Stress biomarker changes following a series of repeated static and dynamic apneas in non-divers.

PURPOSE: This study examined the magnitude of physiological strain imposed by repeated maximal static and dynamic apneas through assessing a panel of stress-related biomarkers. METHODS: Eleven healthy men performed on three separate occasions (≥72-h apart): a series of five repeated maximal (i) static (STA) or (ii) dynamic apneas (DYN) or (iii) a static eupneic protocol (CTL). Venous blood samples were drawn at 30, 90, and 180-min after each protocol to determine ischaemia modified albumin (IMA), neuron-specific enolase (NSE), myoglobin, and high sensitivity cardiac troponin T (hscTnT) concentrations. RESULTS: IMA was elevated after the apnoeic interventions (STA,+86%;DYN,+332%,p ≤ 0.047) but not CTL (p = 0.385). Myoglobin was higher than baseline (23.6 ± 3.9 ng/mL) 30-min post DYN (+70%,38.8 ± 13.3 ng/mL,p = 0.030). A greater myoglobin release was recorded in DYN compared with STA and CTL (p ≤ 0.035). No changes were observed in NSE (p = 0.207) or hscTnT (p = 0.274). CONCLUSIONS: Five repeated maximal DYN led to a greater muscle injury compared with STA but neither elicited myocardial injury or neuronal-parenchymal damage.

Exploring the impact of exercise and essential amino acid plus cholecalciferol supplementation on physical fitness and body composition in multiple sclerosis: A case study.

Key Clinical Message: In MS patients, especially those frail or malnourished, combining home-based exercise twice weekly with essential amino acids and vitamin D may improve body composition, strength, and physical performance, enabling long-term functional improvements. Abstract: Multiple sclerosis (MS) is associated with reduced bone and muscle strength and function. We aimed to investigate the effectiveness of a 24-week intervention in a 57-year-old frail female with MS. The participant completed a 2×/week exercise intervention and ingested 2×/day a supplement containing 7.5 g essential amino acids and 500 IU cholecalciferol. Body composition, 6-m gait speed (GS), handgrip strength (HGS), 30-sec arm-curl test (30ACT), 6-min walking test (6MWT), 30-sec chair-stand test (30CST), and plasma concentrations of 25-hydroxyvitamin D3 [25(OH)D3], insulin-like growth factor 1 (IGF-1), and amino acids were assessed at baseline, and at Weeks 12 and 24. Plasma 25(OH)D3 increased from 23.2 to 41.3 ng/mL and IGF-1 from 131.6 to 140.7 ng/mL from baseline to post-intervention. BMI, total lean tissue mass (LTM), fat mass, bone mineral content, and the sum of 17 amino acids increased by 3.8, 1.0, 3.5, 0.2, and 19%, respectively, at Week 24. There were clinically significant increases in regional LTM (6.9% arms and 6.3% legs) and large increases in GS (67.3%), dominant HGS (31.5%), non-dominant HGS (11.8%), dominant 30ACT (100%), non-dominant 30ACT (116.7%), 6MWT (125.6%), and 30CST (44.4%). The current intervention was effective in improving components of physical fitness and body composition in a female with MS.

The skeletal muscle fiber periphery: A nexus of mTOR-related anabolism.

Skeletal muscle anabolism is driven by numerous stimuli such as growth factors, nutrients (i.e., amino acids, glucose), and mechanical stress. These stimuli are integrated by the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signal transduction cascade. In recent years, work from our laboratory and elsewhere has sought to unravel the molecular mechanisms underpinning the mTOR-related activation of muscle protein synthesis (MPS), as well as the spatial regulation of these mechanisms within the skeletal muscle cell. These studies have suggested that the skeletal muscle fiber periphery is a region of central importance in anabolism (i.e., growth/MPS). Indeed, the fiber periphery is replete with the substrates, molecular machinery, and translational apparatus necessary to facilitate MPS. This review provides a summary of the mechanisms underpinning the mTOR-associated activation of MPS from cell, rodent, and human studies. It also presents an overview of the spatial regulation of mTORC1 in response to anabolic stimuli and outlines the factors that distinguish the periphery of the cell as a highly notable region of skeletal muscle for the induction of MPS. Future research should seek to further explore the nutrient-induced activation of mTORC1 at the periphery of skeletal muscle fibers.

