RT Journal Article
T1 Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging
A1 Macho González, Adrián
A1 Khawaja, Rabia
A1 Martín-Segura, Adrián
A1 Santiago-Fernández, Olaya
A1 Sereda, Rebecca
A1 Lindenau, Kristen
A1 McCabe, Mericka
A1 Jafari, Maryam
A1 Scrivo, Aurora
A1 Gómez-Sintes, Raquel
A1 Chavda, Bhakti
A1 Sáez-Ibáñez, Ana Rosa
A1 Tasset, Inmaculada
A1 Arias, Esperanza
A1 Xie, Xianhong
A1 Kim, Mimi
A1 Kaushik, Susmita
A1 Cuervo, Ana María
AB 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.
PB Nature
YR 2025
FD 2025
LK https://hdl.handle.net/20.500.14352/118248
UL https://hdl.handle.net/20.500.14352/118248
LA eng
NO Khawaja RR, Martín-Segura A, Santiago-Fernández O, Sereda R, Lindenau K, McCabe M, Macho-González A, Jafari M, Scrivo A, Gomez-Sintes R, Chavda B, Saez-Ibanez AR, Tasset I, Arias E, Xie X, Kim M, Kaushik S, Cuervo AM. Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging. Nat Aging 2025:1–18. https://doi.org/10.1038/s43587-024-00799-6.
DS Docta Complutense
RD 19 abr 2025