Many countries face an unprecedented challenge in aging demographics. This has led to an exponential growth in research on aging, which, coupled to a massive financial influx of funding in the private and public sectors, has resulted in seminal insights into the underpinnings of this biological process. However, critical validation in humans has been hampered by the limited translatability of results obtained in model organisms, additionally confined by the need for extremely time-consuming clinical studies in the ostensible absence of robust biomarkers that would allow monitoring in shorter time frames. In the future, molecular parameters might hold great promise in this regard. In contrast, biomarkers centered on function, resilience, and frailty are available at the present time, with proven predictive value for morbidity and mortality. In this review, the current knowledge of molecular and physiological aspects of human aging, potential antiaging strategies, and the basis, evidence, and potential application of physiological biomarkers in human aging are discussed.

The majority of exercise physiology research has been conducted in males, resulting in a skewed biological representation of how exercise impacts the physiological system. Extrapolating male-centric physiological findings to females is not universally appropriate and may even be detrimental. Thus, addressing this imbalance and taking into consideration sex as a biological variable is mandatory for optimization of precision exercise interventions and/or regimens. Our present analysis focused on establishing multiomic profiles in young, exercise-naïve males (n = 23) and females (n = 17) at rest and following acute exercise. Sex differences were characterized at baseline and following exercise using skeletal muscle and extracellular vesicle transcriptomics, whole blood methylomics, and serum metabolomics. Sex-by-time analysis of the acute exercise response revealed notable overlap, and divergent molecular responses between males and females. An exploratory comparison of two combined exercise regimens [high-intensity tactical training (HITT) and traditional (TRAD)] was then performed using singular value decomposition, revealing latent data structures that suggest a complex dose-by-sex interaction response to exercise. These findings lay the groundwork for an understanding of key differences in responses to acute exercise exposure between sexes. This may be leveraged in designing optimal training strategies, understanding common and divergent molecular interplay guiding exercise responses, and elucidating the role of sex hormones and/or other sex-specific attributes in responses to acute and chronic exercise.NEW & NOTEWORTHY This study examined methylomics, transcriptomics, and metabolomics in circulation and/or skeletal muscle of young, healthy, exercise-naïve males and females before and after exposure to either traditional combined exercise (TRAD) and high-intensity tactical training (HITT). Across 40 young adults, we found an overlapping yet considerably sex-divergent response in the molecular mechanisms activated by exercise. These findings may provide insight into optimal training strategies for adaptation when considering sex as a biological variable.

Low-carbohydrate, high-fat diets enhance lipid metabolism and decrease reliance on glucose oxidation in athletes, but the associated gene expression patterns remain unclear. The purpose of this study was to determine whether coordinated molecular pathways in skeletal muscle may be revealed by differential expression of genes driven by dietary profile, exercise, and/or their interaction. We investigated the skeletal muscle transcriptome in elite ultra-endurance athletes habitually (~ 20 months) consuming a high-carbohydrate, low-fat (HC, n = 10, 33 ± 6y, VO2max = 63.4 ± 6.2 mL O2•kg-1•min-1) or low-carbohydrate, high-fat (LC, n = 10, 34 ± 7y, VO2max = 64.7 ± 3.7 mL O2•kg-1•min-1) diet. Skeletal muscle gene expression was measured at baseline (BL), immediately-post (H0), and 2 h (H2) after 3 h submaximal treadmill running. Diet induced a coordinated but divergent expression pattern at BL where LC had higher expression of genes associated with lipid metabolism. Exercise resulted in a dynamic but uniform gene response, with no major differences between groups (H0). At H2, gene expression patterns were associated with differential pathway activity, including inflammation/immunity, suggesting a diet-specific influence on early muscle recovery. These results indicate that low-carbohydrate, high-fat diets lead to differences in resting and exercise-induced skeletal muscle gene expression patterns, underlying our previous findings of differential fuel utilization in elite ultra-endurance athletes.

The use of a fixed theoretical-proportional-factor (TPF15) is one of the indirect highest-oxygen-consumptions (HOC) assessment methods, but it may not accurately reflect the physiological differences across various sports (cycling-triathlon-running-football-multisport). The aim of this study is to evaluate the variability of TPF across different sports, proposing a series of sport-specific new TPF values for more accurate HOC estimation.

A sample of 340 adults (26.01 ± 7.18 years) performed a maximal-incremental-test using sport-specific-ergometers. HOC was considered for cycling V ˙ O 2peak , whereas for the other investigated sports it was consideredV ˙ O 2max . HOC was directly measured using a gas-analyzer, and TPF values were calculated using heart rate (HR): the ratio of HRmax/HRrest multiplied for the measured values of HOC. A one-way ANOVA was used to measure differences and Bland-Altman plots were constructed to compare predicted and actual V ˙ O 2max /V ˙ O 2peak .