Leucine ingestion promotes mTOR translocation to the periphery and enhances total and peripheral RPS6 phosphorylation in human skeletal muscle.

The activation of the mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of protein synthesis, by anabolic stimuli (such as muscle contraction or essential amino acids) involves its translocation to the cell periphery. Leucine is generally considered the most anabolic of amino acids for its ability to independently modulate muscle protein synthesis. However, it is currently unknown if free leucine impacts region-specific mTORC1-mediated phosphorylation events and protein-protein interactions. In this clinical trial (NCT03952884; registered May 16, 2019), we used immunofluorescence methods to investigate the role of dietary leucine on the postprandial regulation of mTORC1 and ribosomal protein S6 (RPS6), an important downstream readout of mTORC1 activity. Eight young, healthy, recreationally active males (n = 8; 23 ± 3 yrs) ingested 2 g of leucine with vastus lateralis biopsies collected at baseline, 30, 60, and 180 min postprandial. Leucine promoted mTOR translocation to the periphery (~ 18-29%; p ≤ 0.012) and enhanced mTOR localization with the lysosome (~ 16%; both p = 0.049) at 30 and 60 min post-feeding. p-RPS6Ser240/244 staining intensity, a readout of mTORC1 activity, was significantly elevated at all postprandial timepoints in both the total fiber (~ 14-30%; p ≤ 0.032) and peripheral regions (~ 16-33%; p ≤ 0.014). Additionally, total and peripheral p-RPS6Ser240/244 staining intensity at 60 min was positively correlated (r = 0.74, p = 0.036; r = 0.80, p = 0.016, respectively) with rates of myofibrillar protein synthesis over 180 min. The ability of leucine to activate mTORC1 in peripheral regions favors an enhanced rate of MPS, as this is the intracellular space thought to be replete with the cellular machinery that facilitates this anabolic process.

Hyponatremia after Autologous Breast Reconstruction: A Cohort Study Comparing Two Fluid Management Protocols.

BACKGROUND: Perioperative fluid management is an important component of enhanced recovery pathways for microsurgical breast reconstruction. Historically, fluid management has been liberal. Little attention has been paid to the biochemical effects of different protocols. This study aims to reduce the risk of postoperative hyponatremia by introducing a new fluid management protocol. METHODS: A single-institution cohort study comparing a prospective series of patients was managed using a new "modestly restrictive" fluid postoperative fluid management protocol to a control group managed with a "liberal" fluid management protocol. RESULTS: One-hundred thirty patients undergoing microsurgical breast reconstruction, at a single institution during 2021, are reported. Hyponatremia is demonstrated to be a significant risk with the original liberal fluid management protocol. At the end of the first postoperative day, mean fluid balance was +2,838 mL (± 1,630 mL). Twenty-four patients of sixty-five (36%) patients had low blood sodium level, 14% classified as moderate-to-severe hyponatremia. Introducing a new, "modestly-restrictive" protocol reduced mean fluid balance on day 1 to +844 mL (±700) (p ≤ 0.0001). Incidence of hyponatremia reduced from 36 to 14% (p = 0.0005). No episodes of moderate or severe hyponatremia were detected. Fluid intake, predominantly oral water, between 8am and 8pm on the first postoperative day is identified as the main risk factor for developing hyponatremia (odds ratio [OR]: 7; p = 0.019). Modest fluid restriction, as guided by the new protocol, protects patients from low sodium level (OR: 0.25; confidence interval: 95%; 0.11-1.61; p = 0.0014). CONCLUSION: The original "liberal" fluid management protocol encouraged unrestricted postoperative oral intake of water. Patients were often advised to consume in excess of 5 L in the first 24 hours. This unintentionally, but frequently, was associated with moderate-to-severe hyponatremia. We present a new protocol characterized by early cessation of intravenous fluid and an oral fluid limit of 2,100 mL/day associated with a significant reduction in the incidence of hyponatremia and fluid overload.

