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Thymic involution is a key factor in human immune aging, leading to reduced thymic output and a decline in recent thymic emigrant (RTE) naive T cells in circulation. Currently, the precise definition of human RTEs and their corresponding cell surface markers lacks clarity. Analysis of single-cell RNA-seq/ATAC-seq data distinguished RTEs by the expression of SOX4, IKZF2, and TOX and CD38 protein, whereby surface CD38 hi expression universally identified CD8 + and CD4 + RTEs. We further determined the dynamics of RTEs and mature cells in a cohort of 158 individuals, including age-associated transcriptional reprogramming and shifts in cytokine production. Spectral cytometry profiling revealed two axes of aging common to naive CD8 + and CD4 + T cells: (1) a decrease in CD38 ++ cells (RTEs) and (2) an increase in CXCR3 hi cells. Identification of RTEs enables direct assessment of thymic health. Furthermore, resolving the dynamics of naive T cell remodeling yields insight into vaccination and infection responsiveness throughout aging., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

INTRODUCTION: Accessible spaceflight may seem a distant concept. As part of a diverse European Space Agency funded Topical Team, we are working on the physiological feasibility of space missions being undertaken by people with physical disabilities. Here, the first activity of this team is presented in the form of key lessons learned from aviation to inform new work on space missions. DISCUSSION: The first lesson is agreeing on realistic expectations about impairments, their severity, and the possibility of flying independently. This is important in terms of astronaut recruitment and societal expectations. The second lesson relates to training and adjustments for people with disabilities. Flexibility is important while maintaining safety for everyone involved. The third lesson is about managing unconscious bias from the different stakeholders. We conclude by arguing that engagement with people from different backgrounds is essential for the success of the first space mission with people with physical disabilities. Miller-Smith MJ, Tucker N, Anderton R, Caplin N, Harridge SDR, Hodkinson P, Narici MV, Pollock RD, Possnig C, Rittweger J, Smith TG, Di Giulio I. Lessons for flying astronauts with disabilities drawn from experience in aviation . Aerosp Med Hum Perform. 2024; 95(9):716-719.

Changes in myonuclear architecture and positioning are associated with exercise adaptations and ageing. However, data on the positioning and number of myonuclei following exercise are inconsistent. Additionally, whether myonuclear domains (MNDs; i.e., the theoretical volume of cytoplasm within which a myonucleus is responsible for transcribing DNA) and myonuclear positioning are altered with age remains unclear. The aim of this investigation was to investigate relationships between age and activity status and myonuclear domains and positioning. Vastus lateralis muscle biopsies from younger endurance-trained (YT) and older endurance-trained (OT) individuals were compared with age-matched untrained counterparts (YU and OU; OU samples were acquired during surgical operation). Serial, optical z-slices were acquired throughout isolated muscle fibres and analysed to give three-dimensional coordinates for myonuclei and muscle fibre dimensions. The mean cross-sectional area (CSA) of muscle fibres from OU individuals was 33%-53% smaller compared with the other groups. The number of nuclei relative to fibre CSA was 90% greater in OU compared with YU muscle fibres. Additionally, scaling of MND volume with fibre size was altered in older untrained individuals. The myonuclear arrangement, in contrast, was similar across groups. Fibre CSA and most myonuclear parameters were significantly associated with age in untrained individuals, but not in trained individuals. These data indicate that regular endurance exercise throughout the lifespan might better preserve the size of muscle fibres in older age and maintain the relationship between fibre size and MND volumes. Inactivity, however, might result in reduced muscle fibre size and altered myonuclear parameters., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292., (© 2024. The Author(s).)

INTRODUCTION: G tolerance has been widely assessed using Peripheral Light Loss (PLL), but this approach has several limitations and may lack sensitivity. The aim of this study was to investigate the use of a foveal visual endpoint for centrifuge research (Grating Loss; GL) and assess its repeatability, reliability, and usability with PLL as a reference. METHODS: A total of 11 subjects undertook centrifuge assessment. Gradual onset sessions (GOR; 0.1 G · s -1 ) measured both endpoints simultaneously and were performed twice, consisting of six determinations with anti-G suits activated (GOR-On) and six without (GOR-Off). Four determinations of each endpoint were also taken during rapid onset runs (ROR; 3 G · s -1 ). Usability was scored subjectively. RESULTS: The GL endpoint was reached 0.3-0.5 G z lower than PLL with each endpoint correlating strongly in GOR-Off (r = 0.93), GOR-On (r = 0.95), and ROR (r = 0.86). The GL had excellent test-retest repeatability (intraclass correlation coefficient: GOR-Off/On = 0.99, ROR = 0.92) and low within-subject variability. Between-subject variance equaled PLL in all conditions. Subjective usability endpoint ratings were equal for all conditions. DISCUSSION: For the 11 individuals tested, the GL was a reliable, repeatable, and usable endpoint, with similar performance to PLL. GL may prove useful as a supplementary endpoint for human centrifuge research as a secondary data point or to reduce fatigue in repeated measurements. The foveal GL stimulus was lost before PLL, contrary to popular models of visual changes under +G z . Britton J, Connolly DM, Hawarden DE, Stevenson AT, Harridge SDR, Green NDC, Pollock RD. Initial investigation of a grating stimulus as a visual endpoint for human centrifuge research . Aerosp Med Hum Perform. 2023; 94(12):894-901.