Actual HOC was significantly greater than those predicted by the fixed TPF15 (P < 0.001). Sport-specific new TPF values ranged from 16.55 in multisport to 20.15 in cycling, consistently exceeding the old fixed TPF15, and predicting therefore better HOC. The new TPF exhibited a closer agreement with the directly measuredV ˙ O 2max /V ˙ O 2peak  compared to the TPF15. Furthermore, the new TPF reduced the typical-measurement-error (14.94-17.78%) compared to TPF15 (15.63-24.13%).

This study suggests that new TPF values predictV ˙ O 2max /V ˙ O 2peak  with higher accuracy compared to the traditional method. The use of HRmax and HRrest values allows to customize training programs for different athletes. Future research should focus on validating these findings across larger populations of athletes.

Sarcopenia is an age-related muscle atrophy syndrome characterized by the loss of muscle strength and mass. Although many agents have been used to treat sarcopenia, there are no successful treatments to date. In this study, we identified Danshensu sodium salt (DSS) as a substantial suppressive agent of muscle atrophy. We used a D-galactose (DG)-induced aging-acceleration model, both in vivo and in vitro, to confirm the effect of DSS on sarcopenia. DSS inhibits the expression of muscle atrophy-related factors (MuRF1, MAFbx, myostatin, and FoxO3a) in DG-induced mouse C2C12 and human skeletal muscle cells. Additionally, DSS restored the diameter of reduced C2C12 myotubes. Next, we demonstrated that DSS stimulates AMPK and PGC1α through CaMKII. DSS inhibits the translocation of FoxO3a into the nucleus, thus inhibiting muscle atrophy in a calcium-dependent manner. DSS initiated the protein-protein interaction between FoxO3a and PGC1α. The reduction of the PGC1α-FoxO3a interaction by DG was restored by DSS. Also, DSS suppressed increased intracellular reactive oxygen species (ROS) by DG. In animal models, DSS administration improved mouse muscle mass and physical performance (grip strength and hanging test) under DG-induced accelerated aging conditions. These findings demonstrated that DSS attenuates muscle atrophy by inhibiting the expression of muscle atrophy-related factors. Therefore, DSS may be a potential therapeutic agent for the treatment of sarcopenia.

We previously observed a range of whole muscle and individual slow and fast myofiber size responses (mean: +4 to -24%) in quadriceps (vastus lateralis) and triceps surae (soleus) muscles of individuals undergoing 70 days of simulated microgravity with or without the NASA SPRINT exercise countermeasures program. The purpose of the current investigation was to further explore, in these same individuals, the content of myonuclei and satellite cells, both of which are key regulators of skeletal muscle mass. Individuals completed 6° head-down-tilt bedrest (BR, n = 9), bedrest with resistance and aerobic exercise (BRE, n = 9), or bedrest with resistance and aerobic exercise and low-dose testosterone (BRE + T, n = 8). The number of myonuclei and satellite cells associated with each slow [myosin heavy chain (MHC) I] and fast (MHC IIa) myofiber in the vastus lateralis was not changed (P > 0.05) pre- to postbedrest within the BR, BRE, or BRE + T groups. Similarly, in the soleus, the number of myonuclei associated with each slow and fast myofiber, and the number of satellite cells associated with each slow myofiber were not changed (P > 0.05) pre- to postbedrest within the BR, BRE, or BRE + T groups. It appears that even with relatively large perturbations in muscle mass over a few months of simulated microgravity, or with partially or completely effective exercise countermeasures, human skeletal muscle tightly regulates the abundance of myonuclei and satellite cells. Thus, exercise countermeasures efficacy for skeletal muscle atrophy appears to be independent of myonuclei and satellite cell abundance.NEW & NOTEWORTHY This study showed that after 70 days of simulated microgravity, human skeletal muscle does not alter the number of nuclei or satellite cells associated with slow or fast myofibers in the two muscle groups most negatively influenced by microgravity exposure [i.e., quadriceps (vastus lateralis) and triceps surae (soleus)]. Furthermore, the efficacy of exercise countermeasures for maintaining the mass of these muscles does not appear to be related to the myocellular content of nuclei or satellite cells.

