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Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging
Rabia R Khawaja, Adrián Martín-Segura, Olaya Santiago-Fernández, Rebecca Sereda, Kristen Lindenau, Mericka McCabe, Adrián Macho-González, Maryam Jafari et al.. Nature aging, 2025-02-05
Topic: Disease mechanisms in lab and animal studies
Aging leads to progressive decline in organ and tissue integrity and function, partly due to loss of proteostasis and autophagy malfunctioning. A decrease with age in chaperone-mediated autophagy (CMA), a selective type of lysosomal degradation, has been reported in various organs and cells from rodents and humans. Disruption of CMA recapitulates features of aging, whereas activating CMA in mice protects against age-related diseases such as Alzheimer's, retinal degeneration and/or atherosclerosis. However, sex-specific and cell-type-specific differences in CMA with aging remain unexplored. Here, using CMA reporter mice and single-cell transcriptomic data, we report that most organs and cell types show CMA decline with age, with males exhibiting a greater decline with aging. Reduced CMA is often associated with fewer lysosomes competent for CMA. Transcriptional downregulation of CMA genes may further contribute to CMA decline, especially in males. These findings suggest that CMA differences may influence organ vulnerability to age-related degeneration.
Key findings
- Reduced CMA is often associated with fewer lysosomes competent for CMA.
- These findings suggest that CMA differences may influence organ vulnerability to age-related degeneration.
Study details
- Evidence strengthLow
How this study scored 46/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 26 of the 56 points we could judge it on, which is 46 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature aging) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39910244) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 26 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 26 of the 56 points we could judge it on is 46 out of 100. |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
Khawaja, R. R., Martín-Segura, A., Santiago-Fernández, O., Sereda, R., Lindenau, K., McCabe, M., et al. (2025). Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging. Nature aging. https://doi.org/10.1038/s43587-024-00799-6
Vancouver
Khawaja RR, Martín-Segura A, Santiago-Fernández O, Sereda R, Lindenau K, McCabe M, et al. Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging. Nature aging. 2025. doi:10.1038/s43587-024-00799-6. PMID: 39910244.
BibTeX
@article{khawaja2025-39910244,
author = {Khawaja, Rabia R and Martín-Segura, Adrián and Santiago-Fernández, Olaya and Sereda, Rebecca and Lindenau, Kristen and McCabe, Mericka and Macho-González, Adrián and Jafari, Maryam and others},
title = {{Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging}},
journal = {Nature aging},
year = {2025},
doi = {10.1038/s43587-024-00799-6},
pmid = {39910244},
url = {https://doi.org/10.1038/s43587-024-00799-6}
}