We are pleased to announce the selected performers.
Performer, Organization
Human life expectancy has doubled in the past 100 years.
But for most people, our health span doesn’t match our life span. What if it could?
One of the greatest success stories of the last 100 years is the doubling in human life expectancy, from a global average of 35 years in 1900 to 70 years today1. Advances in medicine, public health, and infrastructure have greatly reduced the number of children dying before adulthood and increased the chances of most adults reaching old age. The rising number of centenarians and supercentenarians (people over 110 years) shows that it is possible for humans to live well for a very long time. Such exceptional individuals have encountered many challenges to their health over the course of their long lives, but they show a remarkable resilience – an ability to ‘bounce back’ after a significant stress event, whether that is a fall, infection, surgery, or major psychosocial stress. Resilience is the result of complex integrated physiological systems that usually maintain function and homeostasis through a series of feedback and feedforward mechanisms. Such biological resilience integrates several features including baseline reserve, ability to detect and adapt to stress, and the speed and appropriateness of responses including the ability to heal and repair. With a high baseline reserve along with correct and timely integration of other components of the stress response, the body can return to a state of homeostasis after disruption.
For most of us, however, our baseline reserves diminish as we get older and our biological maintenance systems start to fail, resulting in around half of adults over 65 suffering from at least two age-related long-term conditions (multimorbidity), increasing to ~80% of over 80s2. Our ability to cope with stress also decreases as we get older, and this loss of resilience makes us vulnerable to sudden and serious health deterioration when we encounter acute illness or injury. Such loss of reliance or vulnerability is encompassed by the clinical term frailty, with half of people 65 and older either frail or pre-frail (at risk of progressing to frailty)3. The consequence of reduced resilience is that the time we spend in good health (our health span) is much shorter than our overall lifespan4.
With increasing ageing of populations around the world, frailty is an important and growing global health problem. Adults over 65 now account for 16% of the USA and Singaporean populations, 19% in the UK and 28% in Japan. By 2050, it is projected that 1.5 billion people will be over the age of 65, and the number of oldest old – over 85 – is set to triple5. A quarter of older people fall every year, with frailty a major contributing factor. In the US, 285,000 of those who fall are hospitalised with hip fracture and 32,000 die6. In the UK, frailty accounts for over 70% of unplanned hospital admissions and 20% of hospital bed occupancy7, as well as an 8- to 10-fold increase in probability of dying after emergency admission to hospital8. Surgery in frail patients comes with higher risks of increased length of hospital stay and adverse outcomes including loss of independence, discharge to long-term care or death8, 9. The negative impact of frailty and age-related ill health on older people, their families, care-givers and societies is unsustainable10.
Importantly, frailty does not just affect those old in years – many women experience rapid declines in their health including cardiovascular disease11 and osteoporosis12 following menopause, and life-saving cancer treatments can accelerate biological ageing13. Soldiers with traumatic injuries or PTSDx4 and young adults after serious road traffic accidents15 show rapid onset of age-related diseases, equivalent to ageing by ~10 years. Sedentary lifestyles, accompanied by lack of adequate physical exercise, increase frailty prevalence ratio almost threefold16. It is now emerging that viruses such as SARS-CoV-2 can also drive premature aging17. With even mild COVID cases showing accelerated neurodegeneration18 and cardiovascular disease19, as many as 76 million people worldwide may experience early onset of age-related conditions and frailty directly as a consequence of the recent pandemic.
Resilience as a new framework to promote healthy ageing.
We already have a strong understanding of biological ageing20, with increasing recognition that age-related diseases, multimorbidity, and indeed frailty, result from fundamental cellular and molecular biological changes driven by ageing processes21. Looking through the lens of resilience gives us a new way to understand health as we age, highlighting the need to restore steady-state and dynamic resilience and to reverse loss of homeostasis in order to prevent frailty and age-related multimorbidity.
