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The Intricate Dance Between Epigenome and Metabolism

The relationship between the epigenome and metabolism plays a crucial role in human physiology, influencing cellular function and overall health. Here are the key points that illustrate this relationship:

 

  • Epigenetic Regulation and Metabolism: Epigenetic mechanisms, such as DNA methylation and histone modifications, regulate gene expression without altering the underlying DNA sequence. These modifications can be influenced by the availability of metabolic substrates, indicating a direct link between cellular metabolism and the epigenome​.


  • Metabolites as Epigenetic Modifiers: Metabolites such as S-adenosylmethionine (SAM), alpha-ketoglutarate (α-KG), acetyl-CoA, and NAD+ are substrates or cofactors for enzymes that modify DNA and histones. This connection allows cellular metabolic states to influence epigenetic landscapes, thereby controlling gene expression and cellular functions​.


  • Aging and Disease: As organisms age, changes in both the epigenome and metabolism are common. For example, mitochondrial dysfunction, which is prevalent in aging, leads to altered levels of metabolites that are crucial for maintaining proper epigenetic marks. This interplay can contribute to aging-related diseases such as age-related macular degeneration and glaucoma​.


  • Environmental and Lifestyle Factors: External factors like diet, stress, and environmental exposures can impact both metabolic processes and epigenetic regulation. For instance, hypoxia affects epigenetic modifiers like the ten-eleven translocation (TET) enzymes, which require oxygen to function, thereby linking environmental conditions directly to epigenetic states​.


  • Bidirectional Influence: There is a bidirectional relationship between metabolism and the epigenome: not only can metabolic states influence epigenetic modifications, but changes in the epigenome can also affect metabolic pathways. For instance, epigenetic changes in genes involved in energy metabolism can lead to metabolic shifts, creating a feedback loop that regulates cellular homeostasis​.


Overall, the intricate relationship between the epigenome and metabolism is fundamental to understanding cellular function, development, and the progression of diseases, highlighting the importance of considering both genetic and metabolic factors in health and disease research.


Mondal, A.K., et al., Epigenome-metabolism nexus in the retina: implications for aging and disease. Trends in Genetics, 2024.

 



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