McDonald Claire, Alderson Craig, Birkbeck Matthew G, Del Din Silvia, Gorman Gráinne S, Hollingsworth Kieren G, Kirk Cameron, Massarella Clare, Rochester Lynn, Tuppen Helen A L, Warren Charlotte, Sayer Avan A, Witham Miles D
AGE Research Group, Faculty of Medical Sciences, Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK.
NIHR Newcastle Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust and Newcastle University, Newcastle Upon Tyne, UK.
Geroscience. 2025 Aug;47(4):6065-6078. doi: 10.1007/s11357-025-01606-9. Epub 2025 Mar 18.
Skeletal muscle nicotinamide adenine dinucleotide (NAD) concentrations are low in people with sarcopenia. Increasing NAD concentrations may offer a novel therapy. This study tested if acipimox (a NAD precursor) improves skeletal muscle NAD concentration and function in people with probable sarcopenia. Participants aged 65 and over with low walk speed (< 0.8 m/s) and low muscle strength (by 2019 European Working Group criteria) were recruited to this before and after, proof-of-concept study. Participants received acipimox 250 mg orally (twice or thrice daily according to creatinine clearance) + aspirin 75 mg daily (to prevent facial flushing) for 4 weeks. Muscle biopsy of the vastus lateralis, P magnetic resonance spectroscopy and a 7-digital mobility assessment were performed before starting acipimox and after 3 weeks of treatment. The primary outcome was change in skeletal muscle NAD concentration. Secondary outcomes included change in phosphocreatine recovery rate and measures of physical performance. Eleven participants (8 women), mean age 78.9 years (SD 4.3), were recruited. Mean walk speed at baseline was 0.69 m/s (SD 0.07). All completed baseline and follow-up visits. Median medication adherence was 95% (range 91-104%). There was no statistically significant difference in the primary outcome of change in NAD concentrations in skeletal muscle between baseline and follow-up [median difference: - 0.003 umol/g (IQR - 0.058 to 0.210); P = 0.26] or secondary outcomes. Nineteen none-serious adverse events were reported. Although the study protocol was feasible and well tolerated, acipimox did not improve skeletal muscle NAD concentration, biochemical markers or physical function in people with probable sarcopenia.
gov Identifier: ISRCTN (ISRCTN87404878).
肌肉减少症患者骨骼肌中的烟酰胺腺嘌呤二核苷酸(NAD)浓度较低。提高NAD浓度可能提供一种新的治疗方法。本研究测试了阿西莫司(一种NAD前体)是否能改善可能患有肌肉减少症患者的骨骼肌NAD浓度和功能。招募了65岁及以上、步行速度低(<0.8米/秒)且肌肉力量低(根据2019年欧洲工作组标准)的参与者进行这项前后对照的概念验证研究。参与者口服阿西莫司250毫克(根据肌酐清除率每日两次或三次)+每日阿司匹林75毫克(以预防面部潮红),持续4周。在开始服用阿西莫司前和治疗3周后,进行股外侧肌肌肉活检、磷磁共振波谱分析和7项数字移动性评估。主要结局是骨骼肌NAD浓度的变化。次要结局包括磷酸肌酸恢复率的变化和身体性能指标。招募了11名参与者(8名女性),平均年龄78.9岁(标准差4.3)。基线时平均步行速度为0.69米/秒(标准差0.07)。所有参与者均完成了基线和随访。药物依从性中位数为95%(范围91 - 104%)。基线和随访之间骨骼肌NAD浓度变化的主要结局[中位数差异:-0.003微摩尔/克(四分位距-0.058至0.210);P = 0.26]或次要结局均无统计学显著差异。报告了19起非严重不良事件。尽管研究方案可行且耐受性良好,但阿西莫司并未改善可能患有肌肉减少症患者的骨骼肌NAD浓度、生化标志物或身体功能。
gov标识符:ISRCTN(ISRCTN87404878)