The importance of telomeres in the maintenance of a healthy human lifespan is also inferred from the study of a variety of inherited degenerative disorders. For instance, patients with autosomal dominant dyskeratosis congenita are now known to carry mutations in either the catalytic, TERT, component of telomerase or in the gene, TERC, that encodes its RNA template53. These patients have shortened telomeres and reduced lifespan, and they show signs of accelerated ageing and bone marrow failure with increased risk of life-threatening infections53. Additional evidence of the relevance of telomeres to the ageing process comes from the analysis of patients, and derivative cells, afflicted with premature-ageing conditions such as Werner syndrome and ataxia telangiectasia (Box 4). However, TERC or TERT mutations have been linked to more organ-restricted dysfunction as well, for instance to idiopathic pulmonary fibrosis (a progressive fatal lung disease with excessive scarring)54 and bone marrow failure syndromes55, highlighting the complex and tissue-specific manifestation of telomere length maintenance defects. Beyond inherited genetic disorders, telomeres also seem to be relevant to ‘acquired’ degenerative conditions associated with chronically elevated tissue turnover. The
