How cell replication ultimately results in aging and the Hayflick limit are not fully understood. Here we show that clock-like accumulation of DNA G-quadruplexes (G4s) throughout cell replication drives conserved aging mechanisms. G4 stimulates transcription-replication interactions to delay genome replication and impairs DNA re-methylation and histone modification recovery, leading to loss of heterochromatin. This creates a more permissive local environment for G4 formation in subsequent generations. As a result, G4s gradually accumulate on promoters throughout mitosis, driving clock-like DNA hypomethylation and chromatin opening. In patients and in vitro models, loss-of-function mutations in the G4-resolving enzymes WRN, BLM and ERCC8 accelerate the erosion of the epigenomic landscape around G4. G4-driven epigenomic aging is strongly correlated with biological age and is conserved in yeast, nematodes, insects, fish, rodents, and humans. Our results revealed a universal molecular mechanism of aging and provided mechanistic insight into how G-quadruplex processor mutations drive premature aging. ### Competing Interest Statement The authors have declared no competing interest.
  • Salamander@mander.xyz
    ·
    6 months ago

    Our generation miiiight still get by without humans being able to dramatically extend their lifespan, but looking at how fast this field is developing, I think it is reasonably likely that our children's or grand children's generation will have to face the social and ethical dilemma of having the ability to cure aging. It's super interesting. Thanks for sharing!

  • ByroTriz@lemmy.ml
    ·
    6 months ago

    For something like this, I expect some drug/supplement do be found rather quickly