Identification of underexplored mesenchymal and vascular-related cell populations in human skeletal muscle.

Skeletal muscle repair and maintenance are directly and indirectly supported by interstitial cell populations such as vascular cells and fibro-adipogenic progenitors (FAPs), a subset of which express Twist2 and possess direct myogenic potential. Furthermore, work in rodents has highlighted the potential of pericytes to act as progenitor cells, giving rise to muscle cells and transdifferentiating into endothelial cells. However, less is understood about these populations in human skeletal muscle. Here, we performed single-cell RNA sequencing (scRNAseq) on ∼2,000 cells isolated from the human semitendinosus muscle of young individuals. This demonstrated the presence of a vascular-related cell type that expressed pericyte and pan-endothelial genes that we localized to large blood vessels within skeletal muscle cross sections and termed endothelial-like pericytes (ELPCs). RNA velocity analysis indicated that ELPCs may represent a "transition state" between endothelial cells and pericytes. Analysis of published scRNAseq data sets revealed evidence for ELPCs in trunk and heart musculature, which showed transcriptional similarity. In addition, we identified a subset of FAPs expressing TWIST2 mRNA and protein. Human TWIST2-expressing cells were anatomically and transcriptionally comparable to mouse Twist2 cells as they were restricted to the myofiber interstitium, expressed fibrogenic genes but lacked satellite cell markers, and colocalized with the FAPs marker PDGFRα in human muscle cross sections. Taken together, these results highlight the complexity of stromal cells residing in human skeletal muscle and support the utility of scRNAseq for discovery and characterization of poorly described cell populations.

Increased protein intake derived from leucine-enriched protein enhances the integrated myofibrillar protein synthetic response to short-term resistance training in untrained men and women: a 4-day randomized controlled trial.

Leucine is a critical amino acid stimulating myofibrillar protein synthesis (MyoPS). The consumption of higher leucine-containing drinks stimulates MyoPS, but we know less about higher leucine solid foods. Here, we examined the effect of short-term resistance exercise training (STRT) combined with supplementation of a protein and leucine-enriched bar, compared with STRT alone, on integrated (%/day) rates of MyoPS and anabolic protein signaling. In a nonblinded, randomized crossover trial, eight young adults performed four sessions of STRT without or while consuming the study bar (STRT+Leu, 16 g of protein containing ∼3 g of leucine) for two 4-day phases, separated by 2 days nonexercise (Rest) washout. In combination with serial muscle biopsies, deuterated water permitted the measurement of MyoPS and protein signaling phosphorylation. MyoPS during STRT (1.43 ± 0.06%/day) and STRT+Leu (1.53 ± 0.06%/day) were greater than Rest (1.31 ± 0.05%/day), and MyoPS during STRT+Leu (1.53 ± 0.06%/day) was greater than STRT alone (1.43 ± 0.06%/day). STRT+Leu increased the ratio of phosphorylated to total mechanistic target of rapamycin and 4EBP1 compared to Rest. Engaging in STRT increased integrated MyoPS and protein signaling in young adults and was enhanced with increased protein intake derived from a leucine-enriched protein bar. This study was registered at clinicaltrials.gov as NCT03796897.

Lean Mass, Muscle Strength, and Muscle Quality in Retired Rugby Players: The UK Rugby Health Project.

Although athletes from sports such as rugby have greater lean mass and strength during their playing careers, little is known about these characteristics post-retirement. Therefore, this study investigated lean mass, strength, and muscle quality in retired elite and amateur rugby players and non-contact athletes. Retired elite male rugby players (n=42, 43.9±10.3 y; 101.1±13.4 kg; 1.82±0.09 m), amateur rugby players (n=46, 48.0±10.5 y; 98.9±16.6 kg; 1.79±0.07 m) and non-contact athletes (n=30, 51.3±12.5 y; 91.3±13.4 kg; 1.79±0.07 m) received one total body dual-energy X-ray absorptiometry assessment of appendicular lean mass (ALM) and ALM index (ALMI). Grip strength was measured, and muscle quality (grip strength/unit of arm lean mass) was calculated. Sarcopenia was identified as ALMI<7.23 kg/m2 and handgrip strength<37.2 kg. Total lean mass, ALM and grip strength were greater in the elite rugby compared to amateur rugby and non-contact groups (p<0.01). There were no significant differences in muscle quality or sarcopenia prevalence. Retired elite rugby players had greater lean mass and grip strength than amateur rugby and non-contact athletes, although muscle quality was similar. The greater lean mass and strength might reflect genetic influences or previous participation in a highly physical sport.

