RESEARCH PAPER

AGING, Vol 4, No 6 , pp 402-416
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Cardioprotective mIGF-1/SIRT1 signaling induces hypertension, leukocytosis and fear response in mice

Giulia Bolasco1, Raffaele Calogero2, Matteo Carrara2, Mumna Al Banchaabouchi1, Daniel Bilbao1, Gianluigi Mazzoccoli3, and Manlio Vinciguerra1,4
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.
Key words:
behaviour, blood pressure, IGF-1, immune system, SIRT1
Received:
5/20/12; Accepted: 6/10/12; Published: 6/11/12
Correspondence:

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.