Telomerase (TERT / TERC)

What it is

Telomerase is a ribonucleoprotein with two essential components:

• TERT — the catalytic reverse-transcriptase protein.
• TERC — the template RNA used to add TTAGGG repeats to chromosome ends.

Plus accessory proteins (dyskerin, TCAB1, others).

Why it matters

Telomerase counteracts replicative telomere shortening (Telomere attrition). It is active in germ-line, stem cells, and ~90% of cancers, and largely silenced in adult somatic cells.

Therapeutic interest

• AAV-TERT gene therapy extended mouse lifespan when delivered to old mice (~24% median lifespan extension) without raising cancer incidence in the original studies.
• TA-65 (a cycloastragenol-based supplement) modestly activates telomerase but has weak healthspan data in humans.
• Telomerase activation in cancer is a known oncogenic feature; any long-term activation strategy must address cancer risk.

The cancer trade-off

Most cancers reactivate telomerase to escape replicative limits. Whole-body telomerase activation in adults is therefore approached cautiously.

Longevity relevance

Telomerase reverse transcriptase (TERT) maintains telomere length by adding TTAGGG repeats to chromosome ends. Its expression is tightly restricted in most somatic tissues, limiting replicative capacity and providing a tumour-suppressor function.

The longevity-cancer trade-off

• Insufficient telomerase: replicative senescence, stem-cell exhaustion, progeroid syndromes (dyskeratosis congenita).
• Excess telomerase / constitutive expression: cancer risk (>80% of human cancers reactivate telomerase).
• Evolution has tuned tissue-specific telomerase to balance regenerative capacity against oncogenic risk.

Interventions

• AAV-based TERT gene therapy: extends mouse lifespan; human trials underway with careful cancer surveillance.
• TA-65 and small-molecule telomerase activators: modest effects; unclear risk-benefit.
• Cyclarity's telomere-independence strategy: alternative to telomerase-based approaches.

Human genetics

• Loss-of-function TERT mutations cause dyskeratosis congenita and short-telomere syndromes.
• Common short-telomere variants associate with elevated cardiovascular and neurodegenerative disease risk.

Related entries

Telomere attrition, Telomere length, TERT, Cancer, Elizabeth Blackburn (via book).

Related entries

Telomere attrition, Telomere length, Maria Blasco.