Challenges of rapamycin repurposing as a potential therapeutic candidate for COVID-19: implications for skeletal muscle metabolic health in older persons.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that has spread worldwide, resulting in over 6 million deaths as of March 2022. Older people have been disproportionately affected by the disease, as they have a greater risk of hospitalization, are more vulnerable to severe infection, and have higher mortality than younger patients. Although effective vaccines have been rapidly developed and administered globally, several clinical trials are ongoing to repurpose existing drugs to combat severe infection. One such drug, rapamycin, is currently under study for this purpose, given its immunosuppressant effects that are mediated by its inhibition of the mechanistic target of rapamycin (mTOR), a master regulator of cell growth. Consistent with this premise, acute rapamycin administration in young healthy humans blocks or attenuates mTOR and its downstream effectors, leading to the inhibition of muscle protein synthesis (MPS). Skeletal muscle mass declines when MPS is chronically lower than muscle protein breakdown. This is consequential for older people who are more susceptible to anabolic resistance (i.e., the blunting of MPS) due to reduced activity, sedentariness, or bed rest such as that associated with COVID-19 hospitalization, and who have also demonstrated a delayed or blunted ability to regain inactivity-induced muscle loss. The lack of studies investigating rapamycin administration on skeletal muscle in older people, and the emergence of effective antiviral medications against severe infection, may indicate the reduced relevance of drug repurposing for present or future pandemics.

Cerebral, cardiac and skeletal muscle stress associated with a series of static and dynamic apnoeas.

PURPOSE: This study sought to explore, for the first time, the effects of repeated maximal static and dynamic apnoeic attempts on the physiological milieu by assessing cerebral, cardiac and striatal muscle stress-related biomarkers in a group of elite breath-hold divers (EBHD). METHODS: Sixteen healthy males were recruited (EBHD = 8; controls = 8). On two separate occasions, EBHD performed two sets of five repeated maximal static apnoeas (STA) or five repeated maximal dynamic apnoeas (DYN). Controls performed a static eupnoeic protocol to negate any effects of water immersion and diurnal variation on haematology (CTL). Venous blood samples were drawn at 30, 90, and 180 min after each protocol to determine S100ß, neuron-specific enolase (NSE), myoglobin, and high sensitivity cardiac troponin T (hscTNT) concentrations. RESULTS: S100ß and myoglobin concentrations were elevated following both apnoeic interventions (p < 0.001; p ≤ 0.028, respectively) but not after CTL (p ≥ 0.348). S100ß increased from baseline (0.024 ± 0.005 µg/L) at 30 (STA, +149%, p < 0.001; DYN, +166%, p < 0.001) and 90 min (STA, +129%, p < 0.001; DYN, +132%, p = 0.008) following the last apnoeic repetition. Myoglobin was higher than baseline (22.3 ± 2.7 ng/ml) at 30 (+42%, p = 0.04), 90 (+64%, p < 0.001) and 180 min (+49%, p = 0.013) post-STA and at 90 min (+63%, p = 0.016) post-DYN. Post-apnoeic S100ß and myoglobin concentrations were higher than CTL (STA, p < 0.001; DYN, p ≤ 0.004). NSE and hscTNT did not change from basal concentrations after the apnoeic (p ≥ 0.146) nor following the eupnoeic (p ≥ 0.553) intervention. CONCLUSIONS: This study suggests that a series of repeated maximal static and dynamic apnoeas transiently disrupt the blood-brain barrier and instigate muscle injury but do not induce neuronal-parenchymal damage or myocardial damage.

