This demo accompanies Crofts, Grenko et al., “A unifying model of stem cell dynamics explains age-related methylation patterns across mammals”, Nature Aging 6, 1319–1329 (2026). DNA methylation changes are reliable biomarkers of aging, but the driving mechanisms remain poorly understood. SCARLET (Stem Cells and Age-ReLated Epigenetic Trajectories) is a parsimonious mathematical model that describes how methylation changes in blood arise and propagate through hematopoietic stem cell divisions.
Z is the fraction of stem cells that are methylated at one CpG site (Z = M / N). As stem cells divide, Z drifts toward a steady level (η) and spreads out between people. The heatmap shows how likely each value of Z is at each age; darker means more likely. Drag the sliders, or type any value into the boxes, to see how each parameter changes it.