Intermittent (or bolus) feeding regimens in critically ill patients have been of increasing interest to clinicians and scientists. Changes in amino acid, fat and carbohydrate metabolites over time might yet deliver other benefits (e.g. modulation of the circadian rhythm and sleep, and impacts on ghrelin secretion, insulin resistance and autophagy). We set out to characterise these changes in metabolite concentration. The Intermittent versus Continuous Feeding in Critically Ill paitents study (NCT02358512) was an eight-centre single-blinded randomised controlled trial. Patients were randomised to received a continuous (control arm) or intermittent (6x/day, intervention arm) enteral feeding regimen. Blood samples were taken on trial days 1, 7 and 10 immediately before and 30 min after intermittent feeds, and at equivalent timepoints in the control arm. A pre-planned targeted metabolomic analysis was performend using Nuclear Resonance Spectroscopy. Five hundred and ninety four samples were analysed from 75 patients. A total of 24 amino acid-, 19 lipid based-, and 44 small molecule metabolite features. Across the main two axes of variation (40-60% and 6-8% of variance), no broad patterns distinguished between intermittent or continuous feeding arms, across intra-day sampling times or over the 10 days from initial ICU admission. Logfold decreases in abundance were seen in metabolites related to amino acids (Glutamine - 0.682; Alanine - 0.594), ketone body metabolism (Acetone - 0.64; 3-Hydroxybutyric Acid - 0.632; Acetonacetic Acid - 0.586), fatty acid (carnitine - 0.509) and carbohydrate metabolism ( Maltose - 0.510; Citric Acid - 0.485). 2-3 Butanediol, a by-product of sugar-fermenting microbial metabolism also decreased (- 0.489). No correlation was seen with change in quadriceps muscle mass for any of the 20 metabolites varying with time (all p > 0.05). Increasing severity of organ failure was related to increasing ketone body metabolism (3 Hydroxybutyric Acid-1 and - 3; p = 0.056 and p = 0.014), carnitine deficiency (p = 0.002) and alanine abundancy (p - 0.005). A 6-times a day intermittent feeding regimen did not alter metabolite patterns across time compared to continuous feeding in critically ill patients, either within a 24 h period or across 10 days of intervention. Future research on intermittent feeding regimens should focus on clinical process benefits, or extended gut rest and fasting., (© 2023. The Author(s).)

INTRODUCTION: Consistent blood biomarkers of hypobaric (altitude) decompression stress remain elusive. Recent laboratory investigation of decompression sickness risk at 25,000 ft (7620 m) enabled evaluation of early pathophysiological responses to exertional decompression stress. METHODS: In this study, 15 healthy men, aged 20-50 yr, undertook 2 consecutive (same-day) ascents to 25,000 ft (7620 m) for 60 and 90 min, breathing 100% oxygen, each following 1 h of prior denitrogenation. Venous blood was sampled at baseline (T0), immediately after the second ascent (T8), and next morning (T24). Analyses encompassed whole blood hematology, endothelial microparticles, and soluble markers of cytokine response, endothelial function, inflammation, coagulopathy, oxidative stress, and brain insult, plus cortisol and creatine kinase. RESULTS: Acute hematological effects on neutrophils (mean 72% increase), eosinophils (40% decrease), monocytes (37% increase), and platelets (7% increase) normalized by T24. Consistent elevation (mean five-fold) of the cytokine interleukin-6 (IL-6) at T8 was proinflammatory and associated with venous gas emboli (microbubble) load. Levels of C-reactive protein and complement peptide C5a were persistently elevated at T24, the former by 100% over baseline. Additionally, glial fibrillary acidic protein, a sensitive marker of traumatic brain injury, increased by a mean 10% at T24. CONCLUSIONS: This complex composite environmental stress, comprising the triad of hyperoxia, decompression, and moderate exertion at altitude, provoked pathophysiological changes consistent with an IL-6 cytokine-mediated inflammatory response. Multiple persistent biomarker disturbances at T24 imply incomplete recovery the day after exposure. The elevation of glial fibrillary acidic protein similarly implies incomplete resolution following recent neurological insult. Connolly DM, Madden LA, Edwards VC, D'Oyly TJ, Harridge SDR, Smith TG, Lee VM. Early human pathophysiological responses to exertional hypobaric decompression stress . Aerosp Med Hum Perform. 2023; 94(10):738-749.

INTRODUCTION: Occurrences of severe decompression sickness (DCS) in military parachutist dispatchers at 25,000 ft (7620 m) prompted revision of exposure guidelines for high altitude parachuting. This study investigated residual risks to dispatchers and explored the potential for safely conducting repeat exposures in a single duty period. METHODS: In this study, 15 healthy men, ages 20-50 yr, undertook 2 profiles of repeated hypobaric chamber decompression conducting activities representative of dispatcher duties. Phase 1 comprised two ascents to 25,000 ft (7620 m) for 60 and then 90 min. Phase 2 included three ascents first to 25,000 ft for 60 min, followed by two ascents to 22,000 ft (6706 m) for 90 min. Denitrogenation was undertaken at 15,000 ft (4572 m) with successive ascents separated by 1-h air breaks at ground level. RESULTS: At 25,000 ft (7620 m), five cases of limb (knee) pain DCS developed, the earliest at 29 min. Additionally, multiple minor knee "niggles" occurred with activity but disappeared when seated at rest. No DCS and few niggles occurred at 22,000 ft (6706 m). Early, heavy, and sustained bubble loads were common at 25,000 ft, particularly in older subjects, but lighter and later loads followed repeat exposure, especially at 22,000 ft. DISCUSSION: Parachutist dispatchers are at high risk of DCS at 25,000 ft (7620 m) commensurate with their heavy level of exertion. However, the potential exists for repeated safe ascents to 22,000 ft (6706 m), in the same duty period, if turn-around times breathing air at ground level are brief. Older dispatchers (>40 yr) with functional right-to-left (intracardiac or pulmonary) vascular shunts will be at risk of arterialization of microbubbles. Connolly DM, D'Oyly TJ, Harridge SDR, Smith TG, Lee VM. Decompression sickness risk in parachutist dispatchers exposed repeatedly to high altitude . Aerosp Med Hum Perform. 2023; 94(9):666-677.

Specific force (SF) has been shown to be reduced in some but not all studies of human aging using chemically skinned single muscle fibers. This may be due, in part, not only to the health status/physical activity levels of different older cohorts, but also from methodological differences in studying skinned fibers. The aim of the present study was to compare SF in fibers from older hip fracture patients (HFP), healthy master cyclists (MC), and healthy nontrained young adults (YA) using two different activating solutions. Quadriceps muscle samples and 316 fibers were obtained from HFPs (74.6 ± 4 years, n = 5), MCs (74.8 ± 1, n = 5), and YA (25.5 ± 2, n = 6). Fibers were activated (pCa 4.5, 15°C) in solutions containing either 60 mM N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid pH buffer (TES) or 20 mM imidazole. SF was determined by normalizing force to fiber cross-sectional area (CSA) assuming either an elliptical or circular shape and to fiber myosin heavy chain content. Activation in TES resulted in significantly higher MHC-I SF in all groups and YA MHC-IIA fibers, irrespective of normalization method. Although there were no differences in SF between the participant groups, the ratio of SF between the TES and imidazole solutions was lower in HFPs compared with YAs (MHC-I P < 0.05; MHC-IIA P = 0.055). Activating solution composition, as opposed to donor characteristics, had a more notable effect on single fiber SF. However, this two-solution approach revealed an age-related difference in sensitivity in HFPs, which was not shown in MCs. This suggests further novel approaches may be required to probe age/activity-related differences in muscle contractile quality. NEW & NOTEWORTHY Whether specific force (SF) decreases with advancing age in human single skeletal muscle fibers is uncertain. Equivocal published findings may be due to the different physical activity levels of the elderly cohorts studied and/or different chemical solutions used to measure force. We compared single fiber SF between young adults, elderly cyclists, and hip fracture patients (HFP) using two solutions. The solution used significantly affected force and revealed a difference in sensitivity of HFP muscle fibers.

