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Ítem Adherence to an Early Exercise Plan Promotes Visceral Fat Loss in the First Month Following Bariatric Surgery.(Springer, 2025) Pino-Zuñiga, Johanna; Lillo-Urzua, Paloma; Olivares-Galvez, Mariela; Palacio-Aguero, Ana; Duque, Juan Camilo; Luengas, Rafael; Cancino, JorgeBackground: The evidence supporting the benefits of early exercise in post-bariatric patients is growing. This study analyzed the effects of early exercise (1-week post-bariatric surgery) on body composition in patients with overweight and obesity 1 month after surgery. Methods: Thirty patients (age 36.5 ± 12.3 [range, 18-65] years; body mass index [BMI], 36.2 ± 12.3 kg/m2, range, 29-48) who underwent laparoscopic sleeve gastrectomy for bariatric surgery were instructed to participate in an exercise training program initiated on day 3 post-surgery and to follow a recommended protein intake of 60 g/day. After 1-month post-surgery, patients were stratified into those who adhered to exercise recommendations and those who did not. Pre- and post-differences in total weight loss (TWL), skeletal muscle mass (SMM), fat mass (FM), and visceral fat mass (VFM) were compared. Results: TWL, SMM, and FM loss were similar between non-adherent and adherent subjects (10.2 ± 3.5 kg and 11.9 ± 3.6 kg; p = 0.2; 2.9 ± 1.0 kg and 3.2 ± 1.2; p = 0.2; 6.2 ± 2.1 kg and 7.5 ± 3.6 kg; p = 0.2, respectively), whereas VFM was markedly reduced in the adherent group (29.9 ± 18.2 cm2 vs 14.6 ± 9.4 cm2; p = 0.01) compared to the non-adherent group. When the group was divided according to adherence to exercise and protein intake or non-adherence to both conditions, there was a significant difference in TWL, FM, and VFM losses (p < 0.05). In contrast, no differences in SMM were found. Conclusions: Early exercise training accelerated visceral fat mass loss during the initial recovery period in patients after bariatric surgery. Additionally, adherence to daily protein intake recommendations can increase total body weight and fat mass loss.Ítem Skeletal muscle Rac1 mediates exercise training adaptations towards muscle glycogen resynthesis and protein synthesis(Elsevier, 2025-08-28) Raun, Steffen H.; Henriquez-Olguín, Carlos; Frank, Emma; Schlabs, Farina; Hahn, Nanna Just; Roland Knudsen, Jonas; Ali, Mona S.; Andersen, Nicoline R.; Møller, Lisbeth L.V.; Davey, Jonathan; Qian, Hongwei; Coelho, Ana; Carl, Christian S.; Voldstedlund, Christian T.; Kiens, Bente; Holmdahl, Rikard; Gregorevic, Paul; Jensen, Thomas E.; Deshmukh, Atul S.; Richter, Erik A.; Sylow, LykkeLong-term exercise training elicits tremendous health benefits; however, the molecular understanding is incomplete and identifying therapeutic targets has been challenging. Rho GTPases are among the most regulated groups of proteins after exercise in human skeletal muscle, yet, unexplored candidates for mediating the effects of exercise training. We found that the Rho GTPase Rac1 was activated acutely after multiple exercise modalities in human skeletal muscle. Loss of Rac1 specifically in muscle attenuated contraction-induced muscle protein synthesis, diminished improvements in running capacity, and prevented muscle hypertrophy after exercise training in mice. Additionally, Ncf1* mice revealed that Rac1 regulated glycogen resynthesis via a NOX2-dependent mechanism. Molecularly, Rac1 was required for contraction-induced p38MAPK signaling towards HSP27, MNK1, and CREB phosphorylation. In vivo muscle-targeted overexpression of a hyperactive Rac1-mutant elevated reactive oxidant species production during exercise but did not affect muscle mass. Using mass spectrometry-based proteomics, we found that loss or gain of Rac1 muscle protein affected pathways related to cytoskeleton organization, muscle adaptation, and large ribosomal subunits. Thus, skeletal muscle Rac1 mediates both molecular and functional adaptation to exercise training.Ítem mTOR Ser1261 is an AMPK- dependent phosphosite in mouse and human skeletal muscle not required for mTORC2 activity(John Wiley & Sons Inc., 2025-01-31) Li, Jingwen; Madsen, Agnete B.; Knudsen, Jonas R.; Henríquez-Olguín, Carlos; Persson, Kaspar W.; Li, Zhencheng; Raun, Steffen H.; Li, Tianjiao; Kiens, Bente; Wojtaszewski, Jørgen F. P.; Richter, Erik A.; Nogara, Leonardo; Blaauw, Bert; Ogasawara, Riki; Jensen, Thomas E.The kinases AMPK, and mTOR as part of either mTORC1 or mTORC2, are major orchestrators of cellular growth and metabolism. Phosphorylation of mTOR Ser1261 is reportedly stimulated by both insulin and AMPK activation and a regulator of both mTORC1 and mTORC2 activity. Intrigued by the possibilities that Ser1261 might be a convergence point between insulin