ArticleBiochimica et biophysica acta2015
Hyperhomocysteinemia associated skeletal muscle weakness involves mitochondrial dysfunction and epigenetic modifications.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 73 citations in OpenAlex.
- The first report of primary hypotonia with abnormal electromyogram and CBS mutation in a Chinese child.BMC medical genomics · 2026Article
- Downregulation of microRNA-494 drives mitochondrial biogenesis and function in trained muscle.Experimental physiology · 2026Article
- Genetically Predicted Homocysteine Levels and B Vitamins on Sarcopenia-Related Traits: Insights From an Observational and Mendelian Randomization Analysis.Food science & nutrition · 2026Article
- HHandbook of experimental pharmacology · 2026Review
- Association of serological biomarkers with muscle strength and function in sarcopenia: a cross-sectional study.Annals of medicine · 2025Article
- Association between body folate status and muscle mass: a cross-sectional study of the National Health and Nutrition Examination Survey 2011-2018.Journal of health, population, and nutrition · 2025Article
- DNA Methylation in Periodontal Disease: A Focus on Folate, Folic Acid, Mitochondria, and Dietary Intervention.International journal of molecular sciences · 2025Review
- Nicotinamide N-Methyltransferase (NNMT): A New Hope for Treating Aging and Age-Related Conditions.Metabolites · 2024Review
- Diet-induced hyperhomocysteinemia causes sex-dependent deficiencies in offspring musculature and brain function.Frontiers in cell and developmental biology · 2024Article
- Current approach to the diagnosis of sarcopenia in cardiovascular diseases.Frontiers in nutrition · 2024Review
- Targeting Homocysteine and Hydrogen Sulfide Balance as Future Therapeutics in Cancer Treatment.Antioxidants (Basel, Switzerland) · 2023Review
- Relationship between hyperhomocysteinemia and coexisting obesity with low skeletal muscle mass in asymptomatic adult population.Scientific reports · 2022Article
- Physiological Systems in Promoting Frailty.Comprehensive Physiology · 2022Review
- Association between Elevated Plasma Homocysteine and Low Skeletal Muscle Mass in Asymptomatic Adults.Endocrinology and metabolism (Seoul, Korea) · 2022Article
- Associations between homocysteine, inflammatory cytokines and sarcopenia in Chinese older adults with type 2 diabetes.BMC geriatrics · 2021Article
- Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person.The EPMA journal · 2021Review
- An N-ethyl-N-Nitrosourea Mutagenesis Screen in Mice Reveals a Mutation inAnimals : an open access journal from MDPI · 2021Article
- Regulation of the parental gene GRM4 by circGrm4 RNA transcript and glutamate-mediated neurovascular toxicity in eyes.Molecular and cellular biochemistry · 2021Review
- Remote Hind-Limb Ischemia Mechanism of Preserved Ejection Fraction During Heart Failure.Frontiers in physiology · 2021Article
- Diabetic Retinopathy: Mitochondria Caught in a Muddle of Homocysteine.Journal of clinical medicine · 2020Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
HHcy has been implicated in elderly frailty, but the underlying mechanisms are poorly understood. Using C57 and CBS+/- mice and C2C12 cell line, we investigated mechanisms behind HHcy induced skeletal muscle weakness and fatigability. Possible alterations in metabolic capacity (levels of LDH, CS, MM-CK and COX-IV), in structural proteins (levels of dystrophin) and in mitochondrial function (ATP production) were examined. An exercise regimen was employed to reverse HHcy induced changes. CBS+/- mice exhibited more fatigability, and generated less contraction force. No significant changes in muscle morphology were observed. However, there is a corresponding reduction in large muscle fiber number in CBS+/- mice. Excess fatigability was not due to changes in key enzymes involved in metabolism, but was due to reduced ATP levels. A marginal reduction in dystrophin levels along with a decrease in mitochondrial transcription factor A (mtTFA) were observed. There was also an increase in the mir-31, and mir-494 quantities that were implicated in dystrophin and mtTFA regulation respectively. The molecular changes elevated during HHcy, with the exception of dystrophin levels, were reversed after exercise. In addition, the amount of NRF-1, one of the transcriptional regulators of mtTFA, was significantly decreased. Furthermore, there was enhancement in mir-494 levels and a concomitant decline in mtTFA protein quantity in homocysteine treated cells. These changes in C2C12 cells were also accompanied by an increase in DNMT3a and DNMT3b proteins and global DNA methylation levels. Together, these results suggest that HHcy plays a causal role in enhanced fatigability through mitochondrial dysfunction which involves epigenetic changes.
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