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

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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.