Research Paper Volume 12, Issue 20 pp 20001—20023

Systemic overexpression of C-C motif chemokine ligand 2 promotes metabolic dysregulation and premature death in mice with accelerated aging

Figure 2. Histological phenotypes were altered in the muscles of aged mice. The structural changes in quadriceps muscles are depicted in representative micrographs of tissue stained with hematoxylin and eosin and Sirius red staining and determined by immunohistochemical analysis of β-actin and F4/80 cells. Ccl2 overexpression accelerated the presence of histological alterations (A). Fibrosis was a prominent feature in the progeroid mice, but the relative amount of actin-stained cells was similar among strains, despite major differences in muscle weight. Interestingly, the number of F4/80-stained cells was significantly lower in the progeroid mice. We then used immunoblotting to examine (B) the expression of the markers of macrophage polarization, including cluster of differentiation (CD) 11 and 163, and tumor necrosis factor (TNFα) to indicate the relative anti-inflammatory activity, which was accompanied by lower expression of the major antioxidant enzyme paraoxonase 1 (PON1) in both progeroid strains. The LMNAG609G/+;CGCCL2+/- mice were compared with wild-type mice, as depicted by a p<0.05, and with LA +/- mice, as depicted by b p<0.05, according to the Mann–Whitney U tests (n=15 for each strain). LMNAG609G/+;CGCCL2+/- and LMNAG609G/+ denote progeroid mice overexpressing and not overexpressing Ccl2, respectively.