Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat
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 Par...
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MDPI AG
2016-10-01
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| Series: | Cells |
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| Online Access: | http://www.mdpi.com/2073-4409/5/4/38 |
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| author | Sohair M. Khojah Anthony P. Payne Dagmara McGuinness Paul G. Shiels |
| author_facet | Sohair M. Khojah Anthony P. Payne Dagmara McGuinness Paul G. Shiels |
| author_sort | Sohair M. Khojah |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T19:30:19Z |
| format | Article |
| id | doaj.art-24960e3f5e1643ab99967018ae7cd888 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T19:30:19Z |
| publishDate | 2016-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-24960e3f5e1643ab99967018ae7cd8882023-08-02T04:36:51ZengMDPI AGCells2073-44092016-10-01543810.3390/cells5040038cells5040038Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU RatSohair M. Khojah0Anthony P. Payne1Dagmara McGuinness2Paul G. Shiels3School of Life Sciences, Pharmacology Research Theme, University of Glasgow, Glasgow G12 8QQ, UKSchool of Life Sciences, Pharmacology Research Theme, University of Glasgow, Glasgow G12 8QQ, UKWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UKWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UKThere 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.http://www.mdpi.com/2073-4409/5/4/38AS/AGU ratsirtuinsp16Ink4aSA-β-GalsenescencebrainParkinson’s disease |
| spellingShingle | Sohair M. Khojah Anthony P. Payne Dagmara McGuinness Paul G. Shiels Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat Cells AS/AGU rat sirtuins p16Ink4a SA-β-Gal senescence brain Parkinson’s disease |
| title | Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat |
| title_full | Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat |
| title_fullStr | Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat |
| title_full_unstemmed | Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat |
| title_short | Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat |
| title_sort | segmental aging underlies the development of a parkinson phenotype in the as agu rat |
| topic | AS/AGU rat sirtuins p16Ink4a SA-β-Gal senescence brain Parkinson’s disease |
| url | http://www.mdpi.com/2073-4409/5/4/38 |
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