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Cells 2016, 5(4), 38;

Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat

School of Life Sciences, Pharmacology Research Theme, University of Glasgow, Glasgow G12 8QQ, UK
Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Bor Luen Tang
Received: 30 August 2016 / Revised: 30 September 2016 / Accepted: 1 October 2016 / Published: 17 October 2016
(This article belongs to the Special Issue Sirtuins in Aging and Diseases)
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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. P16INK4a expression 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. View Full-Text
Keywords: AS/AGU rat; sirtuins; p16Ink4a; SA-β-Gal; senescence; brain; Parkinson’s disease AS/AGU rat; sirtuins; p16Ink4a; SA-β-Gal; senescence; brain; Parkinson’s disease

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Khojah, S.M.; Payne, A.P.; McGuinness, D.; Shiels, P.G. Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat. Cells 2016, 5, 38.

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