Exercise training and NR supplementation to improve muscle mass and fitness in adolescent and young adult hematopoietic cell transplant survivors: a randomized controlled trial {1}.
Exercise training and NR supplementation to improve muscle mass and fitness in adolescent and young adult hematopoietic cell transplant survivors: a randomized controlled trial {1}.
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DOI：
10.1186/s12885-022-09845-1
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发表时间：
2022-07-19
期刊：
影响因子：
3.8
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中科院分区：
文献类型：
--
作者：
造血细胞移植（HCT）的进步导致了生存率的显著提高。然而，接受HCT的青少年和年轻人（AYAs）患肌肉减少症（骨骼肌质量损失）的风险很高，因为HCT相关暴露对发育中的肌肉骨骼系统有影响。患有肌肉减少症的HCT幸存者也有额外的非复发死亡率风险。因此，需要增加骨骼肌质量、代谢、力量和功能的干预措施来改善AYA HCT幸存者的健康。骨骼肌高度依赖线粒体能量产生，这反映在氧化磷酸化（OXPHOS）能力上。运动是针对骨骼肌线粒体OXPHOS的一种方法，从而改善肌肉功能和力量。另一种方法是使用“运动增强剂”，如烟酰胺核苷（NR），一种安全且耐受性良好的烟酰胺腺嘌呤二核苷酸（NAD+）前体，一种反过来影响肌肉能量产生的辅助因子。将运动与NR等运动增强剂相结合的干预措施有希望，但尚未在AYA HCT幸存者中进行严格的测试。我们将在AYA HCT幸存者中进行一项随机对照试验，测试16周的室内有氧运动和阻力运动以及NR，主要结果是通过动力测量肌肉力量，关键的次要结果是通过心肺运动测试心血管健康。我们还将通过双能x射线吸收仪测试这些干预措施对i)肌肉质量的影响；ii)通过创新的非侵入性核磁共振技术研究肌肉线粒体OXPHOS， iii)通过代谢组学研究NAD+代谢的循环相关物。将在hct后6-24个月招募80名aya（年龄15-30岁），并随机分为4组：运动+ NR、单独运动、单独NR或对照组。结果将在基线和16周干预后收集。我们预计，在关键结果方面，NR运动比单独运动产生更大的变化，而这种变化将通过肌肉OXPHOS的增加来调节。我们将应用从该试验中获得的见解来开发个性化的、有证据支持的精确计划，以减少高风险癌症幸存者的慢性疾病负担。ClinicalTrials.gov NCT05194397。2022年1月18日注册，https://clinicaltrials.gov/ct2/show/NCT05194397 {2a}。在线版本包含补充材料，可在10.1186/s12885-022-09845-1获得。
Advances in hematopoietic cell transplantation (HCT) have led to marked improvements in survival. However, adolescents and young adults (AYAs) who undergo HCT are at high risk of developing sarcopenia (loss of skeletal muscle mass) due to the impact of HCT-related exposures on the developing musculoskeletal system. HCT survivors who have sarcopenia also have excess lifetime risk of non-relapse mortality. Therefore, interventions that increase skeletal muscle mass, metabolism, strength, and function are needed to improve health in AYA HCT survivors. Skeletal muscle is highly reliant on mitochondrial energy production, as reflected by oxidative phosphorylation (OXPHOS) capacity. Exercise is one approach to target skeletal muscle mitochondrial OXPHOS, and in turn improve muscle function and strength. Another approach is to use “exercise enhancers”, such as nicotinamide riboside (NR), a safe and well-tolerated precursor of nicotinamide adenine dinucleotide (NAD+), a cofactor that in turn impacts muscle energy production. Interventions combining exercise with exercise enhancers like NR hold promise, but have not yet been rigorously tested in AYA HCT survivors. We will perform a randomized controlled trial testing 16 weeks of in-home aerobic and resistance exercise and NR in AYA HCT survivors, with a primary outcome of muscle strength via dynamometry and a key secondary outcome of cardiovascular fitness via cardiopulmonary exercise testing. We will also test the effects of these interventions on i) muscle mass via dual energy x-ray absorptiometry; ii) muscle mitochondrial OXPHOS via an innovative non-invasive MRI-based technique, and iii) circulating correlates of NAD+ metabolism via metabolomics. Eighty AYAs (ages 15-30y) will be recruited 6–24 months post-HCT and randomized to 1 of 4 arms: exercise + NR, exercise alone, NR alone, or control. Outcomes will be collected at baseline and after the 16-week intervention. We expect that exercise with NR will produce larger changes than exercise alone in key outcomes, and that changes will be mediated by increases in muscle OXPHOS. We will apply the insights gained from this trial to develop individualized, evidence-supported precision initiatives that will reduce chronic disease burden in high-risk cancer survivors. ClinicalTrials.gov, NCT05194397. Registered January 18, 2022, https://clinicaltrials.gov/ct2/show/NCT05194397 {2a}. The online version contains supplementary material available at 10.1186/s12885-022-09845-1.
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影响因子：
29
作者：
Frederick DW;Loro E;Liu L;Davila A Jr;Chellappa K;Silverman IM;Quinn WJ 3rd;Gosai SJ;Tichy ED;Davis JG;Mourkioti F;Gregory BD;Dellinger RW;Redpath P;Migaud ME;Nakamaru-Ogiso E;Rabinowitz JD;Khurana TS;Baur JA
通讯作者：
Baur JA
影响因子：
37.8
作者：
Diguet N;Trammell SAJ;Tannous C;Deloux R;Piquereau J;Mougenot N;Gouge A;Gressette M;Manoury B;Blanc J;Breton M;Decaux JF;Lavery GG;Baczkó I;Zoll J;Garnier A;Li Z;Brenner C;Mericskay M
通讯作者：
Mericskay M
影响因子：
8.1
作者：
Amjad S;Nisar S;Bhat AA;Shah AR;Frenneaux MP;Fakhro K;Haris M;Reddy R;Patay Z;Baur J;Bagga P
通讯作者：
Bagga P
影响因子：
8
作者：
DeBrosse, Catherine;Nanga, Ravi Prakash Reddy;McCormack, Shana E.
通讯作者：
McCormack, Shana E.
影响因子：
7.1
作者：
Dollerup, Ole L.;Christensen, Britt;Jessen, Niels
通讯作者：
Jessen, Niels