$60M PROGRAM jointly funded with Temasek Trust

Dynamic Resilience

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?

Dynamic Resilience seeks to identify and validate causal measures and models of health resilience, at multiple scales, with predictive value sufficient to make clinical decisions. Such markers will support the identification of mechanisms, and development and testing of preventative interventions to support health resilience in people at risk of deterioration after a stress event.

Reducing frailty progression by 25% has the potential to prevent 71,000 hospitalizations and 8,000 deaths annually from falls alone in the US, and to benefit 87 million older adults across the world.

One of the greatest success stories of the last century is the doubling in human life expectancy, from a global average of 35 years in 1900 to 70 years today. For most of us, however, the time we spend in good health (our health span) is much shorter than our overall lifespan, with increasing age-related diseases and decreasing ability to cope with stress. This loss of health resilience, termed clinical frailty, makes us vulnerable to sudden and serious health deterioration when we experience acute illness or injury. Frailty is an important and growing global health problem, affecting up to half of adults over 65, as well people who have experienced traumatic injury, COVID infection, life-saving cancer treatment, or menopause, and it can even be driven by sedentary behaviors and poor diet. Frailty makes us less able to live our lives independently, more likely to fall, to be hospitalized, to need long-term care or to die. The negative impact of frailty and age-related ill health on patients, their families, caregivers and societies is unsustainable.

But poor health as we age is not inevitable. The rising number of centenarians and supercentenarians shows that it is possible for humans to live well for a very long time. Such exceptional individuals are remarkably resilient: they enjoy good health for most of their lives and are able to ‘bounce back’ after significant stress events such as falls, infection, surgery, or major psychosocial stresses. Resilience gives us a new way to understand health spans, highlighting the need to restore steady-state and dynamic resilience to prevent frailty and age-related multimorbidity

“Dynamic Resilience is aimed at extending health spans – the duration of life that is spent in good health – so that more people can live fuller and healthier lives for longer.”

– Desmond Kuek, CEO of Temasek Trust

Advances in our understanding of the biological ageing processes that drive age-related diseases, multimorbidity and frailty have supported development of novel ‘anti-ageing’ therapies. These are garnering multi-billion-dollar investments, with teams across the world working on interventions to improve health as we age. But progress in therapy development and clinical trials is limited by lack of robust, reliable, and predictive biomarkers of frailty and resilience, by an incomplete understanding of resilience mechanisms, and by an absence of mechanism-targeting interventions to support resilience and prevent health deterioration. Current frailty scores and indices can provide reasonable predictions of statistical outcomes after a stress event, but they are poor predictors of outcomes for an individual. Even highly accurate molecular ageing clocks measure steady state at a point in time, rather than dynamic resilience – the ability to respond to and recover from stress.

The Dynamic Resilience program has three ambitious and interlinked goals: (1) novel multimodal biomarker signatures of resilience predictive of health outcomes following a stress event using biobanked longitudinal human cohorts; (2) underpinning mechanisms of frailty and resilience using human-centric in vitro and /or in silico stress-testable models at multiple scales (cells, tissue and organism); and (3) proof-of-concept experimental studies and clinical trials of preventative interventions to improve biological resilience in at-risk people prior to predictable stress events (e.g. surgery), targeting reduction in progression to further frailty or death by at least 25% in intervention versus control groups.

“We all share a desire to be healthy and live independently to our last breath. To do so, we will need to be able to measure, support, and maintain robust levels of dynamic resilience."

– Regina E. Dugan, Wellcome Leap CEO

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.

Further details.

To learn more about the program history, performer teams, and process, please visit the Program Details Page.