Fast-Forward Aging: Learning from accelerated cardiovascular and biological aging phenotypes in children with chronic kidney disease.

• Applicant: Dr. Carl Grabitz
• Subject Area: Biogerontology and Geriatric Medicine ; Pediatric and Adolescent Medicine ; Nephrology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 570621931

In chronic kidney disease (CKD), even young individuals can exhibit health complications similar to those of older adults, particularly in the cardiovascular system. This proposal aims to use pediatric CKD as a model for accelerated aging, aiming to decipher how reduced kidney function contributes to rapid biological aging. By leveraging an extensively characterized pediatric cohort, the project will systematically examine epigenetic age—a measure derived from DNA methylation patterns—and correlate it with early cardiovascular changes. The methodology involves high-throughput DNA methylation analysis, enabling a precise assessment of epigenetic age as a surrogate of biological age. These epigenetic data will be integrated with comprehensive clinical, laboratory, cardiovascular, and psychosocial assessments to create a multidimensional phenotype database. Focusing on the differences between dialysis and transplantation, in comparison to healthy controls, the study will identify how varying levels of kidney function impact the trajectory of biological and cardiovascular aging. The current one-year funding period allows to identify and evaluate basic drivers of epigenetic and CV aging derived from routine laboratory, imaging and past medical history. These findings will enable risk stratification and prevention in pediatric CKD. Future projects will harness the potential of the multidimensional data set even further. Differential DNA methylation analysis can identify (epi)genetic drivers, leading to a mechanistic understanding of age acceleration. Diverse interdisciplinary cooperations will aid in validating identified gene loci and other drivers in both experimental models like cell culture and other patient cohorts. Factors augmenting the resilience against age acceleration can ultimately translate into senotherapeutic interventions. These findings can be extrapolated to other age groups, suggesting the potential to enhance the functional reserve of the kidneys and cardiovascular system in the general population.

• DFG Programme: Research Grants