Age-related decline in skeletal muscle structure and function can be mitigated by regular exercise. However, the precise mechanisms that govern this are not fully understood. The nucleus plays an active role in translating forces into biochemical signals (mechanotransduction), with the nuclear lamina protein lamin A regulating nuclear shape, nuclear mechanics and ultimately gene expression. Defective lamin A expression causes muscle pathologies and premature ageing syndromes, but the roles of nuclear structure and function in physiological ageing and in exercise adaptations remain obscure. Here, we isolated single muscle fibres and carried out detailed morphological and functional analyses on myonuclei from young and older exercise-trained individuals. Strikingly, myonuclei from trained individuals were more spherical, less deformable, and contained a thicker nuclear lamina than those from untrained individuals. Complementary to this, exercise resulted in increased levels of lamin A and increased myonuclear stiffness in mice. We conclude that exercise is associated with myonuclear remodelling, independently of age, which may contribute to the preservative effects of exercise on muscle function throughout the lifespan. KEY POINTS: The nucleus plays an active role in translating forces into biochemical signals. Myonuclear aberrations in a group of muscular dystrophies called laminopathies suggest that the shape and mechanical properties of myonuclei are important for maintaining muscle function. Here, striking differences are presented in myonuclear shape and mechanics associated with exercise, in both young and old humans. Myonuclei from trained individuals were more spherical, less deformable and contained a thicker nuclear lamina than untrained individuals. It is concluded that exercise is associated with age-independent myonuclear remodelling, which may help to maintain muscle function throughout the lifespan., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

During voluntary muscle contractions, force output is characterized by constant inherent fluctuations, which can be quantified either according to their magnitude or temporal structure, that is, complexity. The presence of such fluctuations when targeting a set force indicates that control of force is not perfectly accurate, which can have significant implications for task performance. Compared to young adults, older adults demonstrate a greater magnitude and lower complexity in force fluctuations, indicative of decreased steadiness, and adaptability of force output, respectively. The nature of this loss-of-force control depends not only on the age of the individual but also on the muscle group performing the task, the intensity and type of contraction and whether the task is performed with additional cognitive load. Importantly, this age-associated loss-of-force control is correlated with decreased performance in a range of activities of daily living and is speculated to be of greater importance for functional capacity than age-associated decreases in maximal strength. Fortunately, there is evidence that acute physical activity interventions can reverse the loss-of-force control in older individuals, though whether this translates to improved functional performance and whether lifelong physical activity can protect against the changes have yet to be established. A number of mechanisms, related to both motor unit properties and the behavior of motor unit populations, have been proposed for the age-associated changes in force fluctuations. It is likely, though, that age-associated changes in force control are related to increased common fluctuations in the discharge times of motor units., (© 2022 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Chemically skinned fibres allow the study of human muscle contractile function in vitro. A particularly important parameter is specific force (SF), that is, maximal isometric force divided by cross-sectional area, representing contractile quality. Although SF varies substantially between studies, the magnitude and cause of this variability remains puzzling. Here, we aimed to summarize and explore the cause of variability in SF between studies. A systematic search was conducted in Medline, Embase and Web of Science databases in June 2020, yielding 137 data sets from 61 publications which studied healthy, young adults. Five-fold differences in mean SF data were observed. Adjustments to the reported data for key methodological differences allowed between-study comparisons to be made. However, adjustment for fibre shape, swelling and sarcomere length failed to significantly reduce SF variance (I 2 = 96%). Interestingly, grouping papers based on shared authorship did reveal consistency within research groups. In addition, lower SF was found to be associated with higher phosphocreatine concentrations in the fibre activating solution and with Triton X-100 being used as a skinning agent. Although the analysis showed variance across the literature, the ratio of SF in single fibres containing myosin heavy chain isoforms IIA or I was found to be consistent across research groups. In conclusion, whilst the skinned fibre technique is reliable for studying in vitro force generation of single fibres, the composition of the solution used to activate fibres, which differs between research groups, is likely to heavily influence SF values., (© 2021 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

As the inherent ageing process affects every facet of biology, physiology could be considered as the study of the healthy human ageing process. Where biological health is affected by lifestyle, the continual and continuing interaction of this process with physical activity and other lifestyle choices determine whether the ageing trajectory is toward health or disease. The presentation of both these states is further modified in individuals by the interaction of inherent physiological heterogeneity and the heterogeneity associated with responses and adaptions to exercise. The range of heterogeneity in healthy physiology is circumscribed by the necessity to conform to that of the human species. Our hypothesis is that, when sufficient exercise is present, these multiple interactions appear to produce an ageing profile that, while functional ability is in decline, remains synchronous, coherent, and integrated throughout most of life. In the absence of sufficient physical activity, physiology over time is gradually deteriorating toward the production of a lifestyle disease. Here, the ageing process, interacting with individual physiological heterogeneity, probably determines the age of presentation of a disease as well as the order of presentation of subsequent diseases. In this article, we discuss this hypothesis and related concepts in the context of the trajectory of healthy and non-healthy human ageing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lazarus and Harridge.)

INTRODUCTION: Flight-related neck pain (FRNP) is a frequently reported musculoskeletal complaint among military helicopter aircrew. However, despite its prevalence and suspected causes, little is known of the underpinning pain mechanisms or the impact of neck pain on aircrews in-flight task performance. The biopsychosocial (BPS) approach to health, combined with the contemporary conceptualization of musculoskeletal pain, in which injury and pain are not necessarily synonymous, provides a relatively new holistic framework within which to consider the problem of FRNP in military helicopter aircrew. Combining these concepts, a new conceptual model is proposed to illustrate how biopsychosocial factors may influence pain perception, potentially affecting aircrews capacity to process information and, therefore, threatening in-flight task performance. Recommendations are made for considering the underlying pain mechanisms of FRNP to aid prognoses and guide the development of holistic evidence-based countermeasures for FRNP in military helicopter aircrew. Development of instruments able to measure psychosocial factors, such as self-efficacy and functional ability, validated in the military helicopter aircrew population, would assist this task. Vail RE, Harridge SDR, Hodkinson PD, Green NDC, Pavlou M. A novel biopsychosocial approach to neck pain in military helicopter aircrew . Aerosp Med Hum Perform. 2021; 92(5):333341.

Data analysis and knowledge discovery has become more and more important in biology and medicine with the increasing complexity of biological datasets, but the necessarily sophisticated programming skills and in-depth understanding of algorithms needed pose barriers to most biologists and clinicians to perform such research. We have developed a modular open-source software, SIMON, to facilitate the application of 180+ state-of-the-art machine-learning algorithms to high-dimensional biomedical data. With an easy-to-use graphical user interface, standardized pipelines, and automated approach for machine learning and other statistical analysis methods, SIMON helps to identify optimal algorithms and provides a resource that empowers non-technical and technical researchers to identify crucial patterns in biomedical data., Competing Interests: The authors declare no competing interests., (© 2020 The Authors.)

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent., Competing Interests: Dr. Anker reports grants and personal fees from Vifor Int, personal fees from Bayer, personal fees from Boehringer Ingelheim, personal fees from Servier, grants and personal fees from Abbott Vascular, personal fees from Cardiac Dimensions, personal fees from Actimed, personal fees from Astra Zeneca, personal fees from Amgen, personal fees from Bioventrix, personal fees from Janssen, personal fees from Respicardia, personal fees from V-Wave, personal fees from Brahms, personal fees from Cordio, personal fees from Occlutech, outside the submitted work. Dr. Ruiz reports grants from Longeveron Inc, outside the submitted work. Dr. Marzetti reports personal fees from Abbott, personal fees from Nestlè, personal fees from Nutricia, personal fees from ThermoFisher, outside the submitted work. All the other authors have nothing to disclose.

The age-associated reduction in muscle mass is well characterized; however, less is known regarding the mechanisms responsible for the decline in oxidative capacity also observed with advancing age. The purpose of the current study was therefore to compare mitochondrial gene expression and protein content between young and old recreationally active, and older highly active individuals. Muscle biopsies were obtained from the vastus lateralis of young males (YG: 22 ± 3 years) and older (OG: 67 ± 2 years) males not previously engaged in formal exercise and older male master cyclists (OT: 65 ± 5 years) who had undertaken cycling exercise for 32 ± 17 years. Comparison of gene expression between YG, OG, and OT groups revealed greater expression of mitochondrial-related genes, namely, electron transport chain (ETC) complexes II, III, and IV (p < .05) in OT compared with YG and OG. Gene expression of mitofusion (MFN)-1/2, mitochondrial fusion genes, was greater in OT compared with OG (p < .05). Similarly, protein content of ETC complexes I, II, and IV was significantly greater in OT compared with both YG and OG (p < .001). Protein content of peroxisome proliferator-activated receptor gamma, coactivator 1 α (PGC-1α), was greater in OT compared with YG and OG (p < .001). Our results suggest that the aging process per se is not associated with a decline in gene expression and protein content of ETC complexes. Mitochondrial-related gene expression and protein content are substantially greater in OT, suggesting that exercise-mediated increases in mitochondrial content can be maintained into later life., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Creatine dilution (D 3 -cr) is a technique for estimating total skeletal muscle mass (SMM) with practical utility, but has not been applied in athletic populations where body composition may differ to that in the normal population. This study aimed to assess the agreement between SMM derived from both D 3 -cr and that obtained from whole-body magnetic resonance imaging (MRI) in 15 male and 5 female national level kayakers (stature: 182.0 ± 13.1 and 170.0 ± 9.0 cm; body mass: 80.6 ± 9.9 and 66.4 ± 6.0 kg; V̇O 2 peak: 56.5 ± 7.0 and 49.6 ± 4.4 mL kg -1  min -1 , mean ± SD). SMM was determined following 60 mg of dosed D 3 -cr and analysis of expelled urine collected on four subsequent days for creatine, creatinine, D 3 -cr, and D 3 -creatinine using liquid chromatography/mass spectroscopy. SMM was then estimated by assuming a creatine pool size of 4.3 g/kg. During the same time period, a whole-body MRI was undertaken to derive SMM from the analysis of multiple slices taken across the body. A strong positive correlation (F = 74.32; R = 0.90; P < .0001) between the two methods was observed, but the D 3 -cr SMM was found to be significantly higher (43.3 ± 6.8 kg) when compared with MRI (36.3 ± 5.8 kg, P < .0001). However, the difference between the methods was removed when a higher intramuscular creatine pool (5.1 g/kg) was assumed. These data show that D 3 -cr has potential utility in athletes, as referenced against MRI, but show that assumptions regarding creatine pool size need to be carefully considered., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Type 2 Diabetes (T2D) is a major concern among Asian Indians, not least because many develop T2D at despite having a normal BMI (body mass index), and with relatively low body fat. Asian Indians are also generally considered to have relatively low skeletal muscle mass and strength, this has not been explored in the context of T2D. Aim: The present study aimed to compare skeletal muscle mass, function and contractile quality (strength/mass) between healthy controls, those with prediabetes (PD) as well as T2D middle-aged non-obese Asian Indians. Methods: Adult males between the age of 20-50 years, consisting of healthy controls ( n = 44), PD ( n = 125) and T2D ( n = 55) were studied. Skeletal muscle mass was measured using Dual X-ray Absorptiometry (DXA). Isometric and dynamic muscle function was measured using an isokinetic dynamometer (at 0, 60, 120, 180 degree/s). Muscle contractile quality was derived by dividing the peak muscle torque with the respective LMM (lower limb muscle mass). Fasting blood glucose (FBG) and insulin were used to derive insulin resistance (HOMA-IR). Results: The control group was on average 10 years younger than the other two groups ( p < 0.01). The LMM was similar across the three study groups. However, the age-adjusted mean muscle torque was significantly lower in both absolute and normalized isometric and isokinetic strength in PD and T2D groups compared to controls ( p ≤ 0.01), with the difference persisting even after adjusting for age and other covariates. However, there was no difference in muscle strength and contractile quality between the PD and T2D study groups. Conclusions: Muscle strength and contractile quality would appear to be sensitive and early indices of the trajectory toward diabetes in Asian Indians and more so than skeletal muscle mass. It is thus important to recognize the importance of functional measurements among this population when considering the role of muscle in diabetes. The data also would suggest that specific muscle conditioning (e.g., resistance training) might have efficacy in improving function as well as muscle mass, and thus aiding in the prevention of the trajectory toward the development of T2D., (Copyright © 2019 Sambashivaiah, Harridge, Sharma, Selvam, Rohatgi and Kurpad.)

