Physiological health Age (PhysAge): a novel multi-system molecular timepiece predicts health and mortality in older adults

#1

This looks interesting and potentially easy to apply, a little like the Levine Phenotypic clock.

Here, we develop and validate a DNA methylation-based Physiological health Age (PhysAge) score, comprised of eight DNA methylation surrogates to represent multi-system physiology and developed from commonly measured clinical biomarkers: CRP, peak flow, pulse pressure, HDL-cholesterol, Hba1c, waist-to-height ratio (WHR), cystatin C, and dehydroepianrosterone sulphate (DHEAS)

PhysAge and the predominant second-generation epigenetic clocks, PhenoAge, GrimAge2, and DunedinPACE, were tested for their prediction of mortality and multiple age-related clinical measures (i.e., grip strength, gait speed, cognitive function, disability, frailty). PhysAge was comparable to extant clocks in predicting health measures and was indistinguishable from GrimAge2 in predicting mortality, despite not being trained on mortality. Moreover, the eight individual surrogates comprising PhysAge predicted health outcomes better than the measured values in many instances. The established clinical relevance of the biomarkers from which surrogates were derived opens up new opportunities for cross-study and cross-country comparisons of population health. Findings suggest that the DNA methylation PhysAge can be leveraged as a single biomarker to represent multiple physiological systems and offers utility in the context of clinical monitoring.

Full open access paper:

#2

Analysis of the DNAm surrogates revealed the presence of enriched whole bodily expressed phosphoproteins and alternative splicing genes, suggesting that the combined surrogate set consists of diverse, regulatory, and multifunctional proteins involved in a multitude of pathways, specifically involved in signaling and development (SI Appendix 1, Figure S7). These results suggest that our DNAm surrogate sets correlate strongly with signalosomal desynchronization (disruption of cell–cell communication, considered a hallmark of aging [28]) and the impaired activity of pathways.