title: Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat.
abstract: There is a paucity of information on the molecular biology of aging processes in the brain. We have used biomarkers of aging (SA β-Gal, p16Ink4a, Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in the AS/AGU rat, a spontaneous Parkinsonian mutant of PKCγ derived from a parental AS strain. P16INK4aexpression was significantly higher in AS/AGU animals compared to age-matched AS controls (p <0.001) and displayed segmental expression across various brain regions. The age-related expression of sirtuins similarly showed differences between strains and between brain regions. Our data clearly show segmental aging processes within the rat brain, and that these are accelerated in the AS/AGU mutant. The accelerated aging, Parkinsonian phenotype, and disruption to dopamine signalling in the basal ganglia in AS/AGU rats, suggests that this rat strain represents a useful model for studies of development and progression of Parkinson's disease in the context of biological aging and may offer unique mechanistic insights into the biology of aging.
authors.affiliation: School of Life Sciences, Pharmacology Research Theme, University of Glasgow, Glasgow G12 8QQ, UK. smkhojah@yahoo.com.
authors.forename: Sohair M
authors.initials: SM
authors.lastname: Khojah
authors.affiliation: School of Life Sciences, Pharmacology Research Theme, University of Glasgow, Glasgow G12 8QQ, UK. Anthony.Payne@glasgow.ac.uk.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Payne
authors.affiliation: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK. Dagmara.McGuinness@glasgow.ac.uk.
authors.forename: Dagmara
authors.initials: D
authors.lastname: McGuinness
authors.affiliation: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK. Paul.Shiels@glasgow.ac.uk.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Shiels
keywords: AS/AGU rat; Parkinson’s disease; SA-β-Gal; brain; p16Ink4a; senescence; sirtuins