We need to be able to identify and measure the parameters of resilience and the factors and processes in complex biological systems that maintain and restore homeostasis and health. Such processes may include enhanced immunity, better energy management or improved stress responses, as seen in centenarians25. Such parameters and factors, plus validated models associated with these measures at multiple scales – from molecules to tissues and ultimately the whole body – would help to uncover causal mechanisms, identify individuals at risk of stress-event-induced deterioration in health, and accelerate clinical studies of interventions that aim to maintain or restore resilience.
Why now?
We are now in a position to leverage the power of deeply phenotyped longitudinal human cohorts and biobanks, combined with modern -omics technologies and bioinformatics tools in order to identify dynamic prognostic markers of human resilience. We can exploit new in vitro and in silico platforms to establish physiologically relevant human-derived systems to assess responses to stress/challenge. To accomplish this, we will need to draw together academic, clinical and commercial expertise across multiple disciplines (biology, chemistry, engineering, data science, computation/AI, human clinical sciences and trials) to identify personalised biomarkers of physiological resilience and to develop and test new interventions to improve health outcomes in older people.
The Dynamic Resilience program seeks to identify and validate causal measures and models of dynamic resilience, at multiple scales, with predictive value sufficient to make clinical decisions and to test interventions. Importantly, reducing progression to frailty in those over the age of 65 by 25% would protect over 75,000 adults in the UK alone, and potentially as many as 87 million older adults worldwide. It is realistic to believe that this is possible – frailty can be halted and even reversed26.
Program goals.
We have formulated the program goals below to address key fundamental questions to drive the measurement, modelling and testing capabilities needed to advance new methods of promoting healthy, whole lives: How do we measure and identify who is at greatest risk of health deterioration after a stress event? Why do some people stay in good health and others not? (in particular why is it that people who appear equally frail using steady state measures can show very different dynamic responses to stressor events?) What causes increased risk of health deterioration after a stress event (independent of individual disease states)? And how can we promote dynamic resilience and thus healthy aging for a greater number of people worldwide?
The three program goals are:
- Discover and integrate markers of human dynamic resilience that identify individuals prior to a stress event (SE) with prediction accuracy of >85% sensitivity and >90% specificity for clinical outcomes post-SE (e.g., return to health, frailty progression, loss of independence, death).
- Develop multi-scale models that link the biomarkers predictive of loss of steady state and dynamic resilience to mechanism. It will be necessary to show that identified mechanisms (some of which may overlap with known hallmarks of ageing) either promote and maintain homeostasis, or are causative of resilience loss. Such models and demonstration of mechanism can be at the cellular, tissue, system, or whole-body scale.
- Validate the clinical and developmental utility of measures, models, and candidate preventative interventions to promote resilience in at-risk populations by undertaking specific, targeted trials. Of particular interest are trials involving preventative interventions in older adults prior to predictable stress events such as elective laparoscopic or orthopaedic surgery, or cancer therapy and that focus both on demonstrating pre-stressor predictive clinical outcome accuracy of >85% sensitivity and >90% specificity with respect to frailty progression and interventions that seek at least a 25% reduction in the number of patients showing frailty progression following the stress event.
Call for abstracts and proposals.
We are soliciting abstracts and proposals for work over three (3) years (with a potential additional one-year option) in one or more of the following thrust areas (see Thrust areas in full program announcement). Proposers should clearly relate work in these thrust areas to one or more of the program goals.
Program Director.
Lynne Cox, PhD is an Associate Professor of Biochemistry at the University of Oxford. She has expertise in the biological underpinnings of ageing and age-related diseases, specifically cell senescence and premature ageing. She earned her PhD at the University of Cambridge followed by a Royal Society of Edinburgh research fellowship at the University of Dundee. She has contributed to the UK’s national strategy on ageing and co-directs the UK Ageing Research Networks.
Funding Partner.
This program is jointly funded with Temasek Trust.
Process and timeline
Program announcement.
30 DAYS FOR PREPARATION AND SUBMISSION OF ABSTRACT
15-Day Abstract review round.