Chronic, low-grade inflammation increases with aging, contributing to functional declines and diseases that reduce healthspan. Growing evidence suggests that transcripts from repetitive elements (RE) in the genome contribute to this "inflammaging" by stimulating innate immune activation, but evidence of RE-associated inflammation with aging in humans is limited. Here, we present transcriptomic and clinical data showing that RE transcript levels are positively related to gene expression of innate immune sensors, and to serum interleukin 6 (a marker of systemic inflammation), in a large group of middle-aged and older adults. We also: (1) use transcriptomics and whole-genome bisulfite (methylation) sequencing to show that many RE may be hypomethylated with aging, and that aerobic exercise, a healthspan-extending intervention, reduces RE transcript levels and increases RE methylation in older adults; and (2) extend our findings in a secondary dataset demonstrating age-related changes in RE chromatin accessibility. Collectively, our data support the idea that age-related RE transcript accumulation may play a role in inflammaging in humans, and that RE dysregulation with aging may be due in part to upstream epigenetic changes.

This study was designed to evaluate the effects of multiple cold-water immersions performed daily during the preseason period on biochemical, clinical, and neuromuscular aspects of muscle damage of soccer players.

This two-arm, prospectively registered, randomized controlled trial, blinded to statistician and assessors, was conducted at professional football club facilities. Twenty-three under-20 semi-professionals male soccer players were randomly allocated into cold water immersion group (bathtub with water and ice at 10 °C ± 1 °C for 10 min) or control group (rest for 10 min), every day, after training sessions during a preseason. Primary outcome was change in creatine kinase (CK) concentration, and secondary outcomes were changes in vertical jump performance, strength and perception of recovery at baseline (T0) and after protocol training (T1).

Analysis of Covariance (ANCOVA) showed a statistically significant time-group interactions for CK concentration, with an average reduction of 280.39 U/L (CI95% = -519.14, -41.64; d = 0.55) in the cold-water immersion compared to the control group. No differences between groups were observed in any other measures.

Multiple cold-water immersions at 10 °C for 10 min decreases CK concentration but does not change any clinical and neuromuscular markers of muscle damage in soccer players during a 9-day preseason.

Trimethylamine-N-oxide (TMAO) is a gut-derived metabolite associated with cardiovascular disease (CVD). In preclinical and observational studies, resveratrol and exercise training have been suggested as potential strategies to reduce the systemic levels of TMAO. However, evidence from experimental studies in humans remains unknown. This project examined the dose-dependent effects of a combined resveratrol intervention with exercise training on circulating TMAO and other related metabolite signatures in older adults with high CVD risk.

Forty-one older adults [mean (±SD) age of 72.1 (6.8) years] participated in a 12-week supervised center-based, multi-component exercise training intervention [2×/week; 80 min/session] and were randomized to one of two resveratrol dosages [Low: 500 vs. High:1000 mg/day] or a cellulose-based placebo. Serum/plasma were collected at baseline and post-intervention and evaluated for TMAO and associated analytes.

After the 12-week intervention, TMAO concentration increased over time, regardless of treatment [mean (±SD) Placebo: 11262 (±3970); Low:13252 (±1193); High: 12661(±3359) AUC; p = 0.04]. Each resveratrol dose produced different changes in metabolite signatures. Low dose resveratrol upregulated metabolites associated with bile acids biosynthesis (i.e., glycochenodeoxycholic acid, glycoursodeoxycholic acid, and glycocholic acid). High dose resveratrol modulated metabolites enriched for glycolysis, and pyruvate, propanoate, β-alanine, and tryptophan metabolism. Different communities tightly correlated to TMAO and resveratrol metabolites were associated with the lipid and vascular inflammatory clinical markers [|r| > 0.4, p < 0.05].

These findings suggest a distinct dose-dependent adaptation response to resveratrol supplementation on circulating metabolite signatures but not on TMAO among high-risk CVD older adults when combined with an exercise training intervention.

