Telomeres and telomerase in aging, regeneration and cancer.
The finding that telomere shortening limits the replicative lifespan of primary human cells has fueled speculations that telomere shortening plays a role during aging and regeneration of tissues in vivo. Support for this hypothesis comes from studies showing telomere shortening in a variety of human tissues as a consequence of aging and chronic disease. Studies in telomerase-deficient mice have given first experimental support that telomere shortening limits the replicative potential of organs and tissues in vivo and have identified telomerase as a promising target to treat regenerative disorders induced by telomere shortening. A potential downside of such an approach could be the development of malignant tumors, which has been linked to reactivation of telomerase in human cancers. In telomerase-deficient mice, telomere shortening showed a dual role in tumorigenesis, enhancing the initiation of tumors by induction of chromosomal instability but inhibiting tumor progression by induction of DNA-damage responses. The success in using telomerase activation for the treatment of regenerative disorders could depend on which of the mechanisms of telomere shortening is dominantly effecting carcinogenesis.
Djojosubroto
Meta Wulandari
MW
Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover Carl-Neuberg-Str. 1 30625 Hannover, Germany.
Choi
Yoon Sik
YS
Lee
Han-Woong
HW
Rudolph
Karl Lenhard
KL
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000235:genetics* / Q000378:metabolism
D019098:Telomerase