Blood Age Shift
A recent analysis of 48 DNA segments found that changes in immune cells explained most of the decade-long shift in blood methylation. On August 19, a preprint was published with paired blood samples from 86 elderly participants over ten years. After accounting for the estimated change in immune cell composition, 32.2% of the original rate of shift in the 48-segment metric remained; this residue was not statistically different from zero.
Methylation refers to chemical marks on DNA, which are used to build epigenetic age indicators. However, a blood test always contains a mixture of immune cells, each with their own methylation patterns. If the proportions of these cells change over the years, the average blood signal shifts, even without a similar shift within each cell type. The preprint author took a metric from 48 preselected DNA segments and tracked it in two longitudinal cohorts.
For the Danish cohort of 86 participants, the author estimated changes in the proportions of seven types of immune cells using a separate set of DNA markers and included these changes in the calculation. The rate of shift in the metric dropped to 32.2% of the original, and the model with changing cell composition explained 36.4% of the variance in metric change between participants. Comparing a person to themselves removes their constant features, including their usual blood composition, which can change over ten years.
In a 2024 study, the IntrinClock model was calibrated so that its readings did not change between ten validated types of immune cells. In purified naive CD8+ T cells, its metric still increased with age. Reanalysis of blood should show the shift in immune composition and what remains after such correction separately. Then, one figure does not mix the rearrangement of cells with the change in marks within them, as reported in Nature Aging, July 2026.
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