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1.
J Frailty Aging ; 10(1): 2-9, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33331615

RESUMO

Telomeres are repetitive nucleotide sequences that together with the associated sheltrin complex protect the ends of chromosomes and maintain genomic stability. Evidences from various organisms suggests that several factors influence telomere length regulation, such as telomere binding proteins, telomere capping proteins, telomerase, and DNA replication enzymes. Recent studies suggest that micronutrients, such as vitamin D, folate and vitamin B12, are involved in telomere biology and cellular aging. In particular, vitamin D is important for a range of vital cellular processes including cellular differentiation, proliferation and apoptosis. As a result of the multiple functions of vitamin D it has been speculated that vitamin D might play a role in telomere biology and genomic stability. In this study, our main goal is investigating the relationship between telomerase enzyme and vitamin D. Findings of this study suggest that higher vitamin D concentrations, which are easily modifiable through nutritional supplementation, are associated with longer LTL, which underscores the potentially beneficial effects of this hormone on aging and age-related diseases. Vitamin D may reduce telomere shortening through anti-inflammatory and anti-cell proliferation mechanisms. Significant Low levels of telomerase activity create short telomeres, which in turn signal exit from the cell cycle resulting in cell senescence and apoptosis. In follow-up examination, the patients who remained vitamin D deficient tended to have shorter telomeres than those patients whose 25-hydroxyvitamin D levels were depleted. Increasing 25-hydroxyvitamin D levels in patients with SLE may be beneficial in maintaining telomere length and preventing cellular aging. Moreover, anti-telomere antibody levels may be a promising biomarker of SLE status and disease activity.


Assuntos
Senescência Celular/fisiologia , Telômero/metabolismo , Vitamina D/sangue , Vitamina D/metabolismo , Envelhecimento/sangue , Envelhecimento/genética , Envelhecimento/metabolismo , Envelhecimento/patologia , Humanos , Telomerase/genética , Telomerase/metabolismo , Telômero/genética
2.
Vasc Health Risk Manag ; 16: 535-543, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33324067

RESUMO

Introduction: The aim of this study was to evaluate the relationship between adipokines and arterial stiffness in a group of 85 elderly subjects and the role of leptin and adiponectin on subclinical vascular damage, defined by a PWV>10 m/s. Methods: In each subject, we evaluated anthropometry, body composition by DXA (fat mass, fat mass%, lean mass), metabolic variables, leptin, adiponectin, systolic, diastolic, mean arterial pressure and pulse pressure (SBP, DBP, MAP, PP), carotid-femoral pulse wave velocity (cfPWV) and carotid-radial pulse wave velocity (crPWV). Results: In the study population, significant associations were observed between cfPWV and crPWV, age, SBP, MAP, waist circumference, fat body mass and leptin. The study population was subdivided in 2 subgroups according to adipokine patterns: group 1 included patients with high adiponectin and low leptin, and group 2 patients had high leptin and low adiponectin. SBP, PP, cfPWV were significantly higher in subjects with high leptin and low adiponectin (group 2). Even after adjustment for gender, fat mass%, MAP, HDL cholesterol and triglycerides, cfPWV was higher in group 2 than group 1. In a logistic binary regression on the entire population, considering subclinical vascular damage as a dependent variable and age, gender, MAP, fat mass%, triglycerides, HDL cholesterol and category of subjects with high leptin and low adiponectin as independent variables, MAP and category of subjects with high leptin and low adiponectin were significant predictors (OR, respectively, 1.09 and 3.61). Conclusion: In conclusion, in the elderly, the presence at the same time of high leptin levels and low adiponectin levels seems to have synergic effects on arterial stiffness.


Assuntos
Adiponectina/sangue , Envelhecimento/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Leptina/sangue , Rigidez Vascular , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Composição Corporal , Doenças Cardiovasculares/diagnóstico , Feminino , Humanos , Masculino , Fatores de Risco
3.
Nat Commun ; 11(1): 5982, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239617

RESUMO

Expanding the mass of pancreatic insulin-producing beta cells through re-activation of beta cell replication has been proposed as a therapy to prevent or delay the appearance of diabetes. Pancreatic beta cells exhibit an age-dependent decrease in their proliferative activity, partly related to changes in the systemic environment. Here we report the identification of CCN4/Wisp1 as a circulating factor more abundant in pre-weaning than in adult mice. We show that Wisp1 promotes endogenous and transplanted adult beta cell proliferation in vivo. We validate these findings using isolated mouse and human islets and find that the beta cell trophic effect of Wisp1 is dependent on Akt signaling. In summary, our study reveals the role of Wisp1 as an inducer of beta cell replication, supporting the idea that the use of young blood factors may be a useful strategy to expand adult beta cell mass.


