Institute of Medical Systems Biology, Ulm University, Ulm, Germany.
International Graduate School of Molecular Medicine, Ulm University, Ulm, Germany.
PLoS One. 2018 Mar 29;13(3):e0195126. doi: 10.1371/journal.pone.0195126. eCollection 2018.
Aging is a complex biological process, which determines the life span of an organism. Insulin-like growth factor (IGF) and Wnt signaling pathways govern the process of aging. Both pathways share common downstream targets that allow competitive crosstalk between these branches. Of note, a shift from IGF to Wnt signaling has been observed during aging of satellite cells. Biological regulatory networks necessary to recreate aging have not yet been discovered. Here, we established a mathematical in silico model that robustly recapitulates the crosstalk between IGF and Wnt signaling. Strikingly, it predicts critical nodes following a shift from IGF to Wnt signaling. These findings indicate that this shift might cause age-related diseases.
衰老是一个复杂的生物学过程,决定了生物体的寿命。胰岛素样生长因子 (IGF) 和 Wnt 信号通路控制着衰老过程。这两个通路有共同的下游靶点,允许这些分支之间进行竞争的串扰。值得注意的是,在卫星细胞衰老过程中,IGF 信号向 Wnt 信号的转变已经被观察到。目前还没有发现能够重现衰老的生物学调控网络。在这里,我们建立了一个数学的计算机模型,该模型可以很好地再现 IGF 和 Wnt 信号之间的串扰。引人注目的是,它预测了从 IGF 信号向 Wnt 信号转变后的关键节点。这些发现表明,这种转变可能导致与年龄相关的疾病。