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Polyunsaturated fatty acids (PUFA) are known to have a regulatory effect on oxidative and inflammatory processes. This study aimed to identify the relationship between blood PUFA status and circulatory markers of oxidative stress and inflammation in a cohort of 172 subjects. The population was divided by sex and into three age groups: adults (18-64 years old, n = 69), older adults (65-89 years old, n = 54), and long-lived individuals (LLIs, 90-111 years old, n = 49). Whole blood PUFA content was quantified using gas chromatography. Additionally, serum levels of C-reactive protein (CRP), paraoxonase (PON), Trolox equivalent antioxidant capacity (TEAC), and malondialdehyde (MDA) were measured. Our results showed that a higher omega-3 (n-3) index in adult females was a predictor of lower MDA concentrations (p = 0.038). Conversely, total n-3 PUFA and total n-6 PUFA were positively related to MDA values among older adult females and LLI men (p < 0.05), while total n-6 PUFA was inversely correlated with MDA levels in LLI females (p < 0.05). Interestingly, increased concentrations of total n-3 PUFA and n-3 index were positively correlated with higher TEAC values in LLI men (p = 0.007), while the arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio was inversely correlated with TEAC values among LLI females (p = 0.006). These findings suggest that cellular antioxidant capacity is inversely correlated with changes in the AA/EPA ratio in long-lived females, whereas n-3 PUFA may enhance blood antioxidant capacity in long-lived men. Overall, our study highlights the complex, sex-specific interactions between PUFA profiles and oxidative stress and inflammatory markers across different age groups.
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Biomarcadores , Ácidos Grasos Insaturados , Inflamación , Longevidad , Malondialdehído , Estrés Oxidativo , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Estudios Transversales , Biomarcadores/sangre , Anciano de 80 o más Años , Inflamación/sangre , Longevidad/fisiología , Adulto Joven , Malondialdehído/sangre , Ácidos Grasos Insaturados/sangre , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Adolescente , Ácidos Grasos Omega-3/sangre , Arildialquilfosfatasa/sangre , Antioxidantes/metabolismo , Antioxidantes/análisis , Envejecimiento/sangreRESUMEN
Sleep is a fundamental conserved physiological state across evolution, suggesting vital biological functions that are yet to be fully clarified. However, our understanding of the neural and molecular basis of sleep regulation has increased rapidly in recent years. Among various processes implicated in controlling sleep homeostasis, a bidirectional relationship between sleep and oxidative stress has recently emerged. One proposed function of sleep may be the mitigation of oxidative stress in both brain and peripheral tissues, contributing to the clearance of reactive species that accumulate during wakefulness. Conversely, reactive species, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), at physiological levels, may act as signaling agents to regulate redox-sensitive transcriptional factors, enzymes, and other effectors involved in the regulation of sleep. As a primary sensor of intracellular oxidation, the transcription factor NRF2 is emerging as an indispensable component to maintain cellular redox homeostasis during sleep. Indeed, a number of studies have revealed an association between NRF2 dysfunction and the most common sleep conditions, including sleep loss, obstructive sleep apnea, and circadian sleep disturbances. This review examines the evidence of the intricate link between oxidative stress and NRF2 function in the context of sleep, and highlights the potential of NRF2 modulators to alleviate sleep disturbances.
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Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Sueño , Estrés Oxidativo/fisiología , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Sueño/fisiología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The composition of polyunsaturated fatty acids (PUFA) in the cell membrane plays a crucial role in cell signaling and function. Physical activity can induce shifts in PUFA metabolism, potentially altering their membrane composition. Given the multifaceted regulatory and structural roles of PUFA, training-related fluctuations in PUFA concentrations may impact health and athletic performance in both elite and non-elite athletes, highlighting the critical role of these fatty acids' nutritional intake. The ω-3 index (O3I), a biomarker reflecting the proportion of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in red blood cell membranes, is considered a marker of cardiovascular risk, gaining increasing interest in sports medicine. Dietary interventions aimed at maintaining an optimal O3I may offer several benefits for elite and non-elite athletes, including cardiovascular health performance optimization, recovery, and injury prevention. Here, we discuss emerging evidence on the application of O3I in sports and physical exercise, highlighting its promising role as a biomarker in a wide range of sports practices.
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BACKGROUND: Cellulite represents a common multi-factorial condition that affects nearly all women and is now recognized as a clinical condition associated with systemic factors and negative psychological effects. Several noninvasive and minimally invasive treatments were developed during the last few years, but limited evidence supports many of them due to lack of evidence, insufficient participants, and potential adverse effects. METHODS: This study aimed to evaluate the efficacy of a seaweed mud application in improving both the structure and function of tissues affected by cellulite. Sixty women with cellulite underwent 4-week applications of seaweed mud on the buttocks and thighs. The following assessments were performed at baseline and after the last treatment: photographic, clinical, and anthropometric evaluation; tests for elasticity and hydration; ultrasonography of cellulite nodules; and cellulite biopsies in the trochanteric region. Patient satisfaction was assessed using a 5-point Likert-scale questionnaire. RESULTS: The treatment resulted in a significant improvement in the severity of cellulite severity between the initial assessment and the 4-week follow-up, with enhanced structure, elasticity, and hydration of the affected tissues. Microscopic analysis of the cellulite biopsies revealed a significant restoration of dermal organization with induced collagen synthesis and reduced inflammation, edema, and lipid deposition following the 4-week seaweed mud applications. Additionally, the treatment led to a remarkable improvement in comfort and satisfaction as well as a reduction in body circumferences. CONCLUSIONS: The cosmetic application of seaweed mud has proven to be a safe, non-invasive treatment for improving the tissue alterations characteristic of cellulite.
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Celulitis , Satisfacción del Paciente , Algas Marinas , Muslo , Humanos , Femenino , Proyectos Piloto , Celulitis/terapia , Celulitis/tratamiento farmacológico , Adulto , Nalgas , Persona de Mediana Edad , Resultado del Tratamiento , Peloterapia , Índice de Severidad de la Enfermedad , Elasticidad/efectos de los fármacosRESUMEN
Studies on the COVID-19 pandemic effects on gestational diabetes mellitus (GDM) remain limited and controversial. This study aimed to investigate the impact of the COVID-19 lockdown on the glycemic balance of pregnant women and GDM risk. To this aim, a single-center retrospective cohort analysis assessing glucose homeostasis using the oral glucose tolerance test in 862 pregnant women before (from March 9, 2019 to March 8, 2020 - Group 1), during (from March 9, 2020 to March 8, 2021 - Group 2), and after (from March 9, 2021 to March 8, 2022 - Group 3) the COVID-19 lockdown in Molise, a region of central Italy, was conducted. We observed that the blood glucose concentration of pregnant women was significantly lower during the COVID-19 lockdown than during the previous and following years at all time points evaluated (time 0, 60', and 120'). Specifically, at time 0, it was 82.14 mg/dl for group 2 vs 85.94 for group 1 (p = 0.0001) and 85.87 for group 3 (p = 0.001). Similarly, at 60', it was 121.38 mg/dl for group 2 vs 129.30 mg/dl for group 1 (p = 0.0029) and 131.68 mg/dl for group 3 (p = 0.0006). Moreover, at 120', it was 104.20 mg/dl for group 2 vs 111.51 mg/dl (p = 0.0004) for group 1, and 116.06 mg/dl for group 3 (p = 0.0001). In contrast with previous findings, the COVID-19 lockdown was associated with an improved glycemic balance. Further studies are needed to better clarify the influence of lockdown restrictions on glucose metabolism and, consequently, on GDM risk.
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Decreased adult neurogenesis, or the gradual depletion of neural stem cells in adult neurogenic niches, is considered a hallmark of brain aging. This review provides a comprehensive overview of the intricate relationship between aging, adult neurogenesis, and the potential neuroregenerative properties of astaxanthin, a carotenoid principally extracted from the microalga Haematococcus pluvialis. The unique chemical structure of astaxanthin enables it to cross the blood-brain barrier and easily reach the brain, where it may positively influence adult neurogenesis. Astaxanthin can affect molecular pathways involved in the homeostasis, through the activation of FOXO3-related genetic pathways, growth, and regeneration of adult brain neurons, enhancing cell proliferation and the potency of stem cells in neural progenitor cells. Furthermore, astaxanthin appears to modulate neuroinflammation by suppressing the NF-κB pathway, reducing the production of pro-inflammatory cytokines, and limiting neuroinflammation associated with aging and chronic microglial activation. By modulating these pathways, along with its potent antioxidant properties, astaxanthin may contribute to the restoration of a healthy neurogenic microenvironment, thereby preserving the activity of neurogenic niches during both normal and pathological aging.
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Antioxidantes , Células-Madre Neurales , Humanos , Antioxidantes/farmacología , Enfermedades Neuroinflamatorias , Neurogénesis , Encéfalo , Antiinflamatorios/farmacologíaRESUMEN
The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is well recognized as a critical regulator of redox, metabolic, and protein homeostasis, as well as the regulation of inflammation. An age-associated decline in NRF2 activity may allow oxidative stress to remain unmitigated and affect key features associated with the aging phenotype, including telomere shortening. Telomeres, the protective caps of eukaryotic chromosomes, are highly susceptible to oxidative DNA damage, which can accelerate telomere shortening and, consequently, lead to premature senescence and genomic instability. In this review, we explore how the dysregulation of NRF2, coupled with an increase in oxidative stress, might be a major determinant of telomere shortening and age-related diseases. We discuss the relevance of the connection between NRF2 deficiency in aging and telomere attrition, emphasizing the importance of studying this functional link to enhance our understanding of aging pathologies. Finally, we present a number of compounds that possess the ability to restore NRF2 function, maintain a proper redox balance, and preserve telomere length during aging.
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The recent attention to the risk of potential permanent eye damage triggered by ocular infections has been leading to a deeper investigation of the current antimicrobials. An antimicrobial agent used in ophthalmology should possess the following characteristics: a broad antimicrobial spectrum, prompt action even in the presence of organic matter, and nontoxicity. The objective of this study is to compare the antimicrobial efficacy of widely used ophthalmic antiseptics containing povidone-iodine, chlorhexidine, and liposomes containing ozonated sunflower oil. We determined the minimum inhibitory concentration (MIC) on various microbial strains: Staphylococcus aureus (ATCC 6538), methicillin-resistant Staphylococcus aureus (ATCC 33591), Staphylococcus epidermidis (ATCC 12228), Pseudomonas aeruginosa (ATCC 9027), and Escherichia coli (ATCC 873). Furthermore, we assessed its efficacy in controlling antibiotic resistance, biofilm formation, and bacterial adhesion. All three antiseptic ophthalmic preparations showed significant anti-microbicidal and anti-biofilm activity, with the liposomes containing ozonated sunflower oil with the highest ability to control antibiotic resistance and bacteria adhesion to human corneal cells.
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Estrogen deficiency is a major cause of loss of postmenopausal bone mineral density (BMD). This study aimed to evaluate the effects of equol and resveratrol on bone turnover biomarkers in postmenopausal women. Sixty healthy postmenopausal women were randomly assigned to receive 200 mg fermented soy containing 10 mg equol and 25 mg resveratrol or a placebo for 12 months. Whole-body BMD and bone turnover biomarkers, such as deoxypyridinoline (DPD), tartrate-resistant acid phosphatase 5b (TRACP-5b), osteocalcin, and bone-specific alkaline phosphatase (BAP), were measured at baseline and after 12 months of treatment. At the end of treatment, DPD, osteocalcin, and BAP significantly improved in the active group (p < 0.0001 for all) compared to the placebo group. Conversely, TRACP-5b levels were unaffected by supplementation (p = 0.051). Statistically significant changes in the concentrations of DPD (p < 0.0001), osteocalcin (p = 0.0001), and BAP (p < 0.0001) compared to baseline were also identified. Overall, the intervention significantly increased BMD measured in the whole body (p = 0.0220) compared with the placebo. These data indicate that the combination of equol and resveratrol may positively modulate bone turnover biomarkers and BMD, representing a potential approach to prevent age-related bone loss in postmenopausal women.
