Abstract
Frailty is a common age-related clinical syndrome characterized by a decline in the function of multiple organ systems, increased vulnerability to stressors and huge socio-economic burden. Despite recent research efforts, the physiopathological mechanisms concurring to determine frailty remain elusive and biomarkers able to predate its occurrence in the early stages are still lacking. Beyond its physical component, cognitive decline represents a critical domain of frailty associated with higher risk of adverse health outcomes.
We measured by High Performance Liquid Chromatography (HPLC) a pool of serum amino acids including L-glutamate, L-aspartate, glycine and D-serine, as well as their precursors L-glutamine, L-asparagine and L-serine in a cohort of elderly subjects encompassing the entire continuum from fitness to frailty. These amino acids are known to orchestrate excitatory and inhibitory neurotransmission, and in turn, to play a key role as intermediates of energy homeostasis and in liver, kidney, muscle and immune system metabolism. To comprehensively assess frailty, we employed both the Edmonton Frail Scale (EFS), as a practical tool to capture the multidimensionality of frailty, and the frailty phenotype, as a measure of physical function. We found that D-serine and D-/Total serine ratio were independent predictors of EFS but not of physical frailty. Furthermore, higher glycine levels and D-/Total serine correlated with worse cognition and depressive symptoms in the frail group. These findings suggest that altered homeostasis of D-serine may represent a biochemical signature of frailty, while increased serum glycine and D-/Total serine ratio could be specifically associated with cognitive decline and depression in frail older populations.
*Alberto Imarisio and Isar Yahyavi share first authorship
**Alessandro Usiello and Enza Maria Valente share senior authorship