LAT1 and SNAT2 Protein Expression and Membrane Localization of LAT1 Are Not Acutely Altered by Dietary Amino Acids or Resistance Exercise Nor Positively Associated with Leucine or Phenylalanine Incorporation in Human Skeletal Muscle.

The influx of essential amino acids into skeletal muscle is primarily mediated by the large neutral amino acid transporter 1 (LAT1), which is dependent on the glutamine gradient generated by the sodium-dependent neutral amino acid transporter 2 (SNAT2). The protein expression and membrane localization of LAT1 may be influenced by amino acid ingestion and/or resistance exercise, although its acute influence on dietary amino acid incorporation into skeletal muscle protein has not been investigated. In a group design, healthy males consumed a mixed carbohydrate (0.75 g·kg-1) crystalline amino acid (0.25 g·kg-1) beverage enriched to 25% and 30% with LAT1 substrates L-[1-13C]leucine (LEU) and L-[ring-2H5]phenylalanine (PHE), respectively, at rest (FED: n = 7, 23 ± 5 y, 77 ± 4 kg) or after a bout of resistance exercise (EXFED: n = 7, 22 ± 2 y, 78 ± 11 kg). Postprandial muscle biopsies were collected at 0, 120, and 300 min to measure transporter protein expression (immunoblot), LAT1 membrane localization (immunofluorescence), and dietary amino acid incorporation into myofibrillar protein (ΔLEU and ΔPHE). Basal LAT1 and SNAT2 protein contents were correlated with each other (r = 0.55, p = 0.04) but their expression did not change across time in FED or EXFED (all, p > 0.05). Membrane localization of LAT1 did not change across time in FED or EXFED whether measured as outer 1.5 µm intensity or membrane-to-fiber ratio (all, p > 0.05). Basal SNAT2 protein expression was not correlated with ΔLEU or ΔPHE (all, p ≥ 0.05) whereas basal LAT1 expression was negatively correlated with ΔPHE in FED (r = -0.76, p = 0.04) and EXFED (r = -0.81, p = 0.03) but not ΔLEU (p > 0.05). Basal LAT1 membrane localization was not correlated with ΔLEU or ΔPHE (all, p > 0.05). Our results suggest that LAT1/SNAT2 protein expression and LAT1 membrane localization are not influenced by acute anabolic stimuli and do not positively influence the incorporation of dietary amino acids for de novo myofibrillar protein synthesis in healthy young males.

A muscle-centric view of time-restricted feeding for older adults.

PURPOSE OF REVIEW: The practice of time-restricted feeding (TRF) has received fervent interest in recent years as a strategy to mitigate obesity and metabolic disease. We sought to review the implications of TRF for skeletal muscle health and function in aging. RECENT FINDINGS: TRF has high adherence and can promote body weight loss in older populations. Body weight reductions favor fat mass in the young, however, there is also the potential for undesirable losses in lean mass. There is currently no evidence to support TRF for skeletal muscle function and metabolism in older persons, and only tentative findings in the young. With a narrow eating window of 6-8 h and a prolonged fasting period to minimize daily insulin exposure, TRF may contradict recommended dietary practices for optimizing skeletal muscle anabolism in older people. SUMMARY: TRF might represent a promising intervention to address obesity and its associated metabolic diseases, however, at present there is insufficient evidence for optimizing skeletal muscle mass or health in older individuals. Further research is needed to: (1) ascertain the impact of TRF on body composition, skeletal muscle anabolism, and autophagy in aging, and; (2) delineate the potentially myoprotective roles of dietary protein and exercise within the framework of TRF in older persons.

Consumption of High-Leucine-Containing Protein Bar Following Breakfast Impacts Aminoacidemia and Subjective Appetite in Older Persons.