Assuntos
Envelhecimento/fisiologia , Proteínas de Sinalização Intercelular CCN/metabolismo , Células Secretoras de Insulina/fisiologia , Transplante das Ilhotas Pancreáticas/métodos , Proteínas Proto-Oncogênicas/metabolismo , Envelhecimento/sangue , Animais , Proteínas de Sinalização Intercelular CCN/sangue , Proteínas de Sinalização Intercelular CCN/genética , Proliferação de Células , Células Cultivadas , Meios de Cultura/metabolismo , Diabetes Mellitus/terapia , Feminino , Humanos , Células Secretoras de Insulina/transplante , Masculino , Camundongos , Camundongos Knockout , Cultura Primária de Células/métodos , Proteínas Proto-Oncogênicas/sangue , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais/fisiologia , Desmame
4.
PLoS One ; 15(10): e0241213, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33104754

RESUMO

AIMS: Single measurements of higher levels of soluble tumor necrosis factor receptor I (sTNF-R1) have been shown to be associated with increased risk of mortality. However, up to date, little is known about the underlying temporal dynamics of sTNF-R1 concentrations and their relation with mortality. We aimed to characterize the effect of changes in sTNFR-1 levels on all-cause and cardiovascular mortality, independent from other established risk factors for mortality, including other inflammatory markers. METHODS: We used data of the population based cohort study CARLA and included 1408 subjects with sTNF-R1 measured at baseline (2002-2006) and first follow-up (2007-2010). Cox proportional hazard models were used to assess the association of baseline and follow-up sTNF-R1 measurements with all-cause and cardiovascular mortality during ~10 years since the first follow-up after adjusting for relevant confounders. RESULTS: Based on 211 deaths among 1408 subjects, per each doubling of the baseline sTNF-R1, the risk of all-cause mortality was increased by about 30% (Hazard ratio 1.28, 95% Confidence Interval 0.6-2.7), while per each doubling of the follow-up level of sTNF-R1 mortality was 3-fold (3.11, 1.5-6.5) higher in a model including both measurements and adjusting for confounders. The results were mainly related to the cardiovascular mortality (5.9, 2.1-16.8 per each doubling of follow up sTNF-R1 value). CONCLUSION: Solely the follow-up value, rather than its change from baseline, predicted future mortality. Thus, while sTNF-R1 levels are associated with mortality, particularly cardiovascular, over a long-time period in the general population, if they change, the earlier measurements play no or little role.


Assuntos
Envelhecimento/sangue , Doenças Cardiovasculares/mortalidade , Mortalidade , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
Sci Rep ; 10(1): 15652, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973211

RESUMO

Several blood-based age prediction models have been developed using less than a dozen to more than a hundred DNA methylation biomarkers. Only one model (Z-P1) based on pyrosequencing has been developed using DNA methylation of a single locus located in the ELOVL2 promoter, which is considered as one of the best age-prediction biomarker. Although multi-locus models generally present better performances compared to the single-locus model, they require more DNA and present more inter-laboratory variations impacting the predictions. Here we developed 17,018 single-locus age prediction models based on DNA methylation of the ELOVL2 promoter from pooled data of four different studies (training set of 1,028 individuals aged from 0 and 91 years) using six different statistical approaches and testing every combination of the 7 CpGs, aiming to improve the prediction performances and reduce the effects of inter-laboratory variations. Compared to Z-P1 model, three statistical models with the optimal combinations of CpGs presented improved performances (MAD of 4.41-4.77 in the testing set of 385 individuals) and no age-dependent bias. In an independent testing set of 100 individuals (19-65 years), we showed that the prediction accuracy could be further improved by using different CpG combinations and increasing the number of technical replicates (MAD of 4.17).


Assuntos
Envelhecimento/sangue , Envelhecimento/genética , Metilação de DNA , Elongases de Ácidos Graxos/genética , Loci Gênicos/genética , Laboratórios , Regiões Promotoras Genéticas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Ilhas de CpG/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
PLoS Biol ; 18(9): e3000870, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32986697

RESUMO

Obesity and related metabolic diseases show clear sex-related differences. The growing burden of these diseases calls for better understanding of the age- and sex-related metabolic consequences. High-throughput lipidomic analyses of population-based cohorts offer an opportunity to identify disease-risk-associated biomarkers and to improve our understanding of lipid metabolism and biology at a population level. Here, we comprehensively examined the relationship between lipid classes/subclasses and molecular species with age, sex, and body mass index (BMI). Furthermore, we evaluated sex specificity in the association of the plasma lipidome with age and BMI. Some 747 targeted lipid measures, representing 706 molecular lipid species across 36 classes/subclasses, were measured using a high-performance liquid chromatography coupled mass spectrometer on a total of 10,339 participants from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), with 563 lipid species being validated externally on 4,207 participants of the Busselton Health Study (BHS). Heat maps were constructed to visualise the relative differences in lipidomic profile between men and women. Multivariable linear regression analyses, including sex-interaction terms, were performed to assess the associations of lipid species with cardiometabolic phenotypes. Associations with age and sex were found for 472 (66.9%) and 583 (82.6%) lipid species, respectively. We further demonstrated that age-associated lipidomic fingerprints differed by sex. Specific classes of ether-phospholipids and lysophospholipids (calculated as the sum composition of the species within the class) were inversely associated with age in men only. In analyses with women alone, higher triacylglycerol and lower lysoalkylphosphatidylcholine species were observed among postmenopausal women compared with premenopausal women. We also identified sex-specific associations of lipid species with obesity. Lysophospholipids were negatively associated with BMI in both sexes (with a larger effect size in men), whilst acylcarnitine species showed opposing associations based on sex (positive association in women and negative association in men). Finally, by utilising specific lipid ratios as a proxy for enzymatic activity, we identified stearoyl CoA desaturase (SCD-1), fatty acid desaturase 3 (FADS3), and plasmanylethanolamine Δ1-desaturase activities, as well as the sphingolipid metabolic pathway, as constituent perturbations of cardiometabolic phenotypes. Our analyses elucidate the effect of age and sex on lipid metabolism by offering a comprehensive view of the lipidomic profiles associated with common cardiometabolic risk factors. These findings have implications for age- and sex-dependent lipid metabolism in health and disease and suggest the need for sex stratification during lipid biomarker discovery, establishing biological reference intervals for assessment of disease risk.


Assuntos
Envelhecimento/sangue , Lipidômica , Lipídeos/sangue , Obesidade/metabolismo , Caracteres Sexuais , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Metabolismo dos Lipídeos , Masculino , Menopausa/sangue , Pessoa de Meia-Idade , Circunferência da Cintura
9.
Nature ; 585(7824): 283-287, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32814897

RESUMO

The risk of cancer and associated mortality increases substantially in humans from the age of 65 years onwards1-6. Nonetheless, our understanding of the complex relationship between age and cancer is still in its infancy2,3,7,8. For decades, this link has largely been attributed to increased exposure time to mutagens in older individuals. However, this view does not account for the established role of diet, exercise and small molecules that target the pace of metabolic ageing9-12. Here we show that metabolic alterations that occur with age can produce a systemic environment that favours the progression and aggressiveness of tumours. Specifically, we show that methylmalonic acid (MMA), a by-product of propionate metabolism, is upregulated in the serum of older people and functions as a mediator of tumour progression. We traced this to the ability of MMA to induce SOX4 expression and consequently to elicit transcriptional reprogramming that can endow cancer cells with aggressive properties. Thus, the accumulation of MMA represents a link between ageing and cancer progression, suggesting that MMA is a promising therapeutic target for advanced carcinomas.


