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Mech Ageing Dev ; 194: 111426, 2021 03.
Article de Anglais | MEDLINE | ID: mdl-33385396

RÉSUMÉ

Advanced age is the major risk factor for idiopathic Parkinson's disease (PD), but to date the biological relationship between PD and ageing remains elusive. Here we describe the rationale and the design of the H2020 funded project "PROPAG-AGEING", whose aim is to characterize the contribution of the ageing process to PD development. We summarize current evidences that support the existence of a continuum between ageing and PD and justify the use of a Geroscience approach to study PD. We focus in particular on the role of inflammaging, the chronic, low-grade inflammation characteristic of elderly physiology, which can propagate and transmit both locally and systemically. We then describe PROPAG-AGEING design, which is based on the multi-omic characterization of peripheral samples from clinically characterized drug-naïve and advanced PD, PD discordant twins, healthy controls and "super-controls", i.e. centenarians, who never showed clinical signs of motor disability, and their offspring. Omic results are then validated in a large number of samples, including in vitro models of dopaminergic neurons and healthy siblings of PD patients, who are at higher risk of developing PD, with the final aim of identifying the molecular perturbations that can deviate the trajectories of healthy ageing towards PD development.


Sujet(s)
Vieillissement/métabolisme , Recherche biomédicale , Encéphale/métabolisme , Gériatrie , Médiateurs de l'inflammation/métabolisme , Neurones/métabolisme , Maladie de Parkinson/métabolisme , Facteurs âges , Sujet âgé , Sujet âgé de 80 ans ou plus , Vieillissement/génétique , Vieillissement/anatomopathologie , Encéphale/anatomopathologie , Encéphale/physiopathologie , Études cas-témoins , Europe , Femelle , Génomique , Humains , Mâle , Métabolomique , Activité motrice , Dégénérescence nerveuse , Neurones/anatomopathologie , Maladie de Parkinson/génétique , Maladie de Parkinson/anatomopathologie , Maladie de Parkinson/physiopathologie , Plan de recherche , Transduction du signal , Méthode des jumeaux comme sujet
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