Sex differences in the aging human heart: decreased sirtuins, pro-inflammatory shift and reduced anti-oxidative defense
Sex differences in the aging human heart: decreased sirtuins, pro-inflammatory shift and reduced anti-oxidative defense
复制标题
DOI：
10.18632/aging.101881
复制
发表时间：
2019-04-15
期刊：
影响因子：
5.2
通讯作者：
Regitz-Zagrosek, Vera
中科院分区：
文献类型：
--
作者：
de Arellano, Maria Luisa Barcena;Pozdniakova, Sofya;Regitz-Zagrosek, Vera
衰老与炎症增加和线粒体改变有关！生物发生，促进心血管疾病的发展。新出现的证据表明，sirtuins，这是NAD（+）依赖性脱乙酰酶，在心血管炎症和线粒体的调节作用！生物起源Sirtuins受性或性激素调节，在动物模型中随着衰老而减少。我们假设心脏Sirt 1和Sirt 3发生与年龄相关的变化，并检查这些变化是否与抗氧化防御，炎症状态和线粒体的减少有关！生物起源。使用来自年轻（17-40岁）和老年（50-68岁）个体的人心室组织，我们发现老年女性心脏中的Sirt 1和Sirt 3表达显著低于年轻女性心脏。此外，老年女性心脏中抗氧化蛋白SOD 2的表达低于年轻女性心脏。女性心脏的衰老与心脏巨噬细胞和促炎细胞因子数量的显著增加以及NF-kB上调相关，表明促炎转变。男性心脏中与衰老相关的途径是不同的，没有观察到Sirt 1和Sirt 3或心血管炎症的变化。总之，本研究揭示了老年心脏中Sirt 1和Sirt 3的女性性别特异性下调，以及线粒体的下降！抗氧化防御和促炎性转变在老年女性的心脏，但不是在男性的心脏。
Aging is associated with increased inflammation and alterations in mitochondria! 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 mitochondria! 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 mitochondria! 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 mitochondria! anti-oxidative defense and a pro-inflammatory shift in old female hearts but not in male hearts.