A promising therapeutic peptide and preventive/diagnostic biomarker for age-related diseases: The Elabela/Apela/Toddler peptide

Elabela (ELA), Apela or Toddler peptide is a hormone peptide belonging to the adipokine group and a component of apelinergic system, discovered in 2013-2014. Given its high homology with apelin, the first ligand of APJ receptor, ELA likely mediates similar effects. Increasing evidence shows that ELA has a critical function not only in embryonic development, but also in adulthood, contributing to physiological and pathological conditions, such as the onset of age-related diseases (ARD). However, still little is known about the mechanisms and molecular pathways of ELA, as well as its precise functions in ARD pathophysiology. Here, we report the mechanisms by which ELA/APJ signaling acts in a very complex network of pathways for the maintenance of physiological functions of human tissue and organs, as well as in the onset of some ARD, where it appears to play a central role. Therefore, we describe the possibility to use the ELA/APJ pathway, as novel biomarker (predictive and diagnostic) and target for personalized treatments of ARD. Its potentiality as an optimal peptide candidate for therapeutic ARD treatments is largely described, also detailing potential current limitations

Starting point for eGFR thresholds reassessment on the basis of age and sex/gender to easily differentiate age-dependent renal functional decline from chronic kidney disease (CKD) in men/women

Introduction CKD in adult is identifies when a value of eGFR less than 60mL/min/1.73m2. The use of the fixed thresholds shows different risks as CKD overdiagnosis in elderly people so age and gender differences should be considered. Methods We evaluated the variability of eGFR in 57.449 adults divided in four age-classes (18-40, 40-60, 60-80,80-100) considering the gender. Were included some inflammatory variables and Albumin/Creatinine for kidney injury evaluation. Also included Neutrophils/Lymphocytes and the modified Glasgow Prognostic Score. Data were analysed according to the statistical methodologies in use in our laboratory. Results Analysing 57,449 samples, 51.1% female and 48.9% male showed statistically significant difference for gender (Chi squared test = p<0.001). The higher r correlations coefficient is between age and eGFR: -0.46 (p<0.001) consequently to age’s increases eGFR decrease. The two-way factorial ANOVA revealed the significant effects of Age Class (p<0.001) and Gender (p<0.001) on eGFR. By using a multinomial multivariate logistic regression model for eGFR categories, established the six categories: G1, G2, G3a, G3b, G4 e G5. Detecting significant OR values for CKD, the subjects aged between 18 and 40 years had the lowest OR values, with a decrease of a factor of 0.01 (p<0.001), to develop G2-G5 pathological conditions than older age-classes (80-100 years). This <1 risk trend is maintained in all eGFR strata. In female also reduce the risk to be G2-G5 with respect to G1 by a factor of 0.23 (p<0.001). Analysing the inflammatory risk according to the categories of the modified Glasgow prognostic score, the subjects aged between 18 and 40 years showed the lowest OR values for mGPS2 than 80-100 years class people with a decrease by a factor of 0.03(p<0.001). This <1 risk trend across age groups is maintained in all mGPS strata. In female also appears to decrease the risk to develop a mGPS2 19 cases in males and 25 in females of a factor of 0.44 (p=0.009), given that the other variables in the model are held constant. This <1 risk trend for Gender is maintained in all mGPS strata. Conclusions This study proposes modifying the current eGFR values for CKD across age groups and by sex/gender by considering a larger population sample