Background and aims
Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder characterized by accelerated cardiovascular disease. HGPS patients have a mutation in lamin A synthesis cause progerin irregular accumulation. The chronic inflammatory condition could have a causal role in the premature aging syndrome. Our aims were evaluated the role of C-C motif chemokine ligand 2 (CCL2) in aging development. 
Methods 
We carried out this study using a heterozygous mouse with a mutation in lamin A synthesis and systemic CCL2 overexpression condition (Lmna G609G+/- /CgCcl2 +/-). Lmna G609G+/- and wild type were used as control group. Histological analysis was used to assess muscle and cardiovascular alterations. We performed target metabolomics assays of energy metabolism to understand the muscle metabolic response. Moreover, we determined the state of the AMPK/mTOR in muscle tissue.
Results
Lmna G609G/CgCcl2 +/-seemed healthy until 11 weeks of age. Subsequently, they showed a lipodystrophy, reduction in growth rate, body weight and lordosis. Moreover, these mice exhibited important cardiovascular alterations that could be related to their premature death (22 weeks). H&E staining revealed loss the structure of heart and the muscle layers of aortic and femoral arteries, and sirius red staining showed an unusual collagen deposition. The target metabolomic analyze showed that Lmna G609G/CgCcl2 +/- muscle has important glycolysis depletion and increase of ketone body synthesis. All of them with an increase of cellular senescence and autophagy markers. 
Conclusions 
The inflammation condition is responsible for the development of several important features of HGPS. Information gained through this research could be useful for designing new therapeutic strategies, as CCL2 antagonist in treatment of this pathology.

05 - SYSTEMIC CCL2 OVEREXPRESSION PROMOTES VASCULAR ALTERATIONS IN A MOUSE MODEL OF ACCELERATED AGING.