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Background: Socioeconomic disparities in life expectancy are well-documented in various contexts, including Chile. However, there is a lack of research examining trends in life expectancy inequalities and lifespan variation over time. Addressing these gaps can provide crucial insights into the dynamics of health inequalities. Methods: This study utilizes data from census records, population surveys, and death certificates to compare the life expectancy and the lifespan variation at age 26 of individuals according to their rank in the distribution of years of education within their own birth cohort. The analysis spans three periods (1991, 2002, and 2017) and focuses on two educational groups: individuals in the first (lowest) quintile and tenth (highest) decile of educational attainment. Changes in life expectancy are disaggregated by major causes of death to elucidate their contributions to overall trends. Results: Consistent with existing literature, our findings confirm that individuals with lower education levels experience lower life expectancy and higher lifespan variation compared to their more educated counterparts. Notably, by 2017, life expectancy for individuals in the lowest quintile of education has caught up with that of the top decile in 1991, albeit with contrasting trends between genders. Among women, the gap has reduced, while it has increased for males. Moreover, lifespan variation decreased (increased) over time for individuals in the tenth decile (first quintile). The leading causes of death that explain the increase in life expectancy in women and men in the tenth decile as well as women in the first quintile are cardiovascular, cancer, respiratory and digestive diseases. In the case of males in the first quintile, few gains have been made in life expectancy resulting from cancer and a negative contribution is associated with digestive conditions. Conclusions: This study underscores persistent socioeconomic disparities in life expectancy in Chile, emphasizing the importance of ongoing monitoring of health inequalities across different demographic segments. The gender-specific and educational gradient trends highlight areas for targeted interventions aimed at reducing health disparities and improving overall population health outcomes. Further research is warranted to delve into specific causes of death driving life expectancy differentials and to inform evidence-based policy interventions.

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Macauba (Acrocomia aculeata) is a Brazilian palm tree whose oil in the pulp is rich in oleic acid and carotenoids. However, its physiological function remains unknown. This study aimed to investigate the effects of macauba pulp oil (MPO) on the metabolic link between lipid metabolism and lifespan using Caenorhabditis elegans (C. elegans). C. elegans were treated with 5.0 mg/mL of MPO for analyzing triglyceride and glycerol accumulation, fatty acid profile, gene expression of lipid and oxidative metabolism proteins under cold (4°C) stress conditions, and lifespan analysis under stress conditions such as cold (4°C), heat (37°C), and oxidative (paraquat) stress. MPO significantly suppressed fat accumulation and increased glycerol (a lipolysis index) and the lifespan of C. elegans at low temperature (4°C). This was accompanied by decreased mRNA levels of the genes involved in lipogenesis (spb-1 and pod-2) and increased levels of the genes involved in fatty acid ß-oxidation (acs-2 and nhr-49) and fat mobilization genes (hosl-1 and aak-2). Additionally, MPO treatment modulated fatty acid pools in C. elegans at low temperatures in that MPO treatment decreased saturated fatty acid levels and shifted the fatty acid profile to long-chain fatty acids. Moreover, the effect of MPO on fat accumulation at low temperatures was abolished in fat-7 mutants, whereas both fat-1 and fat-7 contribute, at least in part, to MPO-elevated survival of C. elegans under cold conditions. PRACTICAL APPLICATION: The results obtained in the present study may contribute to the understanding of the health benefits of consuming macauba pulp oil and consequently stimulate economic growth and the industrial application of this new type of oil, which may result in the creation of new jobs and increased value of small producers.

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This paper proposes a pseudo-birth-cohort approach to deal with a lack of longitudinal data to measure health inequities over time. Using Roemer's framework for inequality of opportunity, this study measures ex-ante and ex-post inequalities in malnutrition, a concept that spans both sides of the nutrition continuum. The total contribution of observed circumstances and the direct contribution of observed efforts to the variation of malnutrition are disentangled for people born between 1983 and 1988 in Mexico. Results indicate that inequality of opportunity has been persistent across this 30-year lifespan for that cohort. Some evidence suggests that a lack of opportunities has been transmitted from parents to children and that people's circumstances account for most of the explained variation in the double burden of malnutrition. However, stratifying the analysis by sex shows that efforts account for more of the explained variation of inequality of opportunity for women in their middle adulthood than for men in most of the outcomes analyzed.

