TERT activation targets DNA methylation and multiple aging hallmarks.

ABSTRACT: Insufficient telomerase activity, stemming from low telomerase reverse transcriptase (TERT) gene transcription, contributes to telomere dysfunction and aging pathologies. Besides its traditional function in telomere synthesis, TERT acts as a transcriptional co-regulator of genes pivotal in aging and age-associated diseases. Here, we report the identification of a TERT activator compound (TAC) that upregulates TERT transcription via the MEK/ERK/AP-1 cascade. In primary human cells and naturally aged mice, TAC-induced elevation of TERT levels promotes telomere synthesis, blunts tissue aging hallmarks with reduced cellular senescence and inflammatory cytokines, and silences p16^INK4a expression via upregulation of DNMT3B-mediated promoter hypermethylation. In the brain, TAC alleviat

SUBMITTER: Shim HS 

PROVIDER: S-EPMC11552617 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature