There are several neurological diseases under which processes related to adult brain neurogenesis, such cell proliferation, neural differentiation and neuronal maturation, are affected. Melatonin can exert a relevant benefit for treating neurological disorders, given its well-known antioxidant and anti-inflammatory properties as well as its pro-survival effects. In addition, melatonin is able to modulate cell proliferation and neural differentiation processes in neural stem/progenitor cells while improving neuronal maturation of neural precursor cells and newly created postmitotic neurons. Thus, melatonin shows relevant pro-neurogenic properties that may have benefits for neurological conditions associated with impairments in adult brain neurogenesis. For instance, the anti-aging properties of melatonin seem to be linked to its neurogenic properties. Modulation of neurogenesis by melatonin is beneficial under conditions of stress, anxiety and depression as well as for the ischemic brain or after a brain stroke. Pro-neurogenic actions of melatonin may also be beneficial for treating dementias, after a traumatic brain injury, and under conditions of epilepsy, schizophrenia and amyotrophic lateral sclerosis. Melatonin may represent a pro-neurogenic treatment effective for retarding the progression of neuropathology associated with Down syndrome. Finally, more studies are necessary to elucidate the benefits of melatonin treatments under brain disorders related to impairments in glucose and insulin homeostasis.

Sarcopenia, a complex and debilitating condition characterized by progressive deterioration of skeletal muscle, is the primary cause of age-associated disability and significantly impacts healthspan in elderly patients. Despite its prevalence among the aging population, the underlying molecular mechanisms are still under investigation. The NLRP3 inflammasome is crucial in the innate immune response and has a significant impact on diseases related to inflammation and aging. Here, we investigated the expression of the NLRP3 inflammasome pathway and pro-inflammatory cytokines in skeletal muscle and peripheral blood of dependent and independent patients who underwent hip surgery. Patients were categorized into independent and dependent individuals based on their Barthel Index. The expression of NLRP3 inflammasome components was significantly upregulated in sarcopenic muscle from dependent patients, accompanied by higher levels of Caspase-1, IL-1β and IL-6. Among older dependent individuals with sarcopenia, there was a significant increase in the MYH3/MYH2 ratio, indicating a transcriptional shift in expression from mature to developmental myosin isoforms. Creatine kinase levels and senescence markers were also higher in dependent patients, altogether resembling dystrophic diseases and indicating muscle degeneration. In summary, we present evidence for the involvement of the NLRP3/ASC/NEK7/Caspase-1 inflammasome pathway with activation of pro-inflammatory SASP in the outcome of sarcopenia in the elderly.

Despite efforts to elucidate the cellular adaptations induced by obesity, cellular bioenergetics is currently considered a crucial target. New strategies to delay the onset of the hazardous adaptations induced by obesity are needed. Therefore, we evaluated the effects of 4 weeks of melatonin treatment on mitochondrial function and lipid metabolism in the livers of leptin-deficient mice. Our results revealed that the absence of leptin increased lipid storage in the liver and induced significant mitochondrial alterations, which were ultimately responsible for defective ATP production and reactive oxygen species overproduction. Moreover, leptin deficiency promoted mitochondrial biogenesis, fusion, and outer membrane permeabilization. Melatonin treatment reduced the bioenergetic deficit found in ob/ob mice, alleviating some mitochondrial alterations in the electron transport chain machinery, biogenesis, dynamics, respiration, ATP production, and mitochondrial outer membrane permeabilization. Given the role of melatonin in maintaining mitochondrial homeostasis, it could be used as a therapeutic agent against adipogenic steatosis.

