The present study shows that VitD may prevent endothelial cell death through modulation of the interplay between apoptosis and autophagy. This effect is obtained by inhibiting superoxide anion generation, maintaining mitochondria function and cell viability, activating survival kinases, and inducing NO production.

An important link between brain aging and a class of growth/survival factors called neurotrophins has recently been demonstrated. In particular, brain-derived neurotrophic factor (BDNF) plays a fundamental role during age-related synaptic loss, preventing cerebral atrophy and cognitive decline. The aim of the present study was to investigate whether the use of low dose BDNF sequentially kinetic activated (SKA) was able to counteract some mechanisms underlying the degeneration and aging of nervous tissue by increasing endogenous protection mechanisms. Both in vitro and in vivo experiments were performed to assess the ability of BDNF SKA to protect and regenerate survival-related molecular pathways, studying intestinal absorption in vitro and brain function in vivo. Our pioneering results show that BDNF SKA is able to induce the endogenous production of BDNF, using its receptor TrkB and influencing the apolipoprotein E expression. Moreover, BDNF SKA exerted effects on β-Amyloid and Sirtuin 1 proteins, confirming the hypothesis of a fine endogenous regulatory effect exerted by BDNF SKA in maintaining the health of both neurons and astrocytes. For this reason, a change in BDNF turnover is considered as a positive factor against brain aging.

Brain ageing is a complex multifactorial process characterized by gradual and continuous loss of neuronal functions. It is hypothesized that at the basis of brain ageing as well as age-related diseases, there is an impairment of the antioxidant defense system leading to an increase of oxidative stress. In this study, two different biological aspects involved in brain ageing and neurodegeneration have been investigated: oxidative stress and iron accumulation damage. In primary mouse astrocytes, the stimulation with 50 μM lipoic acid (LA) and 100 nM vitamin D (vitD) was first investigated in a time-course study to determine the dosages to be used in combination and then in a permeability test using an in vitro blood-brain barrier. In a second set of experiments, the role of oxidative stress was investigated pretreating astrocytes with 200 μM H2O2 for 30 min. The ability of vitD and LA alone and combined together to prevent or repair the damage caused by oxidative stress was investigated after 24 h of stimulation by the MTT test, mitochondrial membrane potential measurement, and Western blot analysis. To induce neurodegeneration, cells were pretreated with 300 μM catalytic iron for 6 days and then treated with vitD and LA alone and combined for additional 6 days to investigate the protection exerted by combination, analyzing viability, ROS production, iron concentration, and activation of intracellular pathways. In our study, the combination of LA and vitD showed beneficial effects on viability of astrocytes, since the substances are able to cross the brain barrier. In addition, combined LA and vitD attenuated the H2O2-induced apoptosis through the mitochondrial-mediated pathway. The combination was also able to counteract the adverse conditions caused by iron, preventing its accumulation. All these data support the hypothesis of the synergistic and cooperative activity exerted by LA and vitD in astrocytes indicating a possible new strategy to slow down ageing.

This study compares the absorption characteristics of two iron-based dietary supplements and their biocompatibility to bisglycinate iron, a common chelated iron form. The Caco-2 cell line—a model of human intestinal absorption—and GTL-16 cell line—a model of gastric epithelial cells—were used to perform the experiments; in the first experiments, the kinetics of absorption have been evaluated analyzing the divalent metal transporter 1 (DMT1) expression. Three different iron combinations containing 50 µM iron (named Fisioeme®, Sideral® and bisglycinate) were used for different stimulation times (1–24 h). After this, the effects of the three iron formulations were assessed in both a short and a long time, in order to understand the extrusion mechanisms. The effects of the three different formulations were also analyzed at the end of stimulation period immediately after iron removal, and after some time in order to clarify whether the mechanisms were irreversibly activated. Findings obtained in this study demonstrate that Fisioeme® was able to maintain a significant beneficial effect on cell viability compared to control, to Sideral®, and to iron bisglycinate. This observation indicates that Fisioeme® formulation is the most suitable for gastric and intestinal epithelial cells.

Our model aimed at studying the main nongenetic risk factor for ovarian cancer, providing an alternative interpretation for the role of menstruation in increasing risk of this pathology. This in vitro model mimics several features of the precursor lesions and opens new scenarios for further investigations regarding the correlation between damages produced by repeated retrograde menstruation carcinogenic stimuli.