Resistance training (RT) remains the most effective treatment for age-related declines in muscle mass. However, many older adults experience attenuated muscle hypertrophy in response to RT when compared with younger adults. This may be attributed to underlying molecular processes that are dysregulated by aging and exacerbated by improperly prescribed RT weekly volume, intensity, and/or frequency doses. MicroRNAs (miRNAs) are key epigenetic regulators that impact signaling pathways and protein expression within cells, are dynamic and responsive to exercise stimuli, and are often dysregulated in diseases. In this study, we used untargeted miRNA-seq to examine miRNA in skeletal muscle and serum-derived exosomes of older adults (n = 18, 11 M/7 F, 66 ± 1 yr) who underwent three times per wk RT for 30 wk [e.g., high intensity three times/wk (HHH, n = 9) or alternating high-low-high (HLH) intensity (n = 9)], after a standardized 4-wk washin. Within each tissue, miRNAs were clustered into modules based on pairwise correlation using weighted gene correlation network analysis (WGCNA). Modules were tested for association with the magnitude of RT-induced thigh lean mass (TLM) change [as measured by dual-energy X-ray absorptiometry (DXA)]. Although no modules were unique to training dose, we identified miRNA modules in skeletal muscle associated with TLM gains irrespective of exercise dose. Using miRNA-target interactions, we analyzed key miRNAs in significant modules for their potential regulatory involvement in biological pathways. Findings point toward potential miRNAs that may be informative biomarkers and could also be evaluated as potential therapeutic targets as an adjuvant to RT to maximize skeletal muscle mass accrual in older adults.NEW & NOTEWORTHY In this work, we identified a set of microRNAs correlated with thigh lean mass gains in a group of older adults. To our knowledge, this is the first time these microRNAs have been identified as novel predictive biomarkers correlating with lean mass gains in aging adults. As biomarkers, these may help interventionalists identify older individuals that are positively responding to an exercise intervention.

Exercise scientists (especially in the field of biomolecular research) frequently classify athletic cohorts into categories such as endurance, strength, or mixed, and create a practical framework for studying diverse athletic populations between seemingly similar groups. It is crucial to recognize the limitations and complexities of these classifications, as they may oversimplify the multidimensional characteristics of each sport. If so, the validity of studies dealing with such approaches may become compromised and the comparability across different studies challenging or impossible. This perspective critically examines and highlights the issues associated with current sports typologies, critiques existing sports classification systems, and emphasizes the imperative for a universally accepted classification model to enhance the quality of biomolecular research of sports in the future.

We previously observed lifelong endurance exercise (LLE) influenced quadriceps whole-muscle and myofiber size in a fiber-type and sex-specific manner. The current follow-up exploratory investigation examined myofiber size regulators and myofiber size distribution in vastus lateralis biopsies from these same LLE men (n = 21, 74 ± 1 years) and women (n = 7, 72 ± 2 years) as well as old, healthy nonexercisers (OH; men: n = 10, 75 ± 1 years; women: n = 10, 75 ± 1 years) and young exercisers (YE; men: n = 10, 25 ± 1 years; women: n = 10, 25 ± 1 years). LLE exercised ~5 days/week, ~7 h/week for the previous 52 ± 1 years. Slow (myosin heavy chain (MHC) I) and fast (MHC IIa) myofiber nuclei/fiber, myonuclear domain, satellite cells/fiber, and satellite cell density were not influenced (p > 0.05) by LLE in men and women. The aging groups had ~50%-60% higher proportion of large (>7000 μm2) and small (<3000 μm2) myofibers (OH; men: 44%, women: 48%, LLE; men: 42%, women: 42%, YE; men: 27%, women: 29%). LLE men had triple the proportion of large slow fibers (LLE: 21%, YE: 7%, OH: 7%), while LLE women had more small slow fibers (LLE: 15%, YE: 8%, OH: 9%). LLE reduced by ~50% the proportion of small fast (MHC II containing) fibers in the aging men (OH: 14%, LLE: 7%) and women (OH: 35%, LLE: 18%). These data, coupled with previous findings, suggest that myonuclei and satellite cell content are uninfluenced by lifelong endurance exercise in men ~60-90 years, and this now also extends to septuagenarian lifelong endurance exercise women. Additionally, lifelong endurance exercise appears to influence the relative abundance of small and large myofibers (fast and slow) differently between men and women.

The field of exercise physiology has undergone significant technological advancements since the pioneering works of exercise physiologists in the early to mid-20th century. Historically, the ability to detect metabolites in biofluids from exercising participants was limited to single-metabolite analyses. However, the rise of metabolomics, a discipline focused on the comprehensive analysis of metabolites within a biological system, has facilitated a more intricate understanding of metabolic pathways and networks in exercise. This review explores some of the pivotal technological and bioinformatic advancements that have propelled metabolomics to the forefront of exercise physiology research. Metabolomics offers a unique 'fingerprint' of cellular activity, offering a broader spectrum than traditional single-metabolite assays. Techniques, including mass spectrometry and nuclear magnetic resonance spectroscopy, have significantly improved the speed and sensitivity of metabolite analysis. Nonetheless, challenges persist, including study design and data interpretation issues. This review aims to serve as a guide for exercise physiologists to facilitate better research design, data analysis and interpretation within metabolomics. The potential of metabolomics in bridging the gap between genotype and phenotype is emphasised, underscoring the critical importance of careful study design and the selection of appropriate metabolomics techniques. Furthermore, the paper highlights the need to deeply understand the broader scientific context to discern meaningful metabolic changes. The emerging field of fluxomics, which seeks to quantify metabolic reaction rates, is also introduced as a promising avenue for future research.

