Disease mutations shift epigenetic age in iPSC-derived organoids
In this abstract, epigenetic age rose with serial passaging in lung alveolospheres, and disease-associated mutations drove additional cell-intrinsic shifts in epigenetic age across several models. [1]
Automatic summary · not editorially reviewed
The key findings
Reprogramming somatic cells into iPSCs resets epigenetic age, which complicates modeling age-associated cellular states. [1]
In a lung organoid model (alveolospheres), epigenetic age progressively increased with serial passaging. [1]
Disease-associated mutations in multiple models drove additional, cell-intrinsic shifts in epigenetic age. [1]
The source at a glance
- Study type / format
- In-vitro experimental study (abstract)
- Population / context
- iPSC-derived organoid systems, including a lung alveolosphere model and multiple disease-mutation models
- Summary based on
- Study abstract
- Publication status
- Preprint · peer-review status not confirmed
- Original publication
- October 4, 2026
Reprogramming resets age; organoids may rebuild it
The abstract states that reprogramming somatic cells into induced pluripotent stem cells resets epigenetic age. This makes it hard to model age-associated cellular states and limits iPSC use in aging research beyond the genetic component. The authors note that recent work showed healthy organoids can re-accumulate age-associated epigenetic states over extended culture. Whether disease-associated genetic states can directionally reshape these trajectories after reprogramming was unknown.
Supporting source [1]
Alveolospheres and mutation models in this abstract
The authors describe a reproducible in-vitro approach to re-establish epigenetic aging trajectories using iPSC-derived organoid systems, quantified by multiple epigenetic clock models. They first show that epigenetic age progressively increases with serial passaging in a lung organoid model (alveolospheres). They then show that disease-associated mutations in multiple models drive additional, cell-intrinsic shifts in epigenetic age. The abstract does not name the specific mutations, the number of models, the passage numbers or the clock models used.
Supporting source [1]
Disease state as modulator; in-vitro scope only
The authors conclude that iPSC-derived organoids recapitulate epigenetic aging trajectories over time and highlight disease state as a potent and potentially tractable modulator of epigenetic age in vitro. They suggest the approach could expand the utility of iPSC-based systems for studying molecular mechanisms of human aging. These are in-vitro organoid findings measured by epigenetic clocks; the abstract reports no human lifespan, clinical or causal outcomes. Only the abstract was reviewed, not the full text.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Specific mutations, model numbers, passage numbers and clock models are not reported in the abstract. Findings are in-vitro organoid results measured by epigenetic clocks, not human lifespan or clinical outcomes.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Skvir NJ, Dowrey TW, Cranston SF, MacDonald E, Giadone R, Jones D, Golden CS, Pate B, Labott M, Serrano MA, Alysandratos K, Vanuytsel K, Murphy GJ. · europepmc.org · October 4, 2026