Assistant Professor University of Sao Paulo São Paulo, Sao Paulo, Brazil
Abstract Body : Studies have shown an increase in nuclear factor kappa B (NF-kB) expression in the cardiac tissue of rodents subjected to experimental aging models. Therefore, it is suspected that NF-kB may have important functions in cellular and molecular processes occurring in the heart aging process. The study aims to assess the involvement of NF-kB in senescence mechanisms and other cellular events triggered during cardiac aging. Male transgenic mice (referred to 3M, with specific suppression of NF-kB in cardiomyocytes) and wild-type (WT) C57BL/6, were divided into the following experimental groups: a) Young WT (3 months old); b) Aged WT (18-21 months old); c) Young 3M (3 months old); d) Aged 3M (18-21 months old). Body weight measurements for both strains were taken every three months for 21 months. The Kaplan-Meier estimation method was also performed to observe the survival rate between the experimental groups (WT and 3M). Cardiac trophism parameters were evaluated, including the heart weight/ tibia length ratio (HW/TL) and assessment of cardiomyocyte area in cross-sections on HE-stained histological slides. Quantification of the percentage of lipofuscin from histological slides stained with Sudan Black B was carried out. Protein expression of DNA damage marker (H2A.X) as well as senescence markers (P21 and P53) were evaluated by western blotting. The obtained results were compared using ANOVA two-way, and a value of p< 0.05 was considered statistically significant. There were no significant differences in the evolution of body weight over the aging period between the groups. The lifespan of the 3M group was lower compared to that of the animals in the WT group (p=0.048). Cardiac hypertrophy was observed in both the old WT and 3M groups when compared to their respective young groups. There was a significant increase in the expression of phosphorylated H2A.X in aged 3M and WT mice compared to young WT mice. Lipofuscin pigments in the cardiac tissue of the young WT and 3M groups were practically absent. However, a higher deposition of these pigments was found in aged WT and 3M mice compared to their respective younger groups. Concerning the protein expression of senescence markers, p21 protein levels were increased in both young and aged 3M mice, while p53 was elevated only in the aged 3M mice when compared to the young WT group. These findings collectively suggest that the specific suppression of NF-kB in cardiomyocytes stimulates responses linked to the aging process of the heart. However, these responses closely resemble those observed in the aged WT group. Further investigation will be undertaken to complement the obtained data.
