Serum dysregulation of serine and glycine metabolism as predictive biomarker for cognitive decline in frail elderly subjects.

Frailty is a common age-related clinical syndrome characterized by a decline in the function of multiple organ systems, increased vulnerability to stressors, and a huge socio-economic burden. Despite recent research efforts, the physiopathological mechanisms underlying 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 levels of glycine, glycine/L-serine and D-/Total serine were associated with worse cognition and depressive symptoms in the frail group. These findings suggest that changes in peripheral glycine and serine enantiomers homeostasis may represent a novel biochemical correlate of frailty.

Blood D-serine levels correlate with aging and dopaminergic treatment in Parkinson's disease.

We recently described increased D- and L-serine concentrations in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, the post-mortem caudate-putamen of human Parkinson's disease (PD) brains and the cerebrospinal fluid (CSF) of de novo living PD patients. However, data regarding blood D- and L-serine levels in PD are scarce. Here, we investigated whether the serum profile of D- and L-serine, as well as the other glutamate N-methyl-D-aspartate ionotropic receptor (NMDAR)-related amino acids, (i) differs between PD patients and healthy controls (HC) and (ii) correlates with clinical-demographic features and levodopa equivalent daily dose (LEDD) in PD. Eighty-three consecutive PD patients and forty-one HC were enrolled. PD cohort underwent an extensive clinical characterization. Serum levels of D- and L-serine, L-glutamate, L-glutamine, L-aspartate, L-asparagine and glycine were determined using High Performance Liquid Chromatography. In age- and sex-adjusted analyses, no differences emerged in the serum levels of D-serine, L-serine and other NMDAR-related amino acids between PD and HC. However, we found that D-serine and D-/Total serine ratio positively correlated with age in PD but not in HC, and also with PD age at onset. Moreover, we found that higher LEDD correlated with lower levels of D-serine and the other excitatory amino acids. Following these results, the addition of LEDD as covariate in the analyses disclosed a selective significant increase of D-serine in PD compared to HC (Δ ≈ 38%). Overall, these findings suggest that serum D-serine and D-/Total serine may represent a valuable biochemical signature of PD.

An overview of the nutritional status of childbearing age women, children and adolescents living in a rural area of Madagascar: preliminary results of the Tany Vao project.

OBJECTIVE: To describe the food consumption, nutrition knowledge and nutritional assessment of childbearing age women and their children, living in rural villages in Madagascar. The results presented are related to the Tany Vao research study. DESIGN: A cross-sectional pilot study. SETTING: The study was carried out in Ampanitosoha village on Nosy Mitsio island in Madagascar. PARTICIPANTS: 32 women (14-49 years) and 36 children and adolescents (2-17 years). RESULTS: 70 % of the women lacked nutrition knowledge and did not reach the Minimum Dietary Diversity Index for Women cut-off. The median BMI was 21·1 kg/m2 but 55·2 % of the women exceeded the cut-off for waist-to-hip ratio, 51·7 % for waist-to-height ratio and 81·2 % for mid-upper arm circumference (MUAC). Almost all had adequate intake of energy, protein and carbohydrates, while 27·6 % had excessive fat intake and 75·9 % of added sugars. Over half of the women did not meet the micronutrients Reference Daily Intake (RDI). For children, the MUAC z-score was lower for boys than for girls (P-value = 0·041). CONCLUSIONS: These results underline the importance of increasing women's nutritional knowledge to promote healthy pregnancy and lactation. Moreover, it is fundamental to provide people living in rural areas with sustainable tools to improve dietary diversity and support long-term health.