Metabolic trajectories as frailty sentinel: biochemical pathways interconnected with malnutrition

Life expectancy has almost doubled in the last 150 years, and today, in Italy, the proportion of people aged 65 and older is 21.5%. One of the more represented consequences of age-related decline is the clinical condition of frailty. Frailty is a geriatric syndrome characterized by loss of biological reserves and high vulnerability to stressors. Although frailty is closely related to aging, it differs among people of the same age. However frailty may be prevented to foster a longer and healthier life. There is strong evidence about the role of an unhealthy diet in the increased risk of frailty development. The discovery of endogenous and/or exogenous plasma markers able to identify populations at risk of frailty is crucial for appropriate clinical management. Although cross-sectional studies have identified markers related to frailty, longitudinal investigations failed to distinguish frail from fit older adults, making imperative a deeper characterization of the plasma metabolome over time.

Plasma metabolic longitudinal signatures will be acquired for older Italian adults that underwent clinical diagnosis of frailty within four and/or eight years. Plasma samples will be profiled using FIA-HRMS (fast/robust mass spectrometry solution,) which allows rapid metabolic screening of endogenous/exogenous compounds. Data will be processed by in-house-developed software. Plasma metabolites will be identified by HMDB, a comprehensive, high quality, freely accessible database of small endogenous/exogenous metabolites found in the human body (including food-related molecules). Using advanced statistical strategies, plasma metabolic signatures will be associated with the risk of developing frailty. The anamnestic, biochemical, and dietary information, previously obtained, will be evaluated to characterize their association/correlation with the plasma metabolic trajectories and to model the risk of frailty. Metabolites of interest will be selected for metabolic pathways analysis to identify biochemical pathways related to frailty and nutritional status.

Identifying people at risk of frailty when this condition is still sub-clinical and interventions are most likely to be effective is an urgent need for the care of older persons. 
The project will expect to assess the feasibility of plasma metabolites as prognostic markers of frailty used to identify individuals at risk. This project also expects to determine the association/correlation of plasma metabolites with respect to frailty score, biochemical asset, and nutritional status.
If successful, the project will provide ready-to-use plasma clinical markers to identify adults at risk of frailty. Moreover, it will help to shed light into the mostly unexplored relationships between nutritional status and health outcomes in older adults.