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Epigenetic dysfunctional diseases and therapy for infection and inflammation.

ABSTRACT: Even though the discovery of the term 'epigenetics' was in the 1940s, it has recently become one of the most promising and expanding fields to unravel the gene expression pattern in several diseases. The most well studied example is cancer, but other diseases like metabolic disorders, autism, or inflammation-associated diseases such as lung injury, autoimmune disease, asthma, and type-2 diabetes display aberrant gene expression and epigenetic regulation during their occurrence. The change in the epigenetic pattern of a gene may also alter gene function because of a change in the DNA status. Constant environmental pressure, lifestyle, as well as food habits are the other important parameters responsible for transgenerational inheritance of epigenetic traits. Discovery of epigenetic modifiers targeting DNA methylation and histone deacetylation enzymes could be an alternative source to treat or manipulate the pathogenesis of diseases. Particularly, the combination of epigenetic drugs such as 5-aza-2-deoxycytidine (Aza) and trichostatin A (TSA) are well studied to reduce inflammation in an acute lung injury model. It is important to understand the epigenetic machinery and the function of its components in specific diseases to develop targeted epigenetic therapy. Moreover, it is equally critical to know the specific inhibitors other than the widely used pan inhibitors in clinical trials and explore their roles in regulating specific genes in a more defined way during infection.

SUBMITTER: Samanta S

PROVIDER: S-EPMC5222695 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Epigenetic dysfunctional diseases and therapy for infection and inflammation.

Samanta Saheli S Rajasingh Sheeja S Cao Thuy T Dawn Buddhadeb B Rajasingh Johnson J

Biochimica et biophysica acta. Molecular basis of disease 20161203 2

Even though the discovery of the term 'epigenetics' was in the 1940s, it has recently become one of the most promising and expanding fields to unravel the gene expression pattern in several diseases. The most well studied example is cancer, but other diseases like metabolic disorders, autism, or inflammation-associated diseases such as lung injury, autoimmune disease, asthma, and type-2 diabetes display aberrant gene expression and epigenetic regulation during their occurrence. The change in the ...[more]

PMID: 27919711

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Project description:BACKGROUND:Chronological age is a prominent risk factor for many types of cancers including colorectal cancer (CRC). Yet, the risk of CRC varies substantially between individuals, even within the same age group, which may reflect heterogeneity in biological tissue aging between people. Epigenetic clocks based on DNA methylation are a useful measure of the biological aging process with the potential to serve as a biomarker of an individual's susceptibility to age-related diseases such as CRC. METHODS:We conducted a genome-wide DNA methylation study on samples of normal colon mucosa (N = 334). Subjects were assigned to three cancer risk groups (low, medium, and high) based on their personal adenoma or cancer history. Using previously established epigenetic clocks (Hannum, Horvath, PhenoAge, and EpiTOC), we estimated the biological age of each sample and assessed for epigenetic age acceleration in the samples by regressing the estimated biological age on the individual's chronological age. We compared the epigenetic age acceleration between different risk groups using a multivariate linear regression model with the adjustment for gender and cell-type fractions for each epigenetic clock. An epigenome-wide association study (EWAS) was performed to identify differential methylation changes associated with CRC risk. RESULTS:Each epigenetic clock was significantly correlated with the chronological age of the subjects, and the Horvath clock exhibited the strongest correlation in all risk groups (r > 0.8, p < 1 × 10-30). The PhenoAge clock (p = 0.0012) revealed epigenetic age deceleration in the high-risk group compared to the low-risk group. CONCLUSIONS:Among the four DNA methylation-based measures of biological age, the Horvath clock is the most accurate for estimating the chronological age of individuals. Individuals with a high risk for CRC have epigenetic age deceleration in their normal colons measured by the PhenoAge clock, which may reflect a dysfunctional epigenetic aging process.

Dataset Information

Epigenetic dysfunctional diseases and therapy for infection and inflammation.

Publications

Epigenetic dysfunctional diseases and therapy for infection and inflammation.

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