Background: The rise in prevalence rates of Type 2 Diabetes among Indians is well recognized. The research focus has been primarily to understand the changes in insulin sensitivity and beta cell dysfunction among Indians with Type 2 Diabetes. However, no data are available on the role of peripheral tissue, in particular intramyocellular lipid (IMCL) content and its impact on glucose homeostasis among Indians with prediabetes., Methods: 28 male subjects (20-40 year) were studied. 13 with prediabetes (BMI ranging from 25.4 ± 2.9 kg/m 2 ) and 15 controls (BMI ranging from 24.6 ± 2.8 kg/m 2 ) were recruited. Body composition by dual energy X-ray absorptiometry (DXA), insulin sensitivity, insulin secretion rates were derived using the minimal model of C-peptide secretion and kinetics rates and skeletal muscle strength of the lower limb (quadriceps) was assessed using Isokinetic dynamometry. From muscle biopsy samples of the vastus lateralis, IMCL fat content (Oil red O staining) was determined., Results: The prediabetes group were older compared to controls (P < 0.01), but had similar BMI. The muscle to fat ratio, plasma Insulin, C peptide, HOMA-IR and HOMA % B were also comparable between the groups. IMCL fat content (%) was significantly higher in the prediabetes group compared to controls (7.0 ± 0.7% vs. 2.0 ± 0.3%, P < 0.01). This difference persisted even after controlling for age. Overall the IMCL fat content (%) was positively and significantly associated with HbA1c (r = 0.76, P < 0.01). HOMA-IR was significantly correlated with central (android, trunk) adiposity (kg) (r = 0.71, P < 0.01) but not with IMCL (%)., Conclusions: This is the first direct evidence of existence of significantly higher lipid levels within skeletal muscle cells among normal and overweight young Indians with prediabetes. However, there was no association between IMCL and HOMA-IR among the prediabetes group.

Remodelling of the immune system with age - immunosenescence - is a substantial contributor to poor health in older adults, with increasing risk of infections, cancer and chronic inflammatory disease contributing to age-related multi-morbidity. What is seldom considered when examining the immune response of an aged individual is that the immune system is profoundly influenced by physical activity. Habitual physical activity levels decline with age, with significant consequences for muscle mass and function. Skeletal muscle is a major immune regulatory organ and generates a range of proteins, termed myokines, which have anti-inflammatory and immunoprotective effects. Several studies indicate that maintaining physical activity has immune benefits in older adults, for example, it reduces the systemic inflammation associated with chronic age-related diseases. Here, we discuss how physical activity can prevent or ameliorate age-related multi-morbidity by boosting immune function, and we consider whether physical activity could improve immunotherapy outcomes in age-related conditions such as cancer.

INTRODUCTION: Physical conditioning may improve aircrew performance during exposure to high +G z acceleration, although few studies have directly assessed this. The present study investigated the effects of a 12-wk Aircrew Conditioning Programme (ACP) on markers of G tolerance. The ACP comprises aerobic and muscle strengthening exercise performed twice weekly and targets improved fitness and reduced injury risk. METHODS: There were 36 UK Royal Air Force and Royal Navy aircrew who volunteered; 17 performed the ACP (Ex) and 19 acted as a control group (Con). Centrifuge testing was performed before and after the intervention. Relaxed G tolerance (RGT) and straining G tolerance (SGT), which had the addition of muscle tensing, were assessed. G endurance was also determined via repeated simulated air combat maneuvers (SACMs). During these centrifuge runs a number of physiological variables were recorded. RESULTS: During the G profile to determine RGT, neither RGT, HR, nor blood pressure responses were affected by the ACP. During SGT profiles, a lower HR at a given +G z (+5.5 G z ) level following the ACP was observed (Ex: pre 146.0 ± 4.4, post 136.9 ± 5.6 bpm; Con: pre 148.0 ± 3.2, post 153.1 ± 3.3 bpm). BP was maintained and there was a tendency toward an improved SGT. The ACP increased the proportion of individuals completing the number of SACM profiles, although no meaningful differences were found between groups in other variables. CONCLUSION: Overall the ACP has no negative effect on RGT, reduced the physiological strain associated with a given level of +G z (during SGT), and tended to improve the ability to tolerate repeated G z exposure. Slungaard E, Pollock RD, Stevenson AT, Green NDC, Newham DJ, Harridge SDR. Aircrew conditioning programme impact on +Gz tolerance . Aerosp Med Hum Perform. 2019; 90(9):764-773.

VGLL proteins are transcriptional co-factors that bind TEAD family transcription factors to regulate events ranging from wing development in fly, to muscle fibre composition and immune function in mice. Here, we characterise Vgll3 in skeletal muscle. We found that mouse Vgll3 was expressed at low levels in healthy muscle but that its levels increased during hypertrophy or regeneration; in humans, VGLL3 was highly expressed in tissues from patients with various muscle diseases, such as in dystrophic muscle and alveolar rhabdomyosarcoma. Interaction proteomics revealed that VGLL3 bound TEAD1, TEAD3 and TEAD4 in myoblasts and/or myotubes. However, there was no interaction with proteins from major regulatory systems such as the Hippo kinase cascade, unlike what is found for the TEAD co-factors YAP (encoded by YAP1 ) and TAZ (encoded by WWTR1 ). Vgll3 overexpression reduced the activity of the Hippo negative-feedback loop, affecting expression of muscle-regulating genes including Myf5 , Pitx2 and Pitx3 , and genes encoding certain Wnts and IGFBPs. VGLL3 mainly repressed gene expression, regulating similar genes to those regulated by YAP and TAZ. siRNA-mediated Vgll3 knockdown suppressed myoblast proliferation, whereas Vgll3 overexpression strongly promoted myogenic differentiation. However, skeletal muscle was overtly normal in Vgll3 -null mice, presumably due to feedback signalling and/or redundancy. This work identifies VGLL3 as a transcriptional co-factor operating with the Hippo signal transduction network to control myogenesis., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

