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.
  • SalamanderA
    5•4 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!

    • @Valmond@lemmy.mindoki.com
      3•4 months ago

      That’s a no brainer. Nothing in history have made people suffer as much as aging.

      If you’re agains prolonging healthy lifespan (or outright rejuvenation) then I guess you’re against our treatments we already have that extends healthy lifespan like cancer treatments, or any kind of medication?

      • SalamanderA
        0•4 months ago

        It is not something that I frame as something to be “in favor of” or “against”. I think it adds complexity.

        I do not think it is a “no brainer” at all!! Will it be so expensive that only the rich can live forever? Does society agree to only let specific people, like nobel prize winners, drink the elixir? Or do we just let everyone live forever? Or… how long? Do we end people’s lives at some age? Do we force people to have less children? If so, who enforces this, and how?..

        then I guess you’re against our treatments we already have that extends healthy lifespan like cancer treatments, or any kind of medication?

        Our current generation is dealing with what happens when you have for-profit pharmaceutical industries in a capitalist world. Not everyone who has cancer gets to receive an equal level of treatment. The whole system is plagued with social and ethical dilemmas!

        • @Valmond@lemmy.mindoki.com
          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.