and AMPK signaling in skeletal muscle, we investigated the regulation and function of this site using a combination of human exercise, transgenic mouse, and cell culture models. Ser1261 phosphorylation on mTOR did not respond to insulin in any of our tested models, but instead responded acutely to contractile activity in human and mouse muscle in an AMPK activity-dependent manner. Contraction-stimulated mTOR Ser1261 phosphorylation in mice was decreased by Raptor muscle knockout (mKO) and increased by Raptor muscle overexpression, yet was not affected by Rictor mKO, suggesting most of Ser1261 phosphorylation occurs within mTORC1 in skeletal muscle. In accordance, HEK293 cells mTOR Ser1261Ala mutation strongly impaired phosphorylation of mTORC1 substrates but not mTORC2 substrates. However, neither mTORC1 nor mTORC2-dependentÍtem Intracellular and extracellular redox signals during exercise and aging(Elsevier, 2025-10-29) Caporossi, Daniela; Jackson, Malcom J.; Henríquez-Olguín, CarlosRegular physical activity enhances systemic health and resilience, partly through the generation of reactive oxygen species (ROS) that serve as key modulators of redox-sensitive signaling pathways. This review explores how redox signaling mediates both local and systemic responses to exercise, with particular focus on skeletal muscle and aging. We first examine the compartmentalized generation of ROS within myofibers, highlighting the distinct contributions of mitochondrial and NADPH oxidase systems and the context-dependent nature of oxidative eustress versus distress. We then detail how redox signals initiate adaptive responses that extend beyond muscle through the release of exerkines, cytokines, peptides, and metabolites, and their packaging within extracellular vesicles (EVs). These circulating factors facilitate interorgan communication and reinforce systemic redox homeostasis. Aging disrupts these processes, leading to impaired redox signaling, neuromuscular degeneration, and diminished responsiveness to exercise. Notably, animal models such as Sod1-deficient mice underscore the importance of neuronal redox control in sarcopenia. Finally, we highlight how exercise-induced EVs may counteract age-associated dysfunction by delivering redox-regulatory molecules to distant tissues. Understanding the molecular interplay between redox signals and systemic adaptation offers promising avenues for therapeutic strategies targeting metabolic and neuromuscular decline in aging.Ítem Activin receptor type IIA/IIB blockade increases muscle mass and strength, but compromises glycemic control in mice(Elsevier, 2025-09-27) Carlsson, Michala; Ali, Mona Sadek; Frank, Emma; Mármol, Joan M.; Ali, Mona Sadek; Raun, Steffen H.; Battey, Edmund; Resen Andersen, Nicoline; Irazoki, Andrea; Lund, Camilla; Henríquez-Olguín, Carlos; Kubec Højfeldt, Martina; Blomquist, Pauline; Duch Bromer, Frederik; Mocciaro, Gabriele; Lodberg, AndreasBrix Folsted Andersen, Christian; Eijken, Marco; Mæchel Fritzen, Andreas; Roland Knudsen, Jonas; Richter, Erik A.; Sylow, LykkePurpose: Blocking the Activin receptor type IIA and IIB (ActRIIA/IIB) has clinical potential to increase muscle mass and improve glycemic control in obesity, cancer, and aging. However, the impact of blocking ActRIIA/IIB on strength, metabolic regulation, and insulin action remains unclear. Methods: Here, we investigated the effect of short- (10 mg kg− 1 bw, once, 40h) or long-term (10 mg kg− 1 bw, twice weekly, 21 days) antibody treatment targeting ActRIIA/IIB αActRIIA/IIB) in lean and diet-induced obese mice and engineered human muscle tissue. Results: Short-term α ActRIIA/IIB administration in lean mice increased insulin-stimulated glucose uptake in skeletal muscle by 76—105%. Despite this, αActRIIA/IIB-treated mice exhibited 33% elevated blood glucose and glucose intolerance. Long-term αActRIIA/IIB treatment increased muscle mass (+20%) and reduced fat mass (− 8%) in obese mice but failed to enhance insulin-stimulated glucose uptake in muscle or adipose tissue. Instead, it induced glucose intolerance, cardiac hypertrophy with glycogen accumulation, and elevated hepatic triacylglycerol and glucose output in response to pyruvate. Concomitantly, long-term αActRIIA/IIB treatment increased strength (+30%) in mouse soleus muscle and prevented activin A-induced loss of tissue strength in engineered human muscle tissue. Surprisingly, long-term α ActRIIA/IIB treatment lowered volitional running (− 250%). Conclusions: Our findings demonstrate that, in accordance with human studies, ActRIIA/IIB blockade holds promise for increasing muscle mass, strength, and muscle insulin sensitivity. However, contrary to the improved glycemic control in humans, ActRIIA/IIB blockade in mice causes severe glucose intolerance and lowers voluntary physical activity. Our study underscores the complex metabolic and functional consequences of ActRIIA/IIB blockade, and highlight species differences on glycemic control, which warrant further investigation.