Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, United States.
Institute of Animal Health and Food Safety, Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain.
Am J Physiol Heart Circ Physiol. 2024 Sep 1;327(3):H660-H665. doi: 10.1152/ajpheart.00464.2024. Epub 2024 Jul 26.
Endothelial function declines with aging and independently predicts future cardiovascular disease (CVD) events. Diving also impairs endothelial function in humans. Yet, dolphins, being long-lived mammals adapted to diving, undergo repetitive cycles of tissue hypoxia-reoxygenation and disturbed shear stress without manifesting any apparent detrimental effects, as CVD is essentially nonexistent in these animals. Thus, dolphins may be a unique model of healthy arterial aging and may provide insights into strategies for clinical medicine. Emerging evidence shows that the circulating milieu (bioactive factors in the blood) is at least partially responsible for transducing reductions in age-related endothelial function. To assess whether dolphins have preserved endothelial function with aging because of a protected circulating milieu, we tested if the serum (pool of the circulating milieu) of bottlenose dolphins () induces the same arterial aging phenotype as the serum of age-equivalent humans. We incubated conduit arteries from young and old mice with dolphin and human serum and measured endothelial function ex vivo via endothelium-dependent dilation to acetylcholine. Although young arteries incubated with serum from midlife/older adult human serum had lower endothelial function, those incubated with dolphin serum consistently maintained high endothelial function regardless of the age of the donor. Thus, studying the arterial health of dolphins could lead to potential novel therapeutic strategies to improve age-related endothelial dysfunction in humans. We demonstrate that, unlike serum of midlife/older adult humans, age-matched dolphin serum elicits higher endothelial function ex vivo in young mouse carotid arteries, suggesting that the circulating milieu of bottlenose dolphins may be geroprotective. We propose that dolphins are a novel model to investigate potential novel therapeutic strategies to mitigate age-related endothelial dysfunction in humans.
内皮功能随年龄增长而下降，并且独立预测未来的心血管疾病 (CVD) 事件。潜水也会损害人类的内皮功能。然而，海豚作为适应潜水的长寿哺乳动物，经历了组织缺氧再氧化和剪切应力紊乱的反复循环，但没有表现出任何明显的不利影响，因为 CVD 在这些动物中基本上不存在。因此，海豚可能是健康动脉衰老的独特模型，并可能为临床医学提供策略上的见解。新出现的证据表明，循环环境（血液中的生物活性因子）至少部分负责传递与年龄相关的内皮功能下降。为了评估海豚是否由于循环环境受到保护而保持了随年龄增长的内皮功能，我们测试了宽吻海豚 () 的血清（循环环境的混合物）是否会引起与年龄相等的人类血清相同的动脉衰老表型。我们用海豚和人类血清孵育年轻和老年小鼠的大血管，并通过乙酰胆碱诱导的血管舒张来体外测量内皮功能。尽管用来自中年/老年成人血清孵育的年轻动脉的内皮功能较低，但用海豚血清孵育的动脉始终保持较高的内皮功能，而与供体的年龄无关。因此，研究海豚的动脉健康可能会导致潜在的新型治疗策略，以改善人类与年龄相关的内皮功能障碍。我们证明，与中年/老年成人血清不同，年龄匹配的海豚血清在年轻小鼠颈总动脉中体外诱导更高的内皮功能，这表明宽吻海豚的循环环境可能具有抗衰老作用。我们提出，海豚是一种新的模型，可以研究潜在的新型治疗策略，以减轻人类与年龄相关的内皮功能障碍。
