FIGURE 2. Revisiting the telomere hypothesis: role of telomeres in cancer and ageing.

Normal somatic cells, including adult stem cells, suffer progressive telomere attrition coupled to cell division or to increasing age of the organism. This attrition has been proposed to contribute to multiple age-related pathologies. In germline cells, telomere shortening is attenuated owing to high levels of telomerase activity. By contrast, telomere shortening is accelerated in several human premature ageing syndromes, and patients with dyskeratosis congenita and aplastic anaemia show decreased telomerase activity and shortened telomeres owing to mutations in the TERC and TERT telomerase genes. Psychosocial and environmental factors such as perceived stress, social status, smoking and obesity have also been shown to accelerate telomere attrition. In contrast to normal somatic cells, most immortalized cultures cell lines and more than 95% of human tumours aberrantly activate telomerase to achieve immortal growth. Although telomerase activity has been shown to be rate-limiting for mouse ageing and lifespan, it is unknown whether increased telomerase activity will be able to extend the lifespan of organisms.