Normally, I’ll be digging into the science of longevity in this section of Gaming aging. This introductory post shares a bit about the translational geroscience portfolio I oversaw from inception at the University of Oxford between early 2019 and mid-2021.
In 2019, I joined the University of Oxford as Scientific Liaison on a project aiming to accelerate the development of drugs targeting biological drivers of aging. The overarching project was part of a broader program to nurture collaborations across sectors - academia, industry, government, charities. Merging that with drug discovery for aging involved digging deep not only into the scientific and drug discovery challenges of translating early-stage geroscience research, but also into the types of resource and knowledge exchange initiatives that would accelerate the route to clinic for promising interventions.
The team operated in startup-ish style with a short timeline (mid-2021 end date), limited operating resources, and a small distributed team. Our ability to be nimble and act independently (and with urgency) was ‘balanced’ by having five distributed UK institutions as core stakeholders, each of which was an invaluable resource and partner.
My primary responsibility was to seed and develop a ~$1.2M portfolio which a) touched on a variety of biological drivers of aging, b) represented projects in the ‘unfundable’ zone between basic science research and clinical validation, and c) spanned the drug discovery pipeline or supported the drug discovery process (e.g., new tech for screening platforms). (Our PI - the Vice Chancellor of Innovation - had done a long stint leading drug discovery efforts in industry, and our distributed stakeholders mapped out a virtual drug discovery pipeline - so drug discovery was our focus.)
The ‘Bridge’ portfolio ended up as an interesting mix - one that reflected the fascinating tension between geroscience folks who (mostly) don’t default to a disease-centric mindset and drug discovery folks who do. The management group representing our drug-discovery-oriented stakeholders had the final say on funding decisions: advocating for staying true to the geroscience hypothesis (vs defaulting to disease treatment objectives) was an education on the challenges geroscience and longevity interventions face in a broader context.
For our 2020 annual conference, I prepared video overviews of the funded projects in my portfolio (also linked individually at the end of this post). For some higher-level background, I described the motivation behind the portfolio in a blog post on the Oxford project website.
If you’d like more information about an individual project, or to follow up on progress, please reach out - I’ll be happy to connect you with the researcher.
‘Bridge program’ portfolio project overview videos:
WRN reactivation
Autophagy activation via TFEB
Mitigating inflammaging
Identification of lipid mediators provided by autophagy that polarize anti-inflammatory macrophages
Katja Simon (Oxford)
Monitoring mitochondrial function in response to interventions
Raman spectroscopy to determine mitochondrial function and mitochondrial drug accumulation in aging model systems
Karl Morten (Oxford)
Senolytics
Preclinical validation of novel candidate senolytics
Satomi Miwa (Newcastle) & Thomas von Zglinicki (Newcastle)
Rapamycin: impact on muscle/sarcopenia in an older cohort
Reactivating T cells to counter immune aging
Identification of novel epigenetic targets to reactivate exhausted and senescent T cells
Annette von Delft (Oxford)
Biomarkers of healthy and multimorbid aging
Biological insights and biomarkers in healthy, multimorbid, and frail elders
Thomas Jackson (Birmingham)
Protein misfolding: oligomers as biomarkers of aging
Hypoxia, aging, and treatment with oxygen nanobubbles
Repositioning drugs safely for targeting aging
Drug repositioning and combination therapies for healthy aging
John Overington (Medicines Discovery Catapult - now at ExScientiaAI)
