Nucleoli buffer displaced heterochromatin to limit premature aging programs in cells
In cells expressing progerin, the nucleolus sequesters released lamina-associated domains to preserve gene repression and prevent worsening DNA damage.
bioRxiv · Mungo C et al. · Paper published 1 Oct 2026
In cultured cells expressing Progerin, researchers investigated how nucleolar remodeling responds to lamina dysfunction. The team found that the nucleolus acts as a stress-responsive compartment that buffers premature aging signatures. Although Progerin expression disrupts nuclear architecture, repression of lamina-associated domains (LADs) initially persists. These displaced LADs relocate to the nucleolus, where they retain the repressive histone mark H3K9me2 and stay transcriptionally silent. To test this compensatory mechanism, the authors depleted NPM1, a nucleolar factor necessary for nucleolar genome association. Loss of NPM1 eliminated nucleolar buffering, causing relocated LADs to lose H3K9me2. Consequently, LAD-associated genes became derepressed, transcriptional aging programs intensified, and DNA damage increased.
Why it matters
The findings show that nucleolar compartmentalization serves as a structural fail-safe to maintain heterochromatin integrity and epigenome stability during nuclear lamina decline.
Caveats
This work was conducted exclusively in cell models and is reported in a preprint that has not yet undergone peer review.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
Nucleolar buffering of lamina-associated heterochromatin restrains Progerin-induced ageing programs
Mungo C, Bersaglieri C, Paganini D et al.
bioRxiv · 1 Oct 2026 · Preprint, not yet peer-reviewed
- Relevance
- Core geroscience
- News value
- Important
- Evidence
- Cells
- Status
- Preprint
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