Molecular mechanisms of environmental exposures and human disease

• Published in: Nature reviews. Genetics 2023-05, Vol.24 (5), p.332-344
• Main Authors: Wu, Haotian, Eckhardt, Christina M., Baccarelli, Andrea A.
• Format: Article
• Language: English
• Subjects: 631/208/176; 631/208/2489/144; 631/337; 692/420; Agriculture; Animal Genetics and Genomics; Biomedical and Life Sciences; Biomedicine; Cancer Research; DNA Methylation; Environment; Environmental Exposure - adverse effects; Environmental impact; Environmental Pollutants - toxicity; Epigenesis, Genetic; Epigenetics; Extracellular vesicles; Gene expression; Gene Function; Genomes; Histones; Human Genetics; Humans; Life span; Mitochondria; Molecular modelling; Non-coding RNA; Pollutants; Respiratory diseases; Review Article; Vesicles
• ISSN: 1471-0056; 1471-0064
• DOI: 10.1038/s41576-022-00569-3

A substantial proportion of disease risk for common complex disorders is attributable to environmental exposures and pollutants. An appreciation of how environmental pollutants act on our cells to produce deleterious health effects has led to advances in our understanding of the molecular mechanisms underlying the pathogenesis of chronic diseases, including cancer and cardiovascular, neurodegenerative and respiratory diseases. Here, we discuss emerging research on the interplay of environmental pollutants with the human genome and epigenome. We review evidence showing the environmental impact on gene expression through epigenetic modifications, including DNA methylation, histone modification and non-coding RNAs. We also highlight recent studies that evaluate recently discovered molecular processes through which the environment can exert its effects, including extracellular vesicles, the epitranscriptome and the mitochondrial genome. Finally, we discuss current challenges when studying the exposome — the cumulative measure of environmental influences over the lifespan — and its integration into future environmental health research. Environmental pollutants have been shown to disrupt molecular mechanisms underlying common complex diseases. The authors review the interplay of environmental stressors with the human genome and epigenome as well as other molecular processes, such as production of extracellular vesicles, epitranscriptomic changes and mitochondrial changes, through which the environment can exert its effects.