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 language | English |
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Pages (from-to) | 402-416 |
Number of pages | 15 |
Journal | Aging |
Volume | 4 |
Issue number | 6 |
Publication status | Published - Jun 2012 |
Keywords
- Behaviour
- Blood pressure
- IGF-1
- Immune system
- SIRT1
ASJC Scopus subject areas
- Ageing
- Cell Biology