Ageing leads to a gradual deterioration of the organs, with the brain being particularly susceptible, often leading to neurodegeneration. This process includes well-known changes such as tau hyperphosphorylation and beta-amyloid deposition, which are commonly associated with neurodegenerative diseases but are also present in ageing. These structures are triggered by earlier cellular changes such as energy depletion and impaired protein synthesis, both of which are essential for cell function. These changes may in part be induced by environmental pollution, which has been shown to accelerate these processes. Cold Atmospheric Plasma (CAP) or atmospheric pressure gas discharge plasmas have shown promise in activating the immune system and improving cellular function in vitro, although their effects at the organ level remain poorly understood. Our aim in this work is to investigate the effect of a device that combines CAP treatment with the effective removal of environmental nanoparticles, typical products of pollution, on the activity of aged mouse brains. The results showed an increase in energy capacity, a reduction in reticulum stress and an activation of cellular autophagic clearance, minimising aggresomes in the brain. This leads to a reduction in key markers of neurodegeneration such as tau hyperphosphorylation and beta-amyloid deposition, demonstrating the efficacy of the tested product at the brain level.

Background/Objectives: The exposome, encompassing all environmental influences on health, plays a pivotal role in oxidative stress-related diseases. Negative air ions (NAIs), generated via cold atmospheric plasma (CAP), have been proposed as potential modulators of oxidative resilience. This study aims to investigate the metabolic adaptations induced by prolonged exposure to an NAI-enriched environment in mice, focusing on its effects in oxidative stress markers and energy metabolism in liver and blood. Methods: Twenty male C57BL/6J mice were divided into four groups: two experimental groups exposed to NAI-enriched air generated by an Air Cold Atmospheric Plasma–Nanoparticle Removal (aCAP-NR) device for either 18 days (short-term, ST) or 28 days (long-term, LT), and two control groups without exposure. Targeted metabolomics was performed in whole blood and liver using ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS). Statistical and pathway analyses were conducted to assess metabolic alterations. Results: Metabolic profiling revealed significant shifts in oxidative stress-related pathways, including enhanced glutathione metabolism, reduced lipid peroxidation, and modulation of purine metabolism. Short-term exposure led to increased mitochondrial efficiency and energy homeostasis, while long-term exposure induced adaptive metabolic reprogramming, with higher inosine levels suggesting enhanced antioxidant and anti-inflammatory responses. No adverse effects on systemic or hepatic health markers were observed. Conclusions: NAI exposure via aCAP-NR elicits a hormetic response, enhancing metabolic efficiency and resilience to oxidative stress. These findings suggest that controlled environmental enrichment with NAIs may serve as a novel non-invasive strategy for mitigating oxidative damage and improving metabolic health, as hormetic adaptative capacity and resilience to oxidative stress, warranting further translational research.

Background/Objectives: Multiple chemical sensitivity (MCS) is a complex environmental illness characterized by intolerance to various environmental chemicals, affecting multiple organ systems. Despite its prevalence, MCS remains poorly understood, with limited recognition by the World Health Organisation amid challenges in diagnosis due to symptom heterogeneity. This study aimed to investigate the oxidative stress status in patients diagnosed with MCS compared to healthy controls, focusing on plasma and erythrocyte markers. Methods: Blood samples from 40 MCS patients and 40 controls were analyzed for lipid peroxidation (LPO), total antioxidant activity (TAA), adenosine triphosphate (ATP), and antioxidant enzyme activities, alongside glutathione cycle components. Results: Results revealed no significant differences in plasma LPO or TAA between groups, with a reduction in 61% ATP levels in MCS subjects. However, erythrocyte analysis showed reduced levels of glutathione (GSH) and total glutathione in MCS patients. Glutathione peroxidase (GPx) activity also decreased by 15% in erythrocytes of MCS patients, suggesting increased hydrogen peroxide detoxification at the expense of oxidation of GSH to glutathione disulfide (GSSG). Because glutathione reductase activity (GRd) did not change, this GSSG could not be reduced, the GSSG/GSH ratio increased by 46%, indicating heightened intracellular oxidative stress. Catalase (CAT) activity also remained unchanged (reduced by 9%, non-significant). Conclusions: These findings highlight the role of oxidative stress in MCS pathophysiology, particularly the disruption of the glutathione cycle within erythrocytes. The study underscores the need for further research into the molecular mechanisms underlying MCS to improve diagnostic criteria and therapeutic strategies. Understanding intracellular oxidative imbalances may provide insights into the systemic dysfunction observed in MCS patients.