Novel protein biomarkers associated with frailty and its progression


Frailty is a state of increased vulnerability to adverse health outcomes due to reduced physiological reserves, diminished functional capacity, and decreased resilience. It is characterized by a decline in multiple physiological systems (such as muscle strength, endurance, balance, and mobility), as well as cognitive impairments and overall health. The condition is usually (though not exclusively) age-related, and the complex pathophysiology underlying biological ageing has made the identification biomarkers associated with frailty somewhat challenging.

A longitudinal proteomics study from a group at Lund University in Sweden has shed important new light on this subject, identifying multiple proteins associated with frailty and its progression. They used the Olink® Target 96 CVD II panel to look at serum proteins in a population cohort (OPRA)  that was ideally suited to address these questions, with women enrolled at the age of 75 and followed up over the course of 10 years. This longitudinal analysis of subjects with samples taken at the same age facilitated the differentiation of chronological and biological aging.


Using serum samples taken at baseline (age = 75 yrs, n=980), 5 years (n=686) and 10 years (n=318), the relative expression levels of proteins were measured and analyzed in relation to a standard frailty index rating. The association of proteins with frailty status was of specific interest, with the frailty vs non-frailty cutoff set at a frailty index of >0.25. At baseline, 54 proteins were cross-sectionally associated with frailty index, and 32 of these were replicated across all ages. 18 proteins were also reproducibly associated with “frailty status” at the 5yr and 10 yr follow ups.

The longitudinal data was then further interrogated to ask specific questions around the associations between protein expression and protein expression changes with changes in frailty index and frailty status. This identified 8 “core proteins” (CD4, FGF23, Gal-9, PAR-1, REN, TNFRSF10A TNFRSF11A and TNFRSF10B) that are key to these interrelationships. In line with the multi-system deterioration seen in frailty, pathway analysis showed that these proteins may reflect pathologies including the renal system, skeletal homeostasis and TRAIL-activated apoptotic signaling. The authors concluded that these core proteins are convincing candidates to better understand the development and progression of frailty with advancing age, including the intrinsic musculoskeletal component.



Mitchell A, Malmgren L, Bartosch P, et al. Pro-inflammatory proteins associated with frailty and its progression – a longitudinal study in community dwelling women. (2023) Journal of Bone and Mineral Research, DOI: 10.1002/jbmr.4861

A further strength is the large number of protein markers analyzed simultaneously in a multiplex proteomic assay using a PEA technique, which, compared with other assays, is a high-sensitivity, high specificity method without cross-reactivity

Mitchell et al. (2023)

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Olink’s Proximity Extension Assay (PEA) technology has been used for protein biomarker discovery and analysis across a very broad range of disease areas and applications, providing actionable insights into disease biology and helping to drive future development of new and better therapeutics. There are now well over 1200 publications citing the use of our assays and the list is growing rapidly. Please visit our library of publications to see some of the extraordinary work produced by Olink customers.

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