ArticleAging cell2015
Loss of hepatic chaperone-mediated autophagy accelerates proteostasis failure in aging.
Article in Aging cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
115 citing papers in PubMed, 180 citations in OpenAlex.
- Dietary Modulation of CMA: Implications for Cancer Prevention and Therapy.Physiology (Bethesda, Md.) · 2027Review
- Chaperone-mediated autophagy curbs senescence.Nature aging · 2026Article
- 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
- Peptide-mediated inhibition of aberrant chaperone-mediated autophagy in pericytes prevents glioblastoma progression through MAPT/tau secretion.Autophagy · 2026Article
- Chaperone-mediated autophagy is a tumor-suppressive mechanism in hepatocellular carcinoma.Cell reports · 2026Article
- Chaperone-mediated autophagy sustains pericyte stemness necessary for brain tissue homeostasis.Journal of advanced research · 2026Article
- Critical Roles and Molecular Mechanisms of Chaperone-Mediated Autophagy in Infections.International journal of molecular sciences · 2026Review
- Chaperone-mediated autophagy sustains muscle stem cell regenerative functions but declines with age.Nature metabolism · 2025Article
- Stem cell-based therapeutic strategies for liver aging.Liver research (Beijing, China) · 2025Review
- The Role of Intermittent Fasting in the Activation of Autophagy Processes in the Context of Cancer Diseases.International journal of molecular sciences · 2025Review
- Impaired chaperone-mediated autophagy leads to abnormal SORT1 (sortilin 1) turnover and CES1-dependent triglyceride hydrolysis.Autophagy · 2025Article
- Autophagy and Its Association with Macrophages in Clonal Hematopoiesis Leading to Atherosclerosis.International journal of molecular sciences · 2025Review
- P46Shc Inhibits Mitochondrial ACAA2 Thiolase, Exacerbating Mitochondrial Injury and Inflammation in Aging Livers.The American journal of pathology · 2025Article
- Impaired degradation of PLCG1 by chaperone-mediated autophagy promotes cellular senescence and intervertebral disc degeneration.Autophagy · 2025Article
- The lifespan-extending MEK1 inhibitor trametinib promotes regulation of de novo lipogenesis enzymes by chaperone-mediated autophagy.Frontiers in aging · 2025Article
- Deacetylation of HSC70 by SIRT2 promotes chaperone mediated autophagy.Autophagy reports · 2025Article
- Selective protein degradation through chaperone‑mediated autophagy: Implications for cellular homeostasis and disease (Review).Molecular medicine reports · 2025Review
- Calorie restriction and calorie-restriction mimetics activate chaperone-mediated autophagy.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks.International journal of molecular sciences · 2024Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Chaperone-mediated autophagy (CMA), a cellular process that contributes to protein quality control through targeting of a subset of cytosolic proteins to lysosomes for degradation, undergoes a functional decline with age. We have used a mouse model with liver-specific defective CMA to identify changes in proteostasis attributable to reduced CMA activity in this organ with age. We have found that other proteolytic systems compensate for CMA loss in young mice which helps to preserve proteostasis. However, these compensatory responses are not sufficient for protection against proteotoxicity induced by stress (oxidative stress, lipid challenges) or associated with aging. Livers from old mice with CMA blockage exhibit altered protein homeostasis, enhanced susceptibility to oxidative stress and hepatic dysfunction manifested by a diminished ability to metabolize drugs, and a worsening of the metabolic dysregulation identified in young mice. Our study reveals that while the regulatory function of CMA cannot be compensated for in young organisms, its contribution to protein homeostasis can be handled by other proteolytic systems. However, the decline in the compensatory ability identified with age explains the more severe consequences of CMA impairment in older organisms and the contribution of CMA malfunction to the gradual decline in proteostasis and stress resistance observed during aging.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.