Description du projet
Le rôle du stress dans le vieillissement cellulaire
Le vieillissement cellulaire est un processus énigmatique dont nombre d’aspects restent encore méconnus. L’objectif principal du projet NARESICA, financé par l’UE, consiste à étudier le rôle du stress dans le processus de vieillissement. En utilisant la longueur des télomères comme biomarqueur du vieillissement, les chercheurs étudieront la manière dont le stress chronique et, en particulier, les glucocorticoïdes (hormones du stress) accélèrent le vieillissement chez deux espèces aviaires. L’accent sera placé sur plusieurs moteurs potentiels du vieillissement, tels que la fonction mitochondriale, le stress oxydatif, les lésions de l’ADN et la voie de signalisation cellulaire mTOR. Dans l’ensemble, les conclusions du projet dévoileront des informations importantes sur un processus biologique fondamental ayant des implications cliniques.
Objectif
Previous research has identified stress exposure as a key factor influencing health state and ageing rate. The overall aim of the proposed project is to investigate the precise mechanisms linking stress exposure to accelerated cellular ageing (using telomere length as a biomarker of ageing), and to identify potential mechanisms allowing some species to better prevent stress-induced ageing than others. To this aim I will use two avian species (Japanese quail and king penguin) to investigate (1) if chronic stress affects telomere shortening differently between species exhibiting contrasted stress resistance, (2) if glucocorticoid ‘stress’ hormones are directly responsible of the stress-induced alterations in telomere dynamics, (3) by which mechanisms (i.e. alterations of mitochondrial function, oxidative stress and DNA damage, impaired mTOR cellular signalling or telomere maintenance) stress exposure is accelerating telomere shortening, and if king penguin have specific mechanisms preventing/limiting stress-induced telomere shortening, and (4) if chronic stress / glucocorticoid hormones modify the acute oxidative stress responses of individuals. To this end, I will employ experimental approaches manipulating stress exposure and glucocorticoid hormones in captive Japanese quail and wild king penguins, and measure the resulting impact on telomere shortening and its potential cellular drivers (mitochondrial function, oxidative stress, mTOR cellular signalling). This project will enable a two-way transfer of skills and competences between the applicant and the host, by providing training to the applicant regarding mitochondrial biology, cellular signalling and gene expression, and by providing the host with the opportunity to integrate an ageing component through the use of telomeres in his current and future projects.
Champ scientifique
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
69622 Villeurbanne Cedex
France