What this means
Researchers found progerin, a protein tied to a rare premature aging disease, affects cells lining the gut. Early results are not yet checked by other scientists, so more work is needed.
Plain-English summary written by an AI model from the abstract. The original is below.
- Who it was tested in
- Mice with progeria, mouse gut organoids, and single-cell gene studies
- Kind of research
- Early results, not yet checked by other scientists
The science
- Original title
- Progerin disrupts intestinal epithelial homeostasis by impairing mitochondrial metabolism and absorptive enterocyte maturation
- Authors
- Reisacher, C., Singh, M., Arbibe, L.
- Journal
- bioRxiv (preprint, not yet peer reviewed)
- Published
- Oct 14, 2026
- Study type
- Preprint
Abstract
Hutchinson-Gilford progeria syndrome (HGPS) is a segmental premature ageing disease that predominantly affects tissues with high regenerative capacity. Although the intestine is the most rapidly self-renewing tissue of adult mammals, it has so far been considered only as a source of microbiota-derived disturbances in progeria, and whether the intestinal epithelium is itself a target of progerin remains unknown. Here, using the LmnaG609G/G609G and LmnaG609G/+ mouse models, intestinal organoids and single-cell RNA sequencing, we show that progerin is expressed in colonic enterocytes and in SMA+ subepithelial myofibroblasts of the stem-cell niche. Heterozygous progeria mice develop increased intestinal permeability from 30 weeks of age, reaching levels reported in physiologically aged (>20-month-old) mice. Progeria-derived intestinal organoids display reduced mitochondrial oxygen consumption, a compensatory increase in glycolysis and impaired crypt budding. Single-cell transcriptomics of the colonic epithelium and lamina propria revealed that, while lineage composition is preserved, progerin induces a coordinated reprogramming characterised by repression of oxidative phosphorylation and mitochondrial quality-control genes, including Nod2, activation of interferon, TNF-NF-kB and innate defence programs, and up-regulation of RNA-processing and chromatin-associated pathways. Trajectory analysis showed that progeria absorptive enterocytes selectively fail to reach terminal differentiation states and retain progenitor-like WNT, NOTCH and EGFR signatures, while lacking the mitochondrial programs required for maturation. Together, these findings identify the intestinal epithelium as a cell-intrinsic target of progerin and support a model in which mitochondrial insufficiency stalls absorptive enterocyte maturation and weakens the intestinal barrier, recapitulating, prematurely, key features of colon ageing.
Reisacher, C., Singh, M., Arbibe, L. Progerin disrupts intestinal epithelial homeostasis by impairing mitochondrial metabolism and absorptive enterocyte maturation. bioRxiv. 2026. doi:10.64898/2026.10.09.758066. https://doi.org/10.64898/2026.10.09.758066