Pré-Publication, Document De Travail Année : 2022

Induction of telomerase in p21-positive cells counteracts capillaries rarefaction in aging mice lung

Larissa Lipskaia
  • Fonction : Auteur
Marielle Breau
  • Fonction : Auteur
Dmitri Churikov
Laura Braud
  • Fonction : Auteur
Charles Fouillade
Sandra Curras-Alonso
  • Fonction : Auteur
Serge Bauwens
  • Fonction : Auteur
Frederic Jourquin
Frederic Fiore
  • Fonction : Auteur
Rémy Castellano
  • Fonction : Auteur
Emmanuelle Josselin
  • Fonction : Auteur
Carlota Sánchez-Ferrer
  • Fonction : Auteur
Giovanna Giovinazzo
  • Fonction : Auteur
Eric Gilson
Ignacio Flores
  • Fonction : Auteur
Arturo Londono-Vallejo
  • Fonction : Auteur
Serge Adnot
  • Fonction : Auteur
Vincent Géli

Résumé

ABSTRACT Telomerase is required for long-term cell proliferation and linked to stem cells. This is evident in the lung where short telomeres are associated with lung dysfunction. We constructed a mouse model in which the telomerase ( Tert ) is expressed from the p21 Cdkn1a promoter. We found that this peculiar Tert expression curb age-related emphysema and pulmonary perivascular fibrosis in old mice. In old mice lungs, such Tert expression preferentially occurs in endothelial cells where it reduces the number of senescent endothelial cells. Remarkably, we report that Tert counteracts the age-related decline in capillary density. This was associated with an increased number of Cd34+ cells identified as a subclass of capillary cells with proliferative capacity. Expression of catalytically inactive Tert neither prevents the decline of capillary density in old mice nor protects against age-related emphysema and fibrosis. These findings reveal that telomerase decreases age-decline of pulmonary functions by sustaining microvasculature regeneration and outgrowth.

Dates et versions

hal-03872430 , version 1 (25-11-2022)

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Larissa Lipskaia, Marielle Breau, Christelle Cayrou, Dmitri Churikov, Laura Braud, et al.. Induction of telomerase in p21-positive cells counteracts capillaries rarefaction in aging mice lung. 2022. ⟨hal-03872430⟩

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