Vascular endothelial function declines with age on average, but there is high variability in the magnitude of this decline within populations. Measurements of frailty, known as frailty index (FI), can be used as surrogates for biological age, but it is unknown if frailty relates to the age-related decline in vascular function. To examine this relation, we studied young (4-9 months) and old (23-32 months) C57BL6 mice of both sexes. We found that FI was greater in old compared with young mice, but did not differ between old male and female mice. Middle cerebral artery (MCA) and mesenteric artery endothelium-dependent dilation (EDD) also did not differ between old male and female mice; however, there were sex differences in the relations between FI and EDD. For the MCA, FI was inversely related to EDD among old female mice, but not old male mice. In contrast, for the mesenteric artery, FI was inversely related to EDD among old male mice, but not old female mice. A higher FI was related to a greater improvement in EDD with the superoxide scavenger TEMPOL in the MCAs for old female mice and in the mesenteric arteries for old male mice. FI related to mesenteric artery gene expression negatively for extracellular superoxide dismutase (Sod3) and positively for interleukin-1β (Il1b). In summary, we found that the relation between frailty and endothelial function is dependent on sex and the artery examined. Arterial oxidative stress and pro-inflammatory signaling are potential mediators of the relations of frailty and endothelial function.

中文翻译：

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老年小鼠虚弱与内皮功能障碍关系的性别差异

平均而言，血管内皮功能随着年龄的增长而下降，但这种下降的幅度在人群中存在很大差异。虚弱的测量，称为虚弱指数 (FI)，可用作生物学年龄的替代指标，但尚不清楚虚弱是否与年龄相关的血管功能下降有关。为了检验这种关系，我们研究了两性的年轻（4-9 个月）和老年（23-32 个月）C57BL6 小鼠。我们发现，与年轻小鼠相比，老年小鼠的 FI 更大，但老年雄性和雌性小鼠之间没有差异。大脑中动脉 (MCA) 和肠系膜动脉内皮依赖性扩张 (EDD) 在老年雄性和雌性小鼠之间也没有差异。然而，FI和EDD之间的关系存在性别差异。对于 MCA，FI 与老年雌性小鼠的 EDD 呈负相关，但与老年雄性小鼠无关。相反，对于肠系膜动脉，FI 与老年雄性小鼠的 EDD 呈负相关，但与老年雌性小鼠无关。较高的 FI 与老年雌性小鼠的 MCA 和老年雄性小鼠的肠系膜动脉中的超氧化物清除剂 TEMPOL 对 EDD 的更大改善有关。FI 与肠系膜动脉基因表达相关，对细胞外超氧化物歧化酶 (Sod3) 呈负相关，对白细胞介素-1β (Il1b) 呈正相关。总之，我们发现虚弱和内皮功能之间的关系取决于性别和检查的动脉。动脉氧化应激和促炎信号传导是脆弱和内皮功能关系的潜在介质。较高的 FI 与老年雌性小鼠的 MCA 和老年雄性小鼠的肠系膜动脉中的超氧化物清除剂 TEMPOL 对 EDD 的更大改善有关。FI 与肠系膜动脉基因表达相关，对细胞外超氧化物歧化酶 (Sod3) 呈负相关，对白细胞介素-1β (Il1b) 呈正相关。总之，我们发现虚弱和内皮功能之间的关系取决于性别和检查的动脉。动脉氧化应激和促炎信号传导是脆弱和内皮功能关系的潜在介质。较高的 FI 与老年雌性小鼠的 MCA 和老年雄性小鼠的肠系膜动脉中的超氧化物清除剂 TEMPOL 对 EDD 的更大改善有关。FI 与肠系膜动脉基因表达相关，对细胞外超氧化物歧化酶 (Sod3) 呈负相关，对白细胞介素-1β (Il1b) 呈正相关。总之，我们发现虚弱和内皮功能之间的关系取决于性别和检查的动脉。动脉氧化应激和促炎信号传导是脆弱和内皮功能关系的潜在介质。总之，我们发现虚弱和内皮功能之间的关系取决于性别和检查的动脉。动脉氧化应激和促炎信号传导是脆弱和内皮功能关系的潜在介质。总之，我们发现虚弱和内皮功能之间的关系取决于性别和检查的动脉。动脉氧化应激和促炎信号传导是脆弱和内皮功能关系的潜在介质。