Using an epigenetic clock to assess liver disease

This 2018 UC San Diego human study investigated the capability of the epigenetic clock methodology to detect biological aging with nonalcoholic steatohepatitis (NASH) patients:

“The ability to measure a surrogate marker of liver aging from a peripheral blood sample has broad implications for assessing clinically “silent” chronic diseases, such as NASH, and, potentially, their response to interventions.

In the current study, we validate the utility of the Horvath clock in measuring age acceleration in a defined cohort of NASH patients with moderate to severe liver fibrosis.”

The study demonstrated several aspects of age acceleration and disease conditions, including:

– Use of clinical trial data.

“This study, however, included patients who were part of a clinical trial in which protocol-obtained biopsies were read by a central pathologist (ZG) and morphometric quantification of collagen standardized.”

– Continuous measures were more relevant than “Stage X” measures.

“The findings in the current work are in contrast to an earlier study that found no association of DNAm with the NAFLD activity score or stage of liver fibrosis in patients with NASH. Importantly, that study assessed liver fibrosis based on conventional histological staging only, using the ordinal METAVIR classification. Similarly, we also found no difference in age acceleration between patients with stage 2 and 3 fibrosis according to the NASH Clinical Research Network (CRN) classification.

On the contrary, by evaluating two continuous measures of fibrosis (hepatic collagen content by morphometry and the serum ELF test), which have a greater dynamic range than traditional histological staging, we found that patients with higher age acceleration have increased hepatic fibrosis.”

– Causalities may not necessarily be ascribed.

“Although these reports establish a potential relationship between fibrosis and specific epigenetic modifications, targeted individual CpG sites may not accurately reflect the complex interaction between causal and compensatory measures in chronic diseases such as NASH.” “DNA methylation signatures reflect aging in patients with nonalcoholic steatohepatitis”


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