From 19th to 22nd November 2018, 26 researchers representing nine countries and a variety of academic disciplines met in Snekkersten, Denmark, to reach evidence-based consensus about physical activity and older adults. It was recognised that the term 'older adults' represents a highly heterogeneous population. It encompasses those that remain highly active and healthy throughout the life-course with a high intrinsic capacity to the very old and frail with low intrinsic capacity. The consensus is drawn from a wide range of research methodologies within epidemiology, medicine, physiology, neuroscience, psychology and sociology, recognising the strength and limitations of each of the methods. Much of the evidence presented in the statements is based on longitudinal associations from observational and randomised controlled intervention studies, as well as quantitative and qualitative social studies in relatively healthy community-dwelling older adults. Nevertheless, we also considered research with frail older adults and those with age-associated neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, and in a few cases molecular and cellular outcome measures from animal studies. The consensus statements distinguish between physical activity and exercise. Physical activity is used as an umbrella term that includes both structured and unstructured forms of leisure, transport, domestic and work-related activities. Physical activity entails body movement that increases energy expenditure relative to rest, and is often characterised in terms of intensity from light, to moderate to vigorous. Exercise is defined as a subset of structured physical activities that are more specifically designed to improve cardiorespiratory fitness, cognitive function, flexibility balance, strength and/or power. This statement presents the consensus on the effects of physical activity on older adults' fitness, health, cognitive functioning, functional capacity, engagement, motivation, psychological well-being and social inclusion. It also covers the consensus on physical activity implementation strategies. While it is recognised that adverse events can occur during exercise, the risk can be minimised by carefully choosing the type of activity undertaken and by consultation with the individual's physician when warranted, for example, when the individual is frail, has a number of co-morbidities, or has exercise-related symptoms, such as chest pain, heart arrhythmia or dizziness. The consensus was obtained through an iterative process that began with the presentation of the state-of-the-science in each domain, followed by group and plenary discussions. Ultimately, the participants reached agreement on the 30-item consensus statements., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Dietary inorganic nitrate prevents aspects of cardiac mitochondrial dysfunction induced by hypoxia, although the mechanism is not completely understood. In both heart and skeletal muscle, nitrate increases fatty acid oxidation capacity, and in the latter case, this involves up-regulation of peroxisome proliferator-activated receptor (PPAR)α expression. Here, we investigated whether dietary nitrate modifies mitochondrial function in the hypoxic heart in a PPARα-dependent manner. Wild-type (WT) mice and mice without PPARα ( Ppara -/- ) were given water containing 0.7 mM NaCl (control) or 0.7 mM NaNO 3 for 35 d. After 7 d, mice were exposed to normoxia or hypoxia (10% O 2 ) for the remainder of the study. Mitochondrial respiratory function and metabolism were assessed in saponin-permeabilized cardiac muscle fibers. Environmental hypoxia suppressed mass-specific mitochondrial respiration and additionally lowered the proportion of respiration supported by fatty acid oxidation by 18% ( P < 0.001). This switch away from fatty acid oxidation was reversed by nitrate treatment in hypoxic WT but not Ppara mice. Our findings indicate that PPARα plays a key role in mediating cardiac metabolic remodeling in response to both hypoxia and dietary nitrate supplementation.-Horscroft, J. A., O'Brien, K. A., Clark, A. D., Lindsay, R. T., Steel, A. S., Procter, N. E. K., Devaux, J., Frenneaux, M., Harridge, S. D. R., Murray, A. J. Inorganic nitrate, hypoxia, and the regulation of cardiac mitochondrial respiration-probing the role of PPARα.-/- mice, indicating a PPARα-dependent effect. Hypoxia increased hexokinase activity by 33% in all mice, whereas lactate dehydrogenase activity increased by 71% in hypoxic WT but not Ppara -/- mice. Our findings indicate that PPARα plays a key role in mediating cardiac metabolic remodeling in response to both hypoxia and dietary nitrate supplementation.-Horscroft, J. A., O'Brien, K. A., Clark, A. D., Lindsay, R. T., Steel, A. S., Procter, N. E. K., Devaux, J., Frenneaux, M., Harridge, S. D. R., Murray, A. J. Inorganic nitrate, hypoxia, and the regulation of cardiac mitochondrial respiration-probing the role of PPARα.

