Kidney function is very important to long-term health, influencing the operation of other organs. This is well illustrated by research into klotho, a longevity associated gene that appears to primarily function in the kidney, yet improves numerous measures of cognitive and cardiovascular aging when highly expressed. Here, researchers show that epigenetic age acceleration, in which epigenetic age is higher than chronological age, is associated with worse kidney function. Epigenetic age is in effect an assessment of cellular reactions to the aged tissue environment of damage, dysfunction, and altered signaling, and it is interesting to see it reflect kidney function in this way.
The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies.
We identified 23 significant associations in our large trans-ethnic meta-analysis with a consistent direction of effect across studies. Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as the 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate).
Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging, and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease.