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.
  • @Valmond
    3•4 months ago

    Okay, thanks for the answer but I think it’s only moot points ;

    Yes, not everyone gets a cancer treatment when they need it, but that doesn’t mean we should not pursue better cancer treatments. Maybe share wealth better?

    All, or at least the large majority of technological advancements are for the rich for starters when it doesn’t work that well, then it becomes available to the middle class and it works better and are cheaper and then it becomes super cheap and ubiquitous, basically everyone has accass to it.

    I don’t know your age but mobile phones was like that crazy expensive and only worked in some cities. Smartphones were similar and many medical treatments are the same, cardio vascular treatments like stents and bypass are done on the regular today for example.