Investigation of mitochondria-associated proteins in the ageing process
Lead Research Organisation:
University of Nottingham
Department Name: School of Veterinary Medicine and Sci
Abstract
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Organisations
Publications
Ingram T
(2016)
Proteomic profiling of mitochondria: what does it tell us about the ageing brain?
in Aging
Pollard AK
(2019)
A comparison of the mitochondrial proteome and lipidome in the mouse and long-lived Pipistrelle bats.
in Aging
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M008770/1 | 30/09/2015 | 31/03/2024 | |||
| 1644980 | Studentship | BB/M008770/1 | 30/09/2015 | 31/01/2020 |
| Description | Firstly, in mouse brain and muscle mitochondria, the expression of potential biological markers of ageing, carbonic anhydrase-II and -III were shown across adulthood. A window of increasing carbonic anhydrase expression between 12-18 months of age was identified. Targeted inhibition of C. elegans CA orthologue, cah-2, at middle age significantly increased lifespan. Treatment of C. elegans with the carbonic anhydrase-II inhibitor, dorzolamide hydrochloride, at middle age showed a trend toward increased lifespan, but this did not reach significance. Secondly, the long-lived bat (P. pipistrellus) was shown to have high levels of fatty acid binding protein 3 (FABP3) in muscle mitochondria, compared to short-lived mice. Increasing FABP3 levels was connected to high free fatty acid levels. Knockdown of FABP3 C. elegans orthologues altered mitochondrial morphology, oxygen consumption and significantly reduced lifespan. Thirdly, the healthspan promoting lifestyle intervention, exercise, was assessed. D. melanogaster were exercised on the bespoke Ingram Counterbalanced Exercise machine. The proteomic profiles of mitochondria isolated from exercised and non-exercised wild-type and Pink1-/- D. melanogaster were examined. The mitochondrial proteome displayed exercise-related changes. Interestingly, exercise caused sweeping mitochondrial protein expression reductions to Pink1-/- D. melanogaster with exercise. Fourthly, the cerebellar mitochondrial inflammatory marker profiles of females and males with and without Parkinson's disease were surveyed. This study found that inflammatory marker changes manifest differently with disease progression between sexes. Interestingly, the control female group showed a distinctive inflammatory profile, characterised by highly variant inflammatory marker levels. |
| Exploitation Route | This work can easily be extended to continue following the identified potential biological markers of ageing and add to their relevance. Clinical trials targeting these biological markers. The designed fly exercise machine may generate numerous collaborative activities. |
| Sectors | Education Healthcare |