Assuntos
Envelhecimento/metabolismo , Progressão da Doença , Ácido Metilmalônico/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias/patologia , Adulto , Idoso , Envelhecimento/sangue , Envelhecimento/genética , Animais , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Ácido Metilmalônico/sangue , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Neoplasias/sangue , Neoplasias/genética , Fatores de Transcrição SOXC/metabolismo , Transdução de Sinais , Transcriptoma/genética , Fator de Crescimento Transformador beta/metabolismo
10.
Sci Rep ; 10(1): 13521, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32782304

RESUMO

Little is known about vitamin D status in older adults in South America, where exposures to ultra-violet radiation are high. We examined the distribution of serum 25-hydroxyvitamin D (25OHD) concentration and its determinants in a nationally representative sample of Brazilians aged 50 years and older. Explanatory variables included environment and individuals' characteristics from the ELSI baseline survey (2015-16). Among the 2,264 participants (mean age = 62.6 years), the geometric mean of 25OHD concentration was 66.8 nmol/L. The prevalence of vitamin D deficiency (< 30 nmol/L) and insufficiency (< 50 nmol/L) were 1.7% (95% CI 1.0, 2.8) and 16% (95% CI 12, 20), respectively. Mean concentrations were lower in those geographical regions situated at lower latitudes. Those at the oldest age, women, self-classified as Black and Brown, living in urban areas and current smokers were more likely to have vitamin D insufficiency, independent of each other and other relevant factors. In contrast, individuals who eat fish regularly were considerably less likely to present lower concentration. Based on these findings it is possible to estimate that about 875,000 older Brazilians have vitamin D deficiency and 7.5 million its insufficiency.


Assuntos
Envelhecimento/sangue , Vitamina D/sangue , Idoso , Brasil , Feminino , Humanos , Estudos Longitudinais , Masculino
11.
Med Hypotheses ; 143: 110127, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32759008

RESUMO

Fenofibrate, which is a PPAR-alfpha agonist, increases the level of sulfatide. In this letter we hypothesize on the background of various findings that this is beneficial against COVID-19. Fenofibrate has been used for decades against hypercholesterolemia and has no serious side effects. Therefore, a trial giving fenofibrate to patients with corona virus infection is recommended.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Fenofibrato/farmacologia , Hipolipemiantes/farmacologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Sulfoglicoesfingolipídeos/sangue , Adulto , Envelhecimento/sangue , Criança , Reposicionamento de Medicamentos , Fenofibrato/uso terapêutico , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipertensão/sangue , Hipertensão/complicações , Hipolipemiantes/uso terapêutico , PPAR alfa/antagonistas & inibidores , Internalização do Vírus
12.
Biochim Biophys Acta Mol Basis Dis ; 1866(11): 165914, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768678

RESUMO

Chagas disease, triggered by the flagellate protozoan Trypanosoma cruzi (T. cruzi) plays a potentially threat to historically non-endemic areas. Considerable evidence established that the immuno-endocrine balance could deeply influence the experimental T. cruzi progression inside the host's body. A high-resolution multiple reaction monitoring approach (MRMHR) was used to study the influence of melatonin on adrenal and plasma steroidal hormones profile of T. cruzi infected Wistar rats. Young (5 weeks) and middle-aged (18 months) male Wistar rats received melatonin (5 mg/Kg, orally) during the acute Chagas disease. Corticosterone, 11-dehydrocorticosterone (11-DHC), cortisol, cortisone, aldosterone, progesterone and melatonin concentration were evaluated. Interleukin-1 alpha and ß (IL-1α and ß), IL-6 and transforming growth factor beta (TGF-ß) were also analyzed. Our results revealed an increased production of corticosterone, cortisone, cortisol and aldosterone in middle-aged control animals, thus confirming the aging effects on the steroidal hormone profile. Serum melatonin levels were reduced with age and predominantly higher in young and middle-aged infected rats. Melatonin treatment reduced the corticosterone, 11-DHC, cortisol, cortisone, aldosterone and progesterone in response to T. cruzi infection. Decreased IL-1 α and ß concentrations were also found in melatonin treated middle-aged infected animals. Melatonin treated middle-aged control rats displayed reduced concentrations of TGF-ß. Melatonin levels were significantly higher in all middle-aged rats treated animals. Reduced percentages of early and late thymocyte apoptosis was found for young and middle-aged melatonin supplemented rats. Finally, our results show a link between the therapeutic and biological effects of melatonin controlling steroidal hormones pathways as well as inflammatory mediators.


