Deane Colleen S, Willis Craig R G, Gallagher Iain J, Brook Matthew S, Gharahdaghi Nima, Wylie Lee J, Wilkinson Daniel J, Smith Kenneth, Atherton Philip J, Etheridge Timothy
Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
Human Development & Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.
Transl Exerc Biomed. 2024 Nov 25;1(3-4):277-294. doi: 10.1515/teb-2024-0030. eCollection 2024 Sep.
To examine the effect of the NAD precursor, nicotinic acid (NA), for improving skeletal muscle status in sedentary older people.
In a double-blind, randomised, placebo-controlled design, 18 sedentary yet otherwise healthy older (65-75 y) males were assigned to 2-weeks of NA (acipimox; 250 mg × 3 daily, n=8) or placebo (PLA, n=10) supplementation. At baseline, and after week 1 and week 2 of supplementation, a battery of functional, metabolic, and molecular readouts were measured.
Resting and submaximal respiratory exchange ratio was lower (p<0.05) after 2 weeks in the NA group only, but maximal aerobic and anaerobic function and glucose handling were unchanged (p>0.05). Bayesian statistical modelling identified that leak, maximal coupled and maximal uncoupled mitochondrial respiratory states, increased over the 2-week supplemental period in the NA group (probability for a positive change (pd) 85.2, 90.8 and 95.9 %, respectively) but not in PLA. Citrate synthase and protein content of complex II (SDHB) and V (ATP5A) electron transport chain (ETC) components increased over the 2-week period in the NA group only (pd 95.1, 74.5 and 82.3 %, respectively). Mitochondrial and myofibrillar protein synthetic rates remained unchanged in both groups. NA intake altered the muscle transcriptome by increasing the expression of gene pathways related to cell adhesion/cytoskeleton organisation and inflammation/immunity and decreasing pathway expression of ETC and aerobic respiration processes. NAD-specific pathways (e.g., NAD biosynthetic processes) and genes (e.g., ) were uniquely regulated by NA.
NA might be an effective strategy for improving ageing muscle mitochondrial health.
研究烟酰胺腺嘌呤二核苷酸（NAD）前体烟酸（NA）对改善久坐不动的老年人骨骼肌状态的作用。
采用双盲、随机、安慰剂对照设计，将18名久坐但身体健康的老年（65 - 75岁）男性分为两组，分别给予2周的NA（阿西莫司；250毫克，每日3次，n = 8）或安慰剂（PLA，n = 10）补充剂。在基线时以及补充剂使用第1周和第2周后，测量一系列功能、代谢和分子指标。
仅NA组在2周后静息和次最大呼吸交换率降低（p < 0.05），但最大有氧和无氧功能以及葡萄糖处理能力未改变（p > 0.05）。贝叶斯统计模型确定，NA组在2周补充期内，线粒体泄漏、最大偶联和最大解偶联呼吸状态增加（正向变化概率（pd）分别为85.2%、90.8%和95.9%），而PLA组未增加。仅NA组在2周内柠檬酸合酶以及电子传递链（ETC）复合物II（SDHB）和V（ATP5A）的蛋白质含量增加（pd分别为95.1%、74.5%和82.3%）。两组的线粒体和肌原纤维蛋白合成率均保持不变。NA摄入通过增加与细胞粘附/细胞骨架组织以及炎症/免疫相关的基因途径表达，并降低ETC和有氧呼吸过程的途径表达，改变了肌肉转录组。NAD特异性途径（如NAD生物合成过程）和基因（如）受到NA的独特调控。
NA可能是改善衰老肌肉线粒体健康的有效策略。