Hypoxia is a feature of many disease states where convective oxygen delivery is impaired, and is known to suppress oxidative metabolism. Acclimation to hypoxia thus requires metabolic remodelling, however hypoxia tolerance may be aided by dietary nitrate supplementation. Nitrate improves tissue oxygenation and has been shown to modulate skeletal muscle tissue metabolism via transcriptional changes, including through the activation of peroxisome proliferator-activated receptor alpha (PPARα), a master regulator of fat metabolism. Here we investigated whether nitrate supplementation protects skeletal muscle mitochondrial function in hypoxia and whether PPARα is required for this effect. Wild-type and PPARα knockout (PPARα -/- ) mice were supplemented with sodium nitrate via the drinking water or sodium chloride as control, and exposed to environmental hypoxia (10% O 2 ) or normoxia for 4 weeks. Hypoxia suppressed mitochondrial respiratory function in mouse soleus, an effect partially alleviated through nitrate supplementation, but occurring independently of PPARα. Specifically, hypoxia resulted in 26% lower mass specific fatty acid-supported LEAK respiration and 23% lower pyruvate-supported oxidative phosphorylation capacity. Hypoxia also resulted in 24% lower citrate synthase activity in mouse soleus, possibly indicating a loss of mitochondrial content. These changes were not seen, however, in hypoxic mice when supplemented with dietary nitrate, indicating a nitrate dependent preservation of mitochondrial function. Moreover, this was observed in both wild-type and PPARα -/- mice. Our results support the notion that nitrate supplementation can aid hypoxia tolerance and indicate that nitrate can exert effects independently of PPARα., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Loss of skeletal muscle mass and muscle weakness are common in a variety of clinical conditions with both wasting and weakness associated with an impairment of physical function. β-Hydroxy-β-methylbutyrate (HMB) is a nutrition supplement that has been shown to favorably influence muscle protein turnover and thus potentially plays a role in ameliorating skeletal muscle wasting and weakness., Objectives: The aim of this study was to investigate the efficacy of HMB alone, or supplements containing HMB, on skeletal muscle mass and physical function in a variety of clinical conditions characterized by loss of skeletal muscle mass and weakness., Methods: A systematic review and meta-analysis of randomized controlled trials reporting outcomes of muscle mass, strength, and physical function was performed. Two reviewers independently performed screening, data extraction, and risk-of-bias assessment. Outcome data were synthesized through meta-analysis with the use of a random-effects model and data presented as standardized mean differences (SMDs)., Results: Fifteen randomized controlled trials were included, involving 2137 patients. Meta-analysis revealed some evidence to support the effect of HMB alone, or supplements containing HMB, on increasing skeletal muscle mass (SMD = 0.25; 95% CI: -0.00, 0.50; z = 1.93; P = 0.05; I2 = 58%) and strong evidence to support improving muscle strength (SMD = 0.31; 95% CI: 0.12, 0.50; z = 3.25; P = 0.001; I2 = 0%). Effect sizes were small. No effect on bodyweight (SMD = 0.16; 95% CI: -0.08, 0.41; z = 1.34; P = 0.18; I2 = 67%) or any other outcome was found. No study was considered to have low risk of bias in all categories., Conclusion: HMB, and supplements containing HMB, increased muscle mass and strength in a variety of clinical conditions, although the effect size was small. Given the bias associated with many of the included studies, further high-quality studies should be undertaken to enable interpretation and translation into clinical practice. The trial was registered on PROSPERO as CRD42017058517., (Copyright © American Society for Nutrition 2019.)

This brief review focuses on the relationships and interactions between human ageing, exercise and physiological function. It explores the importance of the selection of participants for ageing research, the strengths and deficiencies of both cross-sectional and longitudinal studies, and the complexities involved in understanding time-dependent, lifelong physiological processes. As being physically active is crucial to fostering healthy ageing, it is essential that participants in health and ageing research are defined in terms of their physical activity/exercise status as well as other lifestyle factors. Comparisons of exercisers with non-exercisers has suggested that there is a mosaic of regulation of ageing both within and across physiological systems. We suggest that four broad categories exist which encompass this regulation. These are (i) systems and indices that are age dependent, but activity independent; (ii) systems that are age dependent, but also malleable by exercise; (iii) systems that are not age affected but are altered by exercise; and (iv) systems that are neither age nor activity dependent. We briefly explore the concept of a mosaic of regulation in a selection of physiological systems. These include skeletal muscle, the immune and endocrine systems, gastrointestinal as well as cognitive function. We go onto examine how these categories might fit within the broad framework of understanding the physiology of human ageing., (© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.)

At high altitude oxygen delivery to the tissues is impaired leading to oxygen insufficiency (hypoxia). Acclimatisation requires adjustment to tissue metabolism, the details of which remain incompletely understood. Here, metabolic responses to progressive environmental hypoxia were assessed through metabolomic and lipidomic profiling of human plasma taken from 198 human participants before and during an ascent to Everest Base Camp (5,300 m). Aqueous and lipid fractions of plasma were separated and analysed using proton ( 1 H)-nuclear magnetic resonance spectroscopy and direct infusion mass spectrometry, respectively. Bayesian robust hierarchical regression revealed decreasing isoleucine with ascent alongside increasing lactate and decreasing glucose, which may point towards increased glycolytic rate. Changes in the lipid profile with ascent included a decrease in triglycerides (48-50 carbons) associated with de novo lipogenesis, alongside increases in circulating levels of the most abundant free fatty acids (palmitic, linoleic and oleic acids). Together, this may be indicative of fat store mobilisation. This study provides the first broad metabolomic account of progressive exposure to environmental hypobaric hypoxia in healthy humans. Decreased isoleucine is of particular interest as a potential contributor to muscle catabolism observed with exposure to hypoxia at altitude. Substantial changes in lipid metabolism may represent important metabolic responses to sub-acute exposure to environmental hypoxia.

Background: Exercise training improves cardiometabolic outcomes in 'mean terms', but little information is available in children about the impact of the frequency/week and the wide inter-individual variability to exercise training reported in adults., Objectives: We compared the effects of resistance training (RT) and high-intensity interval training (HIT), and 'high' and 'low' frequency of training/week, for their effectiveness in decreasing insulin resistance (IR) levels in schoolchildren. A second aim was to decscribe and compare the prevalence of non-responders (NRs) between the different frequencies of training protocol., Methods: Fifty-three schoolchildren with IR were randomly assigned into four groups: RT at high frequency (three times/week), HIT at high frequency, RT at a low frequency (two times/week) and HIT at low frequency. The intervention lasted 6 weeks. Blood samples and body composition, blood pressure and performance measurements were taken before and after the intervention., Results: The prevalence of NRs was similar between the RTHF and HITHF (25.0% vs. 25.0%, P > 0.05) and RTLF and HITLF groups (20.0% vs. 46.6%, P = 0.174) for decreasing homeostasis model assessment of IR. However, significant differences in the prevalence of NRs were detected between RTHF and HITHF groups in fasting glucose (FGL) (18.7% vs. 58.3%, P < 0.031)., Conclusions: Both RT and HIT improves the glucose control parameters in schoolchildren over 6 weeks, but only HIT is independent of a high or low frequency of training/week. The prevalence of NRs is similar for decreasing homeostasis model assessment of IR comparing each exercise mode in high vs. low frequency/week. However, both high- and low-frequency RT and HIT results in differences in the prevalence of NRs for FGL and other cardiometabolic and performance outcomes., (© 2018 World Obesity Federation.)

