Scientists are always working against the clock, and recently, a team led by Wolfgang Wagner (RWTH Aachen University, Germany) used their ever-evaporating time to explore a potential link between telomere shortening and epigenetic clock acceleration in premature-aging associated bone marrow failure syndromes and describe a new disease biomarker!
Patients with premature aging and difficult-to-diagnose bone marrow failure syndromes such as Dyskeratosis congenita and idiopathic aplastic anemia share many features, and the Wagner lab aimed to evaluate telomere shortening and epigenetic clock acceleration in patient blood samples. While their study reports a disconnect between these aging measures, their epigenetic evaluation has highlighted DNA methylation of the PRDM8 gene as a useful disease biomarker.
Cypris, Eipel, and Beier and colleagues didn´t dawdle, dilly-dally, or delay, so let’s hurry up and read their exciting new findings!
- Age predictions based on telomere shortening and DNA methylation in bone marrow failure syndrome patients reveal significant differences when compared to chronological age
- A lack of correlation between aging measures suggests two independent premature aging processes
- DNA methylation analysis by MassARRAY technology and barcoded bisulfite amplicon sequencing confirms a previous link between PRDM8 gene methylation and bone marrow failure syndromes
- While PRDM8 methylation also occurs in premature aging diseases, DNA methylation status doesn´t correlate with epigenetic clock acceleration or telomere shortening
- Furthermore, DNA methylation doesn´t significantly influence PRDM8 gene expression, a finding attributed to low basal levels of expression in blood
- Induced pluripotent stem cells (iPSCs) with CRISPR/Cas9-mediated PRDM8 gene knockouts suffer from disrupted hematopoietic and neuronal differentiation, which represent a link to phenotypes observed in premature aging syndromes
- DNA methylation patterns in iPSCs, assessed using the Illumina Infinium MethylationEPIC BeadChip system, suggest that PRDM8 doesn’t influence epigenetic aging when evaluated with Horvath’s epigenetic clock
While the authors are in a hurry to connect epigenetic clock acceleration, telomere shortening, and PRDM8 gene methylation with bone marrow failure syndromes, their data doesn´t support a direct link between these critical components; however, this finding raises more exciting questions that future research will aim to answer (rapidly!). Meanwhile, their current results support PRDM8 methylation as a new disease biomarker (an important discovery, as not all patients possess shortened telomeres or disease-associated mutations) and the potential cause of the hematopoietic/neuronal phenotypes observed in premature aging-related syndromes.
So don´t drag your feet and hurry on over Clinical Epigenetics, August 2020.