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以增强功能能力 并减少衰老过程中的脆弱 虚弱是一种生理储备不足的状况，会增加对福尔斯的敏感性， 住院、残疾和死亡率。虚弱的发生率 在65岁以后增加，从10%增加到50%。 其中85岁或以上;因此，超过900万退伍军人 要么虚弱要么有虚弱的危险运动已被证明对 然而，老年人很少达到推荐的 每周150分钟中等强度的持续运动 （MICT），因为缺乏时间和害怕受伤是最常见的 隔栏.高强度间歇训练（HIIT）正在兴起， 因为它可以安全地提供力量和耐力， 比MICT更低的时间承诺。 此外，运动可以提高烟酰胺腺嘌呤 二核苷酸（NAD+）水平，一种必需的辅酶， 线粒体和细胞功能随着年龄的增长而下降。 补充烟酰胺核苷（NR）也可以 增加NAD+，这两种干预措施作为一种 衰老和相关疾病的治疗策略， 脆弱因此，本项目的目标是：1）比较 HIIT与MICT对身体机能、虚弱 和寿命，和2）检查NR是否可以增加 对HIIT或MICT的反应。 HIIT ±烟酰胺核苷（NR） 在衰老过程中减少脆弱。 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方案增强身体表现，减少虚弱， 28月龄的老年小鼠（相当于65 - 80岁的人）。这一提议的假设是 HIIT锻炼将以一种上级于MICT的方式减少虚弱并延长寿命， 这些益处将通过NR补充而增强。为了验证这个假设，24个月大的 小鼠将被给予HIIT或MICT方案直到生命结束以评估存活益处，同时还被 纵向评估身体表现和虚弱的改善。接下来，除了HIIT 或MICT，老年小鼠将接受安慰剂或NR补充剂，并在28个月大时检查， 评估对肌肉生理、身体表现和虚弱的影响。这项研究将提供一个 在人类中成功实施HIIT和NR补充的临床试验蓝图，因此 允许开发个性化干预措施，改善老年人的生活质量 老百姓。

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.