A minimally invasive stable-isotope approach to determine nutrient handling across the life-course.

一种微创稳定同位素方法，用于确定整个生命过程中的营养处理。

• 批准号: 2747743
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2747743
• 关键词: minimally; invasive; stable; isotope; approach

Background: The UK's ageing population is an established and future timebomb for health and social care systems, recognised in recent government measures to increase national insurance taxation. One of the major road-blocks to healthy, independent ageing is the loss of muscle mass and function, in a process called sarcopenia, which has established epidemiological links to both morbidity and mortality. Despite the salient mechanisms underpinning sarcopenia remaining elusive, an established contributor is the development of "anabolic resistance". This phenomenon manifests in skeletal muscle cells becoming resistant to key environmental cues regulating muscle maintenance i.e. contractile activity and food (protein) intake. While we, as a research group, have contributed greatly to the discovery of anabolic resistance, the physiological, metabolic and molecular changes that underlie this phenomenon are still unknown; limiting the development of mitigating interventions. Reflecting this, a major driver of research in this area remains to seek means by which to maximise older muscle responses to nutritional and contractile stimuli. Our project will contribute significantly to this agenda. One emerging proposition is that changes in digestion and gut function with ageing may limit the availability and uptake of ingested dietary proteins for skeletal muscle building. However, the main issue with methods to assess digestibility are the insurmountable challenges in obtaining ileal samples in humans (due to the need to sample at the distal intestinal site of amino acid absorption via nasogastric ultrasound guided cannulae). Herein, we propose a solution; to validate and use a novel approach of a universally intrinsically labelled protein (Spirulina) that will "report" how different protein sources are digested. This project will have a significant impact on both health biosciences and nutrition product development. Aim: To validate a minimally-invasive method to assess protein digestibility, and to determine the impact of age and physical activity on nutrient handling of standard and 'enhanced' protein sources. Hypotheses: Ageing is associated with impaired nutrient handling of high-quality protein (i.e., whey protein (WP)); Purified beta-lactoglobulin (BL) (from Arla Food Ingredients (AFI)); yielding ~40% higher leucine content and ~20% higher essential amino acid content, will elicit favourable digestibility and anabolic profiles in older people; Age-associated reductions in nutrient handling of WP will be mitigated by life-long exercise. Project Plan: Phase 1 - To validate a minimally-invasive stable-isotope tracer methodology using labelled Spirulina (U-13C AA, Cambridge Isotope Laboratories, MA, USA), to determine protein digestibility in humans. Phase 2 - To recruit older adults to participate in a 2-arm cross over study to assess the digestibility of WP versus BL from AFI, and to determine the relationship between digestibility and markers of skeletal muscle anabolism both at rest and in response to acute resistance exercise (i.e. contractile activity). Phase 3 - To recruit young and older adults, and masters athletes to participate in a study to assess differences in digestibility as a function of age and physical activity. Expected outcomes & impact: A strong relationship with AFI, >3 high-quality scientific papers and conference presentations, outreach activities for older adults, implications for nutritional policy recommendations.

背景：英国的老龄化人口是卫生和社会护理系统的既定且未来的炸弹，在最近的政府措施中认可了增加国家保险税。在一个称为肌肉减少症的过程中，健康，独立衰老的主要道路之一是肌肉质量和功能的丧失，该过程已经建立了与发病率和死亡率的流行病学联系。尽管基于肌肉减少症的显着机制仍然难以捉摸，但既定的贡献者都是“合成代谢抗性”的发展。这种现象表现在骨骼肌细胞中，对调节肌肉维持的关键环境提示具有抵抗力，即收缩活动和食物（蛋白质）摄入。尽管作为一个研究小组，我们为发现合成代谢性抗性做出了巨大贡献，但这种现象仍然是未知的生理，代谢和分子变化。限制缓解干预措施的发展。反映这一点，这一领域的主要研究驱动力仍然需要寻求最大化较早的肌肉对营养和收缩刺激的反应的手段。我们的项目将为这一议程做出重大贡献。一个新兴的主张是，随着衰老的衰老，消化和肠道功能的变化可能会限制骨骼肌建设中摄入的饮食蛋白的可用性和摄取。但是，评估消化率的方法的主要问题是在人类中获得回肠样品所面临的挑战（由于需要通过鼻腔超声引导的插管在氨基酸吸收的远端肠道位点进行采样）。在此，我们提出了一个解决方案。验证和使用普遍固有标记的蛋白质（螺旋藻）的新方法，该方法将“报告”如何消化不同的蛋白质来源。该项目将对健康生物科学和营养产品开发产生重大影响。目的：验证一种评估蛋白质消化率的最小侵入性方法，并确定年龄和体育活动对标准和“增强”蛋白质来源的养分处理的影响。假设：衰老与高质量蛋白的营养处理受损有关（即乳清蛋白（WP））；纯化的β-乳球蛋白（BL）（来自Arla食品成分（AFI））；亮氨酸含量高约40％，必需氨基酸含量高约20％，将引起老年人的有利消化率和合成代谢的特征。与年龄相关的WP养分处理减少将通过终身运动来减轻。项目计划：第1阶段 - 使用标记的螺旋藻（U-13C AA，剑桥同位素实验室，美国马萨诸塞州）验证微创稳定 - 异位示踪方法，以确定人类的蛋白质消化率。第2阶段 - 招募老年人参加了2臂交叉的研究，以评估WP与AFI的BL的消化率，并确定在休息和急性抵抗运动（即收缩活动）时，在休息和响应骨骼肌肉代谢的骨骼肌肉合成代谢之间的关系。 第三阶段 - 招募年轻和老年人，硕士运动员参加一项研究，以评估消化率的差异，这是年龄和体育锻炼的功能。预期的结果与影响：与AFI的牢固关系，> 3个高质量的科学论文和会议演讲，对老年人的外展活动，对营养政策建议的影响。