[The natural history of telomeres].
Telomeres are end chromosome structures, which may shorten because of DNA end replication problem and non-reparability of free-radical damage to telomeric DNA. Telomerase is an enzyme serving to maintain telomere length at a species-specific level. The absence of telomerase in somatic cells is widely believed to be the cause of the limited proliferative potential of somatic cells achieved when telomere length, which diminishes over successive cell generations, becomes critically short. However, telomeres are known to be highly heterogenous with regard to their length even in cloned cell populations. In this review data on telomer length distribution and changes in characteristics of these distributions observed over time are considered along with hypotheses about the nature of these phenomena. The following conclusions are drawn: causes of the known features of telomere length distribution are not limited to mere scattering and measurement error, and so any concepts concerning the relationships between telomere length and cell fate should take characteristics of telomere heterogeneity in consideration; the ratio of the initial telomere length and the rate of telomere shortening does not determine the proliferative potential of non-transformed cell populations and does not limit the lifespans of multicellular organisms; telomerase functions in non-germinal cells are either unnecessary or unknown; telomere heterogeneity may result from the stochastic nature of events committing cells to terminal differentiation and/or the loss of cell capacity to proliferate.
Golubev
A G
AG
Research Institute for Experimental Medicine of Russian Academy of Medical Sciences, 12 Acad. Pavlov Str., 197376, Saint-Petersburg, Russia. scgolub@spb.cityline.ru
D000375:Aging / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D005609:Free Radicals; D006801:Humans; D008297:Male; D019098:Telomerase / Q000235:genetics / Q000502:physiology; D016615:Telomere / Q000235:genetics / Q000502:physiology*
D005609:Free Radicals; D019098:Telomerase