Researchers pharmacologically reactivated transcription of the TERT gene and produced a rejuvenating effect in multiple tissues in mice. In a study published in Cell, the authors used a high-throughput strategy to screen more than 650,000 molecules and identified a novel, TERT-activating compound (TAC). This small molecule acts on MEK/ERK/AP-1 signaling and thereby specifically upregulates TERT gene transcription and restores physiological TERT levels of young cells.

Telomerase reverse transcriptase, the protein encoded by TERT, is the catalytic subunit of telomerase, i.e. the enzyme that is essential in maintaining telomere length. Normally, its expression is repressed in postnatal somatic cells. In addition to its traditional function in telomere synthesis, TERT also acts as a co-regulator in the transcription of genes that are involved in aging and in aging-associated disorders.

The researchers investigated the mechanisms of TERT upregulation via TAC and its effects on diverse hallmarks of aging in human cells and in the mouse model. They found that TAC treatment resulted in rejuvenation of various tissues and improved cognitive ability and enhanced neuromuscular function in mice. Formation of new neurons was stimulated in the hippocampus of mice. The expression of genes involved in learning, memory and synaptic biology was increased and TAC treatment also led to decreased cellular senescence.