Long-Term Assessments Needed to Evaluate Impact of Accelerated Aging on EoE Progression

Elizabeth T Jensen, MPH, PhD

According to new findings, patients with with eosinophilic esophagitis (EoE) exhibit persistence of significant accelerated molecular aging of the esophagus relative to patient chronologic age after an initial 8-week course of topical steroids, irrespective of histologic treatment response.

“Long term assessments are needed to evaluate the implications of accelerated aging on disease progression, complications, and comorbidities,” wrote study author Elizabeth T Jensen, MPH, PhD, Wake Forest University School of Medicine.

The findings were presented at the 2022 Digestive Disease Week Annual Meeting in San Diego, California.

Previous findings showed that individuals with EoE exhibit accelerated epigenetic molecular aging of the esophagus relative to patient chronologic age. The implications of advanced molecular aging in patients with EoE are unknown and post-treatment molecular aging has not previously been examined, investigators said.

Thus, the current study aimed to determine whether post-treatment esophageal cells from EoE patients exhibit molecular aging, as well as compare post-treatment molecular age to pre-treatment molecular age. Further, it aimed to determine whether post-treatment molecular age relative to chronologic age differs as a result of treatment response.

Investigators extracted from esophageal biopsies obtained at the diagnostic endoscopy and initial post-treatment endoscopy following 8 weeks of topical corticosteroid treatment. The histologic treatment response was defined as an absence of any esophageal eosinophilia (0 eos/hpf)

Additionally, the study authors noted that pre- and post-treatment DNA methylation was assayed on the Illumina Human Methylation450 and MethylationEPIC BeadChips, respectively. Arrays were processed using standard protocol and best practices for normalization and quality control, investigators said.

Furthermore, normalized β values for 353 CpG probes were submitted to an online DNA methylation age calculator in order to calculate a patient’s methylation age. A Mann Whitney U test evaluated the difference between molecular age and chronologic age post-treatment, molecular age post- and pre-treatment and responded versus non-responder.

From a total of 14 individuals with both pre- and post-treatment samples, there were 7 responders (57% female: 100% white, 100% atopic) and 7 non-responders (57% female; 100% white; 71% atopic).

In the responder cohort, peak eosinophils decreased from 155 ± 108 eos/hpf to 0 ± 0 eos/hpf post-treatment, but were unchanged in the non-responders (baseline: 137±152 eos/hpf; post-treatment 147 ± 82 eos/hpf).

The median patient chronological age at diagnosis was 36.5 years. The median molecular age was 48.9 years pre-treatment and 46.4 years post-treatment. Then, investigators noted that post-treatment, molecular age remained significantly greater than chronological age (P <.001), with a median difference of 18.6 years.

No difference in median molecular age was found when comparing pre- and post-treatment (P <.44), according to investigators. Moreover, no significant difference in accelerated aging was seen by treatment responder status.

The study, “Accelerated Molecular Aging Persists Despite Successful Treatment and Histologic Resolution in Eosinophilic Esophagitis,” was presented at DDW 2022.