Skeletal muscle protein metabolism in the elderly: Interventions to counteract the 'anabolic resistance' of ageing

Age-related muscle wasting (sarcopenia) is accompanied by a loss of strength which can compromise the functional abilities of the elderly. Muscle proteins are in a dynamic equilibrium between their respective rates of synthesis and breakdown. It has been suggested that age-related sarcopenia is due to: i) elevated basal-fasted rates of muscle protein breakdown, ii) a reduction in basal muscle protein synthesis (MPS), or iii) a combination of the two factors. However, basal rates of muscle protein synthesis and breakdown are unchanged with advancing healthy age. Instead, it appears that the muscles of the elderly are resistant to normally robust anabolic stimuli such as amino acids and resistance exercise. Ageing muscle is less sensitive to lower doses of amino acids than the young and may require higher quantities of protein to acutely stimulate equivalent muscle protein synthesis above rest and accrue muscle proteins. With regard to dietary protein recommendations, emerging evidence suggests that the elderly may need to distribute protein intake evenly throughout the day, so as to promote an optimal per meal stimulation of MPS. The branched-chain amino acid leucine is thought to play a central role in mediating mRNA translation for MPS, and the elderly should ensure sufficient leucine is provided with dietary protein intake. With regards to physical activity, lower, than previously realized, intensity high-volume resistance exercise can stimulate a robust muscle protein synthetic response similar to traditional high-intensity low volume training, which may be beneficial for older adults. Resistance exercise combined with amino acid ingestion elicits the greatest anabolic response and may assist elderly in producing a 'youthful' muscle protein synthetic response provided sufficient protein is ingested following exercise

The role of protein hydrolysates for exercise-induced skeletal muscle recovery and adaptation:a current perspective

The protein supplement industry is expanding rapidly and estimated to have a multi-billion market worth. Recent research has centred on understanding how the manufacturing processes of protein supplements may impact muscle recovery and remodeling. The hydrolysed forms of protein undergo a further heating extraction process during production which may contribute to amino acids (AA) appearing in circulation at a slightly quicker rate, or greater amplitude, than the intact form. Whilst the relative significance of the rate of aminoacidemia to muscle protein synthesis is debated, it has been suggested that protein hydrolysates, potentially through the more rapid delivery and higher proportion of di-, tri- and smaller oligo-peptides into circulation, are superior to intact non-hydrolysed proteins and free AAs in promoting skeletal muscle protein remodeling and recovery. However, despite these claims, there is currently insufficient evidence to support superior muscle anabolic properties compared with intact non-hydrolysed proteins and/or free AA controls. Further research is warranted with appropriate protein controls, particularly in populations consuming insufficient amounts of protein, to support and/or refute an important muscle anabolic role of protein hydrolysates. The primary purpose of this review is to provide the reader with a current perspective on the potential anabolic effects of protein hydrolysates in individuals wishing to optimise recovery from, and maximise adaptation to, exercise training

Improving Physiological Relevance of Cell Culture: The Possibilities, Considerations and Future Directions of the Ex Vivo Co-Culture Model

In vitro models provide an important platform for the investigation of cellular growth and atrophy to inform, or extend mechanistic insights from, logistically challenging in vivo trials. While these models allow for the identification of candidate mechanistic pathways, many models involve supraphysiological dosages, non-physiological conditions, or experimental changes relating to individual proteins or receptors, all of which limit translation to human trials. To overcome these drawbacks, the use of ex vivo human plasma and serum has been used in cellular models to investigate changes in myotube hypertrophy, cellular protein synthesis, anabolic and catabolic markers in response to differing age, disease states, and nutrient status. However, there are currently no concurrent guidelines outlining the optimal methodology for this model. This review discusses the key methodological considerations surrounding the use of ex vivoplasma and serum, with a focus in application to skeletal muscle cell lines (i.e., C2C12, L6 and LHCN-M2) and human primary skeletal muscle cells (HSMC) as a means to investigate molecular signaling in models of atrophy and hypertrophy, alongside future directions