Assuntos
Citocinas/sangue , Melatonina/sangue , Envelhecimento/sangue , Envelhecimento/metabolismo , Aldosterona/sangue , Animais , Apoptose/efeitos dos fármacos , Corticosterona/sangue , Cortisona/sangue , Interleucina-1alfa/sangue , Interleucina-1beta/sangue , Masculino , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem , Timócitos/efeitos dos fármacos , Timócitos/metabolismo , Trypanosoma cruzi/patogenicidade
13.
Nat Commun ; 11(1): 3820, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732919

RESUMO

Supercentenarians (those aged ≥110 years) are approaching the current human longevity limit by preventing or surviving major illness. Identifying specific biomarkers conducive to exceptional survival might provide insights into counter-regulatory mechanisms against aging-related disease. Here, we report associations between cardiovascular disease-related biomarkers and survival to the highest ages using a unique dataset of 1,427 oldest individuals from three longitudinal cohort studies, including 36 supercentenarians, 572 semi-supercentenarians (105-109 years), 288 centenarians (100-104 years), and 531 very old people (85-99 years). During follow-up, 1,000 participants (70.1%) died. Overall, N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin-6, cystatin C and cholinesterase are associated with all-cause mortality independent of traditional cardiovascular risk factors and plasma albumin. Of these, low NT-proBNP levels are statistically associated with a survival advantage to supercentenarian age. Only low albumin is associated with high mortality across age groups. These findings expand our knowledge on the biology of human longevity.


Assuntos
Envelhecimento/sangue , Biomarcadores/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Albumina Sérica/análise , Inquéritos e Questionários/estatística & dados numéricos , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Feminino , Humanos , Longevidade/fisiologia , Estudos Longitudinais , Masculino , Análise Multivariada , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida
14.
Toxicol Lett ; 333: 222-231, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798538

RESUMO

Despite many hypothesized benefits of dietary isoflavone genistein (GEN) deriving from soy-based products, questions surrounding GEN's developmental effects are increasing. To understand if in utero GEN exposure modulated postnatal respiratory allergies in the middle age, we conducted a time course study in the B6C3F1 offspring (PND 240-330) using a common household allergen (house dust mites: HDM; 10 µg/mouse for PND 240 and 290, and 50 µg/mouse for PND 330, a middle age in mice) following intranasal instillation, a physiological route of allergen exposure. GEN was administered to dams by gavage from gestational day 14 to parturition at a physiologically relevant dose (20 mg/kg body weight). Female and male offspring were sensitized with HDM allergens beginning about one month prior to sacrifice followed by challenges with three weekly dosings of HDM extracts, and they were euthanized at day 3 following the final HDM exposure. In utero exposure to GEN decreased HDM allergen-induced respiratory allergy in male B6C3F1 offspring at PND 330 as reflected by decreases in airway hyperresponsiveness (e.g., Penh value), HDM-specific IgG1 (a Th2 type Ab) and the activity of eosinophil peroxidase in the lung (an indication of eosinophil recruitment to the lungs). However, in utero exposure to GEN had minimal effects on HDM allergen-induced respiratory allergy in the middle-aged female offspring. Changes in serum total IgE, HDM-specific IgE, and lung histopathology scores in both male and female offspring were not biologically significant. Overall, in utero GEN exposure exerted a protective effect on respiratory allergy in the middle-aged male, but not female, B6C3F1 offspring following later-life HDM exposures.


Assuntos
Envelhecimento/imunologia , Genisteína/farmacologia , Pulmão/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Hipersensibilidade Respiratória/prevenção & controle , Envelhecimento/sangue , Alérgenos/imunologia , Animais , Peroxidase de Eosinófilo/metabolismo , Eosinófilos/efeitos dos fármacos , Eosinófilos/enzimologia , Feminino , Genisteína/administração & dosagem , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Pulmão/embriologia , Pulmão/imunologia , Pulmão/patologia , Masculino , Exposição Materna , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/imunologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/sangue , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/patologia
15.
Science ; 369(6500): 167-173, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32646997

RESUMO

Reversing brain aging may be possible through systemic interventions such as exercise. We found that administration of circulating blood factors in plasma from exercised aged mice transferred the effects of exercise on adult neurogenesis and cognition to sedentary aged mice. Plasma concentrations of glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (Gpld1), a GPI-degrading enzyme derived from liver, were found to increase after exercise and to correlate with improved cognitive function in aged mice, and concentrations of Gpld1 in blood were increased in active, healthy elderly humans. Increasing systemic concentrations of Gpld1 in aged mice ameliorated age-related regenerative and cognitive impairments by altering signaling cascades downstream of GPI-anchored substrate cleavage. We thus identify a liver-to-brain axis by which blood factors can transfer the benefits of exercise in old age.