A sedentary lifestyle and Olympic participation are contrary risk factors for global mortality and incidence of cancer and cardiovascular disease. Extracellular vesicle miRNAs have been described to respond to exercise. No molecular characterization of young male sedentary people versus athletes is available; so, our aim was to identify the extracellular vesicle miRNA profile of chronically trained young endurance and resistance male athletes compared to their sedentary counterparts. A descriptive case-control design was used with 16 sedentary young men, 16 Olympic male endurance athletes, and 16 Olympic male resistance athletes. Next-generation sequencing and RT-qPCR and external and internal validation were performed in order to analyze extracellular vesicle miRNA profiles. Endurance and resistance athletes had significant lower levels of miR-16-5p, miR-19a-3p, and miR-451a compared to sedentary people. Taking all together, exercise-trained miRNA profile in extracellular vesicles provides a differential signature of athletes irrespective of the type of exercise compared to sedentary people. Besides, miR-25-3p levels were specifically lower in endurance athletes which defines its role as a specific responder in this type of athletes. In silico analysis of this profile suggests a role in adaptive energy metabolism in this context that needs to be experimentally validated. Therefore, this study provides for the first time basal levels of circulating miRNA in extracellular vesicles emerge as relevant players in intertissue communication in response to chronic exercise exposure in young elite male athletes.

Engagement in physical activity, across various sports, promotes a diverse microbiota in active individuals. This study examines the gut microbiota of Colombian athletes, specifically weightlifters (n = 16) and road cyclists (n = 13), compared to non-athletes (n = 15). Using Kruskal-Wallis tests, the physical activity level of a group of non-athletic individuals and the sports experience of a group of professional athletes is analyzed. The median age of participants is 24 years, comprising 25 men and 19 women. The microbiota is collected using fecal samples. Participants provided these samples during their pre-competitive stage, specifically during the concentration phase occurring two weeks prior to national competitions. This timing is chosen to capture the microbial composition during a period of heightened physical preparation. Questionnaire responses and microbial composition assessments identify disparities among groups. Microbial composition analysis explores core microbiome, abundance, and taxonomy using Pavian, MicrobiomeAnalyst 2.0, and GraPhlAn. ANCOM-BC2 reveals differentially abundant species. Road cyclists exhibit decreased Bacteria and increased Archaea abundance. Phylum-level variations included Planctomycetes, Acidobacteria, and Proteobacteria, while Bacteroidetes prevailed. Key families influencing gut microbiota are Bacteroidaceae, Muribaculaceae, and Selenomonadaceae. Weightlifters exhibit unique viral and archaeal community connections, while cyclists showed specialized microbial interplay influenced by endurance exercise. Correlation network analysis emphasizes distinctive microbial interactions within athlete groups, shedding light on the impact of physical activities on gut microbiota and athlete health.

Despite substantial evidence emphasizing the pleiotropic benefits of exercise for the prevention and treatment of various diseases, the underlying biological mechanisms have not been fully elucidated. Several exercise benefits have been attributed to signaling molecules that are released in response to exercise by different tissues such as skeletal muscle, cardiac muscle, adipose, and liver tissue. These signaling molecules, which are collectively termed exerkines, form a heterogenous group of bioactive substances, mediating inter-organ crosstalk as well as structural and functional tissue adaption. Numerous scientific endeavors have focused on identifying and characterizing new biological mediators with such properties. Additionally, some investigations have focused on the molecular targets of exerkines and the cellular signaling cascades that trigger adaption processes. A detailed understanding of the tissue-specific downstream effects of exerkines is crucial to harness the health-related benefits mediated by exercise and improve targeted exercise programs in health and disease. Herein, we review the current in vivo evidence on exerkine-induced signal transduction across multiple target tissues and highlight the preventive and therapeutic value of exerkine signaling in various diseases. By emphasizing different aspects of exerkine research, we provide a comprehensive overview of (i) the molecular underpinnings of exerkine secretion, (ii) the receptor-dependent and receptor-independent signaling cascades mediating tissue adaption, and (iii) the clinical implications of these mechanisms in disease prevention and treatment.