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Crossbred cattle are commonly used for milk production in the tropics, combining the potential benefits of pure breeds with the heterosis effects of the offspring. However, no comprehensive assessment of lifetime productivity for crossbred versus purebred cattle in low-altitude tropical environments has been carried out. The present study compares the lifetime productivity of purebred Holstein (HO, n = 17,269), Gyr (GY4, n = 435), and Brahman (BR4, n = 622) with crossbreds Gyr × Holstein (GY × HO, n = 5521) and Brahman×Holstein (BR × HO, n = 5429) cows from dairy farms located in low and medium altitude tropical regions in Costa Rica. The production traits of interest were age at first calving (AFC), days open (DO), milk production per lactation (TMP), lactation length (LLEN), age at culling (ACUL), and number of lactations (NLAC). Estimates of heterosis were also calculated. The AFC for GY × HO crosses (33-34 months) was not significantly different (p > .05) from HO (33.8 months). For BR × HO crosses, a significant (p < .05) decrease in AFC (BR3HO1 35.6 months, BR2HO2 34.5 months, and BR1H03 33.3 months) was observed as the fraction of HO breed increased. Estimates of heterosis for AFC were favourable for both crosses, of a magnitude close to 3%. The DO for F1 crosses (GY2HO2 94 days; BR2HO2 96 days) was significantly (p < .05) lower than HO (123 days). Estimates of heterosis for DO were also favourable and above 15% for both crosses. The TMP and LLEN were higher for HO (TMP = 5003 kg; LLEN = 324 days) compared with GY × HO (TMP = 4428 to 4773 kg; LLEN = 298 to 312 days) and BR × HO (TMP = 3950 to 4761 kg; LLEN = 273 to 313 days) crosses. Heterosis for TMP was favourable but low for both crosses, with a magnitude below 3.0%. The NLAC for HO (4.6 lactations) was significantly (p < .05) lower than F1 (GY2HO2, 5.8 lactations; BR2HO2, 5.4 lactations). Heterosis for NLAC was above 6.0% for both crosses. Overall, estimates of lifetime income over feed costs per cow on average were USD 2637 (30.3%) and USD 734 (8.4%) higher in F1 GY × HO and BR × HO, respectively, compared to HO. In conclusion, crossbred animals, specifically those with Gyr and Brahman genetics, extend the productive lifespan, increasing economic returns.

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Tocoyena formosa has a persistent floral nectary that continues producing nectar throughout flower and fruit development. This plant also presents an intriguing non-anthetic nectary derived from early-developing floral buds with premature abscised corolla. In this study, we characterize the structure, morphological changes, and functioning of T. formosa floral nectary at different developmental stages. We subdivided the nectary into four categories based on the floral and fruit development stage at which nectar production started: (i) non-anthetic nectary; (ii) anthetic nectary, which follows the regular floral development; (iii) pericarpial nectary, derived from pollinated flowers following fruit development; and (iv) post-anthetic nectary that results from non-pollinated flowers after anthesis. The nectary has a uniseriate epidermis with stomata, nectariferous parenchyma, and vascular bundles, with a predominating phloem at the periphery. The non-anthetic nectary presents immature tissues that release the exudate. The nectary progressively becomes more rigid as the flower and fruit develop. The main nectary changes during flower and fruit development comprised the thickening of the cuticle and epidermal cell walls, formation of cuticular epithelium, and an increase in the abundance of calcium oxalate crystals and phenolic cells near the vascular bundles. Projections of the outer periclinal walls toward the cuticle in the post-anthetic nectary suggest nectar reabsorption. The anatomical changes of the nectary allow it to function for an extended period throughout floral and fruit development. Hence, T. formosa nectary is a bivalent secretory structure that plays a crucial role in the reproductive and defensive interactions of this plant species.

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Historical demographic research shows that the factors influencing mortality risk are labile across time and space. This is particularly true for datasets that span societal transitions. Here, we seek to understand how marriage, migration, and the local economy influenced mortality dynamics in a rapidly changing environment characterized by high in-migration and male-biased sex ratios. Mortality records were extracted from a compendium of historical vital records for the Baja California peninsula (Mexico). Our sample consists of 1,201 mortality records spanning AD 1835-1900. Findings from Cox proportional hazard models indicate that (1) marriage was associated with a protective effect for both sexes; (2) residing in a mining town was associated with higher mortality for men, but not women; (3) migration was associated with decreased mortality risk for women, but not men; and (4) the risk of mortality increased in the face of infectious disease, but decreased over time. Despite the early initiation of reproduction for women, marriage had a protective effect, likely because marriage linked women to resources. Although mining boomtowns were associated with elevated risk factors generally, only men experienced greater mortality risk, likely due to dangerous working conditions that women did not experience. Last, female, but not male, migrants experienced greater longevity, possibly because exposure to harsh labor conditions eroded the protective effect of selection bias for men. Together, these results shed light on an understudied historical population and broaden our understanding of demographic dynamics in preindustrial settings.

