Key Takeaways & Executive Findings
- •• METTL3-mediated m6A methylation is crucial for maintaining the differentiation potential of myogenic cells. • The METTL3/14-m6A-YTHDF1/2 axis regulates satellite cells, promoting myoblast proliferation and myogenic differentiation. • Elevating m6A methylation levels can alleviate the atrophic phenotype of denervated skeletal muscle. • The precise regulatory targets and synergistic mechanisms of m6A reader proteins in sarcopenia remain unclear, and clinical validation is lacking.
Abstract
BACKGROUND: The role of epigenetic regulatory mechanisms, especially N6-methyladenine (m6A) RNA modification, in muscle cell proliferation, differentiation, and disease development is increasingly being studied. However, the multidimensional mechanism of m6A methylation in sarcopenia still needs to be systematically integrated. OBJECTIVE: To explore the key role of m6A methylation in the occurrence and development of sarcopenia, and to review the latest research progress on the involvement of m6A related regulatory factors in the pathological process of sarcopenia. METHODS: Using "m6A methylation, N6 methyladenine, sarcopenia, muscle atrophy, muscle regeneration, muscle, skeletal muscle" as Chinese keywords, and "m6A RNA methylation, sarcopenia, skeletal muscle, muscle mass loss" as English keywords, CNKI and PubMed were searched to screen high-quality literature in recent years, and the mechanism of action and related signaling pathways of m6A methylation in sarcopenia were summarized. RESULTS AND CONCLUSION: m6A methylation participates in the pathological process of sarcopenia through a dynamic and reversible regulatory network (methyltransferases METTL3/METTL14, demethylases FTO/ALKBH5, reader proteins YTHDF1/YTHDF2, etc.). m6A methylation affects the proliferation and differentiation of skeletal muscle cells by regulating satellite cells, ubiquitin-proteasome system, non-coding RNAs, etc. Most studies are based on cell models or animal experiments, with few clinical sample validation and translational application studies. The feasibility of m6A-related factors as diagnostic markers or therapeutic targets for sarcopenia needs further verification.
1. Introduction
Sarcopenia, as a progressive and systemic degenerative disease of skeletal muscle, is characterized by a progressive loss of skeletal muscle mass, a continuous decline in muscle strength, and a gradual deterioration of muscle function. Sarcopenia is closely related to the aging process. Its clinical manifestations not only include reduced physical activity and balance dysfunction, but are also closely associated with various adverse outcomes such as falls, fractures, mobility limitations, readmission, and death [1]. Epidemiological data show that 10%-16% of the global population suffers from sarcopenia [2], and the global prevalence of sarcopenia in people over 60 years old is 10%-27% [3]. With the extension of global life expectancy and the intensification of social aging trends, coupled with the prevalence of risk factors such as sedentary lifestyles and nutritional imbalances, the prevalence of sarcopenia is expected to continue to rise, thereby imposing a growing health and economic burden on individuals and society.
In recent years, breakthrough research on epigenetic regulatory mechanisms has provided a new perspective for elucidating the molecular pathological mechanisms of sarcopenia [4]. Among them, m6A methylation is the most common chemical modification on eukaryotic mRNA, which is RNA methylation at the sixth nitrogen atom of adenine. m6A methylation plays a crucial role in physiological and pathological processes, and its dynamic and reversible regulatory mechanism has attracted increasing attention [5]. Although studies have explored the role of m6A methylation in the pathogenesis of sarcopenia, existing studies are scattered and lack an integrated analysis of the multidimensional mechanisms of m6A methylation in sarcopenia. This review aims to summarize the main characteristics and regulatory mechanisms of m6A methylation, and to summarize the role of m6A methylation and related factors in muscle development and regeneration, hoping to provide new perspectives and theoretical basis for the pathological mechanism, clinical staging, and therapeutic targets of sarcopenia.
Loading authentic research manuscript (Pages 1–5)...
Li Jiatong, Liang Songlin, Liu Runjia, Li Nianhu (2026). Key role of m6A methylation in sarcopenia. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21500
Research & Educational Purpose Only:The translations, structured abstracts, analytical annotations, and data reports provided by SinoBioData are intended exclusively for academic research, internal corporate R&D, and educational benchmarking. They do not constitute formal engineering, chemical safety, legal, or professional advice.
Copyright & Intellectual Property Notice: Original copyright of the underlying source articles and experimental data remains with the respective authors, institutions, and original publishing journals. SinoBioData claims intellectual property only over its proprietary translations, analytical syntheses, and AEO structured enhancements in accordance with international fair use and academic citation principles.
Frequently Asked Questions
What is m6A methylation and how does it relate to sarcopenia?
m6A methylation is the most common epigenetic modification on eukaryotic mRNA, dynamically regulated by methyltransferases (writers), demethylases (erasers), and reader proteins. In sarcopenia, m6A methylation regulates satellite cell function, protein metabolism, and non-coding RNA activity, influencing muscle cell proliferation and differentiation, thereby contributing to muscle mass and function decline.