Ítem Redox biology at the intersection of physical activity and air pollution: Mechanisms, consequences, and complexity(Free Radical Biology and Medicine, 2025-09-23) Henríquez-Olguín, Carlos; Jeria-Espinoza, Valentina; Opazo-Diaz, Edgardo; Marchini, TimoteoAir pollution and physical inactivity are leading contributors to the global burden of chronic disease and premature mortality. While exercise is a well-established stimulus for physiological adaptations and disease prevention, it also transiently increases reactive oxygen species (ROS) production, which function as essential signals for metabolic remodeling and cellular resilience. In contrast, exposure to air pollution, specifically fine particulate matter (PM2.5), leads to sustained and uncontrolled ROS production, promoting oxidative damage, inflammation, and cardiometabolic dysfunction. This review examines a critical and under-investigated question: How does exercising in polluted environments affect the redox signaling pathways that mediate the health benefits of exercise? We summarize current knowledge at the intersection of exercise physiology, redox biology, and environmental toxicology, with a particular focus on the roles of ROS sources, the scavenger system, and downstream physiological responses. By integrating findings from human and animal studies, we identify factors such as air pollution sources and level of exposure, exercise intensity, and age that shape redox outcomes. We also identify key knowledge gaps to clarify how context-specific redox responses determine whether exercise promotes adaptation or exacerbates pollution-related harm, providing essential insights for future mechanistic research and evidence-based public policies.Ítem Dog companionship and cortisol levels in youth. A systematic review and meta-analysis(Elsevier, 2025) Peña-Jorquera, Humberto; Hernandez-Jaña, Sam; Sanchez-Martinez, Javier; Espinoza-Puelles, Juan Pablo; Martínez-Flores, Ricardo; Barreto-Schuch, Felipe; Yañez-Seplveda, Rodrigo; Delgado-Floody, Pedro; Ferrari, Gerson; Sadarangani, Kabir P.; Cancino, Jorge; Bento-Torres, Joao; Espinoza-Salinas, Alexis; Stamatakis, Emmanuel; Cristi-Montero, CarlosObjective: Traditional and non-traditional strategies have been employed to improve youth health. Dog-assisted interventions have been proposed as a novel strategy to regulate stress and its consequences across all age groups. This systematic review and multilevel meta-analysis assessed the influence of dog-assisted interventions on cortisol levels in youth and explored potential moderators. Sources: We conducted a comprehensive systematic search across multiple databases, including PubMed, Scopus, Web of Science, Cochrane Library, and ScienceDirect, up to June 17, 2024, to evaluate the impact of dog-assisted interventions on youth cortisol levels. Two reviewers independently extracted and verified data from eligible randomized clinical trials, with a third reviewer ensuring accuracy. Cochrane's RoB 2.0 tool was used to assess the risk of bias. Heterogeneity was analyzed using Q and I2 statistics. A random-effects model was employed to calculate effect sizes (ES) using R software. Summary of the findings: Significant cortisol reductions were found for interventions lasting >15 min (ES: 0.65; p = .038), with a non-significant trend towards reduced cortisol in non-medical settings (ES: 0.46; p = .070). No significant effects were observed for shorter interventions, different control groups, or age-specific analyses. Meta-regression analysis revealed significant differences, showing better outcomes with longer intervention times and fewer female participants. Conclusion: Dog-assisted interventions lasting >15 min seem to be a promising and non-traditional strategy for regulating cortisol levels in children and adolescents in stressful situations. This study outlines gaps in the research and future directions.Ítem Block strength training based on age-related functional consequences in older women(PLOS One, 2025) Jofré-Saldía, Emilio; Festa, Raúl Ricardo; Villalobos-Gorigoitía, Álvaro; Jorquera-Aguilera, Carlos; Ojeda, Álvaro Huerta; Cancino, Jorge; Gea-García, Gemma MaríaStrength training is a form of healthy ageing in older women. Although recommendations currently exist, some are very broad or fail to cover the needs of aging. Therefore, the purpose of this study was to analyze the effects of blocks strength training based on age-related functional consequences on functional performance in older adult women. 