Arguably the best available depictions of the global physiological changes produced by age are the profiles of world record performance times in swimming, athletics, and cycling, depicting the trajectory of decline in maximal integrated physiological performance capability. The curves suggest that the aging process produces a synchronized, controlled decrease in physiological performance over the human lifespan. The shape of the performance profile by age is essentially independent of discipline, distance, or phenotype. Importantly, the specific times of performance are not the driving force in the production of the shape of the declining performance profile. We suggest that in these highly trained individuals the shape of the curve is generated by the aging process operating on a physiology optimized for any given age. We hypothesize that with adequate training this same profile and trajectory, but with lower performance times, would be generated by all individuals who engage in sufficient physical activity/exercise. Unlike performance, data obtained from examining individual physiological systems or tissues do not give information on the unceasing and changing global integrating functions of the aging process. However, these data do give valuable information about the integrity of physiological systems at a particular age and allow a direct comparison to be made between the effects of inactivity and physical activity/exercise. Being physically active has been shown to have global protective effects on physiological systems and thus facilitates the aging process by maintaining physiological integrity. There is emerging evidence which suggests that physiological regulation of aging may be multi-compartmentalized. We do not advocate exercise as a panacea, but all the evidence indicates that being physically active and exercising is far superior to any other alternative for achieving optimal aging.

Introduction: The prevalence of flight-related neck pain in all Royal Air Force (RAF) aircrew is 66% and 70% in UK fast-jet aircrew. The RAF Aircrew Conditioning Programme (ACP) has been designed to enhance pilot performance through reducing fatigue and strain injuries, particularly to the neck. Content validity of the ACP was assessed to determine the appropriateness for delivery to aircrew., Methods: Six international medical experts reviewed level two of the ACP, which is delivered to student aircrew who have completed basic instruction in cervical spine stability, core stability and initial technique instruction for strength training. Content validity on overall exercise approach (5 items) and specific exercise session (24 items) was rated on a 4-point Likert-type ordinal scale for Relevance and Simplicity. Four reviewers had experience of delivering an exercise program to aircrew. The item-content validity index (I-CVI) was the proportion of experts rating an item/exercise as acceptable (score 3-4) while protocol-CVI was the average I-CVI across items., Results: Of the suggested exercise sessions, 20 reached an excellent I-CVI (1.00) for Relevance (4 reached acceptable I-CVI (0.83)), and 21 reached an excellent I-CVI (1.00) for Simplicity (3 reached acceptable I-CVI (0.83)). Protocol-CVI for the ACP was excellent for Relevance (0.90) and good for Simplicity (0.83). The need for sufficient supervision during the exercises was recommended for safe exercise execution and to maintain adherence., Conclusion: The ACP demonstrated excellent relevance for the target population. The aircrew require additional supervision with the more complex neck exercises to enhance simplicity with the ACP.Slungaard E, Green NDC, Newham DJ, Harridge SDR. Content validity of level two of the Royal Air Force Aircrew Conditioning Program. Aerosp Med Hum Perform. 2018; 89(10):896-904.

Sedentary time (ST) and moderate-to-vigorous physical activity (MVPA) are associated with cardiometabolic health. Cardiorespiratory fitness (CRF) is also implicated but often overlooked in health recommendations. This study assessed the relationships between ST, MVPA, CRF, and cardiometabolic health in highly active older individuals. 125 healthy amateur cyclists aged 55 to 79 years had their ST and MVPA levels assessed by actigraphy over a 7-day period. CRF was assessed using a maximal effort cycle ergometry test to determine VO 2max with results normalized to both body mass and fat-free mass measured by DXA. Markers of cardiometabolic risk (blood glucose, triglycerides, cholesterol, HDL, LDL, Insulin, HOMA IR, blood pressure, and body fat) were assessed and used to determine cumulative cardiometabolic risk. Multiple linear regression was used to assess ST, MVPA, and CRF associations with cardiometabolic health with the relationship between activity levels and CRF determined. CRF was associated with training volume (P = .003), but not ST or MVPA. A high CRF was associated with lower cumulative cardiometabolic risk, body fat percentage, triglyceride, and HDL levels (P < .05 in all cases). MVPA was negatively associated with body fat percentage, while ST was not associated with any marker of cardiometabolic risk when adjusting for activity levels. An association between CRF and cardiometabolic risk even in a group of older individuals with high fitness levels highlights the importance that CRF may have in maintaining health., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In this study, results are reported from the analyses of vastus lateralis muscle biopsy samples obtained from a subset (n = 90) of 125 previously phenotyped, highly active male and female cyclists aged 55-79 years in regard to age. We then subsequently attempted to uncover associations between the findings in muscle and in vivo physiological functions. Muscle fibre type and composition (ATPase histochemistry), size (morphometry), capillary density (immunohistochemistry) and mitochondrial protein content (Western blot) in relation to age were determined in the biopsy specimens. Aside from an age-related change in capillary density in males (r = -.299; p = .02), no other parameter measured in the muscle samples showed an association with age. However, in males type I fibres and capillarity (p < .05) were significantly associated with training volume, maximal oxygen uptake, oxygen uptake kinetics and ventilatory threshold. In females, the only association observed was between capillarity and training volume (p < .05). In males, both type II fibre proportion and area (p < .05) were associated with peak power during sprint cycling and with maximal rate of torque development during a maximal voluntary isometric contraction. Mitochondrial protein content was not associated with any cardiorespiratory parameter in either males or females (p > .05). We conclude in this highly active cohort, selected to mitigate most of the effects of inactivity, that there is little evidence of age-related changes in the properties of VL muscle across the age range studied. By contrast, some of these muscle characteristics were correlated with in vivo physiological indices., (© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

An insufficient supply of oxygen to the tissues (hypoxia), as is experienced upon high-altitude exposure, elicits physiological acclimatization mechanisms alongside metabolic remodeling. Details of the integrative adaptive processes in response to chronic hypobaric hypoxic exposure remain to be sufficiently investigated. In this small applied field study, subjects (n = 5, male, age 28-54 years) undertook a 40 week Antarctica expedition in the winter months, which included 24 weeks residing above 2500 m. Measurements taken pre- and postexpedition revealed alterations to glucose and fatty acid resonances within the serum metabolic profile, a 7.8 (±3.6)% increase in respiratory exchange ratio measured during incremental exercise (area under curve, P > 0.01, mean ± SD) and a 2.1(±0.8) % decrease in fat tissue (P < 0.05) postexpedition. This was accompanied by an 11.6 (±1.9) % increase (P > 0.001) in VO 2 max corrected to % lean mass postexpedition. In addition, spine bone mineral density and lung function measures were identified as novel parameters of interest. This study provides, an in-depth characterization of the responses to chronic hypobaric hypoxic exposure in one of the most hostile environments on Earth., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)