The molecular basis of ageing in HIV infection. (360G-Wellcome-109975_Z_15_Z)
Age is the most important risk factor for most chronic diseases, but the molecular basis for the observed variation in human ageing remains poorly understood. Treated HIV-infected persons show abnormalities of many of the pathways implicated in ageing, notably persistent low-grade inflammation, mitochondrial dysfunction, and increased ROS (reactive oxygen species). Furthermore, treated HIV-infected persons show increased frailty, considered a convergent phenotype in human ageing, and predictive of adverse health outcomes. Currently however we lack an integrated mechanistic understanding of these observations, and the causal relationships remains to be established. My research goals are therefore to demonstrate: 1) that older HIV-infected persons show an excess of mitochondrial DNA (mtDNA) defects; 2) that correlates of mitochondrial dysfunction include specific anti-retroviral exposures, and that these factors show a causal association in mouse models; 3) the mechanisms (including mi tochondrial ROS production) through which these exposures may drive a mitochondrial defect; and 4) that mitochondrial dysfunction correlates with physiological decline in humans and is causally associated in mouse models. I anticipate that these experiments will both improve our understanding of the long-term complications of treated HIV infection, and increase our knowledge of the molecular basis of normal human ageing.
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Grant Details
Amount Awarded | 419312 |
Applicant Surname | Payne |
Approval Committee | Clinical Interview Committee |
Award Date | 2015-11-19T00:00:00+00:00 |
Financial Year | 2015/16 |
Grant Programme: Title | Postdoctoral Training Fellowship for Clinicians |
Internal ID | 109975/Z/15/Z |
Lead Applicant | Dr Brendan Payne |
Partnership Value | 419312 |
Planned Dates: End Date | 2021-07-31T00:00:00+00:00 |
Planned Dates: Start Date | 2016-09-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | North East |
Sponsor(s) | Prof Sir Doug Turnbull |