Introduction:
The R13 Stress Tests and Biomarkers of Resilience Conference offered a unique convergence of senior and junior investigators, fostering a dynamic exchange of ideas and collaboration.1 As Rising Star investigators, the opportunity to engage with thought leaders and emerging talents in the resilience field was both inspiring and transformative. This think tank event aimed to chart a roadmap for future research on resilience biomarkers, blending insights from seasoned experts with fresh perspectives from up-and-coming researchers.
The first conference in this series focused on building a definition of resilience.2 The third conference will concentrate on targeting and improving resilience. This second conference, therefore, centered on three pivotal themes: the biology of resilience, factors influencing resilience biology, and biomarker testing to predict resilience in older adults. Dynamic and stimulating presentations spanned from the microcellular mechanisms of resilience to the broader social and environmental determinants. Following these talks, participants were divided into pre-selected small groups to develop actionable recommendations to advance the resilience research field.
Biomarker Discussion:
In our small group, which included a diverse array of experts from various disciplines and career stages, we were tasked with developing recommendations for a biomarker panel for use in human resilience research. Using an established definition developed by the Biomarker Definitions Working Group two decades ago, Zeger and colleagues defined a biological marker (biomarker) as a characteristic that is objectively measured and evaluated as an indicator of a normal biological processes, pathogenic processes, or pharmacologic response to a therapeutic intervention (Figure 1).3 After reaching a consensus that this definition appropriately captured our understanding of a biomarker that could be used for resilience, the discussion shifted to what panel of such markers we would recommend.
Figure 1.
Effects of therapeutic interventions on biomarkers and clinical endpoints in clinical trials. Modified from: Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001 Mar;69(3):89–95. doi: 10.1067/mcp.2001.113989. PMID: 11240971.)
We then began by brainstorming potential biomarkers within our group and then expanded the discussion to all conference attendees. This collective brainstorming was visually represented in a word cloud, where terms like “inflammation” and “gait” featured prominently, underscoring the diversity of opinions and the lack of an agreed upon universal resilience biomarker (Figure 2). Despite identifying several key features of resilience biomarkers, we recognized that no single biomarker could universally capture resilience across all conditions and based on these examples, the group discussed the possibility of categorizing resilience biomarkers according to the stressor.
Figure 2.
Word cloud generated by conference attendees during biomarkers discussion session, demonstrates the various areas of interest and disciples working within the resilience space. The more frequent the words appear, the larger they are displayed in the word cloud.
Several essential features of resilience biomarkers were highlighted during the group discussion. 1) The timeline of biomarker measurement is key: it should be measured prior to, during, and/or post-stress. In addition it is important to document the timeline of pre-stressor reserve, stressor duration, dynamic response and outcome when identifying biomarkers of resilience. 2) Cross-sectional biomarkers were considered to be inadequate to measure resilience. They may offer insight into the current state but cannot provide information about its progression over time. 3) Heterogeneity may represent a challenge to identify biomarkers of resilience. Heterogeneity could be a biomarker of resilience, but an excess of heterogeneity might be a marker of loss of resilience. 4) There is a gap in integrating resilience biomarkers across scales/dimensions (molecular, tissue, system, culture etc) and measuring biomarkers simultaneously across these scales. Simultaneously measuring biomarkers across these scales has the potential to enhance our comprehension of resilience significantly.
Ultimately, the group agreed on a common framework for biomarkers of resilience, however the specific conditions might require a specific panel of resilience biomarkers.
Recommendations:
Although there was extensive discussion of potential biomarkers, our group did not find strong evidence to support a universal biomarker panel for all conditions. However, we categorized resilience biomarkers into four broad types: circulating biomarkers (e.g., inflammatory markers), physiologic measures (e.g., heart rate, core body temperature), psychosocial biomarkers (e.g., happiness), and imaging biomarkers (e.g., fMRI). We also identified non-traditional biomarkers, such as dynamic changes across time series and responses to specific stressors. Yet, there were other examples that transcended spatial or temporal dimensions and did not fit as easily into these ‘traditional’ categories, e.g. measuring coupling between dynamic changes across time series, and response to hypoglycemia. In lieu of an in-depth review of biomarkers of resilience, the group focused on a set of guiding questions to focus future scientists engaging in resilience research.
The “Why”: A starting point for selecting a biomarker for resilience should begin with the question “why”, that is, what is the purpose of the resilience biomarker? One might be most interested in predicting resilience, in which case prognostication is the key goal of the biomarker. Another area of investigation might be focused on the mechanisms of resilience, with a future goal of interventions to support resilience, such that a different biomarker would be more appropriate.
The “What”: The group acknowledged the multidimensional nature of biomarker measurement and recommended incorporating spatial and temporal biomarker measurement in future resilience research.
The “When”: When refers both to timing of the stressor in the life-course of the organism or environment, and also how often and the exact time at which one plans to measure the response (e.g. time-series data).
The “How”: Resilience biomarker measurement should provide details of how a sample is collected, e.g. saliva, blood, ex-vivo, and ensure standardization so that it is studied under the same stress and under the same conditions.
In summary, we envision a battery of biomarkers for physiologic, psychological, and behavioral systems. We recommend that biomarkers are measured simultaneously across different scales or dimensions such that we can generate a new knowledge base as to how they interrelate across systems within an organism or person.
Acknowledgments:
We would like to thank the National Institute on Aging and the American Geriatrics Society and R13 conference selection committee for the opportunity to participate in such a riveting conference experience with leaders in this field.
Disclosures:
Funding- Dr. Umoh is part of the Health Services and Outcomes Research for Aging Populations Training Program funded by the National Institute on Aging / National Institutes of Health grant number T32AG066576. Dr. Cheung is funded by the U54 GM115516 from the National Institutes of Health for the Northern New England Clinical and Translational Research Network.
Footnotes
Conflict of Interest: Authors declare no conflicts to report.
References
- 1.Abadir P, Whitson H. Geriatric research through the lens of AGS/NIA U13: Two decades of interdisciplinary dialogues that have propelled the field. J Am Geriatr Soc. 2024;72(5):1623–1626. doi: 10.1111/jgs.18810. [DOI] [PubMed] [Google Scholar]
- 2.Abadir PM, Bandeen-Roche K, Bergeman C, et al. An overview of the resilience world: Proceedings of the american geriatrics society and national institute on aging state of resilience science conference. J Am Geriatr Soc. 2023;71(8):2381–2392. doi: 10.1111/jgs.18388. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95. doi: 10.1067/mcp.2001.113989. [DOI] [PubMed] [Google Scholar]