caenorhabditis elegans
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Published on: April 13, 2018

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Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging

Rabia R Khawaja1,2, Adrián Martín-Segura3,4,5, Olaya Santiago-Fernández3,4

  • 1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA. rabia.khawaja@einsteinmed.edu.

Nature Aging
|February 5, 2025
PubMed

Insights

Aging causes a decline in chaperone-mediated autophagy (CMA), a key cellular process. This study reveals greater CMA decline in males, potentially impacting age-related organ vulnerability.

Area of Science:

  • Cellular Biology
  • Aging Research
  • Molecular Biology

Background:

  • Aging is linked to declining organ function, partly due to impaired proteostasis and autophagy.
  • Chaperone-mediated autophagy (CMA), a vital degradation pathway, decreases with age in various organisms.
  • CMA dysfunction mimics aging, while CMA activation shows protective effects against age-related diseases.

Purpose of the Study:

  • To investigate sex-specific and cell-type-specific differences in chaperone-mediated autophagy (CMA) decline during aging.
  • To explore the molecular mechanisms underlying age-related CMA reduction.

Main Methods:

  • Utilized CMA reporter mice to track CMA activity.
  • Employed single-cell transcriptomic analysis to assess CMA in diverse cell types.
  • Examined lysosome competency and CMA gene expression.

Main Results:

  • Most organs and cell types exhibit reduced CMA with age.
  • Males show a more pronounced decline in CMA compared to females.
  • Decreased CMA correlates with fewer functional lysosomes and transcriptional downregulation of CMA genes, particularly in males.

Conclusions:

  • Age-related CMA decline is widespread, with significant sex-specific differences.
  • Reduced CMA and associated molecular changes may contribute to organ vulnerability in aging.
  • Understanding CMA dynamics is crucial for addressing age-related cellular dysfunction.

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