BACKGROUND: Limited data are available examining dietary interventions for optimizing protein and leucine intake to stimulate muscle protein synthesis (MPS) in older humans. OBJECTIVES: We aimed to investigate the aminoacidemia and appetite responses of older adults after consuming breakfast, a meal frequently consumed with high-carbohydrate and below-par amounts of protein and leucine for stimulating MPS. METHODS: Five men and 3 women (means ± SD; age: 74 ± 7 y, BMI: 25.7 ± 4.9 kg/m2, fat- and bone-free mass: 63 ± 7 kg) took part in this experiment in which they consumed breakfasts with low-protein (LP = 13 ± 2 g), high-protein (HP = 32 ± 5 g), and LP followed by a protein- and leucine-enriched bar formulation 2 h later (LP + Bar = 29 ± 2 g). The LP, HP, and LP + Bar breakfast conditions contained 519 ± 86 kcal, 535 ± 83 kcal, and 739 ± 86 kcal, respectively. Blood samples were drawn for 6 h and analyzed for amino acid, insulin, and glucose concentrations. Visual analog scales were assessed for hunger, fullness, and desire to eat. RESULTS: The net AUC for essential amino acid (EAA) exposure was similar between the LP + Bar and HP conditions but greater in the HP condition compared with the LP condition. Peak leucinemia was higher in the LP + Bar condition compared with the HP, and both were greater than the LP condition. Net leucine exposure was similar between HP and LP + Bar, and both were greater than LP. Hunger was similarly reduced in LP + Bar and HP, and LP + Bar resulted in a greater hunger reduction than LP. Both LP + Bar and HP resulted in greater net fullness scores than LP. CONCLUSIONS: Consuming our bar formulation increased blood leucine availability and net exposure to EAAs to a similar degree as consuming a high-protein meal. High-protein at breakfast results in a greater net exposure to EAAs and leucine, which could support MPS in older persons. This study was registered at clinicaltrials.gov as NCT03712761.

Physiology, pathophysiology and (mal)adaptations to chronic apnoeic training: a state-of-the-art review.

Breath-hold diving is an activity that humans have engaged in since antiquity to forage for resources, provide sustenance and to support military campaigns. In modern times, breath-hold diving continues to gain popularity and recognition as both a competitive and recreational sport. The continued progression of world records is somewhat remarkable, particularly given the extreme hypoxaemic and hypercapnic conditions, and hydrostatic pressures these athletes endure. However, there is abundant literature to suggest a large inter-individual variation in the apnoeic capabilities that is thus far not fully understood. In this review, we explore developments in apnoea physiology and delineate the traits and mechanisms that potentially underpin this variation. In addition, we sought to highlight the physiological (mal)adaptations associated with consistent breath-hold training. Breath-hold divers (BHDs) are evidenced to exhibit a more pronounced diving-response than non-divers, while elite BHDs (EBHDs) also display beneficial adaptations in both blood and skeletal muscle. Importantly, these physiological characteristics are documented to be primarily influenced by training-induced stimuli. BHDs are exposed to unique physiological and environmental stressors, and as such possess an ability to withstand acute cerebrovascular and neuronal strains. Whether these characteristics are also a result of training-induced adaptations or genetic predisposition is less certain. Although the long-term effects of regular breath-hold diving activity are yet to be holistically established, preliminary evidence has posed considerations for cognitive, neurological, renal and bone health in BHDs. These areas should be explored further in longitudinal studies to more confidently ascertain the long-term health implications of extreme breath-holding activity.

A Fish-Derived Protein Hydrolysate Induces Postprandial Aminoacidaemia and Skeletal Muscle Anabolism in an In Vitro Cell Model Using Ex Vivo Human Serum.

