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ROS via RET: a redox regulated pathway to extend lifespan (360G-Wellcome-212241_Z_18_Z)

<p>Reactive Oxygen Species (ROS) play a dual role in cellular physiology.&nbsp; On one hand, ROS are damaging oxidants that have been proposed to cause ageing. On the other, ROS are essential messengers required for maintaining cellular homeostasis.&nbsp; The aged and sick accumulate defective mitochondria that generate high levels of ROS, but antioxidant therapies fail to improve prognosis or extend lifespan. Furthermore, increasing mitochondrial ROS levels in animals extends lifespan rather than reducing it.</p> <p>A new paradigm explains these contradictory results proposing that under normal physiological conditions, ROS are only produced at specific sites (e.g. mitochondria) by specific ROS generators (e.g. respiratory complex I) which regulate distinct redox signalling pathways. Conversely under pathological conditions ROS are produced at unspecific places causing oxidative stress.</p> <p>My laboratory has characterized the first site-specific ROS signalling pathway which regulates animal lifespan: ROS produced via reverse electron transport (RET) at respiratory complex I. This proposal will fully characterize this new redox signalling pathway by addressing three aims: (i) identify the genes and proteins involved in the initiation, amplification and neutralization of ROS-RET, (ii) understand when and where ROS-RET needs to be activated to extend lifespan, and (iii) dissect the pathological consequences of dysregulation of ROS-RET signalling.</p>

£1,512,586

17 Jul 2018

Grant details
Amount Awarded 1512586
Applicant Surname Sanz
Approval Committee Science Interview Panel
Award Date 2018-07-17T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Senior Research Fellowship Basic
Internal ID 212241/Z/18/Z
Lead Applicant Prof Alberto Sanz
Planned Dates: End Date 2020-01-05T00:00:00+00:00
Planned Dates: Start Date 2019-05-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region North East
Sponsor(s) Prof Robert Lightowlers
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