Deleting the mechanosensitive channel Piezo1 prevents gut motility decline in aging mice
Age-related gut stiffening activates smooth muscle Piezo1, triggering calcium signaling that suppresses contractile genes and slows intestinal transit.
bioRxiv : the preprint server for biology · Joshi V et al. · Paper published 7 Sep 2026
In mice, aging slows whole gut and colonic transit, increases regional stiffness, and reduces smooth muscle contractility, according to a new preprint. Researchers investigated how physical tissue changes drive this functional decline. Inducible smooth muscle cell deletion of the mechanosensitive channel Piezo1 preserved youthful gut transit and force generation in older mice, while activating Piezo1 in young mice caused transit delays. Using single-cell transcriptomics, RNA velocity, stiffness-controlled cell and tissue cultures, and pharmacological tools, the team found that Piezo1 couples tissue stiffening to calcium-calcineurin-NFAT signaling. This cascade silences contractile gene programs, promoting a shift from contractile to synthetic smooth muscle cells and increasing gut wall stiffness. Human intestinal smooth muscle cell assays supported this pathway, and human carriers of PIEZO1 gain-of-function variants showed a trend toward delayed colonic transit.
Why it matters
The findings show that age-related physical shifts in extracellular structure actively drive organ decline through specific mechanotransduction signals. Understanding Piezo1 activity highlights mechanical cues as potential targets to treat gastrointestinal and smooth muscle failure during aging.
Caveats
This study is a preprint that has not yet completed peer review. Key functional interventions were conducted in mice, and evidence in humans was limited to cultured cells and an observational transit trend.
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
Maladaptive Piezo1 Mechanotransduction Drives Smooth Muscle Aging in the Gut
Joshi V, Seavey C, Knutson K et al.
bioRxiv : the preprint server for biology · 7 Sep 2026 · Preprint, not yet peer-reviewed
- Relevance
- Core geroscience
- News value
- Important
- Evidence
- Animals
- Status
- Preprint
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