Hofmann Jeffrey W, McBryan Tony, Adams Peter D, Sedivy John M
Department of Molecular Biology, Cell Biology and Biochemistry, Laboratories for Molecular Medicine, Brown University, Providence, RI, 02903, USA.
Age (Dordr). 2014 Jun;36(3):9618. doi: 10.1007/s11357-014-9618-3. Epub 2014 Feb 1.
The Wnt signaling pathway is involved in the regulation of tissue patterning and organ development during embryogenesis and continues to contribute to the maintenance of tissue homeostasis in adulthood. Recently, Wnt signaling has also been implicated in the establishment and progression of replicative cellular senescence. Given the known roles of tissue homeostasis and cellular senescence in aging, we sought to determine whether Wnt signaling changes with age. We examined the expression of 84 Wnt pathway-related genes in the liver, lung, skeletal muscle, and brain tissue from young and old mice. Expression changes were compared with those seen in cellular senescence, and transcription factors that might mediate these changes were predicted bioinformatically. In aggregate, our data are indicative of a general decrease in Wnt signaling with age, especially in the lung and brain. Furthermore, the set of genes that are differentially expressed with age is distinct from the genes differentially expressed in cellular senescence. The transcription factors predicted to regulate these changes, Nf-κB, Myb, Nkx2-1, Nr5a2, and Ep300, are known to regulate inflammation, differentiation, lipid metabolism, and chromatin remodeling, all of which have previously been implicated in aging. Although our study does not address whether altered Wnt signaling is a cause or an effect of aging, the presence of a relationship between the two provides a starting point for further investigation.
Wnt信号通路在胚胎发育过程中参与组织模式形成和器官发育的调控，并在成年期持续维持组织稳态。最近，Wnt信号也与复制性细胞衰老的建立和进展有关。鉴于组织稳态和细胞衰老在衰老过程中的已知作用，我们试图确定Wnt信号是否随年龄变化。我们检测了年轻和年老小鼠肝脏、肺、骨骼肌和脑组织中84个与Wnt通路相关基因的表达。将表达变化与细胞衰老中的变化进行比较，并通过生物信息学预测可能介导这些变化的转录因子。总体而言，我们的数据表明Wnt信号随年龄普遍下降，尤其是在肺和脑中。此外，随年龄差异表达的基因集与细胞衰老中差异表达的基因不同。预测调控这些变化的转录因子Nf-κB、Myb、Nkx2-1、Nr5a2和Ep300，已知可调控炎症、分化、脂质代谢和染色质重塑，所有这些先前都与衰老有关。虽然我们的研究没有探讨Wnt信号改变是衰老的原因还是结果，但两者之间关系的存在为进一步研究提供了一个起点。
