Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown. Rats on IF for 30 days received 1 mg/kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses. Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-κB activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1α, IL-1β and TNF-α levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1β, IFN-γ, RANTES, TNF-α and IL-6 levels. Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection.

Cardiovascular diseases are the most common cause of mortality worldwide. Oxidative stress and inflammation are pathophysiological processes involved in the development of cardiovascular diseases; thus, anti‑inflammatory and antioxidant agents that modulate redox balance have become research targets so as to evaluate their molecular mechanisms of action and therapeutic properties. Astaxanthin, a carotenoid of the xanthophyll group, has potent antioxidant properties due to its molecular structure and its arrangement in the plasma membrane, factors that favor the neutralization of reactive oxygen and nitrogen species. This carotenoid also has prominent anti‑inflammatory activity, possibly interrelated with its antioxidant effect, and is also involved in the modulation of lipid and glucose metabolism. Considering the potential beneficial effects of astaxanthin on cardiovascular health evidenced by preclinical and clinical studies, the aim of the present review was to describe the molecular and cellular mechanisms associated with the antioxidant and anti‑inflammatory properties of this carotenoid in cardiovascular diseases, particularly atherosclerosis. The beneficial properties and safety profile of astaxanthin indicate that this compound may be used for preventing progression or as an adjuvant in the treatment of cardiovascular diseases.

Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of an array of enzymes with important detoxifying and antioxidant functions. Current findings support the role of high levels of oxidative stress in the pathogenesis of neurological disorders. Given the central role played by Nrf2 in counteracting oxidative damage, a number of studies have targeted the modulation of this transcription factor in order to confer neuroprotection. Nrf2 activity is tightly regulated by oxidative stress and energy-based stimuli. Thus, many dietary interventions based on energy intake regulation, such as dietary energy restriction (DER) or high-fat diet (HFD), modulate Nrf2 with consequences for a variety of cellular processes that affect brain health. DER, by either restricting calorie intake or meal frequency, activates Nrf2 thereby triggering its protective effects, whilst HFD inhibit this pathway, thereby exacerbating oxidative stress. Consequently, DER protocols can be valuable strategies in the management of central nervous system (CNS) disorders. Herein, we review current knowledge of the role of Nrf2 signaling in neurological diseases, namely Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and cerebral ischemia, as well as the potential of energy intake regulation in the management of Nrf2 signaling.

Aging is a multifactorial process associated with an increased susceptibility to neurodegenerative disorders which can be related to chronic inflammation. Chronic inflammation, however, can be characterized by the persistent elevated glucocorticoid (GCs) levels, activation of the proinflammatory transcription factor NF-кB, as well as an increase in cytokines. Interestingly, both NF-кB and cytokines can be even modulated by Glycogen Synthase Kinase 3 beta (GSK-3β) activity, which is a key protein that can intermediate inflammation and metabolism, once it has a critical role in AKT signaling pathway, and can also intermediate WNT/β-CATENIN signaling pathway. The aim of this study was to verify age-related changes in inflammatory status, as well as in the AKT and WNT signaling pathways. Results showed an age-related increase in neuroinflammation as indicated by NF-кB activation, TNF-α and GCs increased levels, a decrease in AKT activation and an increase in GSK-3β activity in both 12- and 24- month old animals. Aging also seems to induce a progressive decrease in canonical WNT/β-CATENIN signaling pathway once there is a decrease in DVL-2 levels and in the transcription of Axin2 gene. Little is known about the DVL-2 regulation as well as its roles in WNT signaling pathway, but for the first time it was suggested that DVL-2 expression can be changed along aging.

Aging is characterized by significant physiological changes, with the degree of decline varying significantly among individuals. The preservation of intrinsic capacity over the course of an individual’s lifespan is fundamental for healthy aging. Locomotion, which entails the capacity for independent movement, is intricately connected with various dimensions of human life, including cognition, vitality, sensory perception, and psychological well-being. Notably, skeletal muscle functions as a pivotal nexus within this intricate framework. Any perturbation in its functionality can manifest as compromised physical performance and an elevated susceptibility to frailty. Magnesium is an essential mineral that plays a central role in approximately 800 biochemical reactions within the human body. Its distinctive physical and chemical attributes render it an indispensable stabilizing factor in the orchestration of diverse cellular reactions and organelle functions, thereby rendering it irreplaceable in processes directly impacting muscle health. This narrative review offers a comprehensive exploration of the pivotal role played by magnesium in maintaining skeletal muscle integrity, emphasizing the critical importance of maintaining optimal magnesium levels for promoting healthy aging.

Recent data from epidemiologic studies have shown that the majority of the public health costs are related to age-related disorders, and most of these diseases can lead to neuronal death. The specific signaling mechanisms underpinning neurodegeneration and aging are incompletely understood. Much work has been directed to the search for the etiology of neurodegeneration and aging and to new therapeutic strategies, including not only drugs but also non-pharmacological approaches, such as physical exercise and low-calorie dietary intake. The most important processes in aging-associated conditions, including neurodegeneration, include the mammalian (or mechanistic) target of rapamycin (mTOR), sirtuin (SIRT) and insulin/insulin growth factor 1 signaling (IIS) pathways. These longevity pathways are involved in an array of different processes, including metabolism, cognition, stress response and brain plasticity. In this review we focus on the current advances involving the mTOR, SIRT and IIS longevity pathways during the course of healthy aging processes and neurodegenerative diseases, bringing new insights in the form of a better understanding of the signaling mechanisms underpinning neurodegeneration and how these differ from physiological normal aging processes. This also provides new targets for the therapeutic management and/or prevention of these devastating age-related disorders.