Cardioprotective mIGF-1/SIRT1 signaling induces hypertension, leukocytosis and fear response in mice

Giulia Bolasco, Raffaele Calogero, Matteo Carrara, Mumna Al Banchaabouchi, Daniel Bilbao, Gianluigi Mazzoccoli, Manlio Vinciguerra

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)402-416
Number of pages15
JournalAging
Volume4
Issue number6
Publication statusPublished - Jun 2012

Keywords

  • Behaviour
  • Blood pressure
  • IGF-1
  • Immune system
  • SIRT1

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

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