Blasco Maria A
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, 3 Melchor Fernandez Almagro, 28019 Madrid, Spain.
Nat Chem Biol. 2007 Oct;3(10):640-9. doi: 10.1038/nchembio.2007.38.
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.
端粒缩短与机体衰老同时发生，并且在与端粒酶突变相关的人类疾病背景下会加速，例如某些先天性角化不良、特发性肺纤维化和再生障碍性贫血病例。患有这些疾病的人以及端粒酶RNA组分（Terc）缺陷小鼠的寿命缩短，同时组织更新过早丧失，这表明端粒酶是组织稳态和机体存活的限速因素。这些发现具有特殊意义，因为它们表明端粒酶活性和端粒长度可直接影响干细胞再生组织的能力。如果这是真的，端粒缩短引发的干细胞功能障碍可能是人类和小鼠机体衰老的机制之一。在此，我们将综述目前将端粒缩短与衰老和干细胞功能障碍联系起来的证据。