82 community-dwelling older women (70.17 ± 6.04 y) were randomly assigned to either experimental (n = 40) or control (n = 42) group. Experimental group performed a Block Strength Training (BST) program based on strength, power, and muscular endurance, and different level of effort for 9 weeks, and control maintained daily routine with physical activity recommendations. Functional performance was assessed using absolute handgrip strength [AHS], timed up and go [TUG], two-minutes step test [2MST], five times stand-to-sit test [5-SST], 6-m walking speed test [6-WS] pre-post intervention. Statistical analyses were performed using two-way ANOVA (Time*Group) and effect size (partial eta-squared, ŋP2) with a significance level of p < 0.05. BST improved functional performance in the protocols of AHS (21.51 vs. 23.07-kg; + 7%), TUG (8.22 vs. 7.29-sec; + 11%), 2MST (78.76 vs. 97.18-steps; + 23%), 5-SST (12.68 vs. 9.43-sec; + 26%), and 6-WS (1.16 vs. 1.36- m·s-1; + 17%) compared to control (19.31 vs. 19.66-kg; 8.94 vs. 9.26-sec; 62.68 vs. 63.73-steps; 13.99 vs. 14.25-sec; 1.06 vs. 1.06-m·s-1, respectively) in a Time*Group interaction effect (p < 0.01; ŋP2 > 0.11). This BST is effective in improving overall functional performance and thus reducing the risk of physical frailty in community-dwelling older women. These findings strengthen the approach to exercise programming over recommendations, moving toward effective precision dosing for older adults.Ítem Early Exercise Boosts Visceral Fat Loss Post‑Bariatric Surgery in the First Month(Springer Nature, 2025) Cancino, Jorge; Lillo-Urzua, Paloma; Olivares-Galvez, Mariela; Palacio-Aguero, Ana; Duque, Juan Camilo; Luengas, Rafael; Pino-Zuñiga, JohannaThis letter to the editor addresses critiques of a clinical study evaluating the efficacy of an early, counseling-based physical exercise intervention in post-bariatric patients. The authors highlight the paucity of research regarding proactive modification of body composition within the initial postoperative month, focusing particularly on visceral adipose tissue mass. The implemented protocol consisted of a home-based, unsupervised resistance training regimen employing elastic bands, initiated between postoperative days 5 and 7, following individualized in-hospital familiarization and audiovisual instruction. The intervention demonstrated high feasibility, safety, and clinical applicability, especially for populations with limited access to direct supervision during the early postoperative period. No adverse events were reported. The significant reduction in visceral adiposity observed is underscored as a clinically relevant proxy for improved metabolic risk profile. The use of subjective scales of perceived exertion (such as the Borg Scale) is justified when objective monitoring devices are unavailable. The authors recommend that future research prioritize the identification of determinants influencing patient adherence to exercise prescription within post-bariatric rehabilitation frameworks, aiming to optimize therapeutic outcomes.Ítem Effects of Maca (Lepidium meyenii Walp.) on Physical Performance in Animals and Humans: A Systematic Review and Meta-Analysis(MDPI, 2025) Huerta Ojeda, Álvaro; Rodríguez Rojas, Javiera; Cancino, Jorge; Barahona-Fuentes, Guillermo; Pavez, Leonardo; Yeomans-Cabrera, María-Mercedes; Jorquera-Aguilera, CarlosBackground: Lepidium meyenii Walp. (LmW), known as maca, has been shown to increase physical performance. However, the effect size (ES) of LmW on the different manifestations of physical performance has not yet been described. Objectives: To examine and qualitatively describe the studies published up to 2024 that employed LmW supplementation to increase physical performance in animal and human experimentation. In addition, the ES associated with the different interventions was calculated. Methods: The research followed PRISMA® guidelines for systematic reviews and meta-analyses, using Web of Science, Scopus, SPORTDiscus, PubMed, and MEDLINE databases until 2024. Randomized controlled studies with a pre- and post-test design, conducted both in vitro and in vivo in animals and humans, were included. Methodological quality assessment was performed using the CAMARADES tool for animal studies and the Newcastle Ottawa Scale for human studies. The main variables were the forced swimming test (FST), the rota-rod test (RRT), the grip strength test (GST), blood lactic acid (BLA), and lactic acid (LA). The analysis was conducted with a pooled standardized mean difference (SMD) through Hedges’ g test (95% CI). Results: Twenty-one studies were included in the systematic review and sixteen in the meta-analysis. They revealed a large effect for all outcomes (SMD: FST = 2.26, RRT = 6.26, GST = 5.23, LA = −1.01, and BLA = −1.70). Conclusions: The phytochemical compounds of LmW, mainly macamides, increase physical performance, showing a greater effect at higher doses (dose–response effect).