CD38–NAD⁺–SIRT1–ERRα–NLRP3 pathway in aging donor liver ischemia-reperfusion injury
In this abstract, aging donor livers (age ≥60 years) showed more severe ischemia-reperfusion injury and macrophage pyroptosis than young grafts in mouse models; a CD38–NAD⁺–SIRT1–ERRα–NLRP3 pathway is proposed, and a CD38-inhibitor nanodelivery system reduced these changes. [1]
Automatic summary · not editorially reviewed
The key findings
Analysis of human liver graft samples showed a clinical association of CD38-related NAD⁺ dysregulation with transplantation-associated injury. [1]
In mouse models, aging grafts developed more severe ischemia-reperfusion injury and macrophage pyroptosis than young grafts. [1]
A nanodelivery system carrying the CD38 inhibitor 78c reduced Kupffer cell pyroptosis and attenuated ischemia-reperfusion injury in aging donor livers. [1]
The source at a glance
- Study type / format
- Abstract of a preclinical and human-sample laboratory study
- Population / context
- Aging donor livers (age ≥60 years), human liver graft samples, mouse models and macrophage systems
- Summary based on
- Study abstract
- Original publication
- September 8, 2026
Human graft samples and mouse models of aging liver IRI
The abstract describes analysis of human liver graft samples that showed a clinical association between CD38-related NAD⁺ dysregulation and transplantation-associated injury. Mechanistic work used mouse models and macrophage systems. In these models, aging grafts developed more severe ischemia-reperfusion injury and macrophage pyroptosis than young grafts. The human sample finding is described as an association, not as proof of cause.
Supporting source [1]
CD38 deletion and the proposed CD38–NAD⁺–SIRT1–ERRα–NLRP3 axis
Conditional deletion of CD38 in Kupffer cells partially alleviated these changes in vivo and in vitro. Mechanistically, the abstract links CD38-associated NAD⁺ depletion to impaired SIRT1 activity, reduced deacetylation of ERRα at lysine 129, and altered ERRα-mediated regulation of NLRP3 transcription. The authors describe this pathway as a potential regulatory axis connecting aging-associated metabolic dysfunction with graft susceptibility to ischemia-reperfusion injury.
Supporting source [1]
CD38-inhibitor nanodelivery reduced injury in aging donor livers
The abstract reports that a nanodelivery system carrying the CD38 inhibitor 78c effectively reduced Kupffer cell pyroptosis and attenuated ischemia-reperfusion injury in aging donor livers. These results come from the described mouse and macrophage experiments; the abstract does not report human treatment outcomes. The findings are presented as identifying a potential regulatory pathway, not as an established therapy.
Supporting source [1]
How to interpret this
This is an abstract; the full text was not reviewed. Human graft data are described as a clinical association, while mechanistic and treatment findings come from mouse models and macrophage systems. The abstract does not report human treatment outcomes, and the pathway is described as potential.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Xu XS, Gong JH, Wang R, Liu T, Chen YJ, Liu JY, Li JZ. · europepmc.org · September 8, 2026