DE-SWAN analysis of biomarker trajectories over the life course is highly sensitive to age distribution and model parameterization

Abstract

DE-SWAN is a commonly used method to study how large ensembles of omics biomarkers change across the life course. It has been used to demonstrate apparent repeated accelerations and decelerations of aging rates across the life course, including 2-3 peaks of aging-related changes. This result contradicts what is expected based on the demography of aging and known biological mechanisms. Here, we use simulations to study the robustness of DE-SWAN to the age distribution of the study sample and to choice of window size. We show that under many realistic scenarios, DE-SWAN is highly sensitive to factors unrelated to the underlying rates of change in aging biology. This calls into question the results of previous analyses that have attributed DE-SWAN peaks to acceleration and deceleration of aging. We conclude that the method is unreliable for studying rates of change across the life course under most circumstances.