title: Senescence of Pancreas in Middle-Aged Rats with Normal Vascular Function.
abstract: BACKGROUND In organ transplantation, particularly pancreas transplantation, donor age is a determinant factor for graft survival. Physiological aging is crucial in the progressive deterioration of organs in adulthood. We compared the senescence and function features of pancreas and vascular tissues in young rats and middle-aged rats. MATERIAL AND METHODS Islet morphology and the area of cells secreting insulin or glucagon was investigated using immunohistology in young rats (12 weeks) and middle-aged rats (52 weeks) (n=8). Senescence markers, oxidative stress (ROS), and tissue factor (TF) were measured in the rat pancreases. Circulating microparticles (MPs) were measured as surrogates of vascular cell injury. Vascular function was studied in mesenteric arterial rings. RESULTS Larger islets were twice as frequent in young rats versus middle-aged rats. In middle-aged rats there was a significant decrease of the β-cells/islet area ratio. Western blot analysis showed an increased expression of p53, p21, and p16 senescence markers (2-, 7- and 3-fold respectively) with no modification in caspase-3 activation. A 30% decrease of endothelial nitric oxide synthase (eNOS) was observed together with a 4-fold increase in TF expression. ROS formation increased significantly (2-fold) in middle-aged rats and their main source, determined by pharmacological inhibition, was NADPH oxidase and uncoupled nitric-oxide (NO) synthase. No sign of vascular injury (microparticles) or dysfunction was evidenced. CONCLUSIONS Modification in islet morphology and function were detected in middle-aged rats before any measurement of macro-vascular dysfunction. The data indicate a pancreatic senescence in the process of aging associated with uncontrolled accumulation of oxidative species that suggests a determining role of donor age in transplantation.
authors.affiliation: EA7293, Vascular and Tissular Stress in Transplantation, Federation of Translational Medicine of Strasbourg, Faculty of Medicine, University of Strasbourg, Illkirch-Graffenstaden, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Kassem
authors.affiliation: UMR CNRS 7213, Laboratory of Biophotonics and Pharmacology, Faculty of Pharmacy, University of Strasbourg, Illkirch-Graffenstaden, France.
authors.forename: Zahid Rasul
authors.initials: ZR
authors.lastname: Niazi
authors.affiliation: UMR CNRS 7213, Laboratory of Biophotonics and Pharmacology, Faculty of Pharmacy, University of Strasbourg, Illkirch-Graffenstaden, France.
authors.forename: Malak
authors.initials: M
authors.lastname: Abbas
authors.affiliation: EA7293, Vascular and Tissular Stress in Transplantation, Federation of Translational Medicine of Strasbourg, Faculty of Medicine, University of Strasbourg, Illkirch-Graffenstaden, France.
authors.forename: Ali
authors.initials: A
authors.lastname: El Habhab
authors.affiliation: EA7293, Vascular and Tissular Stress in Transplantation, Federation of Translational Medicine of Strasbourg, Faculty of Medicine, University of Strasbourg, Illkirch-Graffenstaden, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Kreutter
authors.affiliation: UMR CNRS 7213, Laboratory of Biophotonics and Pharmacology, Faculty of Pharmacy, University of Strasbourg, Illkirch-Graffenstaden, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Khemais-Benkhiat
authors.affiliation: UMR CNRS 7213, Laboratory of Biophotonics and Pharmacology, Faculty of Pharmacy, University of Strasbourg, Illkirch-Graffenstaden, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Auger
authors.affiliation: Histology Institute, Federation of Translational Medicine of Strasbourg, University of Strasbourg, Strasbourg, France.
authors.forename: Maria-Cristina
authors.initials: MC
authors.lastname: Antal
authors.affiliation: UMR CNRS 7213, Laboratory of Biophotonics and Pharmacology, Faculty of Pharmacy, University of Strasbourg, Illkirch-Graffenstaden, France.
authors.forename: Valérie B
authors.initials: VB
authors.lastname: Schini-Kerth
authors.affiliation: UMR CNRS 7213, Laboratory of Biophotonics and Pharmacology, Faculty of Pharmacy, University of Strasbourg, Illkirch-Graffenstaden, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Toti
authors.affiliation: EA7293, Vascular and Tissular Stress in Transplantation, Federation of Translational Medicine of Strasbourg, Faculty of Medicine, University of Strasbourg, Illkirch-Graffenstaden, France.|Department of Diabetes and Nutrition Endocrinology, University Hospital of Strasbourg, Strasbourg, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Kessler
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D005934:Glucagon / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010179:Pancreas / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007328:Insulin; D017382:Reactive Oxygen Species; D005934:Glucagon; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; D053148:Caspase 3