RE: Mitochondrien - 17

Associations between Circulating Biomarkers of One-Carbon Metabolism and Mitochondrial D-Loop Region Methylation Levels

Zitat

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Background/Objectives: One-carbon metabolism is a critical pathway for epigenetic mechanisms. Circulating biomarkers of one-carbon metabolism have been associated with changes in nuclear DNA methylation levels in individuals affected by age-related diseases. More and more studies are showing that even mitochondrial DNA (mtDNA) could be methylated. In particular, methylation of the mitochondrial displacement (D-loop) region modulates the gene expression and replication of mtDNA and, when altered, can contribute to the development of human illnesses. However, no study until now has demonstrated an association between circulating biomarkers of one-carbon metabolism and D-loop methylation levels. Methods: In the study presented herein, we searched for associations between circulating one-carbon metabolism biomarkers, including folate, homocysteine, and vitamin B12, and the methylation levels of the D-loop region in DNA obtained from the peripheral blood of 94 elderly voluntary subjects. Results: We observed a positive correlation between D-loop methylation and vitamin B12 (r = 0.21; p = 0.03), while no significant correlation was observed with folate (r = 0.02; p = 0.80) or homocysteine levels (r = 0.02; p = 0.82). Moreover, D-loop methylation was increased in individuals with high vitamin B12 levels compared to those with normal vitamin B12 levels (p = 0.04). Conclusions: This is the first study suggesting an association between vitamin B12 circulating levels and mtDNA methylation in human subjects. Given the potential implications of altered one-carbon metabolism and mitochondrial epigenetics in human diseases, a deeper understanding of their interaction could inspire novel interventions with beneficial effects for human health.

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https://www.mdpi.com/2075-4655/8/4/38

Mitochondria break free: Mitochondria-derived vesicles in aging and associated conditions
https://www.sciencedirect.com/science/ar...568163724003672

Human iPSCs from Aged Donors Retain Their Mitochondrial Aging Signature
https://www.mdpi.com/1422-0067/25/20/11199

Mitochondrial fatty acid oxidation drives senescence
https://pubmed.ncbi.nlm.nih.gov/39454000/

Transfer of mitochondrial DNA into the nuclear genome during induced DNA breaks
https://www.nature.com/articles/s41467-024-53806-0

A nucleic acid prodrug activates mitochondrial respiration and extends lifespan
https://www.biorxiv.org/content/10.1101/...dV67CPVe_LbocyQ

Hallo Prometheus,

die bei der Studie verwendeten Substanzen können evtl. schwere Nebenwirkungen verursachen(?): https://www.biorxiv.org/content/10.1101/...3599v1.full.pdf .

Viele Grüße und einen schönen Tag

Roger

Zitat von Prometheus im Beitrag #409

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@Roger
Schon möglich, aber zumindest im Zytotoxizitäts-Assay haben die Substanzen sehr gut abgeschnitten.... Welche konkreten Nebenwirkungen erwartest du?

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Zitat

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Despite the evidence of the therapeutic effects of ATP derivatives, their efficacy remains controversial. Some reports suggest that ATP administration is ineffective as a pharmaceutical agent because of the limited blood stability of adenosine derivatives and the lack of cell membrane permeability of the negatively charged phosphate groups, hindering entry into cells. Furthermore, cells recognize extracellular ATP as an inflammatory signal. To minimize side effects, ATP administration techniques include drug delivery methods that encapsulate ATP in microparticles such as liposomes, micelles, and nanospheres21. Nevertheless, these approaches have limited utilization and applicability in the treatment of age-related diseases. Owing to the difficulty of increasing intracellular ATP concentrations, the long-term effects of ATP administration as a drug remain unclear.
Therefore, the present study was designed to develop the world’s first prodrug with enhanced biological stability and cellular permeability of adenosine phosphate, capable of stimulating AXP (adenosine monophosphate (AMP), adenosine diphosphate (ADP), and ATP)-associated metabolic pathways, boosting mitochondrial respiration, ATP production, and reducing aging

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https://www.biorxiv.org/content/10.1101/...3599v1.full.pdf

Dabei ist ja erklärt, dass der in der Studie genutzte Stoff gerade in Hinblick auf diese möglichen Probleme entwickelt wurde.

Hallo Prometheus,

es geht konkret um diese Substanzen und ich sehe das kritisch: mononucleoside analogs as a class of nucleoside-based antivirals, such as Sofosbuvir and Remdesivir,
targeting hepatitis C virus23, and COVID-1924.

Viele Grüße

Roger