10/06/2024 - Carine BEAUPERE : Defining the role of adipose-glucocorticoid signaling in age-related cardiometabolic disorders

LES LUNDIS DE SAINT-ANTOINE

Bâtiment Kourilsky - 11h–12h

Salle des Conférences (Rez de Chaussée),

184 rue du Faubourg Saint-Antoine, Paris

***

LUNDI 10 JUIN 2024

Génération de cellules souches hématopoïétiques à partir de cellules souches pluripotentes induites humaines

Carine BEAUPERE

Equipe Bruno FEVE - Centre de Recherche Saint Antoine

invitée par équipe de Bruno FEVE

(carine.beaupere@inserm.fr)

Aging is a progressive physiological decline that predisposes individuals to age-related pathologies such as cardiometabolic diseases, leading causes of death in Europe. Loss of adaptation to various stresses, including metabolic stresses, emerged as both a hallmark and a driver of the aging process. However, comprehend the implication of glucocorticoids (GCs)—central players in the response to metabolic stresses—in organismal aging would be critical. Indeed, prolonged exposure to GCs induce age-related cardiometabolic disorders suggesting that GCs could contribute to premature aging. The project aimed at characterizing the impact of GCs and the glucocorticoid receptor (GR) on the aging process and cellular senescence. Especially, we characterized the impact of supraphysiologic GC treatment on insulin sensitivity and on the expression of senescence marker in insulin-sensitive tissues in young or old animals. We dissected the pro-senescent signals induced by GC/GR in primary adipose stem cells and fibroblasts. In parallel, we investigated how age and cellular senescence can impact tissues or cells sensitivity to GCs. To this end, we aim to establish a mathematical model describing the age-dependent loss in the adaptive response to GCs in order to describe dynamics of activation of GR-downstream targets during cellular senescence and in old or young mice. In fine, our project will help understand not only how GC signaling is affected during the aging process, but also how modulating GC signaling itself may lead to novel therapeutic strategies to delay cardiometabolic disorders and extend healthspan.