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Determining the mechanisms regulating immune-directed clearance of senescent cells to promote healthy ageing (360G-Wellcome-206224_Z_17_Z)

The number of people over the age of 65 is predicted to double by 2060, accompanied by an increase in chronic diseases, which already consume up to 80% of healthcare costs. Developing therapies for chronic ageing diseases is, therefore, an urgent priority. A key driver of ageing diseases is telomere dysfunction and consequent cell senescence. Genetic ablation of senescent cells ameliorates diseases of ageing in mice, highlighting senescence as a promising therapeutic target. The immune system clears senescent cells, but with ageing, senescent cells accumulate causing disease. The mechanisms regulating senescent cell clearance in telomere-dependent ageing in vivo are unknown. I will test the hypothesis that senescent cells are not cleared with ageing due to telomerase-dependent dysfunction of the immune system. I will use the premature ageing telomerase mutant zebrafish I developed, which age in a telomere- dependent manner, and are exceptionally amenable for imaging and genetic manipulation. I will determine which leukocytes clear senescent cells in aged tissues in vivo, identify the key mechanisms involved and determine how these change with ageing. I will then test whether manipulation of these targets is sufficient to prevent or delay tissue degeneration and frailty in old zebrafish.


22 Feb 2017

Grant details
Amount Awarded 1143611
Applicant Surname Henriques
Approval Committee Sir Henry Dale Fellowship Interview Committee
Award Date 2017-02-22T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title Sir Henry Dale Fellowship
Internal ID 206224/Z/17/Z
Lead Applicant Dr Catarina Henriques
Planned Dates: End Date 2023-01-01T00:00:00+00:00
Planned Dates: Start Date 2018-01-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Yorkshire and the Humber
Sponsor(s) Prof Stephen Renshaw
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