A Boolean network of the crosstalk between IGF and Wnt signaling in aging satellite cells

Lea Siegle; Julian D Schwab; Silke D Kühlwein; Ludwig Lausser; Stefan Tümpel; Astrid S Pfister; Michael Kühl; Hans A Kestler

doi:10.1371/journal.pone.0195126

A Boolean network of the crosstalk between IGF and Wnt signaling in aging satellite cells

PLoS One. 2018 Mar 29;13(3):e0195126. doi: 10.1371/journal.pone.0195126. eCollection 2018.

Authors

Lea Siegle^{1

2}, Julian D Schwab^{1

2}, Silke D Kühlwein^{1

2}, Ludwig Lausser¹, Stefan Tümpel³, Astrid S Pfister⁴, Michael Kühl⁴, Hans A Kestler¹

Affiliations

¹ Institute of Medical Systems Biology, Ulm University, Ulm, Germany.
² International Graduate School of Molecular Medicine, Ulm University, Ulm, Germany.
³ Leibniz-Institute on Aging - Fritz Lipmann Institute, Jena, Germany.
⁴ Institute of Biochemistry and Molecular Biology, Ulm University, Ulm, Germany.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging / physiology*
Animals
Cell Physiological Phenomena*
Chronic Disease
Computational Biology / methods*
Computer Simulation
Homeostasis
Insulin-Like Growth Factor I / metabolism*
Wnt Signaling Pathway*

Substances

Insulin-Like Growth Factor I

Grants and funding

The research leading to these results has received funding from the Medien- und Filmgesellschaft Baden-Wuerttemberg (Karl-Steinbuch scholarship to JDS and LS), the European Community’s Seventh Framework Programme (FP7/2007-2013 under grant agreement n°602783), the German Science Foundation (DFG, SFB 1074 project Z1, no 602783 and GRK 2254, no 635514) to HAK, and the Federal Ministry of Education and Research (BMBF, Gerontosys II, Forschungskern SyStaR, ID 0315894A to HAK and MK and e:Med, SYMBOL-HF, ID 01ZX1407A, CONFIRM, ID 01ZX1708C) to HAK.