ArticleNature aging2025
Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging.
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Article in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31citing papers in PubMed
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Who cites it
31 citing papers in PubMed.
- Chaperone-mediated autophagy in physiological homeostasis, disease and ageing.Nature reviews. Molecular cell biology · 2026Review
- Decline of chaperone-mediated autophagy in aging impairs macrophage clearance of senescent cells.Nature aging · 2026Article
- Autophagy Flux Is Remodeled Sex- and Cell Type-Specifically During Human Aging, and Is Linked to Reduced Physical Function in Older Adults.Aging cell · 2026Article
- Advancing aging biomarkers and intervention discovery at the TimePie Longevity Forum.Nature aging · 2026Article
- Peptide-mediated inhibition of aberrant chaperone-mediated autophagy in pericytes prevents glioblastoma progression through MAPT/tau secretion.Autophagy · 2026Article
- Comparative analysis of neuronal proteolytic pathways reveals neuron-specific and sub-compartmental-specific capacities with aging.Cellular and molecular life sciences : CMLS · 2026Article
- Established and emerging roles of lysosomal dysfunction in cardiac aging.Nature cardiovascular research · 2026Review
- Dietary modulation of CMA: implications for cancer prevention and therapy.Physiology (Bethesda, Md.) · 2026Article
- Chaperone-mediated autophagy is a tumor-suppressive mechanism in hepatocellular carcinoma.Cell reports · 2026Article
- Heterogeneity, dynamics and organelle interactions of lipid droplets.Nature reviews. Molecular cell biology · 2026Review
- Two-photon in vivo imaging reveals cell type-specific mitophagy dynamic changes in mouse somatosensory cortex during aging.npj aging · 2026Article
- Chaperone-mediated autophagy is required for regulatory T cell function.Nature communications · 2026Article
- Article
- Cancer and aging: complex associations and therapeutic targets.Molecular biomedicine · 2026Review
- Astrocyte States in Brain Aging and Neurodegeneration: At the Crossroads of Senescence and Reactivity.Neurochemical research · 2026Review
- Immunometabolic resistors of aging in long-lived golden spiny mice.Science advances · 2026Article
- Chaperone mediated autophagy is deficient in spinal motoneurons of ALS patients with TDP-43 proteinopathy.Acta neuropathologica communications · 2026Article
- The Role of Crosstalk Between the Unfolded Protein Response and Autophagy in Diseases Associated with Sympathetic Nervous System Imbalance: Mechanisms and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Unraveling the intersection of aging and Parkinson's disease: a collaborative roadmap for advancing research models.NPJ Parkinson's disease · 2026Review
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
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Authors and funding
18 authors.
Rabia R Khawaja *Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA. rabia.khawaja@einsteinmed.edu.ORCID http://orcid.org/0000-0003-3907-988X
Adrián Martín-Segura *Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID http://orcid.org/0000-0001-9369-0589
Olaya Santiago-FernándezDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID http://orcid.org/0000-0002-5933-3104
Rebecca SeredaDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID http://orcid.org/0000-0002-6168-3226
Kristen LindenauDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID http://orcid.org/0000-0001-6145-5322
Mericka McCabeDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID http://orcid.org/0000-0001-6758-2330
Adrián Macho-GonzálezDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID http://orcid.org/0000-0001-7644-1759
Maryam JafariDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID http://orcid.org/0000-0001-5552-1127
Aurora ScrivoDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
Raquel Gomez-SintesDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID http://orcid.org/0000-0003-2854-6964
Bhakti ChavdaDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
Ana Rosa Saez-IbanezDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
Inmaculada TassetDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
Esperanza AriasInstitute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA.
Xianhong XieDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Mimi KimDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Susmita KaushikDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID http://orcid.org/0000-0002-6096-5387
Ana Maria CuervoDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA. ana-maria.cuervo@einsteinmed.edu.
Funding
Role of Autophagy in T Cell Function and Immunosenescence (Project 3)P01AG031782 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CUERVO, ANA MARIA · 2009 to 2024
$36.2MEinstein-Montefiore Clinical and Translational Science Award HubUM1TR004400 · NCATS · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI Jessica Kahn, Mimi Y Kim · 2023 to 2026
$17.3MTRAINING PROGRAM IN CELLULAR &MOLEC. BIOLOGY &GENETICST32GM007491 · NIGMS · YESHIVA UNIVERSITY · PI QUERY, CHARLES C · 1985 to 2021
$17.0MBronx-Einstein Training in Teaching and Research (BETTR), an IRACDA programK12GM102779 · NIGMS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI Dianne Cox, Johanna Patricia Daily · 2012 to 2026
$9.2MTraining in Aging ResearchT32AG023475 · NIA · ALBERT EINSTEIN COL OF MED YESHIVA UNIV · PI NIR J BARZILAI, DEREK Major HUFFMAN · 2004 to 2026
$8.6MControl of vesicular trafficking in the hepatocyte.R01DK098408 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CUERVO, ANA MARIA, WOLKOFF, ALLAN W · 2013 to 2022
$5.6MDecreased Protein Degradation in AgingR37AG021904 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CUERVO, ANA MARIA · 2013 to 2022
$4.4MDECREASED PROTEIN DEGRADATION IN AGINGR01AG021904 · NIA · YESHIVA UNIVERSITY · PI CUERVO, ANA MARIA · 2003 to 2012
$3.7MUnderstanding Alzheimer's Disease in the Context of the Aging BrainRF1AG054108 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CUERVO, ANA MARIA · 2016 to 2016
$2.1MRole of CMA failure in NASH progression to Hepatocellular CarcinomaR01DK124308 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI ARIAS-PEREZ, ESPERANZA · 2020 to 2023
$1.5MRole of Chaperone-Mediated Autophagy in Cellular SenescenceF31AG084192 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI Rebecca Z Sereda · 2024 to 2026
$133kInstituto Carlos Slim de la Salud (Carlos Slim Health Institute) Margarita Salas ContractJPB Foundation N/AMinisterio de Ciencia Tecnología y Telecomunicaciones (Ministerio de Ciencia Tecnología y Telecomunicaciones de Costa Rica) PID2021-126864NB I00NCATS NIH HHS UM1 TR004400NIA NIH HHS F31 AG084192NIA NIH HHS P01 AG031782NIA NIH HHS R01 AG021904NIA NIH HHS R37 AG021904NIA NIH HHS RF1 AG054108NIA NIH HHS T32 AG023475NIDDK NIH HHS R01 DK098408NIDDK NIH HHS R01 DK124308NIGMS NIH HHS K12 GM102779NIGMS NIH HHS T32 GM007491U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) T32GM007491U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK098408U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK124308U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) IRACDA-BETTRU.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32AG023475U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32GM007491U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG021904U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG031782U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG054108U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) F31 AG08419U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) T32AG023475
Abstract
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.
Indexed as
AgingAutophagyChaperone-Mediated AutophagyAnimalsFemaleHumansLysosomesMaleMiceMice, Inbred C57BLOrgan SpecificitySex CharacteristicsSex Factors
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