Exercising Our Brains, Muscles and Cells to Fight the Ageing Process

Life expectancy is increasing, but the time spent in good health (health-span) is not keeping pace, with implications for health, social care, and pensions resulting in estimated costs more than doubling by 2050. Thus, understanding the many factors that contribute to healthy ageing versus frailty, and potential things we can do to promote healthy ageing is important. For example, how does stress, being physically inactive and poor dietary practices affect our body, leading to unhealthy ageing? As part of the 2015 Pint of Science series, researchers interested in brain health, muscle function and the immune system from the School of Sport, Exercise and Rehabilitation Sciences at the University of Birmingham, UK discussed the effects that ageing itself and stress, physical activity and nutrition can have on our health and wellbeing. The objective of our presentation was to question the lifestyle that we lead and discuss realistic alternatives to incorporate healthy activity, such a exercise, into our lifestyles to improve our healthy ageing. Here, we summarise this presentation and illustrate the effectiveness of physical activity for ageing healthily

Dietary protein recommendations to support healthy muscle ageing in the 21st Century and beyond:considerations and future directions

This review explores the evolution of dietary protein intake requirements and recommendations, with a focus on skeletal muscle remodeling to support healthy ageing based on presentations at the 2023 Nutrition Society summer conference. In this review, we describe the role of dietary protein for metabolic health and ageing muscle, explain the origins of protein and amino acid requirements, and discuss current recommendations for dietary protein intake, which currently sits at ∼0.8g·kg·-1day-1. We also critique existing (e.g., nitrogen balance) and contemporary (e.g., indicator amino acid oxidation) methods to determine protein/amino acid intake requirements and suggest that existing methods may underestimate requirements, with more contemporary assessments indicating protein recommendations may need to be increased to >1.0g·kg·-1day-1. One example of evolution in dietary protein guidance is the transition from protein requirements to recommendations. Hence, we discuss the refinement of protein/amino acid requirements for skeletal muscle maintenance with advanced age beyond simply the dose (e.g., source, type, quality, timing, pattern, nutrient co-ingestion) and explore the efficacy and sustainability of alternative protein sources beyond animal-based proteins to facilitate skeletal muscle remodeling in older age. We conclude that, whilst a growing body of research has demonstrated that animal-free protein sources can effectively stimulate support muscle remodeling in a manner that is comparable to animal-based proteins, food systems need to sustainably provide a diversity of both plant and animal source foods, not least for their protein content but other vital nutrients. Finally, we propose some priority research directions for the field of protein nutrition and healthy ageing

Nutritional Strategies to Offset Disuse-Induced Skeletal Muscle Atrophy and Anabolic Resistance in Older Adults:From Whole-Foods to Isolated Ingredients

Preserving skeletal muscle mass and functional capacity is essential for healthy ageing. Transient periods of disuse and/or inactivity in combination with sub-optimal dietary intake have been shown to accelerate the age-related loss of muscle mass and strength, predisposing to disability and metabolic disease. Mechanisms underlying disuse and/or inactivity-related muscle deterioration in the older adults, whilst multifaceted, ultimately manifest in an imbalance between rates of muscle protein synthesis and breakdown, resulting in net muscle loss. To date, the most potent intervention to mitigate disuse-induced muscle deterioration is mechanical loading in the form of resistance exercise. However, the feasibility of older individuals performing resistance exercise during disuse and inactivity has been questioned, particularly as illness and injury may affect adherence and safety, as well as accessibility to appropriate equipment and physical therapists. Therefore, optimising nutritional intake during disuse events, through the introduction of protein-rich whole-foods, isolated proteins and nutrient compounds with purported pro-anabolic and anti-catabolic properties could offset impairments in muscle protein turnover and, ultimately, the degree of muscle atrophy and recovery upon re-ambulation. The current review therefore aims to provide an overview of nutritional countermeasures to disuse atrophy and anabolic resistance in older individuals

Pre-Sleep Casein Protein Ingestion Does Not Impact Next-Day Appetite, Energy Intake and Metabolism in Older Individuals

