Kidney research reveals a novel DNAm clock measure of biological aging

23 Oct 2023 --- A new DNA methylation (DNAm) clock, a biomarker of aging, has been developed by scientists studying renal health, as they found it to be the most accurate means of assessing the rate of aging in people with chronic kidney disease (CKD).

The research related to the treatment of CKD conducted by scientists based at the Karolinska Institutet, Sweden, and the University of Glasgow, UK, and published in the Journal of Internal Medicine, has led to the discovery of a biochemical assessment of DNA that allows the comparison of biological to chronological age.

“We hope to increase the use of DNAm clocks as a measurement of biological age in patients. It is important to create a reliable biomarker of epigenetic changes or biological aging to enable evaluation of possible effective treatments long before hard point events such as cardiovascular disease, cancer or death occur,” co-author Dr. Helen Erlandsson, a senior consultant of renal medicine at the Karolinska University Hospital, affiliated with Karolinska Institutet, tells Nutrition Insight. 

According to Erlandsson, additional research is needed to further utilize the potential of the new clock in determining the effects of lifestyle changes on biological age: “Studies of lifestyle interventions such as a change of diet, increase in physical activity or cessation of smoking should be performed in large populations with an extended follow-up to evaluate the effects on DNAm by using DNAm clocks.” 

Research and findings 
The study collected data on clinical variables from three different cohorts of end-stage CKD patients to estimate their biological age based on blood biomarkers, skin autofluorescence and DNAm.  DNA clocks could enable the pre-emptive evaluation and treatments for cardiovascular health and cancer.

Healthy participants representative of the general population were included as controls. The researchers measured changes in the biological ages one year after a kidney transfer in patients in the DNAm cohort. 

 They determined accelerated biological aging among the CKD population in all of the cohorts. However, the biological age estimation achieved through blood biomarkers and skin autofluorescence was found to be improbable. 

“The new epigenetic clock offers a measurement of biological aging which does not create implausible high values in the CKD population,” explains Erlandsson. “When we compared the results from the DNAm clocks, we found reasonable results in contrast to the unrealistic high estimates of biological age measured by skin autofluorescence and Phenoage equations in the CKD population.”

In contrast, according to DNAm testing, the average biological age of CKD patients was  4.9 years higher among those with kidney transplantation and 5.9 years higher among those on dialysis, compared to their counterparts in the general population.

This aging acceleration reduced significantly one year after the kidney transplantation but not after a year on dialysis. 

Applications and limitations
Erlandsson outlines the study’s implications as being applicable to determining the effects of lifestyle choices, such as diet, on kidney health and biological aging.  DNAm clocks could expand the understanding of different dietary and lifestyle interventions.

“DNAm clocks can potentially expand the understanding of different dietary and lifestyle interventions. The burden of lifestyle causes epigenetic changes which can be measured by the DNAm clock,” she explains. 

“Methylation tagging of DNA is impacted by what we eat and also our gut microbiome. As a result, this new clock has real potential to evaluate lifestyle interventions, including diet, that could benefit the public and help address issues such as health inequalities,” says Paul Shiels, lead author of the study for the University of Glasgow. 

Erlandsson  outlines the variability between technical replicates as a potential limitation to the applications of DNAm bio-clocks. “In order to reduce the statistical noise of each individual clock, a novel Composite clock (the Glasgow-Karolinska clock) was evaluated in our study. We used the first generation of DNAm clocks, the Horvath and Hannum clocks, and a second generation DNAm clock, called the Phenoage clock.”

“The latter was developed to improve upon the first generation by training the model not on chronological age but on an estimate of biological age based on nine whole blood parameters, chronological age and the aging clock combined. The Glasgow-Karolinska clock is a combination of the first and second generation DNAm clocks.” 

She asserts that further studies in larger populations are warranted to confirm these recent findings.

By Milana Nikolova