On July 20, Ronald DePinho proposed testing TERT, a component of telomerase, as a general regulator of aging
On July 20, Ronald DePinho proposed testing TERT, a component of telomerase, as a general regulator of aging
In a perspective article for Nature Aging, DePinho proposes testing whether brief, controlled increases in TERT affect several features of aging, while measuring the risk of tumor growth at the same time.
Telomeres protect the ends of chromosomes. In many adult cells, they shorten with each division, while telomerase can extend them. TERT is the protein component of telomerase that participates in this process. In DePinho's article, he proposes that TERT has a broader role.
In his model, TERT connects telomere status with gene activity, inflammatory signaling, cells that have stopped dividing, and stem cell reserves. DePinho proposes testing whether a single controlled mechanism can alter several aging processes at once. Such an experiment should help distinguish changes caused by TERT itself from those that arise through other mechanisms.
The idea has some preclinical support. In a 2024 study, DePinho's group screened approximately 653 thousand compounds and identified a small molecule called TAC that increased TERT production. In primary human cells and naturally aged mice, TAC reduced markers of cellular senescence and inflammatory signaling. In the mouse brain, the authors also reported less neuroinflammation and preserved cognitive function.
These results need to be separated into effects of TERT and effects of TAC itself. The activator affects cells through the MEK/ERK/AP-1 signaling pathway, so future experiments should isolate the contribution of TERT, identify the tissues to target, and compare brief activation regimens.
Telomerase helps cells retain their capacity to divide, and tumor cells use the same capacity to support their growth. A genetic study linked inherited variants associated with longer telomeres to an increased risk of several types of cancer. Testing TERT should therefore measure both changes in features of aging and the risk of tumor growth within the same experiment. This is how the author proposes identifying a regimen in which improved regeneration does not come at the cost of increased cancer risk.