High intensity interval training and nicotinamide riboside treatment to enhance functional capacity and reduce frailty during aging

高强度间歇训练和烟酰胺核苷治疗可增强功能能力并减少衰老过程中的虚弱

• 批准号: 10663245
• 负责人: Bruce R. Troen
• 金额: --
• 依托单位: KANSAS CITY VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10663245
• 关键词: Acceleration; Activities of Daily Living; Affect; Age; Age Months; Aging; Animal Model; Biomass; Cell physiology; Cessation of life; Clinical; Clinical Research; Clinical Trials; Coenzymes; Data; Development; Diagnosis; Dose; Elderly; Exercise; Foundations; Fright; Goals; Harvest; Health; Health Care Costs; Healthcare Systems; Histology; Hospitalization; Human; Incidence; Injury; Interval training; Intervention; Intramuscular; Longevity; MicroRNAs; Mitochondria; Mus; Muscle; Muscle Fibers; Nicotinamide adenine dinucleotide; Outcome; Physical Exercise; Physical Performance; Physiological; Placebos; Predisposition; Publishing; Quality of Care; Quality of life; Recommendation; Regimen; Risk; Serum; Supplementation; Testing; Therapeutic; Time; Training; Veterans; age related; aged; anti aging; biomarker development; disability; end of life; exercise intervention; exercise regimen; fall risk; falls; frailty; functional disability; healthspan; human old age (65+); improved; innovation; military veteran; mortality; mortality risk; muscle form; muscle physiology; nicotinamide riboside supplementation; nicotinamide-beta-riboside; optimal treatments; personalized intervention; predictive marker; prognostic; prognostic index; prognostic signature; programs; response; sarcopenia; sedentary

High intensity interval training and nicotinamide riboside treatment to enhance functional capacity and reduce frailty during aging Frailty is a condition of poor physiological reserve that increases susceptibility to falls, hospitalization, disability, and mortality. The incidence of frailty increases after the age 65, growing from 10% to as many as 50% of those 85 years or older; therefore over 9 million veterans are either frail or at risk for frailty. Exercise has proven benefits for frailty, yet older adults rarely attain the recommended 150 minutes a week of moderate intensity continuous exercise (MICT), as lack of time and fear of injury are the most common barriers. High intensity interval training (HIIT) is emerging as an alternative as it can safely provide strength and endurance benefits with lower time commitments than (MICT). Additionally, exercise can boost nicotinamide adenine dinucleotide (NAD+) levels, an essential co-enzyme for mitochondrial and cellular function that declines with aging. Supplementation with nicotinamide riboside (NR) can also increase NAD+, and both interventions are gaining support as a therapeutic strategy for aging and related conditions such as frailty. Therefore, the goals of this project are: 1) compare the impacts of HIIT versus MICT on physical performance, frailty, and lifespan, and 2) examine whether NR can augment the benefits in response to HIIT or MICT. HIIT ± nicotinamide riboside (NR) reduces frailty during aging. The premise for this study is based upon our recently published study demonstrating that a 10 minute long, 3-days a week HIIT regimen enhances physical performance and reduces frailty in aged mice 28 months of age (equivalent to a 65-80 year old human). The hypothesis of this proposal is that HIIT exercise will reduce frailty and increase lifespan, in a manner that is superior to MICT, and that these benefits will be enhanced with NR supplementation. To test this hypothesis, 24-month-old mice will be given HIIT or MICT regimens until end of life to assess survival benefits, while also being longitudinally assessed for improvement in physical performance and frailty. Next, in addition to HIIT or MICT, aged mice will receive placebo or NR supplementation and examined at 28 months of age to assess impacts upon muscle physiology, physical performance, and frailty. This study will provide a clinical trial blueprint for successful implementation of HIIT and NR supplementation in humans, thus permitting the development of personalized interventions that improve the quality of life of the aging veteran population.

高强度间隔训练和烟酰胺核糖苷治疗以增强功能能力 并减少衰老期间的脆弱 脆弱的是身体储备差的条件，可提高对跌倒的敏感性， 住院，残疾和死亡率。脆弱的事件 65岁以后增加，从10％增长到多达50％ 在这85岁或以上；因此，超过900万退伍军人是 脆弱或有脆弱的风险。锻炼已被证明对 脆弱的，但老年人很少能获得推荐的 每周150分钟中等强度连续锻炼 （MICT），因为缺乏时间和对伤害的恐惧是最常见的 障碍。高强度间隔训练（HIIT）正在出现 可以安全地提供力量和耐力的替代方案 比（MICT）较低的时间承诺的好处。 此外，运动可以增强烟酰胺腺嘌呤 Dinucleotide（NAD+）水平，这是一种必需的共生酶 随着衰老而下降的线粒体和细胞功能。 补充烟酰胺核苷（NR）也可以 增加NAD+，两种干预措施都获得了支持 衰老和相关状况的治疗策略，例如 脆弱。因此，该项目的目标是：1）比较 HIIT与MICT对身体绩效的影响，脆弱， 和寿命，以及2）检查NR是否可以增加 响应HIIT或MICT的好处。 HIIT±烟酰胺核苷（NR） 减少衰老期间脆弱。 这项研究的前提是基于我们最近发表的研究，表明 10分钟长，每周3天HIIT方案可增强身体表现并减少脆弱性 年龄28个月大的老鼠（相当于65-80岁的人）。该提议的假设是 这种HIIT运动会以优于MICT和 NR补充将增强这些好处。为了检验这一假设，24个月大 老鼠将获得HIIT或MICT方案，直到评估生存益处，同时也 纵向评估了身体表现和脆弱的改善。接下来，除了HIIT 或MICT，老年小鼠将接受安慰剂或NR补充，并在28个月大时检查到 评估对肌肉生理，身体表现和脆弱的影响。这项研究将提供 临床试验蓝图成功实施了人类中的HIIT和NR补充，因此 允许发展个性化干预措施，以改善衰老的生活质量 资深人口。