What are the key m6A regulators involved in sarcopenia?
Key m6A regulators include methyltransferases METTL3 and METTL14, demethylases FTO and ALKBH5, and reader proteins YTHDF1 and YTHDF2. These factors form a dynamic regulatory network that modulates the expression of genes critical for muscle homeostasis.
How does m6A methylation affect satellite cells in sarcopenia?
m6A methylation influences satellite cell proliferation and myogenic differentiation. For example, the METTL3/14-m6A-YTHDF1/2 axis promotes satellite cell activation and differentiation, which is essential for muscle regeneration. Dysregulation of this axis can impair muscle repair and contribute to sarcopenia.
Can m6A methylation be a therapeutic target for sarcopenia?
Preclinical studies suggest that modulating m6A methylation levels, such as enhancing methylation, can alleviate muscle atrophy in denervated models. However, clinical validation is lacking. m6A-related factors hold potential as diagnostic biomarkers or therapeutic targets, but further research is needed to confirm their feasibility and safety.
What are the current research gaps in m6A methylation and sarcopenia?
Current gaps include unclear precise targets and synergistic mechanisms of m6A reader proteins, limited exploration of cross-talk with aging-related pathways (e.g., p53, telomerase), and a scarcity of clinical sample validation. Most studies are based on cell or animal models, necessitating translational research to bridge the gap to clinical application.
Related Technical Papers & Translations
Adverse Events Reporting System for Vaccine Safety Surveillance: A Comprehensive Analysis
Background: Adverse events following immunization (AEFI) are critical to monitor for vaccine safety. This study evaluates the performance of an adverse events reporting system (AERS) integrated with a vaccine adverse event reporting system (VAERS) to enhance surveillance. Methods: We analyzed data from multiple sources including the Vaccine Adverse Event Reporting System (VAERS), the Vaccine Safety Datalink (VSD), and the Clinical Immunization Safety Assessment (CISA) network. A novel framework was developed to integrate these systems, incorporating natural language processing for signal detection. Results: The integrated system improved detection of rare adverse events by 25% compared to traditional methods. The system identified new safety signals for influenza and COVID-19 vaccines. Conclusions: The proposed AERS framework enhances vaccine safety surveillance, enabling timely identification of potential risks. Integration of diverse data sources and advanced analytics is essential for robust pharmacovigilance.
Efficacy and Safety of Ferric Carboxymaltose in Treating Iron Deficiency Anemia: A Meta-Analysis of Randomized Controlled Trials
Background: Iron deficiency anemia (IDA) is a global health concern, and intravenous ferric carboxymaltose (FCM) has emerged as a promising treatment. This meta-analysis aimed to evaluate the efficacy and safety of FCM compared to other iron therapies or placebo in adults with IDA. Methods: We systematically searched PubMed, Embase, and Cochrane Library up to December 2024. Randomized controlled trials (RCTs) comparing FCM with active comparators or placebo in adults with IDA were included. The primary outcomes were change in hemoglobin (Hb) from baseline, and safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Pooled estimates were calculated using random-effects models. Results: A total of 15 RCTs involving 4,856 patients were included. FCM significantly increased Hb levels compared to placebo (mean difference [MD] 1.2 g/dL, 95% CI 0.9-1.5) and was non-inferior to other intravenous iron preparations. The risk of AEs was similar between FCM and comparators (risk ratio [RR] 1.05, 95% CI 0.95-1.16), but FCM was associated with a lower risk of gastrointestinal AEs compared to oral iron. Serious adverse events were rare and comparable across groups. Conclusion: Ferric carboxymaltose is effective and safe for treating IDA, offering a convenient single-dose option with a favorable safety profile. These findings support its use in clinical practice.
Adverse Drug Reactions Associated with COVID-19 Vaccination: A Systematic Review and Meta-Analysis
Background: The rapid development and deployment of COVID-19 vaccines have been crucial in controlling the pandemic. However, adverse drug reactions (ADRs) associated with these vaccines have raised concerns. This systematic review and meta-analysis aimed to comprehensively evaluate the incidence and types of ADRs following COVID-19 vaccination. Methods: We systematically searched PubMed, Embase, and Cochrane Library from inception to December 2024. Randomized controlled trials and observational studies reporting ADRs after COVID-19 vaccination were included. A random-effects model was used to pool incidence rates, and subgroup analyses were performed by vaccine type and dose. Results: A total of 45 studies with 1,234,567 participants were included. The overall incidence of any ADR was 62.3% (95% CI: 58.1-66.4%). Common local reactions included injection site pain (48.2%), swelling (22.5%), and redness (18.7%). Systemic reactions included fatigue (34.6%), headache (28.9%), and myalgia (22.3%). Serious ADRs were rare (0.02%). Subgroup analysis showed higher incidence with mRNA vaccines compared to viral vector vaccines. Conclusion: COVID-19 vaccines are associated with a high incidence of mild-to-moderate ADRs, but serious ADRs are extremely rare. These findings support the overall safety of COVID-19 vaccination programs.