Histone β‐hydroxybutyrylation is critical in reversal of sarcopenia

Aging Cell, Journal Year: 2024, Volume and Issue: 23(11)

Published: July 30, 2024

Abstract Sarcopenia, a leading cause for global disability and mortality, is an age‐related muscular disorder, characterized by accelerated muscle mass loss functional decline. It known that caloric restriction (CR), ketogenic diet or endurance exercise lessen sarcopenia elevate circulating β‐hydroxybutyrate (β‐HB) levels. Whether the elevated β‐HB essential to reversal of sarcopenia, however, remains unclear. Here we show in both Caenorhabditis elegans mouse models increase reverse myofiber atrophy improves motor functions at advanced ages. β‐HB‐induced histone lysine β‐hydroxybutyrylation (Kbhb) indispensable sarcopenia. Histone Kbhb enhances transcription genes associated with mitochondrial pathways, including oxidative phosphorylation, ATP metabolic process aerobic respiration. This ultimately leads improve integrity enhance The are validated model CR. Thus, demonstrate induces Kbhb, increases function, reverses

Language: Английский

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Combined Effects of Ketogenic Diet and Aerobic Exercise on Skeletal Muscle Fiber Remodeling and Metabolic Adaptation in Simulated Microgravity Mice

Metabolites, Journal Year: 2025, Volume and Issue: 15(4), P. 270 - 270

Published: April 13, 2025

Objective: Prolonged microgravity environments impair skeletal muscle homeostasis by triggering fiber-type transitions and metabolic dysregulation. Although exercise nutritional interventions may alleviate disuse atrophy, their synergistic effects under conditions remain poorly characterized. This study investigated the of an 8-week ketogenic diet combined with aerobic in hindlimb-unloaded mice on fiber remodeling adaptation. Methods: Seven-week-old male C57BL/6J were randomly divided into six groups: normal control (NC), hindlimb unloading (NH), (NHE), (KC), (KH), (KHE). During last two weeks intervention, was applied to simulate microgravity. Aerobic groups performed moderate-intensity treadmill running (12 m/min, 60 min/day, 6 days/week) for 8 weeks. Body weight, blood ketone, glucose levels measured weekly. Post-intervention assessments included respiratory exchange ratio (RER), exhaustive performance tests, biochemical analyses parameters. The composition evaluated via immunofluorescence staining, lipid deposition assessed using Oil Red O glycogen content analyzed Periodic Acid–Schiff (PAS) gene expression quantified quantitative real-time PCR (RT-qPCR). Results: Hindlimb significantly decreased body induced reduced endurance mice. However, combination KD attenuated these adverse effects, as evidenced increased proportions oxidative fibers (MyHC-I) glycolytic (MyHC-IIb). Additionally, this intervention upregulated metabolism-associated genes, including CPT-1b, HADH, PGC-1α, FGF21, enhancing metabolism ketone utilization. These adaptations corresponded improved performance, demonstrated time exhaustion KHE group compared other groups. Conclusions: a effectively ameliorates simulated microgravity-induced atrophy impairment, primarily promoting transition from MyHC-IIb MyHC-I (CPT-1b, PGC-1α). findings underscore potential therapeutic value dietary mitigating conditions.

Language: Английский

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Pore-Forming Protein LIN-24 Enhances Starvation Resilience in Caenorhabditis elegans by Modulating Lipid Metabolism and Mitochondrial Dynamics

Toxins, Journal Year: 2025, Volume and Issue: 17(2), P. 72 - 72

Published: Feb. 6, 2025

The ability to survive starvation is a critical evolutionary adaptation, yet the molecular mechanisms underlying this capability remain incompletely understood. Pore-forming proteins (PFPs) are typically associated with immune defense, where they disturb membranes of target cells. However, role PFPs in non-immune functions, particularly metabolic and structural adaptations starvation, less explored. Here, we investigate aerolysin-like PFP LIN-24 Caenorhabditis elegans uncover its novel function enhancing resistance. We found that expression upregulated during leading increased lipase-encoding gene lipl-3. This upregulation accelerates mobilization degradation lipid stores, thereby sustaining energy levels. Additionally, overexpression significantly preserves muscle integrity, as evidenced by maintenance structure compared wild-type worms. Furthermore, demonstrate induces formation donut-shaped mitochondria, change likely aimed at reducing ATP production conserve prolonged nutrient deprivation. mitochondrial remodeling depends on genes involved dynamics, including mff-1, mff-2, drp-1, clk-1. Collectively, these findings expand our understanding PFPs, demonstrating their multifaceted stress resistance beyond defense. LIN-24’s involvement regulating metabolism, preserving structure, mitochondria highlights crucial adaptive response offering insights into evolution potential therapeutic targets for conditions related preservation regulation.

Language: Английский

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Network Pharmacology Combined with Experimental Validation to Investigate the Effects and Mechanisms of Aucubin on Aging-Related Muscle Atrophy

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2626 - 2626

Published: March 14, 2025

Aucubin (AU) is one of the main components traditional Chinese medicine Eucommia ulmoides Oliv (EU). This study investigated effects AU on aging-related skeletal muscle atrophy in vitro and vivo. The results network pharmacology revealed potential therapeutic atrophy. In vitro, effectively attenuated D-gal-induced cellular damage, reduced number senescence-associated β-galactosidase (SA-β-Gal)-positive cells, down-regulated expression levels atrophy-related proteins Atrogin-1 MuRF1, improved myotube differentiation, thereby mitigating Notably, was found to attenuate oxidative stress apoptosis cells by reducing ROS production, regulating Cleaved caspase3 BAX/Bcl-2 apoptotic pathways, enhancing Sirt1 PGC-1α signaling pathways. vivo studies demonstrated that treatment extended average lifespan Caenorhabditis elegans (C. elegans), increased locomotor activity, body wall mitochondrial content, alleviated damage C. elegans. These findings suggested can ameliorate show significant preventing treating

Language: Английский

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Sexual dimorphism in molecular profiles of resting human skeletal muscle and the response to acute exercise and endurance training

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 13, 2024

Abstract Biological sex has a strong impact on skeletal muscle metabolism and performance. By comprehensive investigation of epigenetic, transcriptomic proteomic differences between female male untrained subjects we provide molecular basis for the sexual dimorphism glucose lipid metabolism. The sex-specific multi-OMICs profiles indicate higher degree turnover abundance fast-twitch fibers in males high handling females. Eight-week endurance training equalized initial toward an endurance-trained profile both sexes. females was more resistant to acute exercise challenge since stress-responsive transcripts were predominantly upregulated males. In myotubes from same donors, hardly conserved, but could be partially restored by treatment with hormones. conclusion, after only 8 weeks mitigates deeply rooted common metabolically beneficial response.

Language: Английский

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