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Osteoporosis Posmenopáusica , Posmenopausia , Humanos , Femenino , Equol/farmacología , Resveratrol/farmacología , Resveratrol/uso terapéutico , Fosfatasa Ácida Tartratorresistente , Osteocalcina , Densidad Ósea , Fosfatasa Alcalina/uso terapéutico , Biomarcadores , Remodelación Ósea , Osteoporosis Posmenopáusica/tratamiento farmacológicoRESUMEN
Dietary supplementation with nutraceuticals can promote optimal immune system activation, modulating different pathways that enhance immune defenses. Therefore, the immunity-boosting effects of nutraceuticals encompass not only immunomodulatory but also antioxidant, antitumor, antiviral, antibacterial, and antifungal properties, with therapeutic effects against diverse pathological conditions. However, the complexity of the pathways that regulate the immune system, numerous mechanisms of action, and heterogeneity of the immunodeficiencies, and subjects treated make their application in the clinical field difficult. Some nutraceuticals appear to safely improve immune system function, particularly by preventing viral and bacterial infections in specific groups, such as children, the elderly, and athletes, as well as in frail patients, such as those affected by autoimmune diseases, chronic diseases, or cancer. Several nutraceuticals, such as vitamins, mineral salts, polyunsaturated omega-3 fatty acids, many types of phytocompounds, and probiotic strains, have the most consolidated evidence in humans. In most cases, further large and long-term randomized clinical trials are needed to confirm the available preliminary positive data.
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Accumulating evidence suggests that fatty acids (FAs) play an essential role in regulating skeletal muscle mass and function throughout life. This systematic review and meta-analysis aimed to examine the relationship between dietary or circulatory levels of monounsaturated FAs (MUFAs) and sarcopenia in observational studies. A comprehensive literature search was performed in three databases (PubMed, Scopus, and Web of Science) from inception until August 2022. Of 414 records, a total of 12 observational studies were identified for this review. Ten studies were meta-analysed, comprising a total of 3704 participants. The results revealed that MUFA intake is inversely associated with sarcopenia (standardized mean difference = - 0.28, 95% CI - 0.46 to - 0.11; p < 0.01). Despite the limited number of studies, our results suggest that lower MUFA intake is associated with a higher risk of sarcopenia. However, the available evidence is still insufficient and further investigations are needed to demonstrate this relationship.
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Ácidos Grasos Monoinsaturados , Sarcopenia , Humanos , Ácidos Grasos , Dieta , Estudios Observacionales como AsuntoRESUMEN
Cellular senescence has long been considered a permanent state of cell cycle arrest occurring in proliferating cells subject to different stressors, used as a cellular defense mechanism from acquiring potentially harmful genetic faults. However, recent studies highlight that senescent cells might also alter the local tissue environment and concur to chronic inflammation and cancer risk by secreting inflammatory and matrix remodeling factors, acquiring a senescence-associated secretory phenotype (SASP). Indeed, during aging and age-related diseases, senescent cells amass in mammalian tissues, likely contributing to the inevitable loss of tissue function as we age. Cellular senescence has thus become one potential target to tackle age-associated diseases as well as cancer development. One important aspect characterizing senescent cells is their telomere length. Telomeres shorten as a consequence of multiple cellular replications, gradually leading to permanent cell cycle arrest, known as replicative senescence. Interestingly, in the large majority of cancer cells, a senescence escape strategy is used and telomere length is maintained by telomerase, thus favoring cancer initiation and tumor survival. There is growing evidence showing how (poly)phenols can impact telomere maintenance through different molecular mechanisms depending on dose and cell phenotypes. Although normally, (poly)phenols maintain telomere length and support telomerase activity, in cancer cells this activity is negatively modulated, thus accelerating telomere attrition and promoting cancer cell death. Some (poly)phenols have also been shown to exert senolytic activity, thus suggesting both antiaging (directly eliminating senescent cells) and anticancer (indirectly, via SASP inhibition) potentials. In this review, we analyze selective (poly)phenol mechanisms in senescent and cancer cells to discriminate between in vitro and in vivo evidence and human applications considering (poly)phenol bioavailability, the influence of the gut microbiota, and their dose-response effects.
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Neoplasias , Telomerasa , Animales , Humanos , Telomerasa/metabolismo , Fenoles/farmacología , Supervivencia Celular , Fenol , Envejecimiento/fisiología , Neoplasias/genética , Proliferación Celular/fisiología , Mamíferos/metabolismoRESUMEN
Although autism spectrum disorder (ASD) is a multifaceted neurodevelopmental syndrome, accumulating evidence indicates that oxidative stress and inflammation are common features of ASD. Flavonoids, one of the largest and best-investigated classes of plant-derived compounds, are known to exert antioxidant, anti-inflammatory, and neuroprotective effects. This review used a systematic search process to assess the available evidence on the effect of flavonoids on ASD. A comprehensive literature search was carried out in PubMed, Scopus, and Web of Science databases following the PRISMA guidelines. A total of 17 preclinical studies and 4 clinical investigations met our inclusion criteria and were included in the final review. Most findings from animal studies suggest that treatment with flavonoids improves oxidative stress parameters, reduces inflammatory mediators, and promotes pro-neurogenic effects. These studies also showed that flavonoids ameliorate the core symptoms of ASD, such as social deficits, repetitive behavior, learning and memory impairments, and motor coordination. However, there are no randomized placebo-controlled trials that support the clinical efficacy of flavonoids in ASD. We only found open-label studies and case reports/series, using only two flavonoids such as luteolin and quercetin. These preliminary clinical studies indicate that flavonoid administration may improve specific behavioral symptoms of ASD. Overall, this review is the first one to systematically report evidence for the putative beneficial effects of flavonoids on features of ASD. These promising preliminary results may provide the rationale for future randomized controlled trials aimed at confirming these outcomes.
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Sirtuin 1 (SIRT1) belongs to the histone deacetylase enzyme family and its activity regulates various signaling networks associated with aging. SIRT1 is widely involved in a large number of biological processes, including senescence, autophagy, inflammation, and oxidative stress. In addition, SIRT1 activation may improve lifespan and health in numerous experimental models. Therefore, SIRT1 targeting is a potential strategy to delay or reverse aging and age-related diseases. Although SIRT1 is activated by a wide array of small molecules, only a limited number of phytochemicals that directly interact with SIRT1 have been identified. Using the Geroprotectors.org database and a literature search, the aim of this study was to identify geroprotective phytochemicals that might interact with SIRT1. We performed molecular docking, density functional theory studies, molecular dynamic simulations (MDS), and absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction to screen potential candidates against SIRT1. After the initial screening of 70 phytochemicals, crocin, celastrol, hesperidin, taxifolin, vitexin, and quercetin had significant binding affinity scores. These six compounds established multiple hydrogen-bonding and hydrophobic interactions with SIRT1 and showed good drug-likeness and ADMET properties. In particular, crocin was further analyzed using MDS to study its complex with SIRT1 during simulation. Crocin has a high reactivity to SIRT1 and can form a stable complex with it, showing a good ability to fit into the binding pocket. Although further investigations are required, our results suggest that these geroprotective phytochemicals, especially crocin, are novel interacting partners of SIRT1.
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Simulación de Dinámica Molecular , Sirtuina 1 , Simulación del Acoplamiento Molecular , Sirtuina 1/metabolismo , Fitoquímicos/farmacología , Fitoquímicos/químicaRESUMEN
PURPOSE: The potential mechanisms of endocrine therapy for thrombosis remain currently unclear, and more studies are warranted for further investigation and elucidation. However, high plasma concentration of lipoprotein(a) (Lp(a)) is a recognized prothrombotic factor. The aim of our study was to systematically evaluate the effect of different anti-oestrogen therapy on plasma Lp(a) level in postmenopausal women. METHODS: A systematic literature search was conducted in multiple electronic databases to identify the randomized, double-blind, placebo-controlled clinical studies on this topic. Effect size for changes in Lp(a) was expressed as mean difference (MD) and 95% confidence intervals (CI). RESULTS: Data were pooled from 10 clinical trials comprising 24 treatment arms, which included 2049 women (1128 women in the active-treated arms and 921 women in the control arms). Meta-analysis of data suggested that anti-oestrogen therapy in women significantly reduced Lp(a) [MD = -5.92% (95%CI: -9.05%,-2.8%)]. CONCLUSIONS: This observation is of both clinical and pathophysiological relevance, also in view that the identification of molecular determinants and cellular pathways implicated in Lp(a) synthesis and metabolism is still of concern as a critical issue in lipidology and CV prevention.
