Biology subjects

Chwalek, K.

Publications and source records attributed to Chwalek, K..

3 recordsLinked to original sources

bioRxiv2025

Multiomic clocks to predict phenotypic age in mice

Biological age refers to a persons overall health in aging, as distinct from their chronological age. Diverse measures of biological age, referred to as "clocks", have been developed in recent years and enable risk assessments, and an estimation of the efficacy of longevity interventions in animals and humans. While most clocks are trained to predict chronological age, clocks have been developed to predict more complex composite biological age outcomes, at least in humans. These composite outcomes can be made up of a combination of phenotypic data, chronological age, and disease or mortality risk. Here, we develop the first such composite biological age measure for mice: the mouse phenotypic age model (Mouse PhenoAge). This outcome is based on frailty measures, complete blood counts, and mortality risk in a longitudinally assessed cohort of male and female C57BL/6 mice. We then develop clocks to predict Mouse PhenoAge, based on multi-omic models using metabolomic and DNA methylation data. Our models accurately predict Mouse PhenoAge, and residuals of the models are associated with remaining lifespan, even for mice of the same chronological age. These methods offer novel ways to accurately predict mortality in laboratory mice thus reducing the need for lengthy and costly survival studies.

systems biology↗

bioRxiv2023

Measuring technical variability in Illumina DNA methylation microarrays

DNA methylation microarrays have become a widely used tool for investigating epigenetic modifications in various aspects of biomedical research. However, technical variability in methylation data poses challenges for downstream applications such as predictive modeling of health and disease. In this study, we measure the impact of common sources of technical variability in Illumina DNA methylation microarray data, with a specific focus on positional biases inherent within the microarray technology. By utilizing a dataset comprised of multiple, highly similar technical replicates, we identified a chamber number bias, with different chambers of the microarray exhibiting systematic differences in fluorescence intensities and their derived methylation beta values, which are only partially corrected for by existing preprocessing methods, and demonstrate that this positional bias can lead to false positive results during differential methylation testing. Additionally, our investigation identified outliers in low-level fluorescence data which might play a role in contributing to predictive error in computational models of health-relevant traits such as age.

bioinformatics↗

bioRxiv2019

Reversal of ageing- and injury-induced vision loss by Tet-dependent epigenetic reprogramming

Ageing is a degenerative process leading to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise, which disrupts youthful gene expression patterns that are required for cells to function optimally and recover from damage1-3. Changes to DNA methylation patterns over time form the basis of an ageing clock4, 5, but whether old individuals retain information to reset the clock and, if so, whether this would improve tissue function is not known. Of all the tissues in the body, the central nervous system (CNS) is one of the first to lose regenerative capacity6, 7. Using the eye as a model tissue, we show that expression of Oct4, Sox2, and Klf4 genes (OSK) in mice resets youthful gene expression patterns and the DNA methylation age of retinal ganglion cells, promotes axon regeneration after optic nerve crush injury, and restores vision in a mouse model of glaucoma and in normal old mice. This process, which we call recovery of information via epigenetic reprogramming or REVIVER, requires the DNA demethylases Tet1 and Tet2, indicating that DNA methylation patterns dont just indicate age, they participate in ageing. Thus, old tissues retain a faithful record of youthful epigenetic information that can be accessed for functional age reversal.

molecular biology↗