Ítem Adaptación transcultural del cuestionario para valoración del fitness cardiorrespiratorio: CLINIMEX Aerobic Fitness Questionnaire(Sociedad Chilena de Medicina del Deporte, 2025) Cancino, Jorge; Barrera-Cifuentes, María Paz; Cruz-Alaniz, Nicolás; León-Carrasco, BárbaraObjetivo: Adaptar transculturalmente al español chileno el CLINIMEX Aerobic Fitness Questionnaire para estimar el fitness cardiorrespiratorio. Métodos: Se realizó una traducción inicial por dos traductoras bilingües de lengua materna chilena y una retrotraducción por dos traductores bilingües de lengua materna portuguesa. Luego, un comité de expertos revisó el cuestionario antes de su aplicación a un primer grupo de 40 personas mayores de 18 años. Tras confirmar su comprensibilidad, se aplicó la versión final a un grupo de 20 personas. Resultados: En la primera fase, un 27,5% (n=11) tuvo dificultades con el término “hatha”, un 10% (n=4) con “spinning”, un 7,5% (n=3) con “hidrogimnasia” y un 2,5% (n=1) con “musculación”. En el segundo grupo, el fitness cardiorrespiratorio estimado fue de 10.8±2.8 METs (rango 5-16). Conclusión: Se logró la adaptación del cuestionario CLINIMEX al español chileno. Esta adaptación constituye un paso fundamental para avanzar en el proceso de validación del instrumento en nuestra población y entregar una herramienta sencilla para la valoración clínica del fitness respiratorio. Objective: To carry out the cross-cultural adaptation of the CLINIMEX Aerobic Fitness Questionnaire intoChilean Spanish for the estimation of cardiorespiratory fitness. Methods: An initial translation was performed by two bilingual translators whose native language is Chilean Spanish, followed by a back-translation by two bilingual translators whose native language is Portuguese. A committee of experts then reviewed the questionnaire before it was administered to a first group of 40 individuals aged 18 and older. After confirming its comprehensibility, the final version was administered to a second group of 20 participants. Results: In the first phase, 27.5% (n=11) had difficulties with the term “hatha,” 10% (n=4) with “spinning,” 7.5% (n=3) with “hydrogymnastics,” and 2.5% (n=1) with “strength training.” In the second group, the estimated cardiorespiratory fitness was 10.8±2.8 METs (range 5–16). Conclusion: The CLINIMEX questionnaire was successfully adapted into Chilean Spanish. This adaptation represents a key step toward the validation of the instrument in our population and provides a simple tool for the clinical assessment of cardiorespiratory fitness.Ítem Revisiting insulin-stimulated hydrogen peroxide dynamics reveals a cytosolic reductive shift in skeletal muscle(Elsevier, 2025-04-25) Henríquez-Olguín, Carlos; Gallero, Samantha; Reddy, Anita; Persson, Kaspar W.; Schlabs, Farina L.; Voldstedlund, Christian T.; Valentinaviciute, Gintare; Meneses-Valdés, Roberto; Sigvardsen, Casper M.; Kiens, Bente; Chouchani, Edward T.; Richter, Erik A.; Jensen, Thomas E.The intracellular redox state is crucial for insulin responses in peripheral tissues. Despite the longstanding belief that insulin signaling increases hydrogen peroxide (H2O2) production leading to reversible oxidation of cysteine thiols, evidence is inconsistent and rarely involves human tissues. In this study, we systematically investigated insulin-dependent changes in subcellular H2O2 levels and reversible cysteine modifications across mouse and human skeletal muscle models. Utilizing advanced redox tools including genetically encoded H2O2 sensors and non-reducing immunoblotting we consistently observed no increase in subcellular H2O2 levels following insulin stimulation. Instead, stoichiometric cysteine proteome analyses revealed a selective pro-reductive shift in cysteine modifications affecting insulin transduction related proteins, including Cys179 on GSK3β and Cys416 on Ras and Rab Interactor 2 (RIN2). Our findings challenge the prevailing notion that insulin promotes H2O2 generation in skeletal muscle and suggest that an insulin-stimulated pro-reductive shift modulates certain aspects of insulin signal transduction.