Frailty is a biological syndrome which has offered since its inception great opportunities to provide explanations to many of the facts underlying the usual functional deterioration observed in people as they age. Among its most relevant contributions, it has opened the possibility of detecting people at risk for developing serious and life-threatening adverse events, including death, disability, hospitalization or institutionalization, showing its potential spontaneous reversibility and, accordingly, giving a chance to stop and reverse the process of the so-called non-catastrophic disability. Moreover, in the last few years several well-designed, big clinical trials have come to show how the condition can be reversed through a therapeutic intervention, mainly based in physical exercise programs, nutritional interventions and retargeting the aims in some usual conditions like diabetes or hypertension (Bernabei et al., 2022; Rodriguez-Mañas et al., 2019; Trombetti et al., 2018), although showing some controversial results.

One of the usual concerns in the field of frailty is the way of detecting the condition and of monitoring its evolution along the time. This is due mainly to the lack of tools to detect the syndrome with a good sensitivity, specificity, and predictive values. Moreover, taking into account that the concept of frailty has been mainly developed and checked in community-dwelling environments, there is a huge number of instruments to detect and assess frailty lacking data about that necessary information for any diagnostic and prognostic tool (Faller et al., 2019).

In addition, the agreement between those instruments is quite poor, as it is the differences in their capability to make a prognosis of the distinct adverse events associated to frailty, suggesting the existence of several subtypes of frailty that will be captured differentially by each instrument and with different consequences for the patient (Checa-Lopez et al., 2023; Oviedo-Briones et al., 2021, 2022; Vergara et al., 2019).

Finally, the prevalence, the characteristics, the phenotypes and the outcomes of frail older people in healthcare settings are different from those in the community, making the previously mentioned issues of the utmost relevance (Oviedo-Briones et al., 2021, 2022). In fact, one of the usual claiming about the difficulties to translate and implement frailty in the clinical daily practice is the uncertainty of the available tools for detecting and follow-up it in these settings, where diagnostic accuracy is mandatory (Rodriguez-Mañas et al., 2017; Rodriguez-Mañas and Fried, 2015).

Taken as a whole, the need for finding biomarkers, able to contribute to provide more accurate diagnostic and a better monitoring of frailty, a highly dynamic condition, has emerged as a relevant issue to be tackled, and because of that should be incorporated to the research priorities in the field (Rodríguez-Mañas and Rodriguez-Sánchez, 2021). However, although several efforts have been done in recent years our knowledge about biomarkers of frailty, its performance and its usefulness in the clinical arena is far to be satisfactory. As a consequence, they are not generally used and the issue is still in the research field (LeBrasseur et al., 2021; L Rodriguez-Mañas et al., 2020).

For the purposes of this review, we have divided the biomarkers in laboratory biomarkers, image biomarkers and clinical biomarkers, although it would be worthy to check in future research the performance of the combination in the improved diagnosis and monitoring of frailty.