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.

高强度间歇训练和烟酰胺核苷治疗以增强功能能力 并减少衰老过程中的虚弱 虚弱是一种生理储备能力较差的情况，会增加跌倒的可能性， 住院、残疾和死亡率。衰弱的发生率 65岁以后增加，从10%增长到多达50% 85 岁或以上的人；因此，超过 900 万退伍军人 虚弱或有虚弱的风险。运动已被证明有好处 身体虚弱，但老年人很少达到推荐的水平 每周 150 分钟中等强度持续运动 (MICT)，因为缺乏时间和担心受伤是最常见的 障碍。高强度间歇训练 (HIIT) 正在兴起 一种替代方案，因为它可以安全地提供力量和耐力 与 (MICT) 相比，花费更少的时间即可获得好处。 此外，运动可以增加烟酰胺腺嘌呤 二核苷酸 (NAD+) 水平，一种必需的辅酶 线粒体和细胞功能随着衰老而下降。 补充烟酰胺核苷（NR）也可以 增加 NAD+，这两种干预措施都作为一种方法获得了支持 衰老和相关病症的治疗策略，例如 虚弱。因此，该项目的目标是：1）比较 HIIT 与 MICT 对身体表现、虚弱、 和寿命，2) 检查 NR 是否可以增强 HIIT 或 MICT 的益处。 HIIT ± 烟酰胺核苷 (NR) 减少衰老过程中的虚弱。 这项研究的前提是基于我们最近发表的研究，该研究表明 每周 3 天、时长 10 分钟的 HIIT 疗法可增强身体表现并减少身体虚弱 28个月大的老年小鼠（相当于65-80岁的人类）。该提案的假设是 HIIT 锻炼能够以优于 MICT 的方式减少虚弱并延长寿命，并且 补充 NR 可以增强这些益处。为了检验这个假设，24 个月大的 小鼠将接受 HIIT 或 MICT 治疗直至其生命结束，以评估生存益处，同时也 纵向评估身体机能和虚弱程度的改善。接下来，除了HIIT 或 MICT，老年小鼠将接受安慰剂或 NR 补充剂，并在 28 个月大时进行检查，以 评估对肌肉生理学、身体表现和虚弱的影响。这项研究将提供一个 人类成功实施 HIIT 和 NR 补充剂的临床试验蓝图，因此 允许开发个性化干预措施以改善老年人的生活质量 退伍军人人口。