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BACKGROUND AND AIMS: Orchid seeds are reputed to be short lived in dry, cold storage conditions, potentially limiting the use of conventional seed banks for long-term ex situ conservation. This work explores whether Cattleya seeds are long lived or not during conventional storage (predried to ~12 % relative humidity, then stored at -18 °C). METHODS: We explored the possible interaction of factors influencing seed lifespan in eight species of the genus Cattleya using physiological (germination and vigour), biochemical (gas chromatography), biophysical (differential scanning calorimetry) and morphometric methods. Seeds were desiccated to ~3 % moisture content and stored at -18 °C for more than a decade, and seed quality was measured via three in vitro germination techniques. Tetrazolium staining was also used to monitor seed viability during storage. The morphometric and germination data were subjected to ANOVA and cluster analysis, and seed lifespan was subjected to probit analysis. KEY RESULTS: Seeds of all Cattleya species were found to be desiccation tolerant, with predicted storage lifespans (P50y) of ~30 years for six species and much longer for two species. Cluster analysis showed that the three species with the longest-lived seeds had smaller (9-11 %) airspaces around the embryo. The post-storage germination method impacted the quality assessment; seeds equilibrated at room temperature for 24 h or in 10 % sucrose solution had improved germination, particularly for the seeds with the smallest embryos. Chromatography revealed that the seeds of all eight species were rich in linoleic acid, and differential scanning calorimetry identified a peak that might be auxiliary to selecting long-lived seeds. CONCLUSIONS: These findings show that not all orchids produce seeds that are short lived, and our trait analyses might help to strengthen prediction of seed longevity in diverse orchid species.

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BACKGROUND: Improving the mating competitiveness and survival of sterile males are direct means to increase the effectiveness of the sterile insect technique (SIT). Some insecticide growth regulators, such as the juvenile hormone analogue (JHA) methoprene, have been used to improve the mating competitiveness of male tephritid flies by reducing their sexual maturation period. However, the application of methoprene reduces fly resistance to stress and decreases survival. Here, we compared the effects of methoprene and pyriproxyfen (PPF), another JHA, in Anastrepha ludens males. PPF is an insect growth regulator that exhibits higher negative effects on the larval molting process than methoprene or natural juvenile hormone. Both compounds were administered at two doses (0.05% and 0.10%) via the male diet immediately after emergence. RESULTS: Our results show that both PPF and methoprene reduced male sexual maturation. However, PPF-treated males exhibited a shorter maturation period and obtained more matings at a given age than methoprene-treated males. No significant differences were observed between the two PPF doses tested (0.05% and 0.10%). Male survival was equally reduced by the two compounds. CONCLUSION: Our results demonstrate that PPF accelerated sexual development without reducing the mating propensity of sterile male flies and can be used as a suitable alternative for methoprene. © 2023 Society of Chemical Industry.

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Emerging evidence suggests that immune receptors may participate in many aging-related processes such as energy metabolism, inflammation, and cognitive decline. CD300f, a TREM2-like lipid-sensing immune receptor, is an exceptional receptor as it integrates activating and inhibitory cell-signaling pathways that modulate inflammation, efferocytosis, and microglial metabolic fitness. We hypothesize that CD300f can regulate systemic aging-related processes and ultimately healthy lifespan. We closely followed several cohorts of two strains of CD300f-/- and WT mice of both sexes for 30 months and observed an important reduction in lifespan and healthspan in knockout mice. This was associated with systemic inflammaging, increased cognitive decline, reduced brain glucose uptake observed by 18FDG PET scans, enrichment in microglial aging/neurodegeneration phenotypes, proteostasis alterations, senescence, increased frailty, and sex-dependent systemic metabolic changes. Moreover, the absence of CD300f altered macrophage immunometabolic phenotype. Taken together, we provide strong evidence suggesting that myeloid cell CD300f immune receptor contributes to healthy aging.

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[This corrects the article DOI: 10.3389/fnins.2023.1214468.].

