Telomere

Telomeres are specialised nucleoprotein structures composed of tandem TTAGGG hexanucleotide repeats and the associated shelterin protein complex (TRF1, TRF2, POT1, TPP1, TIN2, RAP1) that cap the ends of linear eukaryotic chromosomes. They serve two essential functions: protecting chromosome ends from being recognised as double-strand breaks (preventing inappropriate non-homologous end-joining, chromosomal fusions, and end resection) and providing a buffer against the 'end-replication problem' — the inability of DNA polymerase to fully replicate the lagging strand at chromosome termini. In most somatic cells telomeres shorten by ~50–200 base pairs per cell division. Critical telomere shortening triggers cellular senescence or apoptosis via a p53/p21-driven DNA-damage response. The reverse transcriptase telomerase (catalytic subunit hTERT plus RNA template hTR) extends telomeres in stem cells, germ cells, and most cancers but is largely silenced in differentiated somatic cells, which is the mechanistic basis of the Hayflick replicative limit. Telomere length is a much-studied biomarker of biological age and is associated with mortality, age-related disease, and lifestyle factors. In peptide research, telomere biology is the central mechanistic hypothesis for epitalon, whose telomerase-upregulating activity in cultured human fibroblasts (Khavinson et al., 2003) is its principal published finding. Telomere biology also intersects with the broader sirtuin/NAD⁺ longevity axis.