By Aliza Becker, BA, MPS

DNA damage in the body is responsible for both normal aging and the emergence of certain health conditions.¹ The first part of this series examined effects of the diet on telomeres, which caps the ends of individual chromosomes to prevent them from fraying or becoming entangled with one another.² Shorter telomeres may predispose individuals to different diseases and an increased risk of mortality,³ and research suggests that diet can influence telomere length. Meanwhile, the second part of this series explored the impact of diet on DNA replication, which is crucial for tissue growth and repair within the body. The final part of this series will explore the effects food can have on gene expression.

Understanding Gene Expression

Broadly, gene expression is the process by which information from a gene (a segment of DNA) is ultimately used to synthesize a product, such as a protein, with functional effects.⁴ DNA is converted into messenger RNA during the process of transcription, which is then decoded into amino acids via the process of translation to form the aforementioned proteins.⁵ These proteins ultimately go on to exert functional effects elsewhere in the body. These two steps, which occur following DNA replication, wherein two identical DNA strands are created, are collectively known as gene expression.   

Different genes may be expressed differently in response to internal stimuli, such as hormones and metabolic activities, or external stimuli like climate (temperature, humidity), pollution, and diet.^6–8 The diet’s effects on gene expression may be realized through several mechanisms, the first of which is the regulation of transcription factors, which are proteins that bind to specific DNA sequences near genes to control the transcription of a gene into messenger RNA. Consider the consumption of carbohydrates, which are eventually broken down into individual monosaccharides through digestion that may end up in the bloodstream as glucose following conversion by the liver, prompting cells in the pancreas to secrete insulin.⁹  The produced insulin activates insulin receptors that subsequently initiate a cascade of signaling events that promote the activation of transcription factors that regulate the expression of genes involved in glucose and lipid metabolism.¹⁰ For example, it is known that insulin signaling induces fatty acid and cholesterol synthesis via the regulation of SREBP transcription factors which also promotes fatty acid synthesis through activation of USF1 and LXR.¹¹ Meanwhile, AMP-activated protein kinase, an enzyme, may be activated when glucose levels are low, triggering other transcription factors that upregulate genes involved in energy production while inhibiting those involved in energy-consuming processes like glucose and lipid production (such as via the transcription factor SREBP-1c, which controls the synthesis of lipids from glucose in the liver¹²) to restore energy balance.^13,14 

To keep with the example, the concentration and duration of insulin exposure can also lead to the expression of distinct sets of genes: while short-term insulin exposure in response to rising blood glucose levels following a meal may only activate genes involved in the process of glucose uptake into cells, such as the SLC2 genes, which encode for a family of glucose transporter proteins—most notably, GLUT4—responsible for facilitating glucose transport across cell membranes,¹⁵ more prolonged exposure to insulin—which may result from insulin resistance, wherein the pancreas produces more insulin to account for a reduced cellular response to existing insulin—can lead to the downregulation of insulin receptors and alterations in gene expression related to glucose metabolism, ultimately further contributing to insulin resistance.¹⁶

Meanwhile, another mechanism by which the diet may influence gene expression is by supporting epigenetic modifications—reversible changes to DNA that regulate gene activity without altering the DNA sequence itself—through its inclusion of various nutrients enabling the availability of enzymes required for these changes.^17,18 Two prominent types of changes are DNA methylation and histone modification. Importantly, DNA methylation involves the addition of a methyl group to the cytosine residues in DNA, which can act as a physical barrier preventing the binding of transcription factors or other regulatory proteins to ultimately inhibit gene expression.¹⁹ As the primary enzymes involved in DNA methylation, DNA methyltransferases require specific nutrients to function properly; these include vitamin B9 and other B-vitamins (B2, B6, B12), which are essential for the production of S-adenosylmethionine, the universal methyl donor in methylation reactions, or zinc, which acts as a co-factor to support these enzymes’ ability to efficiently catalyze the addition of methyl groups to DNA.^20,21 In related fashion, histone modifications refer to the addition or removal of chemical groups (such as acetyl or methyl groups) to the histone proteins around which DNA is wrapped to either “relax” the chromatin (DNA packaging) structure, making genes more accessible for “activation” (transcription), or to “tighten” the structure up, similarly silencing gene expression.²² Vitamin B9 and other B-vitamins are also required for histone modification,¹⁸ along with vitamin C and iron, which act as co-factors for enzymes involved in histone modification.²³  

Conclusion

This third and final installment of the “Nutrients for DNA Damage and Repair” series concludes the series by briefly discussing the impact that diet has on gene expression. When combined with the other two parts covering telomere health and DNA replication, the overall message of this series is clear: following a healthy, balanced diet is necessary for fundamental processes within the body to occur without error. This will allow the achievement of wellbeing at even the smallest levels, with larger resulting effects.

