Telomere length stem cells and aging端粒长度干细胞和衰老.pdfVIP

R E V I E W Telomere length, stem cells and aging Maria A Blasco Telomere shortening occurs concomitant with organismal aging, and it is accelerated in the context of human diseases associated with mutations in telomerase, such as some cases of dyskeratosis congenita, idiopathic pulmonary fibrosis and aplastic anemia. People with these diseases, as well as Terc-deficient mice, show decreased lifespan coincidental with a premature loss of tissue renewal, which suggests that telomerase is rate-limiting for tissue homeostasis and organismal survival. These findings have gained special relevance as they suggest that telomerase activity and telomere length can directly affect the ability of stem cells to regenerate tissues. If this is true, stem cell dysfunction provoked by telomere shortening may be one of the mechanisms responsible for organismal aging in both humans and mice. Here, we will review the current evidence linking telomere shortening to aging and stem cell dysfunction. Telomeres are specialized chromatin structures at the ends of eukaryotic in vivo, thus leading to cell loss and tissue dysfunction. On the other hand, chromosomes that prevent the chromosome ends from being recognized telomere shortening may also impair the ability of stem cells to regenerate as a DNA break1. In vertebrates, telomeres are composed of TTAGGG tissues, thus leading to tissue failure10. Here, we will review recent data repeats bound by a protein complex called shelterin (also known as the suggesting the importance of telomere length in cancer and aging. telosome)2,3. Shelterin components have roles in chromosome protection and in the regulation of telomere length2,3. The telomere structure Telomere repeats are generated by a cellular reverse transcriptase known Vertebrate telomeres end in a 3′ overhang of the G-rich strand (G- as telomerase (telomerase reverse trans