The role of telomerase expression and telomere length maintenance in humanand mouse

The molecular regulation of telomere length has been well elucidated by a s eries of elegant studies over the past decade. More recently, experimental evidence has accrued that addresses the challenging question of if and how telomere length regulation may contribute to normal human aging or to human disease. Recent studies in mice have provided a mammalian precedent indica ting that telomerase deficiency can lead to in vivo dysfunction, most proba bly as a consequence of progressive telomere shortening. In humans, the evi dence that telomere shortening might lead to in vivo dysfunction is far les s direct, although the recent description of telomerase deficiency and telo mere shortening associated with the DKC syndrome is suggestive of such a li nk. Methodologies exist and continue to be developed that are increasingly capable of manipulating telomerase activity and telomere length in human ce lls. It remains to be determined whether scientifically rigorous and (equal ly important) medically ethical approaches will emerge to directly assess t he ability of telomere length modulation to correct functional disorders of human cellular function ex vivo or, more challenging still, in vivo.