Restoring lost epigenetic instructions reversed aging hallmarks in mammalian cells

English digest

What if aging is not primarily about broken DNA — but about your cells gradually forgetting how to read the instructions they already have?

Researchers at Harvard Medical School developed a two-track experimental strategy to disentangle epigenetic drift from DNA sequence damage as causes of aging. First, they engineered a mouse model in which CRISPR-mediated double-strand breaks were introduced and then perfectly repaired, leaving the DNA sequence intact but forcing the chromatin architecture to reorganize — mimicking the epigenetic disruption that accumulates naturally over decades. They then applied a gene therapy delivering three Yamanaka reprogramming factors (Oct4, Sox2, and Klf4, abbreviated OSK) to both this artificially aged model and to naturally old mice showing visual decline, measuring DNA methylation patterns, gene expression profiles, and visual function before and after treatment.