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Identifier 000426442
Title The role of autophagy in lifespan regulation upon inhibition of protein synthesis in Caenorhabditis elegans
Alternative Title Η αυτοφαγία ως μηχανισμός ρύθμισης του προσδόκιμου ζωής υπό συνθήκες μειωμένης πρωτεïνοσύνθεσης στο νηματώδη Caenorhabditis elegans
Author Μυτιληναίου, Ειρήνη Γ.
Thesis advisor Ταβερναράκης, Νεκτάριος
Reviewer Αλεξανδράκη, Δέσποινα
Ποϊράζη, Παναγιώτα
Abstract Autophagy is a conserved degradation pathway which regulates several aspects of cellular homeostasis. Based on its key role in recycling and quality control, autophagy is associated with enhanced longevity and healthspan. Under the same concept of cellular homeostasis and energetic balance, conditions that attenuate protein synthesis lead to lifespan extension in several model organisms. Additionally, reduction in ribosomal proteins or genetic inhibition of ribosome biogenesis genes promotes longevity. The mTOR signaling pathway stands as common sensor and modulator of autophagy, protein synthesis and ribosomal biogenesis in lifespan regulation. We used Caenorhabditis elegans as a model in order to investigate the implication of autophagy in lifespan extension under conditions of reduced protein synthesis and also examine the possibility of selective degradation of ribosomes through the autophagic pathway. Our results indicate that core components of the autophagic machinery are required, at least in some cases, for the longevity associated with translation inhibition. Survival assays, involving a variety of mutant strains and RNAi treatments against key players of the translational machinery, suggest that autophagy is essential for lifespan extension observed upon reduced protein synthesis. RNAi-mediated knockdown of ribosomal genes leads to an increase of the autophagic flux while the number of autophagosomes is also markedly increased in mutant strains characterized by reduced global protein synthesis. Furthermore, RNAi-mediated knockdown of a LIR-bearing ribosomal protein (RPS-24) ameliorates the polyglutamine aggregation phenotype in a nematode model of Huntington’s disease. In conclusion, our results suggest a role of autophagy in lifespan regulation under conditions of protein synthesis inhibition. We anticipate that further work will elucidate the complex interplay between autophagy and protein synthesis and provide evidence concerning its regulation.
Language English
Subject Ribosomes
Ριβοσώματα
Issue date 2019-11-29
Collection   Faculty/Department--Faculty of Sciences and Engineering--Department of Biology--Post-graduate theses
  Type of Work
Permanent Link https://elocus.lib.uoc.gr//dlib/8/6/1/metadata-dlib-1575285954-247175-19675.tkl Bookmark and Share
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