Note: Please consult your primary care physician or nutritionist about what may be the best diet for you. 

Sources

1. Guo J, Huang X, Dou L, et al. Aging and aging-related diseases: from molecular mechanisms to interventions and treatments. Sig Transduct Target Ther. 2022;7:391.
2. NIH National Human Genome Research Institute. Telomere. Updated 27 Nov 2024. Accessed 27 Nov 2024. https://www.genome.gov/genetics-glossary/Telomere
3. Schneider CV, Schneider KM, Teumer A, et al. Association of telomere length with risk of disease and mortality. JAMA Intern Med. 2022;182(3):291–300.
4. National Human Genome Research Institute. Gene expression. Accessed 22 Nov 2024. https://www.genome.gov/genetics-glossary/Gene-Expression. 
5. Clancy S, Brown W. Translation: DNA to mRNA to protein. Nature Ed. 2008;1(1):101.
6. Virolainen SJ, VonHandorf A, Viel KCMF, et al. Gene–environment interactions and their impact on human health. Genes Immun. 2022;24(1):1–11.
7. Pascual-Ahuir A, Fita-Torró J, Proft M. Capturing and understanding the dynamics and heterogeneity of gene expression in the living cell. Int J Mol Sci. 2020;21(21):8278.
8. Stucki D, Freitak D, Sundström L. Survival and gene expression under different temperature and humidity regimes in ants. PLoS One. 2017;12(7):e0181137.
9. Becker A. Sugar and the human body. Nutr Health Rev. 2021;137:4–12.
10. Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018;98(4):2133–2223.
11. Cell Signaling Technology. Insulin receptor signaling. Revised Sep 2016. Accessed 24 Nov 2024. https://www.cellsignal.com/pathways/insulin-receptor-signaling-pathway
12. Ferré P, Phan F, Foufelle F. SREBP-1c and lipogenesis in the liver: an update1. Biochem J. 2021;478(20):3723–3739.
13. Long YC, Zierath JR. AMP-activated protein kinase signaling in metabolic regulation. J Clin Invest. 2006;116(7):1776–1783.
14. Jäger S, Handschin C, St-Pierre J, et al. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci U S A. 2007;17;104(29):12017–12022.
15. Mueckler M, Thorens B. The SLC2 (GLUT) family of membrane transporters. Mol Aspects Med. 2013;34(0):121–138.
16. Bano S, More S, Mongad DS, et al. Prolonged exposure to insulin might cause epigenetic alteration leading to insulin resistance (online ahead of print October 29, 2024). FEBS Open Bio.
17. Handy DE, Castro R, Loscalzo J. Epigenetic modifications: basic mechanisms and role in cardiovascular disease. Circulation. 2011;123(19):2145–2156.
18. Choi S-W, Friso S. Epigenetics: a new bridge between nutrition and health. Adv Nutr. 2010;1(1):8–16.
19. Biomodal. How DNA methylation affects gene expression. 19 Aug 2024. Accessed 24 Nov 2024. https://biomodal.com/blog/how-dna-methylation-affects-gene-expression/ 
20. Azimi Z, Isa MR, Khan J, et al. Association of zinc level with DNA methylation and its consequences: a systematic review. Heliyon. 2022;8(10):e10815.
21. Anderson OS, Sant KE, Dolinoy DC. Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J Nutr Biochem. 2012;23(8):853–859.
22. Tryon WW. Core network principles: the explanatory nucleus. In: Cognitive Neuroscience and Psychotherapy. 1st ed. Academic Press; 2014:125–222.
23. Khajebishak Y, Alivand M, Faghfouri AH, et al. The effects of vitamins and dietary pattern on epigenetic modification of non-communicable diseases. Int J Vitam Nutr Res. 2023;93(4):362–377.