Longevity Briefs: Regrowing Telomeres To Reverse Ageing

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Telomeres, the genetic caps that protect the ends of our chromosomes from damage, become shorter each time a cell divides. This process, known as telomere attrition, is considered to be one of the main hallmarks of ageing. Once telomeres become too short, cells are no longer able to divide, contributing to ageing and disease. Our cells retain the ability to elongate shortened telomeres, but the enzyme necessary to do this – telomerase – is suppressed in most of our cells. 

Studies in mice have used genetic techniques to reactivate telomerase and found that mice live longer and get fewer age related diseases overall, though sometimes at the cost of slightly increased cancer incidence (since cancer cells usually need to regrow their telomeres if they are to continue dividing forever). Telomerase could be reactivated in humans using gene therapy, but gene therapy is expensive and doesn’t always reach the tissues and organs we want it to.

The discovery:

In this study, researchers identified a new small molecule that can increase telomerase activity in a wide range of tissues. To do this, they produced mouse cells that contained the human version of the TERT gene, which encodes the main component of the telomerase enzyme (telomerase reverse transcriptase). TERT is not only important for telomere restoration, but also modulates the activity of genes related to ageing. Researchers then screened over 650,000 compounds in an attempt to identify small molecules that could activate the human TERT gene.

After narrowing these down to a single molecule called TERT activator compound (TAC) that could specifically increase TERT gene activity, they moved to experiments in 12-14 month-old mice with the human version of TERT. Despite TAC being cleared from the body within 3 hours of being injected, it was able to activate TERT in numerous tissues and organs including the central nervous system. This was associated with significant reductions in inflammation and the number of senescent cells (cells that are unable to divide). It also stimulated neurogenesis (the production of new neurons) and improved performance in cognitive tests and tests of neuromuscular function (such as grip strength and ability to remain on a rotating rod).

The implications:

This study provides more evidence that TERT could be targeted to reverse ageing and improve various biological functions, and identifies a small molecule that could potentially be used to do just that, though the study didn’t investigate whether the mice that received TAC actually lived longer than the controls. Activating TERT for only a temporary period of time could also get around the problem of increased cancer incidence.

Slow careful research will be needed before this makes its way anywhere near human trials. The sample sizes in this study were small, with only 6 mice per group in the cognitive and neuromuscular tests. It’s also important to keep in mind that the mice used in this study were highly inbred and tend to develop a lot of health problems that genetically diverse organisms don’t suffer from. This makes them less than ideal for extrapolating the benefits of TERT activation in humans.