Assuntos
Envelhecimento/sangue , Encéfalo/fisiologia , Cognição/fisiologia , Fígado/enzimologia , Neurogênese , Fosfolipase D/sangue , Condicionamento Físico Animal , Animais , Circulação Sanguínea , Encéfalo/irrigação sanguínea , Disfunção Cognitiva/sangue , Disfunção Cognitiva/fisiopatologia , Glicosilfosfatidilinositóis/metabolismo , Camundongos , Fosfolipase D/metabolismo , Regeneração , Transdução de Sinais
16.
Sci Rep ; 10(1): 11358, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32647178

RESUMO

Tuberculosis (TB) is a chronic infection that can affect individuals of all ages. The description of determinants of immunopathogenesis in TB is of tremendous interest due to the perspective of finding a reliable host-directed therapy to reduce disease burden. The association between specific biomarker profiles related to inflammation and the diverse clinical disease presentations in TB has been extensively studied in adults. However, relatively scarce data on profiling the inflammatory responses in pediatric TB are available. Here, we employed the molecular degree of perturbation (MDP) score adapted to plasma biomarkers in two distinct databanks from studies that examined either adults or children presenting with pulmonary or extrapulmonary disease. We used multidimensional statistical analyses to characterize the impact of age on the overall changes in the systemic inflammation profiles in subpopulation of TB patients. Our findings indicate that TB results in significant increases in molecular perturbation, with the highest values being detected in adult patients. Furthermore, there were unique differences in the biomarker perturbation patterns and the overall degree of inflammation according to disease site and age. Importantly, the molecular degree of perturbation was not influenced by sex. Our results revealed that aging is an important determinant of the differences in quality and magnitude of systemic inflammatory perturbation in distinct clinical forms of TB.


Assuntos
Envelhecimento/imunologia , Citocinas/sangue , Inflamação/diagnóstico , Tuberculose/imunologia , Adolescente , Adulto , Fatores Etários , Envelhecimento/sangue , Biomarcadores/sangue , Criança , Pré-Escolar , Citocinas/imunologia , Feminino , Humanos , Lactente , Inflamação/sangue , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Tuberculose/sangue , Tuberculose/microbiologia
17.
Br J Haematol ; 191(2): 207-211, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32679621

RESUMO

A low count of CD4+ and CD8+ lymphocytes is a hallmark laboratory finding in the coronavirus disease 2019 (COVID-19). Using flow cytometry, we observed significantly higher CD95 (Fas) and PD-1 expression on both CD4+ T and CD8+ T cells in 42 COVID-19 patients when compared to controls. Higher CD95 expression in CD4+ cells correlated with lower CD4+ counts. A higher expression of CD95 in CD4+ and CD8+ lymphocytes correlated with a lower percentage of naive events. Our results might suggest a shift to antigen-activated T cells, expressing molecules increasing their propensity to apoptosis and exhaustion during COVID-19 infection.


Assuntos
Linfócitos T CD4-Positivos/química , Linfócitos T CD8-Positivos/química , Subpopulações de Linfócitos/química , Linfopenia/etiologia , Receptor de Morte Celular Programada 1/sangue , Receptor fas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Envelhecimento/imunologia , Apoptose , /complicações , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Prognóstico
18.
Mov Disord ; 35(11): 1905-1913, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32633860

