Pharmacological TERT activation attenuates phenotypes of natural aging

“Given the established benefits of genetic TERT activation on diseases of aging, we sought to identify compounds capable of derepressing TERT expression in adult somatic cells”, explains Ron DePinho, the corresponding author of the study.

“We developed a cell-based high-throughput screening assay to identify compounds that modulate transcriptional activity of the human TERT transgene in mouse fibroblasts carrying a bacterial artificial chromosome (BAC) containing the human TERT gene locus with a luciferase reporter. Following an initial screen of 653,000 compounds, subsequent secondary and confirmation screening using primary human cells led to the discovery of TAC, which is capable of modestly inducing the transcription activity of TERT gene to levels found in young tissues, confirmed in vivo using naturally aged mice”, continues Hong Seok Shim, first author of the study.