Abstract
Rationale & ObjectiveDeterioration of kidney graft function is associated with accelerated cellular senescence. Marine n-3 polyunsaturated fatty acids (PUFAs) have favorable properties that may counteract cellular senescence development and damage caused by the senescence-associated secretory phenotype (SASP) secretome. Our objective was to investigate the potential effects of marine n-3 PUFA supplementation on the SASP secretome in kidney transplant recipients.Study DesignExploratory substudy of the Omega-3 Fatty Acids in Renal Transplantation trial.Setting & ParticipantsAdult kidney transplant recipients with a functional kidney graft (defined as having an estimated glomerular filtration rate of >30 mL/min/1.73 m2) 8 weeks after engraftment were included in this study conducted in Norway.Analytical ApproachThe intervention consisted of 2.6 g of a marine n-3 PUFA or olive oil (placebo) daily for 44 weeks. The outcome was a predefined panel of SASP components in the plasma and urine.ResultsA total of 132 patients were enrolled in the Omega-3 Fatty Acids in Renal Transplantation trial, and 66 patients were allocated to receive either the study drug or placebo. The intervention with the marine n-3 PUFA was associated with reduced plasma levels of granulocyte colony-stimulating factor, interleukin 1α, macrophage inflammatory protein 1α, matrix metalloproteinase (MMP)-1, and MMP-13 compared with the intervention in the control group.LimitationsPost hoc analysis.ConclusionsThe results suggest that marine n-3 PUFA supplementation has mitigating effects on the plasma SASP components granulocyte colony-stimulating factor, interleukin 1α, macrophage inflammatory protein 1α, MMP-1, and MMP-13 in kidney transplant recipients. Future studies with kidney transplant recipients in maintenance phase, combined with an evaluation of cellular senescence markers in kidney transplant biopsies, are needed to further elucidate the potential antisenescent effect of marine n-3 PUFAs. This trial is registered as NCT01744067.
Highlights
Cellular senescence, the permanent arrest of cell growth, is essential for embryonic organ development, tissue repair and cancer protection 1
We looked for effects on components of the senescence-associated secretory phenotype, and we found that intervention with marine n-3 fatty acids was associated with lower plasma levels of granulocyte colony-stimulating factor, interleukin 1α, macrophage inflammatory protein 1α, matrix metalloproteinase (MMP)-1 and MMP13
Senescent cells are characterized by expression of p16INK4a, increased senescence-associated galactosidase activity, resistance to apoptosis and a senescence-associated secretory phenotype (SASP) 2
Summary
A total of 132 patients were enrolled in the ORENTRA trial, and 66 patients were allocated to receive either study drug or placebo. Future studies with kidney transplant recipients in maintenance phase combined with evaluation of cellular senescence markers in kidney transplant biopsies are needed to further elucidate the potential anti-senescent effect of marine n-3 PUFA. Plain-language summary: Deterioration of kidney transplant function is associated with accelerated cellular senescence In this exploratory sub-study of the randomized controlled trial ORENTRA, we investigated the potential anti-senescent effects of marine n-3 fatty acid supplementation by analyzing plasma and urine samples from 132 incident kidney. We looked for effects on components of the senescence-associated secretory phenotype, and we found that intervention with marine n-3 fatty acids was associated with lower plasma levels of granulocyte colony-stimulating factor, interleukin 1α, macrophage inflammatory protein 1α, matrix metalloproteinase (MMP)-1 and MMP13. Future studies with kidney transplant recipients in maintenance phase combined with evaluation of senescence markers in kidney transplant biopsies are encouraged to further elucidate the potential anti-senescent effect of marine n-3 fatty acids
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