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Unravelling the Sex-Frailty Paradox: Identification of Sex-Specific Determinants of Frailty

Award Number: R01AG101742
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2031

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Unravelling the Sex-Frailty Paradox: Identification of Sex-Specific Determinants of Frailty - Project summary/abstract Frailty is a clinically significant indicator of biological aging and a strong predictor of adverse outcomes, including mortality. Notably, women tend to exhibit higher frailty scores than men at comparable ages, yet experience lower mortality—a phenomenon termed the sex-frailty paradox. The biological and socio-environmental underpinnings of this paradox remain poorly understood. This project addresses the gap by pursuing three integrated aims: (1) to benchmark the performance and potential sex bias of commonly used frailty assessment tools across multiple large-scale, global human datasets; (2) to identify sex-specific, modifiable molecular and environmental drivers of frailty using AI-powered analysis of multi-omic and exposome data; and (3) to test causal biological mechanisms of sex differences in frailty using genetically diverse UM-HET3 mice and Four Core Genotype (4CG) mouse models. As an early career researcher PI Kane will be supported by a team of experts in sex differences, large-scale clinical data analysis and systems biology. Completion of this project will result in better understanding of the sex-frailty paradox and its underlying mechanisms, and inform the development of precision tools and targeted interventions for the detection, prevention and treatment of frailty for all older adults.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $614,032 )
2026	2026	INSTITUTE FOR SYSTEMS BIOLOGY	401 TERRY AVE N	SEATTLE	WA	98109	KING	USA	Aging Research	000	1	6/18/2026	NEW	$614,032
														Subtotal = $614,032

Grand Total All Awards = $614,032

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Unravelling the Sex-Frailty Paradox: Identification of Sex-Specific Determinants of Frailty

Award Number: R01AG101742

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2031

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