Sirtuin-1 expression and activity is diminished in aged liver grafts.
Journal Article (Journal Article)
The cellular mechanisms underlying impaired function of aged liver grafts have not been fully elucidated, but mitochondrial dysfunction appears to be contributory. Sirtuin1 has been identified as a key mediator of mitochondrial recovery following ischemia-reperfusion injury. The purpose of this study was to determine whether differences exist in sirtuin-1 expression/activity in old vs. young liver grafts and to determine correlations with mitochondrial function, graft metabolic function, and graft injury. Old and young rat liver grafts (N = 7 per group) were exposed to 12 h of static cold storage (SCS), followed by a 2 h period of graft reperfusion ex vivo. Sirtuin1 expression and activity, mitochondrial function, graft metabolic function, and graft injury were compared. Sirtuin1 expression is upregulated in young, but not old, liver grafts in response to cold storage and reperfusion. This is associated with diminished tissue ATP, antioxidant defense, and graft metabolic function in old liver grafts. There was no evidence of increased inflammation or histologic injury in old grafts. Sirtuin1 expression is diminished in old liver grafts and correlates with mitochondrial and metabolic function. The sirtuin pathway may represent a target for intervention to enhance the function of aged liver grafts.
Full Text
Duke Authors
Cited Authors
- Scheuermann, U; Seyferth, ER; Abraham, N; Kesseli, SJ; Halpern, SE; Zhu, M; Song, M; Hartwig, MG; Parker, W; Kwun, J; Cherry, AD; Lee, J; Barbas, AS
Published Date
- July 17, 2020
Published In
Volume / Issue
- 10 / 1
Start / End Page
- 11860 -
PubMed ID
- 32681076
Pubmed Central ID
- PMC7367862
Electronic International Standard Serial Number (EISSN)
- 2045-2322
Digital Object Identifier (DOI)
- 10.1038/s41598-020-68314-6
Language
- eng
Conference Location
- England