Understanding the factors that contribute to exercise response variation is the first step in achieving the goal of developing personalized exercise prescriptions. This review discusses the key molecular and other mechanistic factors, both extrinsic and intrinsic, that influence exercise responses and health outcomes. Extrinsic characteristics include the timing and dose of exercise, circadian rhythms, sleep habits, dietary interactions, and medication use, whereas intrinsic factors such as sex, age, hormonal status, race/ethnicity, and genetics are also integral. The molecular transducers of exercise (i.e., genomic/epigenomic, proteomic/post-translational, transcriptomic, metabolic/metabolomic, and lipidomic elements) are considered with respect to variability in physiological and health outcomes. Finally, this review highlights the current challenges that impede our ability to develop effective personalized exercise prescriptions. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) aims to fill significant gaps in the understanding of exercise response variability, yet further investigations are needed to address additional health outcomes across all populations.

Skeletal muscle has an enormous plastic potential to adapt to various external and internal perturbations. Although morphological changes in endurance-trained muscles are well described, the molecular underpinnings of training adaptation are poorly understood. We therefore aimed to elucidate the molecular signature of muscles of trained male mice and unravel the training status-dependent responses to an acute bout of exercise. Our results reveal that, even though at baseline an unexpectedly low number of genes define the trained muscle, training status substantially affects the transcriptional response to an acute challenge, both quantitatively and qualitatively, in part associated with epigenetic modifications. Finally, transiently activated factors such as the peroxisome proliferator-activated receptor-γ coactivator 1α are indispensable for normal training adaptation. Together, these results provide a molecular framework of the temporal and training status-dependent exercise response that underpins muscle plasticity in training.

Ionizing radiation and microgravity are two considerable health risks encountered during deep space exploration. Both have deleterious effects on the human body. On one hand, weightlessness is known to induce a weakening of the immune system, delayed wound healing and musculoskeletal, cardiovascular, and sensorimotor deconditioning. On the other hand, radiation exposure can lead to long-term health effects such as cancer and cataracts as well as have an adverse effect on the central nervous and cardiovascular systems. Ionizing radiation originates from three main sources in space: galactic cosmic radiation, solar particle events and solar winds. Furthermore, inside the spacecraft and inside certain space habitats on Lunar and Martian surfaces, the crew is exposed to intravehicular radiation, which arises from nuclear reactions between space radiation and matter. Besides the approaches already in use, such as radiation shielding materials (such as aluminium, water or polyethylene), alternative shielding materials (including boron nanotubes, complex hybrids, composite hybrid materials, and regolith) and active shielding (using fields to deflect radiation particles) are being investigated for their abilities to mitigate the effects of ionizing radiation. From a biological point of view, it can be predicted that exposure to ionizing radiation during missions beyond Low Earth Orbit (LEO) will affect the human body in undesirable ways, e.g., increasing the risks of cataracts, cardiovascular and central nervous system diseases, carcinogenesis, as well as accelerated ageing. Therefore, it is necessary to assess the risks related to deep space exploration and to develop mitigation strategies to reduce these risks to a tolerable level. By using biomarkers for radiation sensitivity, space agencies are developing extensive personalised medical examination programmes to determine an astronaut's vulnerability to radiation. Moreover, researchers are developing pharmacological solutions (e.g., radioprotectors and radiomitigators) to proactively or reactively protect astronauts during deep space exploration. Finally, research is necessary to develop more effective countermeasures for use in future human space missions, which can also lead to improvements to medical care on Earth. This review will discuss the risks space travel beyond LEO poses to astronauts, methods to monitor astronauts' health, and possible approaches to mitigate these risks.

We assessed the feasibility of the Molecular Transducers of Physical Activity Consortium (MoTrPAC) human adult clinical exercise protocols, while also documenting select cardiovascular, metabolic, and molecular responses to these protocols. After phenotyping and familiarization sessions, 20 subjects (25 ± 2 yr, 12 M, 8 W) completed an endurance exercise bout (n = 8, 40 min cycling at 70% V̇o2max), a resistance exercise bout (n = 6, ∼45 min, 3 sets of ∼10 repetition maximum, 8 exercises), or a resting control period (n = 6, 40 min rest). Blood samples were taken before, during, and after (10 min, 2 h, and 3.5 h) exercise or rest for levels of catecholamines, cortisol, glucagon, insulin, glucose, free fatty acids, and lactate. Heart rate was recorded throughout exercise (or rest). Skeletal muscle (vastus lateralis) and adipose (periumbilical) biopsies were taken before and ∼4 h following exercise or rest for mRNA levels of genes related to energy metabolism, growth, angiogenesis, and circadian processes. Coordination of the timing of procedural components (e.g., local anesthetic delivery, biopsy incisions, tumescent delivery, intravenous line flushes, sample collection and processing, exercise transitions, and team dynamics) was reasonable to orchestrate while considering subject burden and scientific objectives. The cardiovascular and metabolic alterations reflected a dynamic and unique response to endurance and resistance exercise, whereas skeletal muscle was transcriptionally more responsive than adipose 4 h postexercise. In summary, the current report provides the first evidence of protocol execution and feasibility of key components of the MoTrPAC human adult clinical exercise protocols. Scientists should consider designing exercise studies in various populations to interface with the MoTrPAC protocols and DataHub.NEW & NOTEWORTHY This study highlights the feasibility of key aspects of the MoTrPAC adult human clinical protocols. This initial preview of what can be expected from acute exercise trial data from MoTrPAC provides an impetus for scientists to design exercise studies to interlace with the rich phenotypic and -omics data that will populate the MoTrPAC DataHub at the completion of the parent protocol.

