Pathophysiological Epigenetic Mechanisms in the Development of Chronic Diseases

Bizhanova D.K; Sharipova P.A

doi:10.51699/cajmns.v7i2.3167

Authors

Bizhanova D.K Faculty of Medicine, Tashkent State Medical University
Sharipova P.A PhD (Candidate of Medical Sciences), Associate Professor of the Department of Physiology and Pathology, Tashkent State Medical University, Tashkent

DOI:

https://doi.org/10.51699/cajmns.v7i2.3167

Keywords:

epigenetics, chronic diseases, DNA methylation, histone modifications, microRNA, inflammation, diabetes, cardiovascular diseases, autoimmune diseases, neurodegenerative disorders

Abstract

Epigenetic mechanisms, which are processes that regulate the expression of genes without changing the DNA sequence. These mechanisms are critical for adaptation of cells to various environmental cues and the ability of cells to sustain transcriptional activity. Recent research indicates that epigenetic changes are associated with the initiation and progression of various chronic diseases as cardiovascular disease, metabolic syndrome, type 2 diabetes mellitus, autoimmune diseases, neurodegenerative diseases, and chronic inflammatory diseases. This influence modifies cellular signalling pathways, phenotypic plasticity and immune regulation as well as metabolic pathways. While there has been groundbreaking progress in understanding genetic determinants of common chronic diseases, classical genetic approaches separate from the epigenome cannot explain all the variance in disease expression and disease processing among those with the same genotype. Such features underline the importance of probing epigenetic regulation and implication of environmental forces including nutrition, stress, lifestyle, and microbiota. We contribute to this knowledge gap by providing a systematic review regarding major epigenetic mechanisms and their role in the pathogenesis of chronic disease, including their potential application as diagnostic markers and therapeutic targets. Epigenetic processes (including DNA methylation, histone modification, and microRNA regulation) and resultant persistent transcriptional changes related to these disturbances are able to affect the molecular pathways in inflammation, metabolic imbalance, immune dysfunction, and cellular phenotypic alteration associated with chronic diseases. This research highlights how the epigenome serves as a unifying linking pin between genetic susceptibility, environmental exposure, metabolic status and immune activity in chronic disease pathogenesis. Knowledge of epigenetic regulation offers prospects for early diagnostic markers, risk stratification and the design of personalised therapeutic strategies with the goals of correcting stable regulatory disturbances that underlie chronic pathology.

References

E. Stylianou, “Epigenetics of chronic inflammatory diseases,” J. Inflamm. Res., vol. 11, pp. 1–14, 2018.

S. Alipour et al., “Epigenetic alterations in chronic disease focusing on Behçet’s disease: Review,” Biomed. Pharmacother., vol. 91, pp. 526–533, 2017.

F. Ramzan, M. H. Vickers, and R. F. Mithen, “Epigenetics, microRNA and Metabolic Syndrome: A Comprehensive Review,” Int. J. Mol. Sci., vol. 22, no. 9, p. 5047, 2021.

B. R. Joubert et al., “DNA methylation in newborns and maternal smoking in pregnancy,” Am. J. Hum. Genet., vol. 98, no. 4, pp. 680–696, 2016.

L. Zhang, Q. Lu, and C. Chang, “Epigenetics in Health and Disease,” in Advances in Experimental Medicine and Biology, vol. 1253, pp. 3–55, 2020.

E. M. Small and E. N. Olson, “Pervasive roles of microRNAs in cardiovascular biology,” Nature, vol. 469, pp. 336–342, 2011.

R. Jaenisch and A. Bird, “Epigenetic regulation of gene expression: How the genome integrates intrinsic and environmental signals,” Nat. Genet., vol. 33, pp. 245–254, 2003.

J. Lambert and H. F. Jørgensen, “Epigenetic regulation of vascular smooth muscle cell phenotypes in atherosclerosis,” Circ. Res., vol. 117, pp. 1100–1112, 2015.

P. A. Jones, “Functions of DNA methylation: islands, start sites, gene bodies and beyond,” Nat. Rev. Genet., vol. 13, pp. 484–492, 2012.

N. Acevedo et al., “Perinatal and early-life nutrition, epigenetics, and allergy,” Nutrients, vol. 13, no. 3, p. 724, 2021.

P. Ntontsi et al., “Genetics and epigenetics in asthma,” Int. J. Mol. Sci., vol. 22, no. 5, p. 2412, 2021.

A. Bird, “DNA methylation patterns and epigenetic memory,” Genes Dev., vol. 16, pp. 6–21, 2002.

C. D. Allis and T. Jenuwein, “The molecular hallmarks of epigenetic control,” Nat. Rev. Genet., vol. 17, pp. 487–500, 2016.

A. P. Feinberg, “The key role of epigenetics in human disease prevention and mitigation,” N. Engl. J. Med., vol. 379, pp. 400–401, 2018.

P. W. Laird, “Principles and challenges of genome-wide DNA methylation analysis,” Nat. Rev. Genet., vol. 11, pp. 191–203, 2010.

A. Portela and M. Esteller, “Epigenetic modifications and human disease,” Nat. Biotechnol., vol. 28, pp. 1057–1068, 2010.

C. López-Otín et al., “The hallmarks of aging,” Cell, vol. 153, pp. 1194–1217, 2013.

K. D. Robertson, “DNA methylation and human disease,” Nat. Rev. Genet., vol. 6, pp. 597–610, 2005.

S. Horvath, “DNA methylation age of human tissues and cell types,” Genome Biol., vol. 14, p. R115, 2013.

M. E. Levine et al., “An epigenetic biomarker of aging for lifespan and healthspan,” Aging (Albany NY), vol. 10, pp. 573–591, 2018.

C. Franceschi et al., “Inflammaging: A new immune-metabolic viewpoint for age-related diseases,” Nat. Rev. Immunol., vol. 18, pp. 576–590, 2018.

H. Cedar and Y. Bergman, “Epigenetics of haematopoietic cell development,” Nat. Rev. Immunol., vol. 11, pp. 478–488, 2011.

H. Wu and Y. Zhang, “Reversing DNA methylation: mechanisms, genomics, and biological functions,” Cell, vol. 156, pp. 45–68, 2014.

J. Gräff and L.-H. Tsai, “Histone acetylation: molecular mnemonics on the chromatin,” Nat. Rev. Neurosci., vol. 14, pp. 97–111, 2013.

A. Bird, “Perceptions of epigenetics,” Nature, vol. 447, pp. 396–398, 2007.

D. R. Donohoe et al., “The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon,” Cell Metab., vol. 16, pp. 400–413, 2012.

A. Koh et al., “From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites,” Cell, vol. 165, pp. 1332–1345, 2016.

I. Tabas and K. E. Bornfeldt, “Macrophage phenotype and function in different stages of atherosclerosis,” Nat. Rev. Immunol., vol. 16, pp. 517–529, 2016.

M. A. Reddy and R. Natarajan, “Epigenetic mechanisms in diabetic complications and metabolic memory,” Nat. Rev. Nephrol., vol. 7, pp. 675–688, 2011.

P. Chi, C. D. Allis, and G. G. Wang, “Covalent histone modifications—miswritten, misinterpreted and mis-erased in human cancers,” Nat. Rev. Cancer, vol. 10, pp. 457–469, 2010.