Fish-derived proteins, particularly fish protein hydrolysates (FPH), offer potential as high-quality sources of dietary protein, whilst enhancing economic and environmental sustainability. This study investigated the impact of a blue whiting-derived protein hydrolysate (BWPH) on aminoacidaemia in vivo and skeletal muscle anabolism in vitro compared with whey protein isolate (WPI) and an isonitrogenous, non-essential amino acid (NEAA) control (0.33 g·kg-1·body mass-1) in an ex vivo, in vitro experimental design. Blood was obtained from seven healthy older adults (two males, five females; age: 72 ± 5 years, body mass index: 24.9 ± 1.6 kg·m2) in three separate trials in a randomised, counterbalanced, double-blind design. C2C12 myotubes were treated with ex vivo human serum-conditioned media (20%) for 4 h. Anabolic signalling (phosphorylation of mTOR, p70S6K, and 4E-BP1) and puromycin incorporation were determined by immunoblotting. Although BWPH and WPI both induced postprandial essential aminoacidaemia in older adults above the NEAA control, peak and area under the curve (AUC) leucine and essential amino acids were more pronounced following WPI ingestion. Insulin was elevated above baseline in WPI and BWPH only, a finding reinforced by higher peak and AUC values compared with NEAA. Muscle protein synthesis, as measured by puromycin incorporation, was greater after incubation with WPI-fed serum compared with fasted serum (P = 0.042), and delta change was greater in WPI (P = 0.028) and BWPH (P = 0.030) compared with NEAA. Myotube hypertrophy was greater in WPI and BWPH compared with NEAA (both P = 0.045), but was similar between bioactive conditions (P = 0.853). Taken together, these preliminary findings demonstrate the anabolic potential of BWPH in vivo and ex vivo, thus providing justification for larger studies in older adults using gold-standard measures of acute and chronic MPS in vivo.

The efficacy of essential amino acid supplementation for augmenting dietary protein intake in older adults: implications for skeletal muscle mass, strength and function.

The primary aim of this review is to evaluate the efficacy of essential amino acid (EAA) supplementation as a strategy to increase dietary protein intake and improve muscle mass, strength and function in older adults. A sufficient daily protein intake is widely recognised to be fundamental for the successful management of sarcopenia in older undernourished adults. In practice, optimising protein intakes in older adults is complex, requiring consideration of the dose and amino acid composition (i.e. a complete EAA profile and abundant leucine content) of ingested protein on a per meal basis, alongside the age-related decline in appetite and the satiating properties of protein. Recent studies in older adults demonstrate that EAA-based supplements are non-satiating and can be administered alongside food to enhance the anabolic properties of a meal containing a suboptimal dose of protein; an effect magnified when combined with resistance exercise training. These findings support the notion that EAA supplementation could serve as an effective strategy to improve musculoskeletal health in older adults suffering from non-communicable diseases such as sarcopenia. Compliance is critical for the long-term success of complex interventions. Hence, aspects of palatability and desire to eat are important considerations regarding EAA supplementation. In conclusion, EAA-based supplements enriched with l-leucine offer an alternative strategy to whole protein sources to assist older adults in meeting protein recommendations. In practice, EAA supplements could be administered alongside meals of suboptimal protein content, or alternatively between meals on occasions when older adults achieve their per meal protein intake recommendations.

The Potential Role of Fish-Derived Protein Hydrolysates on Metabolic Health, Skeletal Muscle Mass and Function in Ageing.

Fish protein represents one of the most widely consumed dietary protein sources by humans. The processing of material from the fishing industry generates substantial unexploited waste products, many of which possess high biological value. Protein hydrolysates, such as fish protein hydrolysates (FPH), containing predominantly di- and tripeptides, are more readily absorbed than free amino acids and intact protein. Furthermore, in animal models, FPH have been shown to possess numerous beneficial properties for cardiovascular, neurological, intestinal, renal, and immune health. Ageing is associated with the loss of skeletal muscle mass and function, as well as increased oxidative stress, compromised vascularisation, neurological derangements, and immunosenescence. Thus, there appears to be a potential application for FPH in older persons as a high-quality protein source that may also confer additional health benefits. Despite this, there remains a dearth of information concerning the impact of FPH on health outcomes in humans. The limited evidence from human interventional trials suggests that FPH may hold promise for supporting optimal body composition and maintaining gut integrity. FPH also provide a high-quality source of dietary protein without negatively impacting on subjective appetite perceptions or regulatory hormones. Further studies are needed to assess the impact and utility of FPH on skeletal muscle health in older persons, ideally comparing FPH to 'established' protein sources or a non-bioactive, nitrogen-matched control. In particular, the effects of acute and chronic FPH consumption on post-exercise aminoacidaemia, skeletal muscle protein synthesis, and intramyocellular anabolic signalling in older adults are worthy of investigation. FPH may represent beneficial and sustainable alternative sources of high-quality protein to support skeletal muscle health and anabolism in ageing, without compromising appetite and subsequent energy intake.

