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

大强度间歇训练和烟酰胺核苷治疗增强功能能力 减少衰老过程中的虚弱 虚弱是一种生理储备不足的状况，会增加跌倒的易感性， 住院、残疾和死亡率。虚弱的发生率 65岁以后增长，从10%增长到50% 在那些85岁或以上的人中；因此超过900万退伍军人 虚弱的或者处于虚弱的危险中的事实证明，锻炼有以下好处 身体虚弱，但老年人很少能达到推荐的水平 每周150分钟中等强度的持续锻炼 (MICT)，因为缺乏时间和害怕受伤是最常见的 障碍。高强度间歇训练(HIIT)作为一种 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，时间承诺较低的福利。 此外，运动还可以提高烟酰胺腺嘌呤 二核苷酸(NAD+)水平，一种重要的辅酶 线粒体和细胞功能随着年龄的增长而衰退。 补充烟酰胺核苷(NR)也可以 增加NAD+，这两种干预措施都获得了支持 针对衰老和相关疾病的治疗策略，如 脆弱。因此，该项目的目标是：1)比较 HIIT与MICT对身体性能、脆弱性、 和寿命，以及2)检查NR是否可以增加 HIIT或MICT带来的好处。 HIIT±烟酰胺核苷(NR) 减少衰老过程中的虚弱。 这项研究的前提是我们最近发表的一项研究表明， 每周3天、长达10分钟的HIIT训练可提高体能并减少身体虚弱 老龄小鼠28个月龄(相当于65-80岁的人)。这项提议的假设是 HIIT运动将以一种优于MICT的方式减少脆弱性并延长寿命，并且 这些好处将随着天然氮的补充而增强。为了检验这一假设，24个月大的 小鼠将被给予HIIT或MICT方案，直到生命结束，以评估生存益处，同时还 对体能和虚弱的改善进行纵向评估。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个月龄时进行检查 评估对肌肉生理、体能和虚弱的影响。这项研究将提供一个 成功实施人类HIIT和NR补充的临床试验蓝图，因此 允许制定个性化干预措施，以提高老年人的生活质量 退伍军人。

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.