SUN1–ApoD feedback loop in cultured fibroblasts and mice: a proposed mechanotransduction route to aging phenotypes
In tissue culture, aged fibroblasts secreted ApoD, which raised SUN1 and disrupted polarity in young fibroblasts; elevated SUN1 in turn increased ApoD expression and secretion, forming a feedback loop. In mice, ApoD induced aging-related phenotypes in muscle. [1]
Automatic summary · not editorially reviewed
The key findings
Aged fibroblasts secreted an activity that induced aging-related polarity defects in young fibroblasts in a tissue culture version of parabiosis. [1]
Elevated SUN1 enhanced ApoD expression and secretion, forming a feedback loop that promotes acquisition of aged phenotypes. [1]
In mice, ApoD induced aging-related phenotypes in muscle. [1]
The source at a glance
- Study type / format
- Preclinical laboratory study (abstract)
- Population / context
- Cultured fibroblasts (aged and young) and mice
- Summary based on
- Study abstract
- Publication status
- Preprint · peer-review status not confirmed
- Original publication
- September 10, 2026
Aged fibroblast secretion tested on young fibroblasts
The authors used a tissue culture version of parabiosis, a setup in which two cell populations share medium. Aged fibroblasts secreted an activity that induced aging-related polarity defects in young fibroblasts. Secretomics identified this factor as apolipoprotein D (ApoD), a circulating protein whose levels are described as rising with age. ApoD increased SUN1 levels and disrupted polarity in fibroblasts through SUN1-promoted coupling of microtubules to the nucleus.
Supporting source [1]
Feedback loop and muscle phenotypes in mice
Elevated SUN1 enhanced ApoD expression and secretion, forming a feedback loop that promotes acquisition of aged phenotypes. In mice, ApoD induced aging-related phenotypes in muscle. Elevated ApoD expression required coupling between SUN1, its outer nuclear membrane binding partner nesprin-2, and microtubules. Broader analysis revealed that this pathway regulates hundreds of genes.
Supporting source [1]
Proposed mechanotransduction pathway, abstract-only scope
The authors conclude that microtubule-nuclear coupling is a direct mechanotransduction pathway controlling gene expression and promoting aging-associated phenotypes. These are cell-culture and mouse findings; the abstract reports no human lifespan or clinical outcomes. The full text was not reviewed, so details of design, sample sizes and follow-up are not assessed here.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Findings come from tissue culture and mice, with no human lifespan or clinical outcomes reported. Design details, sample sizes and follow-up are not given in the abstract.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Chen M, Wilson PC, Yang W, Ma Y, Li Y, Wang X, Bennett RL, Licht JD, Gundersen GG, Chang W. · europepmc.org · September 10, 2026