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Sex differences in the aging human heart: decreased sirtuins, pro-inflammatory shift and reduced anti-oxidative defense.

08:00 EDT 8th April 2019 | BioPortfolio

Summary of "Sex differences in the aging human heart: decreased sirtuins, pro-inflammatory shift and reduced anti-oxidative defense."

Aging is associated with increased inflammation and alterations in mitochondrial biogenesis, which promote the development of cardiovascular diseases. Emerging evidence suggests a role for sirtuins, which are NAD-dependent deacetylases, in the regulation of cardiovascular inflammation and mitochondrial biogenesis. Sirtuins are regulated by sex or sex hormones and are decreased during aging in animal models. We hypothesized that age-related alterations in cardiac Sirt1 and Sirt3 occur in the human heart and examined whether these changes are associated with a decrease in anti-oxidative defense, inflammatory state and mitochondrial biogenesis. Using human ventricular tissue from young (17-40 years old) and old (50-68 years old) individuals, we found significantly lower Sirt1 and Sirt3 expression in old female hearts than in young female hearts. Additionally, lower expression of the anti-oxidative protein SOD2 was observed in old female hearts than in young female hearts. Aging in female hearts was associated with a significant increase in the number of cardiac macrophages and pro-inflammatory cytokines, as well as NF-kB upregulation, indicating a pro-inflammatory shift. Aging-associated pathways in the male hearts were different, and no changes in Sirt1 and Sirt3 or cardiovascular inflammation were observed. In conclusion, the present study revealed a female sex-specific downregulation of Sirt1 and Sirt3 in aged hearts, as well as a decline in mitochondrial anti-oxidative defense and a pro-inflammatory shift in old female hearts but not in male hearts.

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This article was published in the following journal.

Name: Aging
ISSN: 1945-4589
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A homologous family of regulatory enzymes that are structurally related to the protein silent mating type information regulator 2 (Sir2) found in Saccharomyces cerevisiae. Sirtuins contain a central catalytic core region which binds NAD. Several of the sirtuins utilize NAD to deacetylate proteins such as HISTONES and are categorized as GROUP III HISTONE DEACETYLASES. Several other sirtuin members utilize NAD to transfer ADP-RIBOSE to proteins and are categorized as MONO ADP-RIBOSE TRANSFERASES, while a third group of sirtuins appears to have both deacetylase and ADP ribose transferase activities.

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