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Metabolic syndrome (MetS) is defined by the concurrence of different metabolic conditions: obesity, hypertension, dyslipidemia, and hyperglycemia. Its incidence has been increasingly rising over the past decades and has become a global health problem. MetS has deleterious consequences on the central nervous system (CNS) and neurological development. MetS can last several years or be lifelong, affecting the CNS in different ways and treatments can help manage condition, though there is no known cure. The early childhood years are extremely important in neurodevelopment, which extends beyond, encompassing a lifetime. Neuroplastic changes take place all life through - childhood, adolescence, adulthood, and old age - are highly sensitive to environmental input. Environmental factors have an important role in the etiopathogenesis and treatment of MetS, so environmental enrichment (EE) stands as a promising non-invasive therapeutic approach. While the EE paradigm has been designed for animal housing, its principles can be and actually are applied in cognitive, sensory, social, and physical stimulation programs for humans. Here, we briefly review the central milestones in neurodevelopment at each life stage, along with the research studies carried out on how MetS affects neurodevelopment at each life stage and the contributions that EE models can provide to improve health over the lifespan.

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Cuba and Denmark represent states with different welfare models that have reached the same level of life expectancy. The purpose was to investigate and compare mortality changes in the two countries. Systematically collected information on population numbers and deaths for the entire Cuban and Danish populations was the basis of life table data used to quantify differences in the change in age-at-death distributions since 1955, age-specific contributions to differences in life expectancy, lifespan variation, and other changes in mortality patterns in Cuba and Denmark. Life expectancy in Cuba and Denmark converged until 2000, when the increase in life expectancy for Cuba slowed down. Since 1955, infant mortality has fallen in both countries but mostly in Cuba. Both populations experienced compression of mortality as lifespan variation decreased markedly, primarily due to postponement of early deaths. Given the different starting point in the mid-1900s and living conditions for Cubans and Danes, health status achieved among Cubans is striking. A rapidly ageing population is challenging both countries, but Cuban health and welfare are further burdened by a deteriorating economy in recent decades.

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This study aims to report what motivates individuals to be physically active, to determine whether motivating factors influence physical activity (PA) levels, and whether this differs across the lifespan. This is a cross-sectional study with 498 individuals: 117 adolescents, 306 adults, and 75 older adults. PA was assessed using Baecke's questionnaire, and motivating factors for practicing sports were investigated using a scale with twelve questions. The factor analysis identified three motivating factors for sports practice: psychosocial, bodily, and well-being. The scale's overall reliability and internal consistency indicated a Cronbach's alpha of 0.885. The analysis of covariance (ANCOVA) adjusted for sex indicated the three factors as having a significant effect on PA (p < 0.050); however, only the well-being factor showed a significant interaction with age groups (p = 0.023, ηp2 = 0.030). Subsequently, the effect of the well-being factor on PA scores in each age group was explored through regression analyses. Only older adults showed a significant association in the unadjusted [OR = 0.378, p = 0.001, R2 = 0.243] and the sex-adjusted analysis [OR = 0.377, p = 0.001, R2 = 0.288]. These results help us to better understand the underlying motivational reasons in different age groups for engaging in sports.

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In triatomines, blood-feeding triggers many physiological processes including post embryonic development and reproduction. Different feeding habits, such as hematophagy, can shape gene functions to meet the challenges of each type of diet. The gut of blood-sucking insects faces particular challenges after feeding due to the quantity and the quality of the food ingested. A comparison of transcriptomic and proteomic data indicates that post transcriptional regulation of gene expression is crucial in the triatomine gut. It was proposed that eukaryotic translation initiation factor 3 subunit m (eIF3m) and eIF3e define 2 different eIF3 complexes with a distinct affinity for the different mRNAs, thus selecting the set of mRNAs to be translated and constituting a post transcriptional mode of regulation of gene expression. Because the eIF3m is mainly expressed in the gut, we evaluated its relevance in Rhodnius prolixus physiology through RNA interference-mediated gene silencing. The knockdown of eIF3m reduced the digestion rate, affecting the processes triggered by a blood meal. Its silencing inhibited molting and caused premature death in nymphs while impaired ovary development, oviposition and increased resistance to starvation in adult females. The survival of males after feeding (resistance to starvation) was not affected by eIF3m knockdown. The information regarding the eIF3m function in insects is scarce and the phenotypes observed in R. prolixus upon eIF3m silencing are different and more severe than those previously described in Drosophila melanogaster, indicating a pleiotropic role of this gene in triatomines.

