Catalyst Awardee

Project Description

Defining the phenotype-axis of frailty and resilience at single-cell resolution

Jude M. Phillip, PhD | Johns Hopkins University; Jeremy Walston, MD | Johns Hopkins University; Sean Sun, PhD | Johns Hopkins University
Competition Sponsor: US National Academy of Medicine
Awardee Year: 2022

Age is considered a key risk factor for the development and progression of many diseases. However, person-to-person variations in the way diseases manifest in older adults indicates that this risk is not uniform with chronological age. As such, there is a critical need to develop new approaches that capture underlying biological mechanisms of aging to describe disease susceptibility and resilience. In older adults, frailty and resilience lie at polar extremes of each other. Frailty is defined based on a set of clinical features (e.g. gait speed), and shows strong associations with disease susceptibility and death. Resilience on the other hand is difficult to measure at baseline. Here, resilience describes the ability to recover and rebound after injury or exposure to stressors (e.g. sickness, falls, surgery). In many cases, the only true way to determine resilience is to measure clinical features after-the-fact. As such, clinicians are defaulted to ‘trial-and-error’ approaches when treating and selecting older adults for invasive medical procedures. Here, we propose to develop a cell-based approach to determine baseline resilience and frailty in older adults. The premise of the idea is that instead of waiting to measure the responses of older adults to stressors after-the-fact, we can stress their cells within engineered microenvironments to predict baseline resilience and frailty. A key goal is this work is to develop precision aging strategies to help guide interventions and shape treatment options. As a result, it could help preserve healthspan, boast longevity, and reduce treatment-associated healthcare costs.


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