Anti-aging molecule TAC upregulates TERT targets multiple markers of youth

Good news! Progress in the always alluring prospect in the age old quest for the fountain of youth! How many have died to find it?

TERT not terse nor tart! 😊 Compare that to the butchery of cosmetic surgery! 😊

"Researchers ... have demonstrated that therapeutically restoring ‘youthful’ levels of a specific subunit of the telomerase enzyme can significantly reduce the signs and symptoms of aging in preclinical models. If these findings are confirmed in clinical studies, there may be therapeutic implications for age-related diseases such as Alzheimer’s, Parkinson’s, heart disease and cancer.

The study, published today in Cell, identified a small molecule compound that restores physiological levels of telomerase reverse transcriptase (TERT), which normally is repressed with the onset of aging. Maintenance of TERT levels in aged lab models reduced cellular senescence and tissue inflammation, spurred new neuron formation with improved memory, and enhanced neuromuscular function, which increased strength and coordination.

The researchers show that TERT functions not only to extend telomeres, but also acts as a transcription factor to affect the expression of many genes directing neurogenesis, learning and memory, cellular senescence, and inflammation.  ...
A high-throughput screen of over 650,000 compounds identified a small-molecule TERT activating compound (TAC) that epigenetically de-represses the TERT gene and restores physiological expression present in young cells. ..."

From the highlights and abstract:

"Highlights

• TERT has been linked directly or indirectly to all hallmarks of aging

• TERT gene is epigenetically repressed with onset of aging markers in all tissues

• TAC restores TERT levels to promote telomere maintenance and reprogram gene expression

• TAC in aged mice reduces senescence/inflammation and increases neurogenesis/cognition

Summary

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 p16INK4a expression via upregulation of DNMT3B-mediated promoter hypermethylation. In the brain, TAC alleviates neuroinflammation, increases neurotrophic factors, stimulates adult neurogenesis, and preserves cognitive function without evident toxicity, including cancer risk. Together, these findings underscore TERT’s critical role in aging processes and provide preclinical proof of concept for physiological TERT activation as a strategy to mitigate multiple aging hallmarks and associated pathologies."

Anti-aging molecule successfully restores multiple markers of youth In pre-clinical trials, a small molecule effectively regrew neurons, reduced inflammation, and improved memory, speed, coordination, grip strength, and more. The finding could have a profound impact on aging and the diseases that accompany it.

Activating molecular target reverses multiple hallmarks of aging (original news release) MD Anderson researchers identify molecule that reduces age-related inflammation and improves brain and muscle function in preclinical models

TERT activation targets DNA methylation and multiple aging hallmarks (no public access)

Graphical abstract