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OBJECTIVE: To identify the nutrients that influence the performance of working memory, which is greatly affected as age progresses. METHOD: A total of 1646 healthy adults between 21 and 80 years old participated in the study. The daily consumption of 64 nutrients was examined using a food frequency questionnaire that assessed food intake during the previous year. Working memory was measured in the verbal and spatial domains using a computerized task. We examined which nutrients influence working memory across the entire adult lifespan and whether the influence of any of these nutrients on working memory is moderated by individuals' ages. RESULTS: Working memory, across the entire adult lifespan, benefits from the intake of cholesterol, alcohol, gamma- and delta-tocopherol, vitamin B6, and palmitoleic, oleic, alpha linoleic and linoleic acids. Moderator analyses revealed that fats, energy, lactose and sodium negatively influenced working memory in middle-aged and older adults, whereas vitamin D and vitamin C had positive effects on memory beyond 70 years of age. CONCLUSION: Nutrients have the ability to positively or negatively affect working memory, which varies as a function of age.

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Among the diversity of electronic waste, lithium-ion batteries (LIB), specifically those used in the propulsion of electric vehicles (EV), are considered pollutants of significant impact. When not used and disposed of correctly, LIBs can cause damage of various types to health and the environment. The electrochemical instability inherent in these batteries releases toxic gases, risks explosion, and is always associated with a series of electronic circuits composed of various metals, including heavy metals. As a result of public policies to encourage vehicle electrification, the Brazilian EVs sector has shown high growth, even within an economic crisis scenario. In this sense, this study presents a model for estimating the production of electric vehicles and the generation of scrap LIBs, based on time series, combining battery life, car sales data, and the mileage profile covered by a car in Brazil. Around 700 thousand EVs are expected to be circulating in Brazil by 2030, with approximately 500 thousand LIBs to be converted into scrap by 2040. Finally, the delaying effect of the scrap generated from LIBs is highlighted, in line with the battery life, which, in the future, may have a very negative impact on waste management.

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Sex ratio is a crucial demographic parameter for the viability of natural populations, and it is commonly balanced in Neotropical freshwater fish species. This study investigated the sexual proportion of yellow-mandi Pimelodus maculatusin the Upper Uruguay River basin, southern Brazil, between 2000 and 2019. Fish were captured at different sites in a proportion of 2,018 females and 995 males. The total length ranged from 14 to 60 cm for females (31.8 ± 6.8 cm) and 13 to 45 cm for males (26.7 ± 13.6 cm). The frequency of females was higher from class 27 to 51 cm (P < 0.05), with a mean female:male sex ratio of 2.05:1, whereas a 1:1 sex ratio was found in fish shorter than 27 cm. The most important predictor explaining the dominance of females was the length, followed by year, site, and environment. Females are larger and live five years longer than males and they can become more abundant. This disparity in lifespan between females and males, the life history, and social and environmental factors may be associated with the female-biased sex ratio in P. maculatuspopulation of the Uruguay River Basin.(AU)

A proporção sexual é um parâmetro demográfico crucial para a viabilidade das populações naturais e normalmente é equilibrada nas espécies de peixes de água doce neotropicais. Este estudo investigou a proporção sexual do mandi amarelo Pimelodus maculatus na bacia do Alto Rio Uruguai, sul do Brasil, entre 2000 e 2019. Os peixes foram capturados em diferentes locais numa proporção de 2.018 fêmeas e 995 machos. O comprimento total variou de 14 a 60 cm para as fêmeas (31,8 ± 6,8 cm) e de 13 a 45 cm para os machos (26,7 ± 13,6 cm). A frequência de fêmeas foi maior da classe 27 para 51 cm (P < 0,05), com relação média de sexo feminino:sexo masculino de 2,05:1, enquanto a relação de sexo 1:1 foi encontrada em peixes com menos de 27 cm. O preditor mais importante que explica a dominância das fêmeas foi o comprimento, seguido pelo ano, local e ambiente. As fêmeas são maiores e vivem cinco anos a mais do que os machos, podendo tornar-se mais abundantes. Essa disparidade na expectativa de vida entre fêmeas e machos, a história de vida e os fatores sociais e ambientais podem estar associados ao desvio sexual feminino na população de P. maculatus da bacia do Rio Uruguai.(AU)

