Rapamycin does not compromise physical performance or muscle hypertrophy after PoWeR while intermittent rapamycin alleviates glucose disruptions by frequent rapamycin DOI Creative Commons

Christian Elliehausen,

Szczepan S. Olszewski,

Carolyn G. Shult

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

An increasing number of physically active adults are taking the mTOR inhibitor rapamycin off label with goal extending healthspan. However, frequent dosing disrupts metabolic health during sedentary conditions and abates anabolic response to exercise. Intermittent once weekly minimizes many negative side effects in mice. it remains unknown how different schedules impact metabolic, physical, skeletal muscle adaptations voluntary exercise training. Therefore, we tested hypothesis that intermittent (2mg/kg; 1x/week) would avoid detrimental on 8 weeks progressive weighted wheel running (PoWeR) adult female mice (5-month-old) by evading sustained inhibitory signaling more 3x/week). Frequent but not suppressed mTORC1 PoWeR trained improved maximal capacity, absolute grip strength, myofiber hypertrophy no differences between vehicle or treated Conversely, had impaired glucose tolerance insulin sensitivity compared after PoWeR; however, reduced intolerance versus rapamycin. Collectively, these data suggest 1) is largely compatible physical benefits 2) body composition metabolism context may be dosing.

Язык: Английский

The molecular athlete: exercise physiology from mechanisms to medals DOI
Regula Furrer, John A. Hawley, Christoph Handschin

и другие.

Physiological Reviews, Год журнала: 2023, Номер 103(3), С. 1693 - 1787

Опубликована: Янв. 5, 2023

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

Язык: Английский

Процитировано

88
Mitochondrial dysfunction and skeletal muscle atrophy: Causes, mechanisms, and treatment strategies DOI
Gökhan Burçin Kubat, Esmaa Bouhamida, Oner Ulger

и другие.

Mitochondrion, Год журнала: 2023, Номер 72, С. 33 - 58

Опубликована: Июль 13, 2023

Язык: Английский

Процитировано

47
Diet for the prevention and management of sarcopenia DOI Creative Commons
Riccardo Calvani, Anna Picca, Hélio José Coelho‐Júnior

и другие.

Metabolism, Год журнала: 2023, Номер 146, С. 155637 - 155637

Опубликована: Июнь 21, 2023

Sarcopenia is a geriatric condition characterized by progressive loss of skeletal muscle mass and strength, with an increased risk adverse health outcomes (e.g., falls, disability, institutionalization, reduced quality life, mortality). Pharmacological remedies are currently unavailable for preventing the development sarcopenia, halting its progression, or impeding negative outcomes. The most effective strategies to contrast sarcopenia rely on adoption healthier lifestyle behaviors, including adherence high-quality diets regular physical activity. In this review, role nutrition in prevention management summarized. Special attention given current "blockbuster" dietary regimes agents used counteract age-related wasting, together their putative mechanisms action. Issues related design implementation nutritional discussed, focus unanswered questions appropriate timing interventions preserve function into old age. A brief description also provided new technologies that can facilitate personalized plans sarcopenia.

Язык: Английский

Процитировано

43
Molecular control of endurance training adaptation in male mouse skeletal muscle DOI Creative Commons
Regula Furrer, Barbara Heim, Svenia Schmid

и другие.

Nature Metabolism, Год журнала: 2023, Номер 5(11), С. 2020 - 2035

Опубликована: Сен. 11, 2023

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

Язык: Английский

Процитировано

31
Plasma Proteomic Kinetics in Response to Acute Exercise DOI Creative Commons

Michael Mi,

Jacob L. Barber, Prashant Rao

и другие.

Molecular & Cellular Proteomics, Год журнала: 2023, Номер 22(8), С. 100601 - 100601

Опубликована: Июнь 20, 2023

Regular exercise has many favorable effects on human health, which may be mediated in part by the release of circulating bioactive factors during each bout exercise. Limited data exist regarding kinetic responses plasma proteins and after acute Proteomic profiling 4163 was performed using a large-scale, affinity-based platform 75 middle-aged adults who were referred for treadmill stress testing. Plasma quantified at baseline, peak exercise, 1-h postexercise, those with significant changes both timepoints further examined their associations cardiometabolic traits change aerobic training Health, Risk Factors, Exercise Training Genetics Family Study, 20-week intervention study. A total 765 changed (false discovery rate < 0.05) compared to 128 postexercise. The 56 that included midkine, brain-derived neurotrophic factor, metalloproteinase inhibitor 4, coiled-coil domain-containing protein 126 enriched secreted proteins. majority had concordant direction timepoints. Across all assayed, gene set enrichment analysis showed increased abundance coagulation-related Forty-five associated least one measure adiposity, lipids, glucose homeostasis, or cardiorespiratory fitness 20 training. We identified hundreds novel most resolved 1 h into recovery. Proteins sustained recovery particular interest as biomarkers pathways investigation diseases. These will contribute biochemical roadmap publicly available entire scientific community.

