A Frailty-Based Plasma Proteomic Signature Capturing Overall Health and Well-Being in Older Adults

Q: What is the main goal of the study?

To derive and validate a blood-based proteomic signature that captures frailty risk and overall health and well-being in older adults.

Q: How was the proteomic frailty index (pFI) created?

Using a penalized regression method to derive a 25-protein proteomic frailty index predictive of the cumulative frailty index.

Q: Which outcomes were the pFI associated with in the validation cohorts?

The pFI showed significant associations with age-related conditions (e.g., hypertension and diabetes), clinical and functional measures, cognitive scores and incident dementia, and mortality after adjusting for demographic factors.

Sep 29, 2026

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Frailty is an age-related syndrome marked by heightened vulnerability to adverse outcomes under stress. This study derives a blood-based proteomic signature for frailty to clarify frailty biology and support person-specific prediction of frailty risk and other age-related outcomes. A penalized regression framework produced a 25-protein signature (proteomic frailty index, pFI), validated across LonGenity and two independent cohorts, with significant links to multiple clinical, functional, cognitive, dementia, and mortality measures after demographic adjustment.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages2

Reading Time5 min

AccessFree to download

Abstract

Study aim and approach

Discovery of the 25-protein signature

Validation across cohorts

Associations with health, function, cognition, and mortality

Conclusion

608 Innovation in Aging, 2025, Vol. 9, No. S2 Abstract citation ID: igaf122.2086 A FRAILTY-BASED PLASMA PROTEOMIC SIGNATURE CAPTURING OVERALL HEALTH AND WELL-BEING IN OLDER ADULTS Fangyu Liu1, Sanish Sathyan2, Toshiko Tanaka3, Nir Barzilai4, Sofiya Milman5, Keenan Walker3, and Joe Verghese2, 1. National Institute on Aging, United States, 2. Stony Brook University, Stony Brook, New York, United States, 3. National Institute on Aging, Baltimore, Maryland, United States, Innovation in Aging, 2025, Vol. 9, No. S2 609 4. Institute for Aging Research, Bronx, New York, United States, 5. Albert Einstein College of Medicine, Albert Einstein College of Medicine, New York, United States Frailty is an age-related syndrome characterized by an increased vulnerability to adverse health outcomes in the face of stressors. By deriving a blood-based proteomic signature for frailty, the current study aimed to enhance the understanding of frailty biology and derive a person-specific predictor for risk of frailty and other adverse age-related health outcomes. Penalized regression method was used to derive a 25-proteins signature (proteomic frailty index [pFI]) predictive of the cumulative frailty index (FI) in a training set of participants from the LonGenity cohort (N = 440) . The pFI was validated with measured FI at baseline (r = 0 .58) in the validation set (N = 440) from the same cohort and in two other independent cohorts: the Atherosclerosis Risk in Communities (ARIC) study (N= 5195, r = 0.61, p < 0.001) and the Baltimore Longitudinal Study of Aging (BLSA, N = 654, r=0.45, p <0.001). In all three cohorts, the pFI showed significant associations with age-related conditions including hypertension and diabetes, clinical measures of cholesterols, glucose and lipids, and functional measures of gait speed and grip strength (p < 0.001), after adjusting for demographic factors. InARIC, thepFI were also significantly associated with cognitive scores (p < 0.001) and incident dementia (HR [95% CI] = 1.07 [1.05-1.09], follow-up: 7.22 [1.82] years) . The pFI were also associated with mortality (LonGenity: HR [95% CI] = 1.12 [1.07-1.18]; ARIC: HR [95% CI] = 1.13 [1.12–1.14]; BLSA: HR [95% CI] = 1.11 [1 .05–1. 17]) . In conclusion, we derived and validated a 25-protein signature of frailty that also captures overall well-being, health, and risk for key age-related diseases.

FAQs

What is the main goal of the study?

To derive and validate a blood-based proteomic signature that captures frailty risk and overall health and well-being in older adults.

How was the proteomic frailty index (pFI) created?

Using a penalized regression method to derive a 25-protein proteomic frailty index predictive of the cumulative frailty index.

Which outcomes were the pFI associated with in the validation cohorts?

The pFI showed significant associations with age-related conditions (e.g., hypertension and diabetes), clinical and functional measures, cognitive scores and incident dementia, and mortality after adjusting for demographic factors.

Sep 29, 2026

Upload by Valentina