Human skeletal muscle demonstrates remarkable plasticity, adapting to numerous external stimuli including the habitual level of contractile loading. Accordingly, muscle function and exercise capacity encompass a broad spectrum, from inactive individuals with low levels of endurance and strength to elite athletes who produce prodigious performances underpinned by pleiotropic training-induced muscular adaptations. Our current understanding of the signal integration, interpretation, and output coordination of the cellular and molecular mechanisms that govern muscle plasticity across this continuum is incomplete. As such, training methods and their application to elite athletes largely rely on a "trial-and-error" approach, with the experience and practices of successful coaches and athletes often providing the bases for "post hoc" scientific enquiry and research. This review provides a synopsis of the morphological and functional changes along with the molecular mechanisms underlying exercise adaptation to endurance- and resistance-based training. These traits are placed in the context of innate genetic and interindividual differences in exercise capacity and performance, with special consideration given to aging athletes. Collectively, we provide a comprehensive overview of skeletal muscle plasticity in response to different modes of exercise and how such adaptations translate from "molecules to medals."

In this article, we highlight the contributions of passive experiments that address important exercise-related questions in integrative physiology and medicine. Passive experiments differ from active experiments in that passive experiments involve limited or no active intervention to generate observations and test hypotheses. Experiments of nature and natural experiments are two types of passive experiments. Experiments of nature include research participants with rare genetic or acquired conditions that facilitate exploration of specific physiological mechanisms. In this way, experiments of nature are parallel to classical "knockout" animal models among human research participants. Natural experiments are gleaned from data sets that allow population-based questions to be addressed. An advantage of both types of passive experiments is that more extreme and/or prolonged exposures to physiological and behavioral stimuli are possible in humans. In this article, we discuss a number of key passive experiments that have generated foundational medical knowledge or mechanistic physiological insights related to exercise. Both natural experiments and experiments of nature will be essential to generate and test hypotheses about the limits of human adaptability to stressors like exercise. © 2023 American Physiological Society. Compr Physiol 13:4879-4907, 2023.

The background for this paper concerns a high frequency of work-related disorders that may result from physical exposure at work being highly sedentary, repetitive-monotonous, or physically demanding. This may result in levels of physical inactivity or strenuous activity impairing health. The aim is to present an evidence-based exercise prescription for the work-life population and beyond. The exercise program is designed to be feasible for use at the workplace and/or during leisure time and to improve health, workability, productivity, sickness absence, etc. The specific concept of Intelligent Physical Exercise Training, IPET, includes the assessment of several health-related variables, including musculoskeletal disorders, physical capacity, and physical exposure at work and/or daily life activity. An algorithm with cut-points for prescribing specific exercises is provided. Exercise programs in praxis are addressed through descriptions of precise executions of various prescribed exercises and possible alternatives to optimize variation and adherence. Finally, perspectives on the significance of introducing IPET and the ongoing, as well as future lines of development, are discussed.