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Lipoproteína(a) , Posmenopausia , Femenino , Humanos , Terapia de Reemplazo de Hormonas , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
ABSTRACTThe aim of this study was to examine the association between biomarkers of polyunsaturated fatty acids (PUFA), such as omega-3 (ω-3) index and arachidonic acid (AA; 20:4 ω-6)/eicosapentaenoic acid (EPA; 20:5ω-3) ratio (AA/EPA), and the prevalence of running-related injuries (RRI) in a cohort of recreational runners. We performed a retrospective, observational study of 275 non-elite runners (mean age: 41.20 ± 12.47 years) who were not supplemented with ω-3 fatty acids. The training characteristics and RRI were recorded over a period of 12 months through a self-reported questionnaire. Using whole blood samples collected by finger prick, PUFA were quantified by gas chromatography and ω-3 index and AA/EPA ratio measured. A total of 191 RRI cases were reported, with an injury prevalence rate of 50.9% in the overall population. The injured runners ran a significantly greater weekly distance than uninjured subjects (53.54 ± 25.27â km/week; p = 0.007). In a multivariate regression analysis, the lowest number of RRI was associated with higher values of ω-3 index (ß = - 0.237; 95% CI - 0.308 to - 0.164; R2 = 0.172; p < 0.0001), while a higher AA/EPA ratio was correlated with higher number of RRI (ß = 0.019; 95% CI 0.007-0.031; R2 = 0.038; p = 0.003). This study identifies ω-3 index and AA/EPA ratio as potential parameters associated with the risk of RRI. Future research is needed to confirm these results and apply specific nutritional strategies to successfully modify these biochemical variables.Trial registration: ISRCTN.org identifier: ISRCTN12847156..
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Ácidos Grasos Omega-3 , Carrera , Humanos , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Ácidos Grasos Omega-6 , BiomarcadoresRESUMEN
Long-lived individuals (LLIs) are considered an ideal model to study healthy human aging. Blood fatty acid (FA) profile of a cohort of LLIs (90-111 years old, n = 49) from Sicily was compared to adults (18-64 years old, n = 69) and older adults (65-89 years old, n = 54) from the same area. Genetic variants in key enzymes related to FA biosynthesis and metabolism were also genotyped to investigate a potential genetic predisposition in determining the FA profile. Gas chromatography was employed to determine the FA profile, and genotyping was performed using high-resolution melt (HRM) analysis. Blood levels of total polyunsaturated FA (PUFA) and total trans-FA decreased with age, while the levels of saturated FA (SFA) remained unchanged. Interestingly, distinctively higher circulatory levels of monounsaturated FA (MUFA) in LLIs compared to adults and older adults were observed. In addition, among LLIs, rs174537 in the FA desaturase 1/2 (FADS1/2) gene was associated with linoleic acid (LA, 18:2n-6) and docosatetraenoic acid (DTA, 22:4n-6) levels, and the rs953413 in the elongase of very long FA 2 (ELOVL2) was associated with DTA levels. We further observed that rs174579 and rs174626 genotypes in FADS1/2 significantly affect delta-6 desaturase (D6D) activity. In conclusion, our results suggest that the LLIs have a different FA profile characterized by high MUFA content, which indicates reduced peroxidation while maintaining membrane fluidity.
