Rudolph K L, Chang S, Lee H W, Blasco M, Gottlieb G J, Greider C, DePinho R A
Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Cell. 1999 Mar 5;96(5):701-12. doi: 10.1016/s0092-8674(00)80580-2.
Telomere maintenance is thought to play a role in signaling cellular senescence; however, a link with organismal aging processes has not been established. The telomerase null mouse provides an opportunity to understand the effects associated with critical telomere shortening at the organismal level. We studied a variety of physiological processes in an aging cohort of mTR-/- mice. Loss of telomere function did not elicit a full spectrum of classical pathophysiological symptoms of aging. However, age-dependent telomere shortening and accompanying genetic instability were associated with shortened life span as well as a reduced capacity to respond to stresses such as wound healing and hematopoietic ablation. In addition, we found an increased incidence of spontaneous malignancies. These findings demonstrate a critical role for telomere length in the overall fitness, reserve, and well being of the aging organism.
端粒维持被认为在细胞衰老信号传导中发挥作用；然而，与机体衰老过程的联系尚未确立。端粒酶缺失小鼠为在机体水平上理解与关键端粒缩短相关的影响提供了一个机会。我们研究了mTR-/-小鼠衰老群体中的各种生理过程。端粒功能丧失并未引发衰老的全谱经典病理生理症状。然而，年龄依赖性端粒缩短和伴随的基因不稳定与寿命缩短以及对诸如伤口愈合和造血消融等应激的反应能力降低有关。此外，我们发现自发恶性肿瘤的发生率增加。这些发现表明端粒长度在衰老机体的整体健康、储备和福祉中起着关键作用。