Acute exercise elicits dynamic transcriptional changes that, when repeated, form the fundamental basis of health, resilience, and performance adaptations. While moderate-intensity endurance training combined with conventional resistance training (traditional, TRAD) is often prescribed and recommended by public health guidance, high-intensity training combining maximal-effort intervals with intensive, limited-rest resistance training is a time-efficient alternative that may be used tactically (HITT) to confer similar benefits. Mechanisms of action of these distinct stimuli are incompletely characterized and have not been directly compared. We assessed transcriptome-wide responses in skeletal muscle and circulating extracellular vesicles (EVs) to a single exercise bout in young adults randomized to TRAD (n = 21, 12 M/9 F, 22 ± 3 yr) or HITT (n = 19, 11 M/8 F, 22 ± 2 yr). Next-generation sequencing captured small, long, and circular RNA in muscle and EVs. Analysis identified differentially expressed transcripts (|log2FC|>1, FDR ≤ 0.05) immediately (h0, EVs only), h3, and h24 postexercise within and between exercise protocols. In aaddition, all apparently responsive transcripts (FDR < 0.2) underwent singular value decomposition to summarize data structures into latent variables (LVs) to deconvolve molecular expression circuits and interregulatory relationships. LVs were compared across time and exercise protocol. TRAD, a longer but less intense stimulus, generally elicited a stronger transcriptional response than HITT, but considerable overlap and key differences existed. Findings reveal shared and unique molecular responses to the exercise stimuli and lay groundwork toward establishing relationships between protein-coding genes and lesser-understood transcripts that serve regulatory roles following exercise. Future work should advance the understanding of these circuits and whether they repeat in other populations or following other types of exercise/stress.NEW & NOTEWORTHY We examined small and long transcriptomics in skeletal muscle and serum-derived extracellular vesicles before and after a single exposure to traditional combined exercise (TRAD) and high-intensity tactical training (HITT). Across 40 young adults, we found more consistent protein-coding gene responses to TRAD, whereas HITT elicited differential expression of microRNA enriched in brain regions. Follow-up analysis revealed relationships and temporal dynamics across transcript networks, highlighting potential avenues for research into mechanisms of exercise response and adaptation.

To carry out a systematic review and meta-analysis to verify the effects of different exercise training types on body composition and physical performance in older adults with sarcopenic obesity (SO).

Systematic review and meta-analysis.

Older adults (≥60 years).

Database searches were performed in MEDLINE (via PubMed), EMBASE, Cochrane Library, Web of Science, SCOPUS, and LILACS on January 10th, 2023. We included: randomized and/or controlled clinical trials; physical exercise as an intervention; analysis of body composition and/or muscle function; and sarcopenic obesity diagnosis. We used the Risk of Bias 2 tool and PEDro scale. The GRADE certainty of evidence was also performed.

Fourteen studies were included in the systematic review and nine studies in the meta-analysis. A decrease in body fat (%) favoring the exercise group was identified (SMD: -0.34 [95% CI: -0.53 to -0.16]; p=0.0003) (GRADE: ⊕⊕⊕◯ Moderate). Only resistance training showed fat reduction (SMD: -0.27 [95% CI: -0.48 to -0.06]; p=0.01). Increases in upper (SMD: 0.41 [95% CI: 0.04 to 0.78]; p=0.03) (GRADE: ⊕⊕◯◯ Low) and lower (SMD: 0.80 [95% CI: 0.22 to 1.39]; p=0.007) (GRADE: ⊕⊕⊕⊕ High) limb strength was identified with exercise. Chair stand test showed increases with exercise (SMD: 0.73 [95% CI: 0.40 to 1.07]; p<0.0001) (GRADE: ⊕⊕⊕⊕ High), especially for resistance training (SMD: 0.62 [95% CI: 0.21 to 1.02]; p=0.003) and combined training (SMD: 0.99 [95% CI: 0.40 to 1.57]; p=0.0005). The PEDro scale for the studies in our review ranged from 3 to 8 (mean = 5.8 (1.6)), meaning fair methodological quality, and most studies were overall judged with at least low/some concerns in terms of risk of bias.

Overall, moderate to high certainty of evidence was found for body fat, lower limb strength, and chair stand test. On the other hand, low certainty of evidence was found for upper limb strength. Resistance, combined, and aerobic training evoked divergent results between the variables analyzed. Although promising, our results should be considered sparingly, but may guide additional exercise recommendations to improve specific health parameters in older adults with SO.

The purpose of this narrative review is to give an overview about the effects of multimodal prehabilitation and current existing and prospectively planned studies. The potential efficacy of exercise in the context of prehabilitation ranges from preoperatively improving patients' functional capacity to inducing cellular mechanisms that affect organ perfusion via endothelial regeneration, anti-inflammatory processes and tumour defense.

Current studies show that prehabilitation is capable of reducing certain postoperative complications and length of hospital stay in certain patient populations. These findings are based on small to mid-size trials with large heterogeneity, lacking generalizability and evidence that prehabilitation has positive effects on long term survival.

The concept of prehabilitation contains the features, namely preoperative exercise, nutritional intervention and psychological support. Preoperative exercise holds potential molecular effects that can be utilized in the perioperative period in order to improve patients' postoperative outcome. Future multimodal prehabilitation trials must specifically clarify the clinical impact of this concept on patients' quality of life after major cancer surgery and cancer-specific survival.