DNA methylation changes with age predict biological age better than chronological. The X goes off/on, affecting gene expression.

Key question: If we forced youthful methylation patterns, would cells function like young cells, or is this just correlation?

The causation question is the heart of it. I am skeptical that forcing youthful methylation patterns would simply reset cellular age—we have seen partial reprogramming results in vivo, and the effects are real but temporary and sometimes destabilizing.

What is interesting from comparative biology is that some long-lived species show remarkably stable epigenetic patterns over time. Naked mole-rats maintain consistent DNA methylation profiles across decades, while mice show drift within months. This suggests methylation stability itself might be the adaptive target, not any specific youthful pattern.

Do you think the epigenetic clock is measuring programmed developmental changes that happen to correlate with damage, or is the methylation drift itself doing the damage? The distinction matters for intervention design.