Ítem Muscle-specific AXIN1 and AXIN2 double knockout does not alter AMPK/mTORC1 signalling or glucose metabolism(The Physiological Society, 2025-07-01) Persson, Kaspar W.; Meneses-Valdés, Roberto; Andersen, Nicoline R.; Pedersen, Frederik S.; Gallo, Samantha; Hesselager, Sofie A.; Henríquez-Olguín, Carlos; Jensen, Thomas E.AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) are crucial kinase signalling hubs that regulate the balance between catabolism and anabolism in skeletal muscle. The scaffold protein AXIN1 has been proposed to regulate the switch between these pathways and be required for GLUT4 translocation in skeletal muscle and adipocyte cell lines. Muscle-specific AXIN1 knockout (KO) mice exhibit no discernable phenotype, possibly due to compensation by AXIN2 upon AXIN1 loss. Thus we generated and characterized muscle-specific inducible AXIN1 and AXIN2 double knockout (dKO) mice. Surprisingly AXIN1/2 dKO mice displayed normal AMPK and mTORC1 signalling and glucose uptake in response to 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), insulin and in situ muscle contraction. These findings suggest that AXIN proteins are not essential for the regulation of AMPK and mTORC1 signalling or glucose uptake in skeletal muscle. This study challenges the previously indicated critical roles of AXIN1 in exercise-stimulated AMPK activation and GLUT4-mediated glucose uptake in skeletal muscle. KEY POINTS: Phenotyping of tamoxifen-inducible muscle-specific AXIN1/2 double knockout (dKO) mice. We find no evidence for AXIN-dependent AMPK or mTORC1 regulation in skeletal muscle by insulin, AMPK activation or contraction. Glucose uptake regulation by insulin and AMPK activation is normal in AXIN1/2 dKO mice.Ítem NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging(Elsevier, 2025-06-25) Chubanava, Sabina; Karavaeva, Iuliia; Ehrlich, Amy M.; Justicia, Roger M.; Basse, Astrid L.; Kulik, Ivan; Dalbram, Emilie; Ahwazi, Danial; Heaselgrave, Samuel R.; Trost, Kajetan; Stocks, Ben; Hodek, Ondrej; Rodrigues, Raissa N.; Havelund, Jesper F.; Schlabs, Farina L.; Larsen, Steen; Yonamine, Caio Y.; Henríquez-Olguín, Carlos; Giustarini, Daniela; Rossi, Ranieri; Gerhart-Hines, Zachary; Moritz, Thomas; Zierath, Juleen R.; Sakamoto, Kei; Jensen, Thomas E.; Færgeman, Nils J.; Lavery, Gareth G.; Deshmukh, Atul S.; Treebak, Jonas T.Nicotinamide adenine dinucleotide (NAD) is a ubiquitous electron carrier essential for energy metabolism and post-translational modification of numerous regulatory proteins. Dysregulations of NAD metabolism are widely regarded as detrimental to health, with NAD depletion commonly implicated in aging. However, the extent to which cellular NAD concentration can decline without adverse consequences remains unclear. To investigate this, we generated a mouse model in which nicotinamide phosphoribosyltransferase (NAMPT)-mediated NAD+ biosynthesis was disrupted in adult skeletal muscle. The intervention resulted in an 85% reduction in muscle NAD+ abundance while maintaining tissue integrity and functionality, as demonstrated by preserved muscle morphology, contractility, and exercise tolerance. This absence of functional impairments was further supported by intact mitochondrial respiratory capacity and unaltered muscle transcriptomic and proteomic profiles. Furthermore, lifelong NAD depletion did not accelerate muscle aging or impair whole-body metabolism. Collectively, these findings suggest that NAD depletion does not contribute to age-related decline in skeletal muscle function.Ítem CCL5 Induces a Sarcopenic-like Phenotype via the CCR5 Receptor(MDPI, 2025-01-13) Aguirre, Francisco; Tacchi, Franco; Valero-Breton, Mayalen; Orozco-Aguilar, Josué; Conejeros-Lillo, Sanabria; Bonicioli, Josefa; Iturriaga-Jofré, Renata; Cabrera, Daniel; Soto, Jorge A.; Castro-Sepúlveda, Mauricio; Portal-Rodríguez, Marianny; Elorza, ÁLvaro A.; Matamoros, Andrea; Simon, Felipe; Cabello-Verrugio, ClaudioSarcopenia corresponds to a decrease in muscle mass and strength. CCL5 is a new myokine whose expression, along with the CCR5 receptor, is increased in sarcopenic muscle. Therefore, we evaluated whether CCL5 and CCR5 induce a sarcopenic-like effect on skeletal muscle tissue and cultured muscle cells. Electroporation in the tibialis anterior (TA) muscle of mice was used to overexpress CCL5. The TA muscles were analyzed by measuring the fiber diameter, the content of sarcomeric proteins, and the gene expression of E3-ligases. C2C12 myotubes and single-isolated flexor digitorum brevis (FDB) fibers were also treated with recombinant CCL5 (rCCL5). The participation of CCR5 was evaluated using the antagonist maraviroc (MVC). Protein and structural analyses were performed. The results showed that TA overexpression of CCL5 led to sarcopenia by reducing muscle strength and mass, muscle-fiber diameter, and sarcomeric protein content, and by upregulating E3-ligases. The same sarcopenic phenotype was observed in myotubes and FDB fibers. We showed increased reactive oxygen species (ROS) production and carbonylated proteins, denoting oxidative stress induced by CCL5. When the CCR5 was antagonized, the effects produced by rCCL5 were prevented. In conclusion, we report for the first time that CCL5 is a novel myokine that exerts a sarcopenic-like effect through the CCR5 receptor.