Department of Human Physiology, University of Oregon, Eugene, Oregon, USA.
J Gerontol A Biol Sci Med Sci. 2022 Mar 3;77(3):416-423. doi: 10.1093/gerona/glab317.
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 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl 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 proinflammatory signaling are potential mediators of the relations of frailty and endothelial function.
血管内皮功能随年龄增长而平均下降，但人群中这种下降的幅度存在很大差异。被称为虚弱指数（FI）的虚弱测量值可用作生物年龄的替代指标，但尚不清楚虚弱是否与血管功能的年龄相关下降有关。为了研究这种关系，我们研究了年轻（4-9 个月）和年老（23-32 个月）的 C57BL6 雌雄小鼠。我们发现，FI 在年老小鼠中高于年轻小鼠，但在年老雌雄小鼠之间没有差异。大脑中动脉（MCA）和肠系膜动脉内皮依赖性扩张（EDD）在年老雌雄小鼠之间也没有差异；然而，FI 与 EDD 之间的关系存在性别差异。对于 MCA，FI 与年老雌性小鼠的 EDD 呈负相关，但与年老雄性小鼠无关。相比之下，对于肠系膜动脉，FI 与年老雄性小鼠的 EDD 呈负相关，但与年老雌性小鼠无关。FI 较高与 EDD 的改善呈正相关，这种改善与 MCA 中超氧化物清除剂 4-羟基-2,2,6,6-四甲基哌啶-1-氧自由基（4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl）在年老雌性小鼠和肠系膜动脉中在年老雄性小鼠中的作用有关。FI 与肠系膜动脉基因表达呈负相关，与细胞外超氧化物歧化酶（Sod3）负相关，与白细胞介素-1β（Il1b）正相关。总之，我们发现虚弱与内皮功能之间的关系取决于性别和所检查的动脉。动脉氧化应激和促炎信号是虚弱与内皮功能关系的潜在介质。
