Carlson Morgan E, Silva Haroldo S, Conboy Irina M
Department of Bioengineering, University of California, Berkeley, Berkeley, California 94720-1762, USA.
Exp Cell Res. 2008 Jun 10;314(9):1951-61. doi: 10.1016/j.yexcr.2008.03.017. Epub 2008 Apr 7.
The major cell signaling pathways, and their specific mechanisms of transduction, have been a subject of investigation for many years. As our understanding of these pathways advances, we find that they are evolutionarily well-conserved not only individually, but also at the level of their crosstalk and signal integration. Productive interactions within the key signal transduction networks determine success in embryonic organogenesis, and postnatal tissue repair throughout adulthood. However, aside from clues revealed through examining age-related degenerative diseases, much remains uncertain about imbalances within these pathways during normal aging. Further, little is known about the molecular mechanisms by which alterations in the major cell signal transduction networks cause age-related pathologies. The aim of this review is to describe the complex interplay between the Notch, TGFbeta, WNT, RTK-Ras and Hh signaling pathways, with a specific focus on the changes introduced within these networks by the aging process, and those typical of age-associated human pathologies.
主要的细胞信号通路及其特定的转导机制，多年来一直是研究的主题。随着我们对这些通路的理解不断深入，我们发现它们不仅在个体层面，而且在其相互作用和信号整合层面都在进化过程中得到了很好的保留。关键信号转导网络内的有效相互作用决定了胚胎器官发生以及成年后整个生命过程中出生后组织修复的成功。然而，除了通过研究与年龄相关的退行性疾病所揭示的线索外，关于这些通路在正常衰老过程中的失衡仍有许多不确定之处。此外，关于主要细胞信号转导网络的改变导致与年龄相关的病理学的分子机制知之甚少。本综述的目的是描述Notch、TGFβ、WNT、RTK-Ras和Hh信号通路之间的复杂相互作用，特别关注衰老过程在这些网络中引入的变化以及与年龄相关的人类病理学的典型变化。