Ítem The role of the circadian clock in regulating mitochondrial dynamics and their impact on skeletal muscle function and metabolism(The Physiological Society, 2025-06-25) Carriel-Nesvara, Alfonso; Muñoz-Medina, Cristóbal; Deldicque, Louise; Castro-Sepúlveda, MauricioDisruptions in both circadian clock and mitochondrial dynamics in the skeletal muscle (SkM) have been associated with insulin resistance and sarcopenia. Emerging evidence, in resting conditions and in response to metabolic challenges like exercise, suggests the intricate interplay between the circadian clock, mitochondrial dynamics and SkM function. However the molecular mechanisms that connect the circadian clock to mitochondrial dynamics and SkM function remain poorly understood. This review focuses on the role of circadian clock proteins, particularly brain and muscle Arnt-like protein-1 (BMAL1), in regulating mitochondrial dynamics and examines how their dysregulation contributes to metabolic and SkM deterioration. By exploring their interaction we aim to identify potential therapeutic targets that could improve metabolic health and muscle function.Ítem Mechanistic influence of the torque cadence relationship on power output during exhaustive all-out field tests in professional cyclists(Taylor & Francis, 2025-03-15) Leo, Peter; Martinez-Gonzalez, Borja; Mujika, Iñigo; Giorgi, AndreaUnderstanding the torque-cadence-power relationship can be important in assessing a cyclist’s performance potential. This study explored these relationships in elite male cyclists (N = 17; age: 24.1 ± 3.8 years; body mass: 66.0 ± 4.8 kg, critical power (CP): 5.5 ± 0.3 W.kg−1) through sprint, torque, and CP tests conducted in fresh and after accumulated work. Testing protocols, performed during a pre-season training camp, included maximal efforts across varied gear ratios and durations (15 s, 3 min, and 12 min), under stable environmental conditions (15–20°C). Results revealed reduced power output, torque, and cadence after accumulated work compared to fresh conditions (p ≤ .001). Sprint-derived maximum torque (Tmax) was strongly correlated with torque intercepts for CP fresh (r = .558, p = .020) and after accumulated work (r = .556, p = .020). The cadence relationships demonstrated a large negative correlation between maximum cadence (Cmax) and optimum cadence (Copt) from the sprint test and the 15 s, 3 min and 12 min cadence recorded during CP after accumulated work (r = -0.541 to −0.634, p = 0.006 to 0.025). These findings highlight that accumulated work-induced reductions in work capacity (W’) and CP values were accompanied by lower cadences across all effort durations.Ítem What Is “Zone 2 Training”?: Experts’ Viewpoint on Definition, Training Methods, and Expected Adaptations(Human Kinetics, Inc., 2025-02-26) Sitko, Sebastian; Artetxe, Xabier; Bonnevie-Svendsen, Martin; Galán-Rioja, Miguel Ángel; Gallo, Gabriele; Grappe, Frédéric; Leo, Peter; Mateo, Manuel; Mujika, Iñigo; Sanders, Dajo; Seiler, Stephen; Zabala, Mikel; Valenzuela, Pedro L.; Viribay, AitorThe role of high-volume low-intensity training for enhancing endurance performance has gained growing interest in recent years. Specifically, so-called “zone 2 training” is currently receiving much attention, and many propose that this is the target intensity at which a large proportion of total endurance training should be performed. However, despite the popularity of this concept, there is no clear consensus among coaches, athletes, and scientists regarding the definition of zone 2 training. Purpose: This commentary summarizes the perspectives, experience, and knowledge of an expert panel of 14 applied sport scientists and professional coaches with the aim of providing insight and a basis for definitional consensus on zone 2 training. Moreover, potential training strategies at this intensity are proposed, and the expected physiological adaptations when exercising at this intensity and related research gaps are also discussed. Results: Experts reached consensus that zone 2 training should preferably be performed at intensities located immediately below the first lactate or ventilatory threshold through continuous, variable, or interval-type sessions. Furthermore, experts expected a broad range of central and peripheral adaptations from zone 2 training. These expected adaptations might not be unique to zone 2 and could also be induced with sessions performed at slightly higher and lower intensities. Conclusions: This commentary provides practical insight and unified criteria regarding the preferred intensity, duration, and session type for the optimization of zone 2 training based on the perspectives of acknowledged sport scientists and professional coaches.