The protein cargo of extracellular vesicles correlates with the epigenetic aging clock of exercise sensitive DNAmFitAge

Biogerontology, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 8, 2025

Abstract Extracellular vesicles (EVs) are implicated in inter-organ communication, which becomes particularly relevant during aging and exercise. DNA methylation-based clocks reflect lifestyle environmental factors, while regular exercise is known to induce adaptive responses, including epigenetic adaptations. Twenty individuals with High-fitness (aged 57.7 ± 9.8 years) twenty Medium–Low-fitness 57.5 9.7 subjects provided blood samples. EVs were isolated from the samples using a size exclusion chromatography (SEC)-based method, their protein content was analyzed by mass spectrometry (MS). Acceleration of biological age estimator DNAmFitAge (AgeAccelFit) associated cargo EVs, whereas PhenoAge GrimAge acceleration did not show significant relationship. This finding suggests that aging-modulating role may involve communication via EVs. Set Enrichment Analysis performed identify enriched Gene Ontology (GO) terms for sets proteins either correlated AgeAccelFit or detected exclusively high levels aerobic fitness. The further influences inflammation, immune system, cellular repair, adhesion, metabolism coagulation. Our findings help understand preventive exercise, could be mediated part

Language: Английский

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Leveraging microtopography to pattern multi-oriented muscle actuators

Biomaterials Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Simple templating of actuators via micro-topographical patterning (STAMP) enables precisely muscle fibers within engineered tissues, enabling fabrication complex multi-oriented architectures such as a biomimetic iris.

Language: Английский

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Muscle-derived extracellular vesicles mediate crosstalk between skeletal muscle and other organs

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 8, 2025

Skeletal muscle (SKM) has crucial roles in locomotor activity and posture within the body also functions have been recognized as an actively secretory organ. Numerous bioactive molecules are secreted by SKM transported extracellular vesicles (EVs), a novel class of mediators communication between cells organs that contain various types cargo including lipids, proteins nucleic acids. SKM-derived EVs (SKM-EVs) intercellular communicators with significant crosstalk other organs. In this review, we briefly describe biological characteristics, composition, uptake mechanisms EVs, particularly exosomes, comprehensively summarize regulatory effects SKM-EVs on function of, which include myogenesis, repair regeneration, well metabolic regulation. Furthermore, explore impact SKM- bone, cardiovascular system, adipose tissue, nervous system. As emerging evidence suggests involved development regulation type 2 diabetes (T2D), systemic inflammation, chronic diseases, highlight potential therapeutic targets diagnostic biomarkers, emphasizing need for further research to elucidate complex underlying physiological pathological contexts.

Language: Английский

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Causal association of sarcopenia-related traits with brain cortical structure: a bidirectional Mendelian randomization study

Aging Clinical and Experimental Research, Journal Year: 2025, Volume and Issue: 37(1)

Published: Feb. 27, 2025

Abstract Background Patients with sarcopenia often experience cognitive decline, affecting cortical structures, but the causal link remains unclear. We used bidirectional Mendelian randomization (MR) to explore relationship between sarcopenia-related traits and structure. Methods selected genetic variables from genome-wide association study data. Three different MR methods were used: inverse-variance weighted analysis, MR-Egger regression, median test. For significant estimates, we further conducted Cochran’s Q test, intercept leave-one-out analyses, MR-PRESSO assess heterogeneity. Results In forward appendicular lean mass (ALM) decreased thickness (TH) of lateral occipital gyrus increased TH pars opercularis (β = -0.0079 mm, 95% CI: -0.0117 mm -0.0041 P < 0.0001; β 0.0080 0.0042 0.0117 0.0001). reverse a negative correlation was found bankssts ALM, while positive correlations observed frontal pole, rostral anterior cingulate, temporal ALM. The pole positively correlated right hand grip strength (HGS-R) 0.1596 0.1349 0.1843 0.0001), triangularis left-hand (HGS-L) 0.3251 0.2339 0.4163 Conclusions Sarcopenia-related structure have effects, supporting muscle-brain axis theory. This links neurocognitive diseases provides new strategies for prevention intervention both decline.

Language: Английский

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Neuroscience in peripheral cancers: tumors hijacking nerves and neuroimmune crosstalk

MedComm, Journal Year: 2024, Volume and Issue: 5(11)

Published: Oct. 31, 2024

Abstract Cancer neuroscience is an emerging field that investigates the intricate relationship between nervous system and cancer, gaining increasing recognition for its importance. The central governs development of directly affects brain tumors, peripheral (PNS) shapes tumor microenvironment (TME) tumors. Both systems are crucial in cancer initiation progression, with recent studies revealing a more role PNS within TME. Tumors not only invade nerves but also persuade them through remodeling to further promote malignancy, creating bidirectional interaction cancers. Notably, immune cells contribute this communication, forming triangular influences protumor inflammation effectiveness immunotherapy. This review delves into mechanisms connecting focusing on how various cell types influence nerve‒tumor interactions, emphasizing clinical relevance nerve‒immune dynamics. By deepening our understanding interplay nerves, cells, has potential reshape biology insights, inspire innovative therapies, improve outcomes patients.

Language: Английский

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The role of resistance exercise-induced local metabolic stress in mediating systemic health and functional adaptations: could condensed training volume unlock greater benefits beyond time efficiency?

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 16

Published: April 17, 2025

The majority of "specialised" exercise configurations (e.g., supersets, drop sets, blood flow restriction) are being assessed as "shortcuts" to hypertrophy and strength improvements. However, these advanced training techniques may also offer significant benefits for systemic health functional outcomes across recreational clinical populations via locally induced metabolic responses. Stress-regulating mechanisms known enhance the body's resilience by facilitating allostasis, process coordinating adaptive processes in reaction stressors such physical training. Yet, role local stress provoked resistance has not gained much research attention despite its wide potential. Positive effects only linked improved muscular endurance, primary secondary mechanisms, but release myokines, hormones, microRNAs, immune factors, inflammatory substances other endocrine molecules that initiate numerous health-promoting modifications on a level. Resistance strategies maximise accumulation metabolites well defined, although high volume, close proximity failure shorter rests seem be necessity. Additionally, restriction provides potent alternative inducing acidosis, thereby triggering several pathways associated with immunity function even remote muscle tissues. Future is warranted further explore techniques, approaches comparable mental those seen forms high-intensity interval heavy

Language: Английский

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Human iPSC-Derived Motor Neuron Innervation Enhances the Differentiation of Muscle Bundles Engineered with Benchtop Fabrication Techniques

ACS Biomaterials Science & Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Engineered skeletal muscle tissues are critical tools for disease modeling, drug screening, and regenerative medicine, but limited by insufficient maturation. Because innervation is a regulator of development regeneration in vivo, motor neurons hypothesized to improve the maturity engineered tissues. However, impact on phenotype when added prior onset differentiation not clearly established. In this study, benchtop fabrication equipment was used facilely fabricate chambers engineering three-dimensional (3D) muscles bundles measuring their contractile performance. Primary chick myoblasts were embedded an extracellular matrix hydrogel solution differentiated into bundles, with or without addition human induced pluripotent stem cell (hiPSC)-derived neurons. Muscle had neurites distributed throughout volume higher myogenic index compared Innervated also generated significantly twitch tetanus forces response electrical field stimulation after 1 2 weeks noninnervated cultured neurotrophic factors. Noninnervated experienced decline rise fall times as culture progressed, whereas innervated factors maintained more consistent times. expressed highest levels genes slow myosin light chain 3 (MYL3) myoglobin (MB), which associated fibers. These data suggest that neuron enhances structural functional constructs maintains them oxidative phenotype.

Language: Английский

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Actuating Extracellular Matrices Decouple the Mechanical and Biochemical Effects of Muscle Contraction on Motor Neurons

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 10, 2024

Abstract Emerging in vivo evidence suggests that repeated muscle contraction, or exercise, impacts peripheral nerves. However, the difficulty of isolating muscle‐specific impact on motor neurons vivo, as well inability to decouple biochemical and mechanical contraction this setting, motivates investigating phenomenon vitro. This study demonstrates tuning properties fibrin enables longitudinal culture highly contractile skeletal monolayers, enabling functional characterization long‐term secretome harvesting from exercised tissues. Motor stimulated with muscle‐secreted factors significantly upregulate neurite outgrowth migration, an effect size dependent intensity. Actuating magnetic microparticles embedded within hydrogels enable dynamically stretching non‐invasively mimicking effects contraction. Interestingly, axonogenesis is similarly upregulated both mechanically biochemically neurons, but RNA sequencing reveals different transcriptomic signatures between groups, stimulation having a greater cell signaling related synapse maturation. leverages actuating extracellular matrices robustly validate previously hypothesized role for regulating neuron growth maturation bottom‐up through signaling.

Language: Английский

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Recent Advances of Exosomes Derived from Skeletal Muscle and Crosstalk with Other Tissues

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 10877 - 10877

Published: Oct. 10, 2024

Skeletal muscle plays a crucial role in movement, metabolism, and energy homeostasis. As the most metabolically active endocrine organ body, it has recently attracted widespread attention. possesses ability to release adipocytokines, bioactive peptides, small molecular metabolites, nucleotides, other myogenic cell factors; some of which have been shown be encapsulated within vesicles, particularly exosomes. These skeletal exosomes (SKM-Exos) are released into bloodstream subsequently interact with receptor membranes modulate physiological pathological characteristics various tissues. Therefore, SKM-Exos may facilitate diverse interactions between tissues while also serving as biomarkers that reflect states function. This review delves pivotal intricate mechanisms its derived miRNAs maturation rejuvenation muscle, along their intercellular signaling dynamics significance interfacing

Language: Английский

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The unexplored potential of exosomes in the muscle–brain axis

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 122(1)

Published: Dec. 31, 2024

Language: Английский

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