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慢性维生素D缺乏会损害C57BL/6J小鼠的身体机能。

Chronic vitamin D insufficiency impairs physical performance in C57BL/6J mice.

作者信息

Seldeen Kenneth L, Pang Manhui, Leiker Merced M, Bard Jonathan E, Rodríguez-Gonzalez Maria, Hernandez Mireya, Sheridan Zachary, Nowak Norma, Troen Bruce R

机构信息

Division of Geriatrics and Palliative Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Veterans Affairs Western New York Healthcare System, Buffalo, NY 14203, USA.

New York State Center of Excellence in Bioinformatics and Life Sciences and Department of Biochemistry, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, USA.

出版信息

Aging (Albany NY). 2018 Jun 14;10(6):1338-1355. doi: 10.18632/aging.101471.

Abstract

Vitamin D insufficiency (serum 25-OH vitamin D < 30 ng/ml) affects 70-80% of the general population, yet the long-term impacts on physical performance and the progression of sarcopenia are poorly understood. We therefore followed 6-month-old male C57BL/6J mice (=6) consuming either sufficient (STD, 1000 IU) or insufficient (LOW, 125 IU) vitamin D3/kg chow for 12 months (equivalent to 20-30 human years). LOW supplemented mice exhibited a rapid decline of serum 25-OH vitamin D levels by two weeks that remained between 11-15 ng/mL for all time points thereafter. After 12 months LOW mice displayed worse grip endurance (34.6 ± 14.1 versus 147.5 ± 50.6 seconds, p=0.001), uphill sprint speed (16.0 ± 1.0 versus 21.8 ± 2.4 meters/min, p=0.0007), and stride length (4.4 ± 0.3 versus 5.1 ± 0.3, p=0.002). LOW mice also showed less lean body mass after 8 months (57.5% ± 5.1% versus 64.5% ± 4.0%, p=0.023), but not after 12 months of supplementation, as well as greater protein expression of atrophy pathway gene atrogin‑1. Additionally, microRNA sequencing revealed differential expression of mIR‑26a in muscle tissue of LOW mice. These data suggest chronic vitamin D insufficiency may be an important factor contributing to functional decline and sarcopenia.

摘要

维生素D不足(血清25-羟基维生素D<30 ng/ml)影响70-80%的普通人群,但对身体机能和肌肉减少症进展的长期影响却知之甚少。因此,我们对6只6月龄雄性C57BL/6J小鼠进行了为期12个月(相当于人类20-30年)的跟踪研究,这些小鼠分别食用维生素D3含量充足(标准饮食,1000 IU)或不足(低剂量,125 IU)的饲料。低剂量补充组小鼠在两周内血清25-羟基维生素D水平迅速下降,此后所有时间点均维持在11-15 ng/mL之间。12个月后,低剂量组小鼠的握力耐力更差(34.6±14.1秒对147.5±50.6秒,p=0.001)、上坡冲刺速度更慢(16.0±1.0米/分钟对21.8±2.4米/分钟,p=0.0007)、步幅更小(4.4±0.3对5.1±0.3,p=0.002)。低剂量组小鼠在补充8个月后瘦体重也更低(57.5%±5.1%对64.5%±4.0%,p=0.023),但在补充12个月后没有差异,同时萎缩途径基因atrogin-1的蛋白表达更高。此外,微小RNA测序显示低剂量组小鼠肌肉组织中mIR-26a表达存在差异。这些数据表明,慢性维生素D不足可能是导致功能衰退和肌肉减少症的一个重要因素。

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