A systematic review of studies comparing potential biochemical biomarkers of frailty with frailty assessments

The approach to correlate frailty status with potential biomarkers has been generating increasing interest. However, there is currently no standardised definition or agreed biomarker for frailty. Hence, we conducted a systematic review on biomarkers evaluated in the published literature in relation to existing accepted measurements of frailty. The databases PUBMED, EMBASE, Web of Science and Science Direct were searched systematically for articles published from 2009 until July 2017. We included studies on frailty and associated biomarkers among individuals aged 65 years and older. Articles were reviewed by two reviewers independently. We identified 486 titles with 40 papers retained for final review after removal of duplicates and exclusion after the title, abstract and full-text review stages. Large variations in frailty measures and reported biomarkers were present in the published literature. Twenty-six articles recruited subjects from community-dwelling older individuals and 33 used the Fried's criteria. Of 11 studies, which evaluated Interleukin-6 (IL-6) against the Fried criteria, nine studies showed significant associations. Nearly all studies evaluating tumour necrosis factor-α, fibrinogen and C-reactive protein against Fried and Rockwood phenotypes showed positive associations. A large number of protein, nutritional, endocrine and genetic markers have been found to be associated with frailty defined with Fried, Rockwood and several other criteria, but only in isolated studies. The identification of potential biomarkers should be conducted with detailed knowledge of potential mechanistic pathways. It is likely that concurrent usage of clinical and biomarkers will be the favoured approach to the identification and management of frailty in the near future.