Hallmark of aging

Telomere Attrition

Last updated Sun May 17 2026 00:00:00 GMT+0000 (Coordinated Universal Time)

What it is

Telomeres are repetitive (TTAGGG)_n DNA–protein caps at chromosome ends. They protect coding DNA from being degraded or fused. Because DNA polymerase cannot fully replicate the lagging strand at chromosome termini, telomeres shorten by ~50–100 base pairs with each somatic cell division. After roughly 50–70 divisions (the Hayflick limit) telomeres become critically short and the cell triggers replicative senescence or apoptosis.

Why it matters in aging

Short telomeres correlate with shorter healthspan and higher all-cause mortality in epidemiological studies. Inherited telomere-biology disorders (dyskeratosis congenita) cause bone-marrow failure, pulmonary fibrosis, and liver cirrhosis — tissues highly dependent on stem-cell renewal.

Mechanisms

End-replication problem depletes telomeres on dividing cells.
Telomerase (TERT + TERC) can extend telomeres but is largely silenced in adult somatic cells; it is active in germ-line, stem, and many cancer cells.
Shelterin complex (TRF1, TRF2, POT1, TIN2, TPP1, RAP1) suppresses spurious DNA-damage response at chromosome ends.
Oxidative damage accelerates telomere loss independent of replication.

What’s being studied

Telomerase activators (e.g. TA-65) have weak human evidence. AAV-mediated telomerase gene therapy extended mouse lifespan in early proof-of-concept work; human trials are early. Telomere length itself is a noisy biomarker — population averages are useful, but a single individual’s measurement is hard to act on.

References

Blackburn, E. H., Epel, E. S. & Lin, J. Human telomere biology. Science 350, 1193–1198 (2015).
Aubert, G. & Lansdorp, P. M. Telomeres and aging. Physiol. Rev. 88, 557–579 (2008).