Inducing DNA breaks without causing mutations or cancer leads to aging phenotypes in mice.

“DNA breaks are a potent accelerator of epigenetic drift, which some researchers think drives aging.”

“We reported that mice engineered to accumulate controlled, non-mutagenic DNA double-strand breaks - which were designed to (and did) introduce epigenetic noise - developed many hallmarks of aging despite relatively little change to their DNA sequence (Yang et al., Cell, 2023).”

“Over time, after billions of DNA breaks from all kinds of reasons, the epigenetic noise accumulates. The cell slowly forgets its identity. A liver cell starts expressing 5% of the genes for a kidney cell. It loses phenotypic sharpness. That loss of identity is aging.”

“Introducing controlled DNA breaks accelerates biological aging without mutations”

“In my lab @harvardmed we see that very low numbers of DNA breaks in mice don’t cause cancer but they accelerate aging.”

“just by cutting the dna of these mice and not causing mutations not causing cancer but by disrupting those loops and packages we do get aging”

“if we do that over three weeks we will end up with a mouse that's 50 percent older and that clock the methylation clock that forms on the dna that's also 50 older we can read that so these mice are not just looking old they're hunched and gray and they have all sorts of diseases that are that we typically characterize as as aging related diseases they also are literally older if i gave you that mouse and you analyzed it you'd say it's an old mouse”