Blood biomarkers of frailty: a paradigm for aging research

A recent meta-analysis identifies blood indicators as simple, non-invasive, economical and robust biomarkers of frailty.

Scientists at the Geriatrics Department of CHU Lille and Special Interest Group on Ageing Biology of European Geriatric Medicine Society (France) performed a meta-analysis and identified blood biomarkers associated with physical frailty. The results of this study paved the way for the discovery of circulating, robust biomarkers of aging and age-related diseases. The study was led by Aurélie Mailliez and overseen by Dr Éric Boulanger, and their findings were recently published in the journal Experimental Gerontology [1].

Longevity.Technology: Based on their physical condition, aging individuals are often classified as robust, frail or dependent. Frailty is a complex condition particularly common among the elderly. It is caused by dysfunction in numerous biological systems and is characterised by unintentional weight loss, fatigue, and physical and cognitive impairments [2, 3].

Given that frailty is reversible, early detection may enable clinicians to prevent its progression, or even reverse it. However, systematic frailty monitoring in routine clinical practice is hindered by the lack of reliable biomarkers of frailty and other age-related conditions [1].

Stages of aging. From Aurélie Mailliez et al., 2020.

“In the next five years there’s a critical need to be able to measure the validity of interventions without waiting for our whole lifespan. Right now, if we make an intervention that we think will increase lifespan we need to study it for twenty or thirty or forty years for an answer,” says Dr Eric Verdin, Chief Executive Officer, Buck Institute for Research on Aging [4]. “One solution is to develop biomarkers of aging. That is, we need to be able to assess whether a given person is aging well or aging poorly at a biological level.”

In an effort to identify reliable biomarkers of frailty, Aurélie Mailliez and colleagues analysed the data of 67 studies including a total of 32,934 subjects and 6864 frail individuals. This comprehensive meta-analysis led to the identification of C-reactive protein (CRP), albumin, haemoglobin, 25-hydroxyvitamin D and free testosterone (in men) as the most reliable biomarkers of frailty [1].

Specifically, they found that the blood levels of CRP were significantly higher in frail individuals, whereas the circulating levels of albumin, haemoglobin, 25-hydroxyvitamin D, and free testosterone (in men) were significantly lower in the frail group [1].

Interestingly, circulating CRP and albumin are also included in the Levine/Cramer list of biomarkers of aging. The list includes nine blood indicators that can accurately estimate the phenotypic (biological) age. In addition to albumin and CRP, the Levine/Cramer list includes creatine, glucose, lymphocyte percent, mean cell volume, red blood cell distribution width, alkaline phosphatase, and white blood cell count [5].

Mounting evidence suggests the potential value of CRP, albumin, haemoglobin, 25-hydroxyvitamin D, and free testosterone (in men) as simple, non-invasive, economical and robust biomarkers of frailty. Future clinical studies are required to confirm their potential value as a non-invasive clinical tool to screen for frailty and other age-related conditions.


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