Novel Essential Amino Acid Supplements Following Resistance Exercise Induce Aminoacidemia and Enhance Anabolic Signaling Irrespective of Age: A Proof-of-Concept Trial.

We investigated the effects of ingesting a leucine-enriched essential amino acid (EAA) gel alone or combined with resistance exercise (RE) versus RE alone (control) on plasma aminoacidemia and intramyocellular anabolic signaling in healthy younger (28 ± 4 years) and older (71 ± 3 years) adults. Blood samples were obtained throughout the three trials, while muscle biopsies were collected in the postabsorptive state and 2 h following RE, following the consumption of two 50 mL EAA gels (40% leucine, 15 g total EAA), and following RE with EAA (combination (COM)). Protein content and the phosphorylation status of key anabolic signaling proteins were determined via immunoblotting. Irrespective of age, during EAA and COM peak leucinemia (younger: 454 ± 32 µM and 537 ± 111 µM; older: 417 ± 99 µM and 553 ± 136 µM) occurred ~60-120 min post-ingestion (younger: 66 ± 6 min and 120 ± 60 min; older: 90 ± 13 min and 78 ± 12 min). In the pooled sample, the area under the curve for plasma leucine and the sum of branched-chain amino acids was significantly greater in EAA and COM compared with RE. For intramyocellular signaling, significant main effects were found for condition (mTOR (Ser2481), rpS6 (Ser235/236)) and age (S6K1 (Thr421/Ser424), 4E-BP1 (Thr37/46)) in age group analyses. The phosphorylation of rpS6 was of similar magnitude (~8-fold) in pooled and age group data 2 h following COM. Our findings suggest that a gel-based, leucine-enriched EAA supplement is associated with aminoacidemia and a muscle anabolic signaling response, thus representing an effective means of stimulating muscle protein anabolism in younger and older adults following EAA and COM.

Skeletal muscle, haematological and splenic volume characteristics of elite breath-hold divers.

PURPOSE: The aim of the study was to provide an evaluation of the oxygen transport, exchange and storage capacity of elite breath-hold divers (EBHD) compared with non-divers (ND). METHODS: Twenty-one healthy males' (11 EBHD; 10 ND) resting splenic volumes were assessed by ultrasound and venous blood drawn for full blood count analysis. Percutaneous skeletal muscle biopsies were obtained from the m. vastus lateralis to measure capillarisation, and fibre type-specific localisation and distribution of myoglobin and mitochondrial content using quantitative immunofluorescence microscopy. RESULTS: Splenic volume was not different between groups. Reticulocytes, red blood cells and haemoglobin concentrations were higher (+ 24%, p < 0.05; + 9%, p < 0.05; + 3%, p < 0.05; respectively) and mean cell volume was lower (- 6.5%, p < 0.05) in the EBHD compared with ND. Haematocrit was not different between groups. Capillary density was greater (+ 19%; p < 0.05) in the EBHD. The diffusion distance (R95) was lower in type I versus type II fibres for both groups (EBHD, p < 0.01; ND, p < 0.001), with a lower R95 for type I fibres in the EBHD versus ND (- 13%, p < 0.05). Myoglobin content was higher in type I than type II fibres in EBHD (+ 27%; p < 0.01) and higher in the type I fibres of EBHD than ND (+ 27%; p < 0.05). No fibre type differences in myoglobin content were observed in ND. Mitochondrial content was higher in type I than type II fibres in EBHD (+ 35%; p < 0.05), with no fibre type differences in ND or between groups. CONCLUSIONS: In conclusion, EBDH demonstrate enhanced oxygen storage in both blood and skeletal muscle and a more efficient oxygen exchange capacity between blood and skeletal muscle versus ND.