Human diseases of telomerase dysfunction: Insights into tissue aging

被引:100
作者
Garcia, Christine Kim [2 ]
Wright, Woodring E. [1 ]
Shay, Jerry W. [1 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA
[2] Univ Texas SW Med Ctr Dallas, Div Pulm & Crit Care Med, Dept Internal Med, McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA
关键词
D O I
10.1093/nar/gkm644
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
There are at least three human diseases that are associated with germ-line mutations of the genes encoding the two essential components of telomerase, TERT and TERC. Heterozygous mutations of these genes have been described for patients with dyskeratosis congenita, bone marrow failure and idiopathic pulmonary fibrosis. In this review, we will detail the clinical similarities and difference of these diseases and review the molecular phenotypes observed. The spectrum of mutations in TERT and TERC varies for these diseases and may in part explain the clinical differences observed. Environmental insults and genetic modifiers that accelerate telomere shortening and increase cell turnover may exaggerate the effects of telomerase haploinsufficiency, contributing to the variability of age of onset as well as tissue-specific organ pathology. A central still unanswered question is whether telomerase dysfunction and short telomeres are a much more prominent factor than previously suspected in other adult-onset, age-related diseases. Understanding the biological effects of these mutations may ultimately lead to novel treatments for these patients.
引用
收藏
页码:7406 / 7416
页数:11
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