Ítem Current Periodization, Testing, and Monitoring Practices of Strength and Conditioning Coaches(Human Kinetics, Inc., 2025) Washif, Jad Adrian; James, Carl; Pagaduan, Jeffrey; Lim, Julian; Lum, Danny; Raja Azidin, Raja Mohammed Firhad; Mujika, Iñigo; Beaven, Chistopher MartynThis study investigated the periodization, testing, and monitoring practices of strength and conditioning practitioners across different levels of coaching experience and sports. Methods: An online survey was completed by 58 practitioners (25 sports/events) from 9 Southeast and East Asian countries. The survey focused on periodization models, programming frameworks, unloading strategies, fitness assessments, and pretraining readiness monitoring. Frequency analysis and chi-square tests were used to assess data distribution and differences. Results: Hybrid (multiple) periodization was favored over a single model for different training objectives (39%–45%), including very short-term training (≤4 wk). Emerging approaches, including flexible programming, were similarly adopted (43%). Program adjustment was primarily driven by athlete feedback (90%), self-observation (78%), and technical execution (74%). Major programming challenges identified were managing fatigue (72%), optimizing training stimuli (53%), specificity (50%), and adherence (47%). Deloading practices (95%) and tapering applications (91%) were common. Physical performance changes were primarily identified from testing (90%) but also athlete/coach feedback (76%), monitoring (71%), training data (67%), and performance data/statistics (62%). Strength assessments were conducted 2 to 4 times yearly (67%) using 1 to 4 exercises (76%). Pretraining readiness was monitored via conversations (71%), wellness tools (46%), and performance devices (31%). Practitioners also utilized monitoring technology, force plates (21%), and velocity-tracking devices (23%). Training load was commonly quantified using volume load (81%) and session RPE (72%). None of the comparisons differed across experience levels and sports types (P > .05). Conclusion: Practitioners adopted multiple periodization models, incorporating flexible approaches. Unloading strategies were commonly applied alongside various assessment methods. Technologies were used for monitoring, but conversational/subjective methods remained more widespread.Ítem What It Takes to Win: Examining Predicted Versus Actual Swimming Performances at the Paris 2024 Olympic Games, and What Comes Next(Human Kinetics, Inc., 2025-02-13) Powell, Cormac; Pyne, David B.; Crowley, Emmet; Mujika, IñigoPredictions of performances should be evaluated to confirm their accuracy. Work by this group has resulted in 3 sets of predictions being generated for swimming events at the Paris 2024 Olympic Games, using the same statistical approach for each set. Purpose: To examine the accuracy of swimming predictions for the Paris 2024 Olympic Games and generate updated predictions for both the Singapore 2025 World Aquatics Championships and Los Angeles 2028 Olympic Games. Methods: A linear regression and forecasting function was used to generate predictions for the Paris 2024 Olympic Games across 3 performance categories (rank 1st–3rd, 4th–8th, and 9th–16th). Mean absolute error was used to assess the accuracy of the predicted versus actual Paris 2024 Olympic Games times for all events across the 3 performance categories. New predictions for the 2028 Olympic cycle were subsequently generated using results from the World Championships and Olympic Games between 2011 and 2024. Results: Across all events, a mean absolute error value of 0.84% was observed between the Paris 2024 Olympic Games predicted and actual times. Predicted times were highly correlated with actual times (r2 = .99). Across the 3 sets of predictions (created in 2022, 2023, and 2024), the 2023 set of predictions had the lowest overall mean absolute error value (0.55%). Conclusions: The methods used to create predictions for swimming performances at the Paris 2024 Olympic Games were deemed accurate. These methods enable national swimming federations to create a series of predictions for a given major championship, inform athlete identification and development pathways, and allocate appropriate resources, including sport-science provision.