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Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology
Calorie restriction and calorie-restriction mimetics activate chaperone-mediated autophagy
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Conflicts of Interest
Identified Weaknesses
Rating Explanation
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Paper Summary
Paperzilla title
Eat Less, Live Longer? Maybe It's Because Your Cells' Recycling System Gets a Boost!
Calorie restriction (CR) and calorie-restriction mimetics (CRMs) activate chaperone-mediated autophagy (CMA), a cellular recycling process. This activation is due to increased stability of LAMP2A, the CMA receptor, at the lysosome membrane, and is required for the protective effects of CRMs against high-carbohydrate diets in mice.
Possible Conflicts of Interest
A.M.C. is a co-founder and scientific advisor for the autophagy program at Life Biosciences, although they state this is not related to the work reported and has not been supported by the company. A.M.C. has also co-authored positioning papers with the reviewers, although they clarify these were opinion pieces and not collaborative research.
Identified Weaknesses
Exclusive Focus on Male Rodents
The study exclusively focuses on male rodents, neglecting potential sex-specific differences in CMA response and the known influence of sex and strain on the beneficial effects of CR in mice. This limits the generalizability of the findings.
Lack of Long-Term CRM Effects
While the study demonstrates acute CMA activation by CRMs, it doesn't investigate long-term effects or whether the observed LAMP2A stabilization in the liver translates to other tissues. This leaves open the question of whether sustained CRM treatment is necessary for lasting CMA benefits.
Limited Mechanistic Insight into CRM Action
The study doesn't fully investigate the mechanism behind CRM-mediated CMA activation. While it acknowledges potential transcriptional regulation and acetylation changes, it doesn't definitively establish the precise molecular targets and pathways involved.
Limited Scope of CMA Dependence Demonstration
The dependence of CRM's protective effects on CMA is only demonstrated in an acute high-carbohydrate challenge. It remains unclear whether the long-term benefits of CR and CRMs on lifespan and various disease models also depend on functional CMA.
Rating Explanation
This study provides compelling evidence for the role of CMA in mediating the beneficial effects of calorie restriction and its mimetics. The experiments are well-designed, utilizing both in vitro and in vivo models to demonstrate CMA activation and its dependence on LAMP2A stabilization. The study also establishes the importance of CMA for CRM's protective effects against dietary challenges. While the study is limited by its focus on male rodents and lack of long-term data, the findings are significant and open new avenues for gerotherapeutic interventions.
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File Information
Original Title:
Calorie restriction and calorie-restriction mimetics activate chaperone-mediated autophagy
File Name:
jafari-et-al-calorie-restriction-and-calorie-restriction-mimetics-activate-chaperone-mediated-autophagy.pdf
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File Size:
4.08 MB
Uploaded:
July 18, 2025 at 10:02 AM
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