The emergence of diseases associated with telomere dysfunction, including AIDS, 
aplastic anemia and pulmonary fibrosis, has bolstered interest in telomerase 
activators. We report identification of a new small molecule activator, GRN510, 
with activity ex vivo and in vivo. Using a novel mouse model, we tested the 
potential of GRN510 to limit fibrosis induced by bleomycin in mTERT heterozygous 
mice. Treatment with GRN510 at 10 mg/kg/day activated telomerase 2-4 fold both 
in hematopoietic progenitors ex vivo and in bone marrow and lung tissue in vivo, 
respectively. Telomerase activation was countered by co-treatment with 
Imetelstat (GRN163L), a potent telomerase inhibitor. In this model of 
bleomycin-induced fibrosis, treatment with GRN510 suppressed the development of 
fibrosis and accumulation of senescent cells in the lung via a mechanism 
dependent upon telomerase activation. Treatment of small airway epithelial cells 
(SAEC) or lung fibroblasts ex vivo with GRN510 revealed telomerase activating 
and replicative lifespan promoting effects only in the SAEC, suggesting that the 
mechanism accounting for the protective effects of GRN510 against induced lung 
fibrosis involves specific types of lung cells. Together, these results support 
the use of small molecule activators of telomerase in therapies to treat 
idiopathic pulmonary fibrosis.