Exercise protects vascular function by countering senescent cells in older adults

Blood vessels are key conduits for the transport of blood and circulating factors. Abnormalities in blood vessels promote cardiovascular disease (CVD), which has become the most common disease as human lifespans extend. Aging itself is not pathogenic; however, the decline of physiological and biological function owing to aging has been linked to CVD. Although aging is a complex phenomenon that has not been comprehensively investigated, there is accumulating evidence that cellular senescence aggravates various pathological changes associated with aging. Emerging evidence shows that approaches that suppress or eliminate cellular senescence preserve vascular function in aging-related CVD. However, most pharmacological therapies for treating age-related CVD are inefficient. Therefore, effective approaches to treat CVD are urgently required. The benefits of exercise for the cardiovascular system have been well documented in basic research and clinical studies; however, the mechanisms and optimal frequency of exercise for promoting cardiovascular health remain unknown. Accordingly, in this review, we have discussed the changes in senescent endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) that occur in the progress of CVD and the roles of physical activity in CVD prevention and treatment

Exercise for Prevention and Relief of Cardiovascular Disease: Prognoses, Mechanisms, and Approaches

This review is aimed at summarizing the new findings about the multiple benefits of exercise on cardiovascular disease (CVD). We pay attention to the prevalence and risk factors of CVD and mechanisms and recommendations of physical activity. Physical activity can improve insulin sensitivity, alleviate plasma dyslipidemia, normalize elevated blood pressure, decrease blood viscosity, promote endothelial nitric oxide production, and improve leptin sensitivity to protect the heart and vessels. Besides, the protective role of exercise on the body involves not only animal models in the laboratory but also clinical studies which is demonstrated by WHO recommendations. The general exercise intensity for humans recommended by the American Heart Association to prevent CVD is moderate exercise of 30 minutes, 5 times a week. However, even the easiest activity is better than nothing. What is more, owing to the different physical fitness of individuals, a standard exercise training cannot provide the exact treatment for everyone. So personalization of exercise will be an irresistible trend and bring more beneficial effects with less inefficient physical activities. This paper reviews the benefits of exercise contributing to the body especially in CVD through the recent mechanism studies

Optimal Spacing Policy for Vehicle Platoon Control with Road-Friction Coefficient

This paper investigates the vehicle platoon control problems, in which the road-friction coefficient is taken into consideration. In order to improve the vehicle platoon safety in various road-friction conditions, an optimal spacing policy is proposed for the vehicle platoon. In detail, an intervehicle space optimization framework is developed by using a safety cost function and the gradient decent method. In this way, the optimal intervehicle spacing headway is presented such that the vehicle can be safely driven to the desired platoon under various road-friction conditions. Then, based on the proposed optimal spacing policy, we transform this optimal spacing vehicle platoon control problem into a moving target tracking problem. An adaptive distributed integrated sliding mode (DISM)-based vehicle platoon control scheme is proposed such that the vehicles can effectively follow the presented optimal spacing platoon. Moreover, the stability of the proposed vehicle platoon system is strictly analyzed and numerical simulations are provided to verify the proposed approaches

Hydrogen sulfide ameliorates senescence in vascular endothelial cells through ameliorating inflammation and activating PPARδ/SGLT2/STAT3 signaling pathway

Mounting evidence demonstrates that hydrogen sulfide (H2S) promotes anti-inflammatory molecules and inhibits pro-inflammatory cytokines in endothelial cells (ECs). This study aims to investigate the favorable action of H2S on endothelial function in senescence by inhibiting the production of inflammatory molecules. Senescent ECs exhibit a reduction in H 2S, endothelial nitric oxide synthase (eNOS) and peroxisome proliferator-activated receptor δ (PPARδ), coupled with increased inflammatory molecules, sodium glucose transporter type 2 (SGLT2) and phosphorylation of STAT3, which could be reversed by the administration of a slow but sustained release agent of H2S, GYY4137. Decreased production of eNOS and upregulated p-STAT3 and SGLT2 levels in senescent ECs are reversed by replenishment of the SGLT2 inhibitor EMPA and the PPARδ agonist GW501516. The PPARδ antagonist GSK0660 attenuates eNOS expression and increases the production of p-STAT3 and SGLT2. However, supplementation with GYY4137 has no beneficial effect on GSK0660-treated ECs. GYY4137, GW501516 and EMPA preserve endothelial-dependent relaxation (EDR) in D-gal-treated aortae, while GSK0660 destroys aortic relaxation even with GYY4137 supplementation. In summary, senescent ECs manifest aggravated the expressions of the inflammatory molecules SGLT2 and p-STAT3 and decreased the productions of PPARδ, eNOS and CSE. H2S ameliorates endothelial dysfunction through the anti-inflammatory effect of the PPARδ/SGLT2/p-STAT3 signaling pathway in senescent ECs and may be a potential therapeutic target for anti-ageing treatment

Olanzapine-induced endoplasmic reticulum stress and inflammation in the hypothalamus were inhibited by an ER stress inhibitor 4-phenylbutyrate

Antipsychotics are the most important treatment for schizophrenia. However, antipsychotics, particularly olanzapine and clozapine, are associated with severe weight gain/obesity side-effects. Although numerous studies have been carried out to identify the exact mechanisms of antipsychotic-induced weight gain, it is still important to consider other pathways. Endoplasmic reticulum (ER) stress signaling and its associated inflammation pathway is one of the most important pathways involved in regulation of energy balance. In the present study, we examined the role of hypothalamic protein kinase R like endoplasmic reticulum kinase- eukaryotic initiation factor 2α (PERK-eIF2α) signaling and the inflammatory IkappaB kinase β- nuclear factor kappa B (IKKβ-NFκB) signaling pathway in olanzapine-induced weight gain in female rats. In this study, we found that olanzapine significantly activated PERK-eIF2α and IKKβ-NFκB signaling in SH-SY5Y cells in a dose-dependent manner. Olanzapine treatment for 8 days in rats was associated with activated PERK-eIF2α signaling and IKKβ-NFκB signaling in the hypothalamus, accompanied by increased food intake and weight gain. Co-treatment with an ER stress inhibitor, 4-phenylbutyrate (4-PBA), decreased olanzapine-induced food intake and weight gain in a dose- and time-dependent manner. Moreover, 4-PBA dose-dependently inhibited olanzapine-induced activated PERK-eIF2α and IKKβ-NFκB signaling in the hypothalamus. These results suggested that hypothalamic ER stress may play an important role in antipsychotic-induced weight gain