ArticlePLoS genetics2020
Fine-tuning autophagy maximises lifespan and is associated with changes in mitochondrial gene expression in Drosophila.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 70 citations in OpenAlex.
- Intervening in aging and related diseases with gene therapy techniques.Cell reports. Medicine · 2026Review
- Mitonuclear discordance modulates mitochondrial ageing dynamics in naturalProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Autophagy is dispensable in germline stem cells but is required in the cap cells for their maintenance in the Drosophila ovarian niche.Stem cell reports · 2025Article
- Autophagy inhibition in intestinal stem cells favors enteroendocrine cell differentiation through Stat92E activity.Disease models & mechanisms · 2025Article
- Decanoic acid extends lifespan and modulates metabolism in models of PLA2G6-associated neurodegeneration.Disease models & mechanisms · 2025Article
- Enhancing autophagy by redox regulation extends lifespan in Drosophila.Nature communications · 2025Article
- Beacon of Hope for Age-Related Retinopathy: Antioxidative Mechanisms and Pre-Clinical Trials of Quercetin Therapy.Antioxidants (Basel, Switzerland) · 2025Review
- Cardiovascular diseases in the elderly: possibilities for modulating autophagy using non-coding RNAs.Frontiers in cell and developmental biology · 2025Review
- The Critical Role of Autophagy and Phagocytosis in the Aging Brain.International journal of molecular sciences · 2024Review
- Spermidine is essential for fasting-mediated autophagy and longevity.Nature cell biology · 2024Article
- Inhibition of S6K lowers age-related inflammation and increases lifespan through the endolysosomal system.Nature aging · 2024Article
- Distinguishing between driver and passenger mechanisms of aging.Nature genetics · 2024Review
- The bioinformatics analysis and experimental validation of the carcinogenic role of EXO1 in lung adenocarcinoma.Frontiers in oncology · 2024Article
- Autophagy Behavior in Endothelial Cell Regeneration.Current aging science · 2024Review
- Integrative analysis reveals a conserved role for the amyloid precursor protein in proteostasis during aging.Nature communications · 2023Article
- Autophagy: Regulator of cell death.Cell death & disease · 2023Review
- Article
- Toxicity ofLife science alliance · 2023Article
- Repeat length of C9orf72-associated glycine-alanine polypeptides affects their toxicity.Acta neuropathologica communications · 2023Article
- The ABL-MYC axis controls WIPI1-enhanced autophagy in lifespan extension.Communications biology · 2023Article
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Authors and funding
16 authors at 8 institutions in 4 countries.
Funding
Abstract
Increased cellular degradation by autophagy is a feature of many interventions that delay ageing. We report here that increased autophagy is necessary for reduced insulin-like signalling (IIS) to extend lifespan in Drosophila and is sufficient on its own to increase lifespan. We first established that the well-characterised lifespan extension associated with deletion of the insulin receptor substrate chico was completely abrogated by downregulation of the essential autophagy gene Atg5. We next directly induced autophagy by over-expressing the major autophagy kinase Atg1 and found that a mild increase in autophagy extended lifespan. Interestingly, strong Atg1 up-regulation was detrimental to lifespan. Transcriptomic and metabolomic approaches identified specific signatures mediated by varying levels of autophagy in flies. Transcriptional upregulation of mitochondrial-related genes was the signature most specifically associated with mild Atg1 upregulation and extended lifespan, whereas short-lived flies, possessing strong Atg1 overexpression, showed reduced mitochondrial metabolism and up-regulated immune system pathways. Increased proteasomal activity and reduced triacylglycerol levels were features shared by both moderate and high Atg1 overexpression conditions. These contrasting effects of autophagy on ageing and differential metabolic profiles highlight the importance of fine-tuning autophagy levels to achieve optimal healthspan and disease prevention.
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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.