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Insulin signaling, mitochondrial DNA copy number regulation and aging in Caenorhabditis elegans

Mitochondrial dysfunction is considered as a key mechanism of aging but little is known about the impact of mitochondrial biogenesis. Mitochondrial DNA (mtDNA) copy number control is an important aspect of mitochondrial biogenesis and is highly regulated in eukaryotic organisms. By studying mtDNA copy number, our aim is to gain a better understanding of the relationship between mitochondrial biogenesis and aging. We developed an optimized protocol for measuring mtDNA copy number in Caenorhabditis elegans using quantitative real-time PCR (qPCR). We investigated how mtDNA regulation is affected by a variety of aging-related pathways. We found the insulin/IGF-1 signaling (IIS) pathway regulates mtDNA content in a DAF-16- and UCP-4-dependent manner. By utilizing RNA interference (RNAi) against polg-1, we showed that mitochondrial stress likely modulates lifespan through the IIS pathway. Our work identifies IIS as a communications pathway between mitochondria and the nucleus in modulating mitochondrial biogenesis and lifespan in Caenorhabditis elegans.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/1185
Date11 1900
CreatorsHu, Xiaobin
ContributorsLemire, Bernard (Biochemistry), Weiner, Joel (Biochemistry), Glerum, Moira (Medical Genetics), Smiley, James (Medical Microbiology & Immunology)
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeThesis
Format5351029 bytes, application/pdf

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