Telomeres and telomerase in human health and disease.
Epigenetics refers to the durable changes affecting the genome of an individual during development and aging, but which are not necessarily passed on to subsequent generations. Among the best studied of these epigenetic changes is the shortening of chromosome ends or telomeres. Telomeres are specialized structures, consisting of characteristic DNA repeat sequences and the complex of associated proteins, which cap and protect chromosome ends and serve to preserve genome integrity. In most somatic cells, progressive rounds of cell division are associated with telomere shortening. Such progressive attrition of telomere length eventuates in loss of replicative capacity (cellular senescence). In order to protect the germline and the subpopulation of stem cells from senescence, mechanisms have evolved to prevent telomere attrition in these cellular compartments. The most common and best studied mechanism involves the activation of a ribonucleoprotein enzyme complex, known as telomerase. Activity of telomerase circumvents loss of replicative capacity, by preserving telomere length and chromosome integrity. Hence the detailed mechanisms governing the expression and activity of telomerase have been intensively studied in development and differentiation. Early embryonic development and cellular differentiation are associated with a progressive diminution in telomerase activity. This decrease in activity is principally mediated at the level of the promoter for the gene encoding the catalytic unit of the telomerase complex. Unraveling the detailed mechanisms involved in the regulation of telomere length and telomerase activity will have important and far-reaching implications in understanding many aspects of human health and disease, ranging from accelerated aging syndromes to cancer pathogenesis, among others. Furthermore, insights gleaned from continuing research in this area will likely be applicable to the development of strategies to circumvent cellular senescence in regenerative medicine and stem cell therapeutics in the years to come.
Tzukerman
Maty
M
Rambam Medical Center, Haifa, Israel.
Selig
Sara
S
Skorecki
Karl
K
D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics / Q000503:physiopathology; D019098:Telomerase / Q000235:genetics / Q000502:physiology*; D016615:Telomere / Q000235:genetics / Q000502:physiology*
D019098:Telomerase