Research Paper Volume 11, Issue 7 pp 1918—1933
Sex differences in the aging human heart: decreased sirtuins, pro-inflammatory shift and reduced anti-oxidative defense
- 1 Institute of Gender in Medicine and Center for Cardiovascular Research, Charité University Hospital, Berlin, Germany
- 2 DZHK (German Centre for Cardiovascular Research), Berlin Partner Site, Berlin, Germany
- 3 Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, iPATH.Berlin-Immunopathology for Experimental Models, Berlin, Germany
- 4 Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, Hungary
Received: October 17, 2018 Accepted: March 20, 2019 Published: April 8, 2019
https://doi.org/10.18632/aging.101881How to Cite
Copyright: Barcena de Arellano et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.