Язык: Английский

Процитировано

22
Exercise-Specific Adaptations in Human Skeletal Muscle: Molecular Mechanisms of Making Muscles Fit and Mighty DOI Creative Commons

Aaron C. Q. Thomas,

Connor A. Stead, Jatin G. Burniston

и другие.

Free Radical Biology and Medicine, Год журнала: 2024, Номер 223, С. 341 - 356

Опубликована: Авг. 13, 2024

The mechanisms leading to a predominantly hypertrophied phenotype versus oxidative phenotype, the hallmarks of resistance training (RT) or aerobic (AT), respectively, are being unraveled. In humans, exposure naïve persons either AT RT results in their skeletal muscle exhibiting generic 'exercise stress-related' signaling, transcription, and translation responses. However, with increasing engagement RT, responses become refined, typically associated each form exercise emerges. Here, we review some underpinning adaptations how muscles become, through AT, 'fit' 'mighty.' Much our understanding molecular physiology has arisen from targeted analysis post-translational modifications measures protein synthesis. Phosphorylation specific residue sites been dominant focus, canonical signaling pathways (AMPK mTOR) studied extensively context respectively. These alone, along synthesis, have only begun elucidate key differences signaling. Still, yet uncharacterized exist regulation synthesis that drive unique adaptation RT. Omic studies required better understand divergent relationship between phenotypic outcomes training.

Язык: Английский

Процитировано

8
The role of skeletal muscle respiratory capacity in exercise performance DOI Creative Commons
Pablo M. García-Rovés,

Jorge Alvarez-Luis,

Sandra Cutanda-Tesouro

и другие.

Free Radical Biology and Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
Complex II ambiguities—FADH2 in the electron transfer system DOI Creative Commons
Erich Gnaiger

Journal of Biological Chemistry, Год журнала: 2023, Номер 300(1), С. 105470 - 105470

Опубликована: Ноя. 22, 2023

The prevailing notion that reduced cofactors NADH and FADH

Язык: Английский

Процитировано

19
Exercise and ageing impact the kynurenine/tryptophan pathway and acylcarnitine metabolite pools in skeletal muscle of older adults DOI Creative Commons
J. Matthew Hinkley,

Gong Xin Yu,

Robert A. Standley

и другие.

The Journal of Physiology, Год журнала: 2023, Номер 601(11), С. 2165 - 2188

Опубликована: Фев. 23, 2023

Exercise-induced perturbation of skeletal muscle metabolites is a probable mediator long-term health benefits in older adults. Although specific have been identified to be impacted by age, physical activity and exercise, the depth coverage metabolome still limited. Here, we investigated resting exercise-induced metabolite distribution from well-phenotyped adults who were active or sedentary, group young Percutaneous biopsies vastus lateralis obtained before, immediately after 3 h following bout endurance cycling. Metabolite profile was determined tandem mass spectrometry. Mitochondrial energetics permeabilized fibre bundles assessed high resolution respirometry type proportion immunohistology. We found that kynurenine/tryptophan pathway age activity. Specifically, kynurenine elevated adults, whereas downstream (kynurenic acid NAD

Язык: Английский

Процитировано

18
Skeletal muscle BMAL1 is necessary for transcriptional adaptation of local and peripheral tissues in response to endurance exercise training DOI Creative Commons
Mark Viggars,

Hannah E Berko,

Stuart J. Hesketh

и другие.

Molecular Metabolism, Год журнала: 2024, Номер 86, С. 101980 - 101980

Опубликована: Июнь 29, 2024

In this investigation, we addressed the contribution of core circadian clock factor, BMAL1, in skeletal muscle to both acute transcriptional responses exercise and remodeling response training. Additionally, adopted a systems biology approach investigate how loss BMAL1 altered peripheral tissue homeostasis as well training adaptations iWAT, liver, heart, lung male mice.

Язык: Английский

Процитировано

7