All submissions will receive technical and/or programmatic feedback as well as a recommendation to submit or not submit a full proposal.
All submissions will receive technical and/or programmatic feedback as well as a recommendation to submit or not submit a full proposal.
30 DAYS FOR PREPARATION OF FULL PROPOSALS AFTER ABSTRACT FEEDBACK
30-Day Full proposal review round.
25-page full proposals including technical approach, milestones, costs, and key personnel submitted. Proposals should specifically address abstract feedback.
All submissions will receive a ‘selected for funding’ or ‘not selected for funding’ decision. Those selected will proceed to contract signature as the final gate with work expected to commence within approximately 30 days.
All submissions will receive a ‘selected for funding’ or ‘not selected for funding’ decision. Those selected will proceed to contract signature as the final gate with work expected to commence within approximately 30 days.
Mechanics of applying
Who is eligible?
Performers from universities and research institutions: small, medium and large companies (including venture-backed); and government or non-profit research organizations are invited to propose.
Wellcome Leap accepts project proposals from any legal entity, based in any legal jurisdiction, including academic, non-profit, for-profit, and regulatory/professional organizations. Applicants are encouraged to contact Wellcome Leap about joining its Health Breakthrough Network by executing its MARFA (or CORFA for commercial entities) agreement. Full execution of the Wellcome Leap MARFA is not required for application submission but is required for any award.
Wellcome Leap agrees not to use any confidential information disclosed to it in a submitted proposal for any purpose other than the review of a proposal. Wellcome Leap will not use the information contained in a proposal for Leap’s direct or indirect personal or financial benefit and will not make such information available for the direct or indirect personal or financial benefit of any other organization or individual.
Wellcome Leap shall not disclose or permit disclosure of any confidential information with anyone who has not been officially designated by Leap to participate in a review and completed a confidentiality agreement. Wellcome Leap agrees that it shall take all reasonable measures to protect the secrecy of and avoid disclosure or use of confidential information in order to prevent it from falling into the public domain or the possession of unauthorized persons. Such measures shall include, but not be limited to, the same degree of care that Wellcome Leap utilizes to protect its own confidential information, which shall be no less than reasonable care. Wellcome Leap further agrees to promptly notify in writing of any actual or suspected misuse, misappropriation or unauthorized disclosure of submitted confidential information which may come to Leap’s attention.
Notwithstanding the above, Wellcome Leap shall have no liability with regard to any information which Leap can prove:
(i) was in the public domain at the time it was disclosed or has entered the public domain through no fault of Leap;
(ii) was known to Leap, without restriction, at the time of disclosure, as demonstrated by files in existence at the time of disclosure;
(iii) is disclosed with the prior written approval of the submitter;
(iv) becomes known to Leap, without restriction, from a source other than Leap without breach of this statement; or
(v) is disclosed pursuant to the order or requirement of a court, administrative agency, or other governmental body; provided, however, that Leap shall provide prompt notice of such court order or requirement to submitter to enable submitter to seek a protective order or otherwise prevent or restrict such disclosure.
Furthermore, please recognize that Wellcome Leap may already be funding, or considering funding, the same or similar technology as covered by a submitted proposal—or have previously received from third parties—information or proposals similar to that which was submitted, that was not subject to confidentiality.
Wellcome Leap’s adherence to the above use of confidential information shall continue for a period of three (3) years from the receipt date of a submitted proposal.
Application guidelines.
We define three pillars of research development: health application, quantum algorithms, and quantum hardware. Submissions may originate from teams with expertise in any or a combination of the research pillars and should include a clear and concise description of the health challenge they are targeting. In addition, we require measurable technical and scientific deliverables that should include a preliminary estimate of the required quantum computing resources defined above and a detailed description of the quantum hardware platform needed for implementation.
Full proposal application steps.
- Download guidelines
- Download full proposal template (and cost and schedule template)
- Upload your full proposal and submit your application between 3 July 2023 and 10 July 2023,11:59pm ET.