Telomeres protect the chromosome ends for DNA repair and degradation activities and telomerase is the enzyme responsible for maintaining telomere length and for cell self-renewal (Blackburn et al., 2006). Telomerase has two major components: hTERT, the telomerase reverse transcriptase, and hTR, a specialized RNA has a template for telomere repeat addition. The genetic defect caused by mutations in hTERT and hTR accounts 8-15% of IPF familial cases (Armanios, 2012-37,38).
IPF is an age-related disease that majority of the diagnosed IPF patients are after the age of 60 (Raghu et al., 2006). Telomeres and telomerase are susceptible to age-related deterioration. Studies using genetically modified animal models have demonstrated the causal links of telomere dysfunction, cellular senescence and aging. Although telomere attrition manifests during normal physiological aging, pathological telomere dysfunction provokes aging (Blackburn et al., 2006; Flores and Blasco, 2010) and plays a causal role in premature development of various human diseases, including IPF (Tsakiri et al., 2007; Cronkhite et al., 2008). The mechanisms of telomere defects provoking IPF are not fully understood, but numbers of evidence has revealed the causal links of telomere defects with epithelial dysfunction observed in IPF (Alder et al., 2008; Zoz et al., 2011b). Importantly, mutations in telomerase and telomere genes cause abnormal telomere shortening. The shortening of telomere length is a common feature of IPF observed in lymphocytes, granulocytes as well as alveolar epithelial cells, even when no mutations in telomerase genes are detected (Alder et al., 2008). AEC-II cells are the distal stem cells that response to injury and replenish the alveolar epithelial pool. Recent studies using telomeric repeat-binding factor 2 (Trf2) mutant mice model (de Lange, 2009) demonstrate that the telomere dysfunction restricted to AEC-II cells causes their stem cell function failure by inducing senescence and contributes to the pathogenesis of IPF (Alder et al., 2015; Chen et al., 2015).