Maintaining adequate daily protein intake is important to maintain muscle mass throughout the lifespan. In this regard, the overnight period has been identified as a window of opportunity to increase protein intake in the elderly. However, it is unknown whether pre-sleep protein intake affects next-morning appetite and, consequently, protein intake. Therefore, the purpose of the current study was to investigate the effects of a pre-sleep protein drink on next-morning appetite, energy intake and metabolism. Twelve older individuals (eight males, four females; age: 71.3 ± 4.2 years) took part in a single-blind randomised cross-over study. After a standardised dinner, participants consumed either a 40-g protein drink, isocaloric maltodextrin drink, or placebo water control before bedtime. Next-morning appetite, energy intake, resting metabolic rate (RMR), respiratory exchange rate (RER), and plasma acylated ghrelin, leptin, glucose, and insulin concentrations were assessed. No between-group differences were observed for appetite and energy intake at breakfast. Furthermore, RMR, RER, and assessed blood markers were not significantly different between any of the treatment groups. Pre-sleep protein intake does not affect next-morning appetite and energy intake and is therefore a viable strategy to increase daily protein intake in an older population

Postprandial plasma amino acid and appetite responses with ingestion of a novel salmon-derived protein peptide in healthy young adults

This study assessed postprandial plasma aminoacidemia, glycemia, insulinemia and appetite responses to ingestion of a novel salmon-derived protein peptide (Salmon PP) compared with milk protein isolate (Milk PI). In a randomised, participant-blind crossover design, eleven healthy adults (M = 5, F = 6; mean ± sd age: 22 ± 3 years; BMI: 24 ± 3 kg/m2) ingested 0·3 g/kg/body mass of Salmon PP or Milk PI. Arterialised blood samples were collected whilst fasted and over a 240-min postprandial period. Appetite sensations were measured via visual analogue scales. An ad libitum buffet-style test meal was administered after each trial. The incremental AUC (iAUC) plasma essential amino acid (EAA) response was similar between Salmon PP and Milk PI. The iAUC plasma leucine response was significantly greater following Milk PI ingestion (P &lt; 0·001), whereas temporal and iAUC plasma total amino acid (P = 0·001), non-essential amino acid (P = 0·002), glycine (P = 0·0025) and hydroxyproline (P &lt; 0·001) responses were greater following Salmon PP ingestion. Plasma insulin increased similarly above post-absorptive values following Salmon PP and Milk PI ingestion, whilst plasma glucose was largely unaltered. Indices of appetite were similarly altered following Salmon PP and Milk PI ingestion, and total energy and macronutrient intake during the ad libitum meal was similar between Salmon PP and Milk PI. The postprandial plasma EAA, glycine, proline and hydroxyproline response to Salmon PP ingestion suggest this novel protein source could support muscle and possibly connective tissue adaptive remodelling, which warrants further investigation, particularly as the plasma leucine response to Salmon PP ingestion was inferior to Milk PI.</p

Does the muscle protein synthetic response to exercise and amino acid-based nutrition diminish with advancing age? A systematic review

The precise role of age-related muscle anabolic resistance in the progression of sarcopenia and functional decline in older individuals is unclear. The present aim was to assess whether the muscle protein synthesis (MPS) response to acute exercise (endurance or resistance) and/or amino acid-based nutrition is attenuated in older compared with young individuals. A systematic review was conducted on studies that directly examined the influence of age on the MPS response to exercise and/or amino acid-based nutrition. Each study arm was synthesized and reported as providing sufficient or insufficient “evidence of age-related muscle anabolic resistance”. Subsequently, three models were established to compare age-related differences in the MPS response to 1) exercise alone, 2) amino acid-based nutrition alone, or 3) the combination of exercise and amino acid-based nutrition. Following exercise alone, 8 of the 17 study arms provided sufficient evidence of age-related muscle anabolic resistance, while in response to amino acid-based nutrition alone, 8 of the 21 study arms provided sufficient evidence of age-related muscle anabolic resistance. When exercise and amino acid-based nutrition were combined, only 2 of the 10 study arms provided sufficient evidence of age-related muscle anabolic resistance. Our results highlight that optimization of exercise and amino acid-based nutrition is sufficient to induce a comparable MPS response between young and older individuals. However, the exercise volume completed and/or the amino acid/protein dose and leucine content must exceed a certain threshold to stimulate equivalent MPS rates in young and older adults, below which age-related muscle anabolic resistance may become apparent. </jats:p