Accelerated biological aging not a risk factor for severe COVID-19, say researchers

A new study conducted by researchers at RWTH Aachen University in Germany has found no evidence to support the hypothesis that severe outcomes in cases of coronavirus disease 2019 (COVID-19) may be linked to accelerated biological aging.

As a person ages, specific DNA methylation changes occur in the genome that can be combined into “epigenetic clocks” that reflect not only chronological age, but also biological or epigenetic age.

It has recently been suggested that patients with an accelerated epigenetic age are susceptible to more severe COVID-19 outcomes.

Now, Wolfgang Wagner and colleagues say their study did not reveal any evidence that severe COVID-19 outcomes are associated with accelerated epigenetic aging.

The team found that age-associated DNA methylation changes were not generally accelerated in patients with severe COVID-19 outcomes.

“Analysis of epigenetic age in blood is therefore not suitable to stratify elderly patients that are potentially even more susceptible to severe COVID-19 infections,” write the researchers.

A pre-print version of the paper is available on the medRxiv* server, while the article undergoes peer review.

Older age is a risk factor for more severe COVID-19

Older chronological age is a significant risk factor for more severe COVID-19, with severe or even fatal outcomes disproportionately affecting older adults.

However, recently it has been suggested that elderly individuals with an accelerated biological age may be particularly susceptible to severe outcomes.

The process of biological aging is reflected by molecular hallmarks such as epigenetic modifications. During the aging process, DNA methylation changes are acquired at specific CG dinucleotides called “CpG sites.”

“The DNA methylation levels of several age-associated CpGs can therefore be combined into ‘epigenetic clocks’ to predict donor age,” write Wagner and colleagues.

The researchers say a number of diseases, as well as higher all-cause mortality, have previously been associated with accelerated epigenetic aging.

Furthermore, coronavirus infections have been suggested to mediate DNA methylation, they add.

“We, therefore, followed the hypothesis that accelerated epigenetic age increases susceptibility to severe COVID-19 infections,” writes the team.

What did the researchers do?

The team used blood samples collected from 20 patients (aged a mean of 66 years) with COVID-19, 16 of whom had acute respiratory distress syndrome (ARDS).

The Illumina EPIC methylation microarray was used to assesses approximately 850,000 CpG sites across the genomes of samples taken from nine patients.

The results were compared with publicly available DNA methylation profiles of 185 healthy controls generated prior to the first SARS-CoV-2 outbreak.

What did the study find?

Using four different epigenetic age predictors, the team found that epigenetic age clearly correlated with chronological age.

Compared with the control group, samples from the nine COVID-19 patients did not show any evidence of accelerated epigenetic aging. The difference between epigenetic age and chronological age fell at around zero years across all of the predictors.

Next, the team used targeted bisulfite amplicon sequencing to analyze three genomic regions that are highly correlated with chronological age and with a combination of methylated CpGs to estimate the donor age of blood samples from 95 controls and 17 patients with COVID-19.

Again, the analysis revealed no evidence of accelerated epigenetic aging in the COVID-19 samples, even when samples were stratified by the presence or absence of ARDS.

Testing another hallmark of aging

Another hallmark of aging is telomere attrition. One study recently indicated that telomere attrition below the 10th percentile is more frequently identified in the leukocytes of COVID-19 patients compared with those of healthy controls.

Therefore, the team investigated whether this alternative biomarker of biological age was accelerated in the lymphocytes of COVID-19 samples (n=19) using fluorescent in-situ hybridization to analyze telomere length.

Compared with telomere length distribution among 356 healthy controls, there was no evidence of significant telomere attrition among the COVID-19 patients.

The biomarkers are “not suitable” for predicting severe COVID-19 outcomes

The researchers say the findings do not provide evidence that severe outcomes in COVID-19 are associated with accelerated epigenetic aging or significantly shortened telomere length.

“We did not observe signs of premature biological aging in our COVID-19 patients,” they write.

“Our results demonstrate that these biomarkers of biological age are therefore not suitable to predict a higher risk for severe COVID-19 infection in elderly patients,” concludes the team.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Sally Robertson

Written by

Sally Robertson

Sally first developed an interest in medical communications when she took on the role of Journal Development Editor for BioMed Central (BMC), after having graduated with a degree in biomedical science from Greenwich University.


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