RESUMO

BACKGROUND: Young plasma infusions have emerged as a potential treatment for neurodegenerative disease, and convalescent plasma therapy has been used safely in the management of viral pandemics. However, the effect of plasma therapy in Parkinson's disease (PD) is unknown. OBJECTIVES: The objective of this study was to determine the safety, tolerability, and feasibility of plasma infusions in people with PD. METHODS: A total of 15 people with clinically established PD, at least 1 cognitive complaint, and on stable therapy received 1 unit of young fresh frozen plasma twice a week for 4 weeks. Assessments and adverse effects were performed/reported on and off therapy at baseline, immediately after, and 4 weeks after the infusions ended. Adverse effects were also assessed during infusions. The primary outcomes were safety, tolerability, and feasibility. Exploratory outcomes included Unified Parkinson's Disease Rating Scale Part III off medication, neuropsychological battery, Parkinson's Disease Questionnaire-39, inflammatory markers (tumor necrosis factor-α, interleukin-6), uric acid, and quantitative kinematics. RESULTS: Adherence rate was 100% with no serious adverse effects. There was evidence of improvement in phonemic fluency (P = 0.002) and in the Parkinson's Disease Questionnaire-39 stigma subscore (P = 0.013) that were maintained at the delayed evaluation. Elevated baseline tumor necrosis factor-α levels decreased 4 weeks after the infusions ended. CONCLUSIONS: Young fresh frozen plasma was safe, feasible, and well tolerated in people with PD, without serious adverse effects and with preliminary evidence for improvements in phonemic fluency and stigma. The results of this study warrant further therapeutic investigations in PD and provide safety and feasibility data for plasma therapy in people with PD who may be at higher risk for severe complications of COVID-19. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Transfusão de Componentes Sanguíneos/efeitos adversos , Doença de Parkinson/terapia , Plasma , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Antiparkinsonianos/uso terapêutico , Fenômenos Biomecânicos , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/terapia , Terapia Combinada , Estimulação Encefálica Profunda , Estudos de Viabilidade , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/sangue , Doença de Parkinson/psicologia , Risco , Índice de Gravidade de Doença , Distúrbios da Fala/etiologia , Distúrbios da Fala/terapia , Fator de Necrose Tumoral alfa/sangue
19.
Artigo em Inglês | MEDLINE | ID: mdl-32615056

RESUMO

Over the past decades, air pollution has become one of the critical environmental health issues in China. The present study aimed to evaluate links between ambient air pollution and the prevalence of type 2 diabetes mellitus (T2DM) and the levels of glycosylated hemoglobin (HbA1c). A multilevel linear and logistic regression was used to assess these associations among 7,770 participants aged ≥50 years from the WHO Study on global AGEing and adult health (SAGE) in China in 2007-2010. The average exposure to each of pollutants (particulate matter with an aerodynamic diameter of ≤10 µm/≤2.5 µm/≤1 µm [PM10/PM2.5/PM1] and nitrogen dioxide [NO2]) was estimated using a satellite-based spatial statistical model. In logistic models, a 10 µg/m3 increase in PM10 and PM2.5 was associated with increased T2DM prevalence (Prevalence Odds Ratio, POR: 1.27; 95% CI: 1.11, 1.45 and POR: 1.23; 95% CI: 1.03, 1.46). Similar increments in PM10, PM2.5, PM1 and NO2 were associated with increase in HbA1c levels of 1.8% (95% CI: 1.3, 2.3), 1.3% (95% CI: 1.1, 1.5), 0.7% (95% CI: 0.1, 1.3), and 0.8% (95% CI: 0.4, 1.2), respectively. In a large cohort of older Chinese adults, air pollution was liked to both higher T2DM prevalence and elevated HbA1c levels.


Assuntos
Envelhecimento/sangue , Poluentes Atmosféricos/análise , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobina A Glicada/análise , Exposição por Inalação/análise , Material Particulado/análise , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Organização Mundial da Saúde
20.
Sci Rep ; 10(1): 10636, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32606300

RESUMO

It has been suggested that an age-related loss of cognitive function might be driven by atherosclerotic effects associated with altered lipid patterns. However, the relationship between Lipoprotein (a) [Lp(a)] and healthy cognitive aging has not yet been sufficiently investigated. For the current analysis we used the cross-sectional data of 1,380 Berlin Aging Study II (BASE-II) participants aged 60 years and older (52.2% women, mean age 68 ± 4 years). We employed the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-Plus test battery to establish latent factors representing continuous measures of domain specific cognitive functions. Regression models adjusted for APOE genotypes, lipid parameters and other risk factors for cognitive impairment were applied to assess the association between Lp(a) and performance in specific cognitive domains. Men within the lowest Lp(a)-quintile showed better cognitive performance in the cognitive domain executive functions and processing speed (p = 0.027). No significant results were observed in women. The results of the current analysis of predominantly healthy BASE-II participants point towards an association between low Lp(a) concentrations and better cognitive performance. However, evidence for this relationship resulting from the current analysis and the employment of a differentiated cognitive assessment is rather weak.


Assuntos
Envelhecimento/fisiologia , Cognição , Lipoproteínas/sangue , Adulto , Idoso , Envelhecimento/sangue , Feminino , Humanos , Masculino , Memória , Pessoa de Meia-Idade
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