Telomerase reverse transcriptase gene knock-in unleashes enhanced longevity and accelerated damage repair in mice.

While previous research has demonstrated the therapeutic efficacy of telomerase reverse transcriptase (TERT) overexpression using adeno-associated virus and cytomegalovirus vectors to combat aging, the broader implications of TERT germline gene editing on the mammalian genome, proteomic composition, phenotypes, lifespan extension, and damage repair remain largely unexplored. In this study, we elucidate the functional properties of transgenic mice carrying the Tert transgene, guided by precise gene targeting into the Rosa26 locus via embryonic stem (ES) cells under the control of the elongation factor 1α (EF1α) promoter. The Tert knock-in (TertKI) mice harboring the EF1α-Tert gene displayed elevated telomerase activity, elongated telomeres, and extended lifespan, with no spontaneous genotoxicity or carcinogenicity.