Research Paper Volume 4, Issue 6 pp 402—416
Cardioprotective mIGF-1/SIRT1 signaling induces hypertension, leukocytosis and fear response in mice
- 1 European Molecular Biology Laboratory (EMBL)-Mouse Biology Unit, Monterotondo, Italy
- 2 Molecular Biotechnology Center, University of Turin, Italy
- 3 Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS Scientific Institute “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy
- 4 Institute of Hepatology, Birkbeck University of London, UK
Received: May 20, 2012 Accepted: June 10, 2012 Published: June 11, 2012
https://doi.org/10.18632/aging.100464How to Cite
Abstract
Locally acting insulin growth factor isoform (mIGF-1) and the NAD+-dependent protein deacetylase SIRT1 are implicated in life and health span. Heart failure is associated with aging and is a major cause of death. mIGF-1 protects the heart from oxidative stresses via SIRT1. SIRT1 subcellular localization and its genomic regulation by mIGF-1 are unknown. We show here that SIRT1 is located in the nuclei of a significant fraction of cardiomyocytes. Using high throughput sequencing approaches in mIGF-1 transgenic mice, we identified new targets of the mIGF-1/SIRT1 signaling. In addition to its potent cardioprotective properties, cardiac-restricted mIGF-1 transgene induced systemic changes such as high blood pressure, leukocytosis and an enhanced fear response, in a SIRT1-dependent manner. Cardiac mIGF-1/SIRT1 signaling may thus modulate disparate systemic functions.