Amitani Haruka, Chiba Shigeki, Amitani Marie, Michihara Seiwa, Takemoto Risa, Han Likun, Fujita Nina, Takahashi Ryuji, Inui Akio
Pharmacological Department of Herbal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Division of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Front Pharmacol. 2022 Oct 24;13:973897. doi: 10.3389/fphar.2022.973897. eCollection 2022.
With the recent aging of society, the prevention of frailty has become an important issue because people desire both a long and healthy lifespan. Klotho-hypomorphic (kl/kl) mice are known to show phenotypes of premature aging. Ninjin'yoeito (NYT) is a traditional Japanese Kampo medicine used to treat patients with vulnerable constitution, fatigue or physical exhaustion caused by aging and illness. Recent studies have reported the potential efficacy of NYT against frailty. We therefore evaluated the effect of NYT on the gait function, activity, the histopathological status of organs and survival using kl/kl mice as a model of aging-related frailty. Two sets of 28-day-old male kl/kl mice were assigned to the vehicle (non-treated; NT), 3% or 5% NYT dietary groups. One set of groups (NT, n = 18; 3% NYT, n = 11; 5% NYT, n = 11) was subjected to the analysis of free walking, rotarod, and spontaneous activity tests at approximately 58 days old. Thereafter, we measured triceps surae muscles weight and myofiber cross-sectional area (CSA), and quantified its telomere content. In addition, we evaluated bone strength and performed histopathological examinations of organs. Survival was measured in the second set of groups (NT, 3% NYT and 5% NYT group, n = 8 each). In the walking test, several indicators such as gait velocity were improved in the NYT 3% group. Similar results were obtained for the latency to fall in the rotarod test and spontaneous motor activity. Triceps muscle mass, CSA and its telomere content were significantly improved in the NYT 3% group. Bone density, pulmonary alveolus destruction and testicular atrophy were also significantly improved in the NYT 3% group. Survival rate and body weight were both significantly improved in the NYT3% group compared with those in the NT group. Continuous administration of NYT from the early stage of aging improved not only gait performance, but also the survival in the aging-related frailty model. This effect may be associated with the improvements in aging-related organ changes such as muscle atrophy. Intervention with NYT against the progression of frailty may contribute to a longer, healthier life span among the elderly individuals.
随着社会老龄化的加剧，由于人们渴望拥有健康长寿的生活，衰弱的预防已成为一个重要问题。已知klotho基因低表达（kl/kl）小鼠表现出早衰的表型。人参养荣汤（NYT）是一种传统的日本汉方药物，用于治疗体质虚弱、因衰老和疾病导致疲劳或身体疲惫的患者。最近的研究报道了NYT对衰弱的潜在疗效。因此，我们以kl/kl小鼠作为衰老相关衰弱的模型，评估了NYT对步态功能、活动能力、器官组织病理学状态和生存率的影响。将两组28日龄雄性kl/kl小鼠分别分配到载体组（未处理；NT）、3%或5% NYT饮食组。一组（NT，n = 18；3% NYT，n = 11；5% NYT，n = 11）在约58日龄时进行自由行走、转棒和自发活动测试分析。此后，我们测量了腓肠肌重量和肌纤维横截面积（CSA），并对其端粒含量进行了定量分析。此外，我们评估了骨强度并对器官进行了组织病理学检查。在第二组（NT、3% NYT和5% NYT组，每组n = 8）中测量生存率。在行走测试中，3% NYT组的几个指标如步态速度得到改善。转棒测试中的跌落潜伏期和自发运动活动也得到了类似结果。3% NYT组的三头肌质量、CSA及其端粒含量均有显著改善。3% NYT组的骨密度、肺泡破坏和睾丸萎缩也有显著改善。与NT组相比，3% NYT组的生存率和体重均有显著提高。从衰老早期开始持续给予NYT不仅改善了步态表现，还提高了衰老相关衰弱模型中的生存率。这种作用可能与改善衰老相关的器官变化如肌肉萎缩有关。用NYT干预衰弱的进展可能有助于老年人延长健康寿命。
