AgingResearch.NewsJoin free
bioRxiv

Some age-linked DNA marks in organoids did not rely on DNA copying

A cell experiment using mouse colon organoids linked gains in certain DNA marks to biological aging rather than activation of a cancer-linked mutation.

Paper by H. Easwaran, S.-J. Thursby, N. Patel, 10 more authorsS. B. Baylin · Johns Hopkins University (School of Medicine)
A large colon organoid and a smaller one contain similarly marked chromatin, beside a cluster of cells with fewer marks.
Preprint: experiments in single stem cell-derived mouse colon organoid clonesMechanisms

Limit: The reported comparison manipulated a cancer-linked mutation rather than DNA copying directly

Edited by Boris Djordjevic · AgingResearch.News

Paper
Follow

In an experiment in mouse colon organoids, miniature tissue models grown in the lab, researchers tracked DNA methylation, chemical marks on DNA, in cell groups descended from individual stem cells. They compared groups with and without activation of a cancer-linked mutation.

Activating the mutation produced stepwise changes in DNA methylation, while controls changed gradually. But it did not trigger or accelerate methylation gains at certain promoters, gene-control regions marked by Polycomb, a group of gene-silencing proteins. These gains instead tracked with “biological aging” independently of DNA copying. Analyses of separate aging, cancer and cell-line datasets supported this finding. The authors concluded that cancer-linked signaling primarily selected and expanded cell groups with pre-existing, age-associated changes in DNA marking, rather than instructing new methylation.

Why it matters

DNA methylation changes occur early in cancer. The authors say understanding their origins has implications for interpreting cancer biomarkers and identifying aging-associated processes to target for early intervention.

Caveats

The central experiment used mouse organoids grown in the lab, not people. The work is a preprint and has not been peer-reviewed.

Where the evidence stands

DNA methylation

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 193 independent labs in 37 countries
  • 18 findings against
  • Funders: National Institutes of Health and others
  • 41 of 380 findings with company ties

BRAF

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

No results posted: trials that ended over a year ago with no results on ClinicalTrials.gov and no paper reporting them.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 15 independent labs in 8 countries
  • 1 finding against
  • 39 trials, 16 with no results posted
  • Funders: National Cancer Institute and others
  • 1 of 30 findings with company ties
  • 39 of 39 trials sponsored by developers of drugs on it

Comments

Be the first to comment.

More on Epigenomics