Telomeres and human disease

Abstract

Telomeres are specialized structures at chromosome endsrequired for chromosome stability maintenance. They consistof a specific repetitive DNA sequence and a set of associatedproteins that form a protective structure at chromosomeends. The enzyme telomerase, which is active in stemcells but not in normal somatic cells, synthesizes telomericDNA sequence. This enzyme is important for cell proliferativepotential and most cancer cells have active telomerase.Telomeres are shorter in older individuals than in younger individualsand they may be viewed as a “biological clock”. Theevidence is accumulating that telomere maintenance plays asignificant role in the pathology associated with some humandiseases. There are several human genetic diseases that showaccelerated shortening of telomeric DNA sequences includingDyskeratosis congenita, Fanconi anemia, ataxia telangiectasia,Nijmegen breakage syndrome, Werner syndrome,Bloom syndrome, pulmonary fibrosis and ataxia telangiectasialike disease. A common feature of these diseases is acceleratedtelomere shortening due to increased cell turnoverthat eventually leads to signs of premature ageing. Commondiseases lacking an apparent genetic component such as atherosclerosis,heart failure, liver cirrhosis and ulcerative colitis,also show accelerated telomere shortening in affected tissues,that eventually causes tissue specific pathology. Factors thatincrease cell turnover may be detected by measuring telomerelength in the human population and so far several such factorshave been identified including: smoking, obesity and exposureto psychological stress. It is likely that future researchwill reveal an even more extensive role of defective telomeremaintenance in human disease and conditions that elevatedisease risk.