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Resumo O Brasil é um país marcado por forte desigualdade socioeconômica entre as regiões, que, por sua vez, se traduz em diferenciais regionais de mortalidade. Para um bom monitoramento desses diferenciais, é importante uma análise não apenas dos níveis médios de mortalidade, mas também da variação da idade à morte na população. Esse artigo analisa a contribuição das causas de óbito sobre as mudanças na esperança de vida e na dispersão da idade à morte no Brasil e grandes regiões entre 2008 e 2018. Os resultados sugerem aumento dos diferenciais regionais na esperança de vida ao longo da década analisada. No entanto, as diferenças regionais na dispersão da idade à morte se mantiveram praticamente constantes. As mudanças na mortalidade por causa impactam de maneiras diferentes a dispersão da idade à morte em cada região: a redução da mortalidade por causas externas contribui substantivamente para diminuir a variação da idade à morte nas regiões Sul e Sudeste, enquanto a contribuição das mortes por afecções originadas no período perinatal foi substantiva apenas na região Nordeste. Por fim, reafirmamos a importância dos indicadores de dispersão da idade à morte para se ter uma visão mais ampla dos diferenciais regionais de mortalidade no Brasil.

Abstract Brazil is a country marked by substantial socioeconomic inequality among regions, which translates into regional differentials in mortality. For better monitoring these differentials, it is important to analyze not only population average mortality levels, but also the age at death variation. This article analyzes cause-of-death contributions to changes in life expectancy and age-at-death variation in Brazil and its regions between 2008 and 2018. Our results suggest an increase in regional inequalities in life expectancy over the decade. However, regional differences in age-at-death variation remained nearly constant. Changes in mortality by cause impact the age-at-death variation differently in each region: the reduction in mortality from external causes substantially contributed to decreasing the variation in age at death in the South and Southeast regions, whereas the contribution of deaths from conditions originating in the perinatal period was substantive only in the Northeast region. Finally, we reaffirm the importance of age-at-death dispersion indicators to have a broader view of Brazil's regional differentials in mortality.

Resumen Brasil es un país marcado por fuertes desigualdades socioeconómicas entre sus regiones, lo que traduce a su vez se en diferencias regionales en la mortalidad. Para un buen seguimiento de estos diferenciales es importante analizar no solo los niveles medios de mortalidad, sino también la variación de la edad de la muerte en la población. Este artículo analiza la contribución de los grupos de causas de defunción sobre los cambios en la esperanza de vida al nacer y la dispersión de la edad al morir en Brasil y las grandes regiones entre 2008 y 2018. Nuestros resultados sugieren un aumento de las diferencias regionales en la esperanza de vida a lo largo de la década. Sin embargo, las diferencias regionales en la dispersión de la edad al morir se mantuvieron prácticamente constantes. Los cambios en la mortalidad por causas repercuten de forma diferente en la dispersión de la edad al fallecer en cada región: la reducción de la mortalidad por causas externas contribuyó de forma sustantiva a disminuir la variación de la edad al morir en las regiones Sur y Sureste, mientras que la contribución de las muertes por afecciones originadas en el período perinatal fue sustantiva en la región Noreste. Por último, reafirmamos la importancia de los indicadores de dispersión de la edad al morir para tener una visión más general de los diferenciales regionales de mortalidad en Brasil.

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Ezetimibe is an approved drug for lowering plasma LDL (low-density lipoprotein) level via inhibition of cholesterol absorption. Derivatives of ezetimibe reduce inflammatory response and oxidative stress. In the present study, we investigated the effect of dietary supplementation with ezetimibe in response to environmental stressors and found that ezetimibe increases resistance to oxidative stress and ultraviolet irradiation. Ezetimibe also significantly extended lifespan accompanying reduced fertility, which is a common trade-off for longevity in C. elegans. Cellular level of reactive oxygen species was increased and the expression of stress-responsive genes, hsp-16.2 and sod-3, was induced by dietary supplementation with ezetimibe, suggesting a hormetic effect on oxidative stress response and lifespan. Ezetimibe also significantly prevented amyloid beta-induced toxicity and completely reversed increased mortality by high-glucose diet. Nuclear localization of DAF-16 required for the prevention of amyloid beta-induced toxicity was enhanced by ezetimibe supplementation. Lifespan assay using known long-lived mutants, age-1, clk-1, and eat-2, revealed that lifespan extension by ezetimibe specifically overlapped with that of eat-2 mutants, which are genetic models of dietary restriction. Effect of ezetimibe on lifespan of worms fed with diluted bacteria suggested that ezetimibe mimics the effect of dietary restriction on lifespan. These findings suggest that ezetimibe exhibits anti-oxidative and anti-aging effects through hormesis and works as a dietary-restriction mimetic on lifespan extension.

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