MTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.

ABSTRACT: Lung diseases develop when telomeres shorten beyond a critical point. We constructed a mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTert^CI), is expressed from the p21^Cdkn1a locus. Expression of either TERT or TERT^CI reduces global p21 levels in the lungs of aged mice, highlighting TERT non-canonical function. However, only TERT reduces accumulation of very short telomeres, oxidative damage, endothelial cell (ECs) senescence and senile emphysema in aged mice. Single-cell analysis of the lung reveals that p21 (and hence TERT) is expressed mainly in the capillary ECs. We report that a fraction of capillary ECs marked by CD34 and endowed with proliferative capacity declines drastically with age, and this

SUBMITTER: Lipskaia L 

PROVIDER: S-EPMC10933469 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature