Telomere Biology Overview

Telomeres are the protective DNA-protein complexes that cap the ends of eukaryotic chromosomes and are required for genome stability. The essential telomeric DNA consists of a tract of a tandemly repeated short sequence specified and maintained by the highly regulated reverse transcriptase action of the cellular enzyme telomerase. Telomeric DNA is susceptible to natural terminal erosion through a variety of processes including the end replication problem of linear chromosomal DNA, which causes telomeres to get shorter each time a somatic cell divides (Olovnikov 19773; Blackburn 2005), and other processes in cells that can act to diminish telomere length (TL) including nuclease action, replication fork stalling through telomeric DNA repeat tracts, DNA recombination and oxidative damage (Jain and Cooper 2010). While telomerase can counteract shortening by elongating and protecting telomeres, telomerase activity is generally down-regulated in normal human cells (Blackburn 1997). When telomeres become too short, cells become senescent, losing the ability to divide and function normally (Allsopp et al. 1992; Blackburn 200; Armanios and Blackburn 2012). Mutations that decrease telomerase and cause short telomeres in humans lead to a spectrum of premature-onset diseases and conditions collectively termed "telomere syndromes", which share many features of the common diseases of aging in the human population (Armanios and Blackburn 2012). Multiple independent studies have found impaired human telomeric DNA length maintenance to be associated with a wide range of diseases, and for several age-related diseased to predict future risks and outcomes including mortality.