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Ácidos Grasos Monoinsaturados , Ácidos Grasos , Humanos , Anciano , Anciano de 80 o más Años , Ácidos Grasos Monoinsaturados/análisis , Ácidos Grasos Monoinsaturados/metabolismoRESUMEN
Adult neurogenesis deficiency has been proposed to be a common hallmark in different age-related neurodegenerative diseases. The administration of flavonoids is currently reported as a potentially beneficial strategy for preventing brain aging alterations, including adult neurogenesis decline. Flavonoids are a class of plant-derived dietary polyphenols that have drawn attention for their neuroprotective and pro-cognitive effects. Although they undergo extensive metabolism and localize in the brain at low concentrations, flavonoids are now believed to improve cerebral vasculature and interact with signal transduction cascades involved in the regulation of adult neurogenesis. Furthermore, many dietary flavonoids have been shown to reduce oxidative stress and neuroinflammation, improving the neuronal microenvironment where adult neurogenesis occurs. The overall goal of this review is to summarize the evidence supporting the role of flavonoids in modulating adult neurogenesis as well as to highlight how these dietary agents may be promising candidates in restoring healthy brain function during physiological and pathological aging.
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Encéfalo , Polifenoles , Humanos , Adulto , Encéfalo/metabolismo , Polifenoles/farmacología , Polifenoles/metabolismo , Envejecimiento/fisiología , Flavonoides/farmacología , Neurogénesis/fisiologíaRESUMEN
The transcription factor NRF2 and its endogenous inhibitor KEAP1 play a crucial role in the maintenance of cellular redox homeostasis by regulating the gene expression of diverse networks of antioxidant, anti-inflammatory, and detoxification enzymes. Therefore, activation of NRF2 provides cytoprotection against numerous pathologies, including age-related diseases. An age-associated loss of NRF2 function may be a key driving force behind the aging phenotype. Recently, numerous NRF2 inducers have been identified and some of them are promising candidates to restore NRF2 transcriptional activity during aging. Emerging evidence indicates that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and their electrophilic derivatives may trigger a protective response via NRF2 activation, rescuing or maintaining cellular redox homeostasis. In this review, we provide an overview of the NRF2-KEAP1 system and its dysregulation in aging cells. We also summarize current studies on the modulatory role of n-3 PUFAs as potential agents to prevent multiple chronic diseases and restore the age-related impairment of NRF2 function.
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Ácidos Grasos Omega-3 , Factor 2 Relacionado con NF-E2 , Proteína 1 Asociada A ECH Tipo Kelch/genética , Factor 2 Relacionado con NF-E2/genética , Senescencia CelularRESUMEN
Background: Aging is a phenomenon universally involving all organisms, genetically determined, and epigenetically influenced by the environment. Numerous observational studies have shown the positive impact of non-pharmacological approaches started in younger age on chronic conditions affecting the elderly health and survival. This meta-analysis aimed to investigate the effect of beta-carotene on the total and cause-specific mortality as reported by randomized controlled trials (RCTs). Methods: We searched Medline, Scopus, Web of Science, and CENTRAL Cochrane from inception to September 2021. Studies were eligible if enrolled adults with any health condition, compared beta-carotene supplements at any dose with placebo or no intervention, provided information on deaths from any cause, and were RCTs, in English. The risk of bias was assessed by the Cochrane risk of bias tool and the GRADE. Risk ratios and their 95% confidence intervals were used and a P-value less than 0.05 was considered statistically significant. Results: Among 3,942 articles searched, 44 articles on 31 RCTs, which included 216,734 total subjects, 108,622 in beta-carotene supplement groups, and 108,112 in the placebo or no-intervention groups, were involved in the final analyses. In a random-effects meta-analysis of all 31 trials, beta-carotene supplements were found to have no preventive effect on mortality (risk ratio 1.02, 95% confidence interval 0.98-1.05, I 2 = 42%). Further, the analysis showed no preventive effect on cancer, cardiovascular, cerebrovascular, and other mortality causes. Instead, beta-carotene supplementation significantly increased the risk of lung cancer mortality (RR 1.14, 95% CI 1.02, 1.27, I 2 = 3%) but decreased the risk of human immunodeficiency virus-related mortality (RR 0.55, 95% CI 0.33, 0.92, I 2 = 0). Conclusion: More studies should be performed to better define the role of beta-carotene on survival, to confirm or deny our results. Therefore, the possible beneficial or harmful effects of the beta-carotene supplementation on mortality must not be overstated. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=259354], identifier [CRD42021259354].