The Mechanism of Stem Cell Aging

Stem cells have self-renewal ability and multi-directional differentiation potential. They have tissue repair capabilities and are essential for maintaining the tissue homeostasis. The depletion of stem cells is closely related to the occurrence of body aging and aging-related diseases. Therefore, revealing the molecular mechanisms of stem cell aging will set new directions for the therapeutic application of stem cells, the study of aging mechanisms, and the prevention and treatment of aging-related diseases. This review comprehensively describes the molecular mechanisms related to stem cell aging and provides the basis for further investigations aimed at developing new anti-stem cell aging strategies and promoting the clinical application of stem cells.

Targeting Epigenetic Mechanisms in Vascular Aging

Environment, diseases, lack of exercise, and aged tendency of population have becoming crucial factors that induce vascular aging. Vascular aging is unmodifiable risk factor for diseases like diabetes, hypertension, atherosclerosis, and hyperlipidemia. Effective interventions to combat this vascular function decline is becoming increasingly urgent as the rising hospitalization rate caused by vascular aging-related diseases. Fortunately, recent transformative omics approaches have enabled us to examine vascular aging mechanisms at unprecedented levels and precision, which make our understanding of slowing down or reversing vascular aging become possible. Epigenetic viz. DNA methylation, histone modifications, and non-coding RNA-based mechanisms, is a hallmark of vascular aging, its deregulation leads to aberrant transcription changes in tissues. Epigenetics mechanisms by mediating covalent modifications to DNA and histone proteins, consequently, influence the sensitivity and activities of signaling pathways in cells and tissues. A growing body of evidence supports correlations between epigenetic changes and vascular aging. In this article, we will provide a comprehensive overview of epigenetic changes associated with vascular aging based on the recent findings with a focus on molecular mechanisms of action, strategies to reverse epigenetic changes, and future perspectives.

Prebiotic Agrocybe cylindracea crude polysaccharides combined with Lactobacillus rhamnosus GG postpone aging-related oxidative stress in mice

This study aimed to investigate the potential anti-aging mechanisms of Agrocybe cylindracea crude polysaccharides (APS), when used synergistically with Lactobacillus rhamnosus GG (APS+LGG) in a d-galactose-induced aging mice model. In...

Aging Biomarkers for Clinical Trials and Drug Discovery

Developing targeted therapies first requires a working definition of the condition of interest. Unfortunately for aging, this very initial step poses a challenge since chronological age is often not indicative of biological age nor modifiable. This symposium will demonstrate the enormous progress being made towards developing more reliable and valid measures for quantifying biological aging. First, Dr. Albert T. Higgins Chen will show how inaccuracy caused by noise at individual CpG sites can lead to high technical variability in the most widely applied biomarkers of aging—epigenetic clocks. He will further discuss how this can be overcome through novel statistical techniques. Second, Dr. Benoit Lehallier, will discuss plasma proteomic clocks and share insights into their potential roles in Alzheimer's disease and utilization in clinical trials. Third, quantifying the multifactorial aging process can be facilitated by projects incorporating multimodal biomarker data. Pei-Lun Kuo from the Baltimore Longitudinal Study of Aging will present an analysis of longitudinal trajectories of more than 30 phenotypes, which when combined into a single summarized score yield important insights. Fourth, our ability to uncover aging mechanisms and perform drug screens, requires valid and reliable measures that can be applied in vitro. Christopher Minteer who developed in cellulo epigenetic markers will demonstarte how epigenetic aging changes that can be induced in culture shed light on aging in vivo. Finally, a summarizing discussion will be held by Dr. Nir Barzilai, an expert in the field, who is leading the Targeting Aging with Metformin (TAME) clinical trial.

Multi-Omics Interpretation of Anti-Aging Mechanisms for ω-3 Fatty Acids

Aging is one of the hottest topics in biomedicine. Previous research suggested that ω-3 fatty acids have preventive effects on aging. However, most of previous studies on the anti-aging effects of ω-3 fatty acids are focused on clinical observations, and the anti-aging mechanisms of ω-3 fatty acids have not been fully elucidated. This stimulated our interest to use multi-omics data related to ω-3 fatty acids in order to interpret the anti-aging mechanisms of ω-3 fatty acids. First, we found that ω-3 fatty acids can affect methylation levels and expression levels of genes associated with age-related diseases or pathways in humans. Then, a Mendelian randomization analysis was conducted to determine whether there is a causal relationship between the effect of ω-3 fatty acids on blood lipid levels and variation in the gut microbiome. Our results indicate that the impact of ω-3 fatty acids on aging is partially mediated by the gut microbiome (including Actinobacteria, Bifidobacteria and Streptococcus). In conclusion, this study provides deeper insights into the anti-aging mechanisms of ω-3 fatty acids and supports the dietary supplementation of ω-3 fatty acids in aging prevention.

Bisphenol A Induces Accelerated Cell Aging in Murine Endothelium

Bisphenol A (BPA) is a widespread endocrine disruptor affecting many organs and systems. Previous work in our laboratory demonstrated that BPA could induce death due to necroptosis in murine aortic endothelial cells (MAECs). This work aims to evaluate the possible involvement of BPA-induced senescence mechanisms in endothelial cells. The β-Gal assays showed interesting differences in cell senescence at relatively low doses (100 nM and 5 µM). Western blots confirmed that proteins involved in senescence mechanisms, p16 and p21, were overexpressed in the presence of BPA. In addition, the UPR (unfolding protein response) system, which is part of the senescent phenotype, was also explored by Western blot and qPCR, confirming the involvement of the PERK-ATF4-CHOP pathway (related to pathological processes). The endothelium of mice treated with BPA showed an evident increase in the expression of the proteins p16, p21, and CHOP, confirming the results observed in cells. Our results demonstrate that oxidative stress induced by BPA leads to UPR activation and senescence since pretreatment with N-acetylcysteine (NAC) in BPA-treated cells reduced the percentage of senescent cells prevented the overexpression of proteins related to BPA-induced senescence and reduced the activation of the UPR system. The results suggest that BPA participates actively in accelerated cell aging mechanisms, affecting the vascular endothelium and promoting cardiovascular diseases.

Impact of Bias Temperature Instabilities on the Performance of Logic Inverter Circuits Using Different SiC Transistor Technologies

All electronic devices, in this case, SiC MOS transistors, are exposed to aging mechanisms and variability issues, that can affect the performance and stable operation of circuits. To describe the behavior of the devices for circuit simulations, physical models which capture the degradation of the devices are required. Typically compact models based on closed-form mathematical expressions are often used for circuit analysis, however, such models are typically not very accurate. In this work, we make use of physical reliability models and apply them for aging simulations of pseudo-CMOS logic inverter circuits. The model employed is available via our reliability simulator Comphy and is calibrated to evaluate the impact of bias temperature instability (BTI) degradation phenomena on the inverter circuit’s performance made from commercial SiC power MOSFETs. Using Spice simulations, we extract the propagation delay time of inverter circuits, taking into account the threshold voltage drift of the transistors with stress time under DC and AC operating conditions. To achieve the highest level of accuracy for our evaluation we also consider the recovery of the devices during low bias phases of AC signals, which is often neglected in existing approaches. Based on the propagation delay time distribution, the importance of a suitable physical defect model to precisely analyze the circuit operation is discussed in this work too.