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1.
Nutrients ; 13(12)2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34959893

RESUMO

(1) Introduction: vitamin D may maintain the telomere length, either directly or via the inflammation effect and/or modulating the rate of cell proliferation. Whilst results from cross-sectional studies investigating the association between 25(OH)D concentration and telomere length have been mixed, there is a dearth of data from prospective studies which have assessed these associations. This study aimed to examine the association between 25(OH)D concentration in plasma and telomere length in blood cells in very-old adults (≥85 years old) at baseline, 18 months and 36 months by controlling for related lifestyle factors. (2) Methodology: our prospective cohort study comprised 775 participants from the Newcastle 85+ Study who had 25(OH)D measurements at baseline. Plasma 25(OH)D was stratified as <25 nmol/L (low), 25-50 nmol/L (moderate) and >50 nmol/L (high). Peripheral blood mononuclear cell telomere length was measured by quantitative real-time polymerase chain reaction at baseline, 18 and 36 months from baseline. (3) Results: a positive significant association was found between 25(OH)D concentration and telomere length amongst very-old participants at baseline (95% CI = 12.0-110.3, B = 61.2 ± 5.0, p = 0.015). This association was negative at 18 months (95% CI = -59.9--7.5, B = -33.7 ± 13.3, p = 0.012) but was non-significant at 36 months. (4) Conclusion: Circulating 25(OH)D concentration shows inconsistent relationships with telomere length over time in very-old (85+ year old) adults.


Assuntos
Envelhecimento/genética , Envelhecimento/fisiologia , Homeostase do Telômero , Vitamina D/análogos & derivados , Fatores Etários , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Prospectivos , Vitamina D/sangue
2.
Physiol Res ; 70(S2): S135-S144, 2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34904442

RESUMO

The recent COVID-19 pandemic is the defining global health crisis of our time and little is known about this disease. It has been reported that advanced age is considered a major risk factor for COVID-19 complications, and data suggest that this disease is deadlier for men than women but these observations are currently unclear. Regarding androgen action, it has been shown that certain smooth muscles are a target for androgens by inducing an acute relaxing effect in airway and vascular tissues that is nongenomically mediated; likewise, androgens are capable of inducing genomic anti-inflammatory and nongenomic hypotensive responses. The aim of this report is to associate the relationship between COVID-19 and aging men as well as the comorbidities presented in this group of patients linked with androgen deficiency. Remarkably, the nongenomic mechanisms of androgens as potential protectors are reviewed. On this basis, it is suggested that hypotestosteronemia may be a risk factor for COVID-19 severity.


Assuntos
Envelhecimento/sangue , Androgênios/sangue , COVID-19/sangue , COVID-19/diagnóstico , Músculo Liso Vascular/metabolismo , Gravidade do Paciente , Envelhecimento/patologia , Animais , COVID-19/fisiopatologia , Feminino , Humanos , Masculino , Músculo Liso Vascular/patologia , Vasodilatação/fisiologia
3.
Int J Mol Sci ; 22(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34502137

RESUMO

In the bone marrow of vertebrates, two types of stem cells coexist-hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Hematopoiesis only occurs when these two stem cell types and their descendants interact. The descendants of HSCs supply the body with all the mature blood cells, while MSCs give rise to stromal cells that form a niche for HSCs and regulate the process of hematopoiesis. The studies of hematopoiesis were initially based on morphological observations, later extended by the use of physiological methods, and were subsequently augmented by massive application of sophisticated molecular techniques. The combination of these methods produced a wealth of new data on the organization and functional features of hematopoiesis in the ontogenesis of mammals and humans. This review summarizes the current views on hematopoiesis in mice and humans, discusses the development of blood elements and hematopoiesis in the embryo, and describes how the hematopoietic system works in the adult organism and how it changes during aging.


Assuntos
Envelhecimento/sangue , Hematopoese , Células-Tronco Hematopoéticas/citologia , Envelhecimento/metabolismo , Animais , Medula Óssea/crescimento & desenvolvimento , Humanos
4.
BMC Vet Res ; 17(1): 265, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362371

RESUMO

BACKGROUND: Blood biochemistry and reference intervals help to differentiate between healthy and ill dogs as well as to provide information for the prognosis, evaluation, and monitoring; however, these intervals are often obtained from adult animals. It is essential to understand that puppies and adults are physiologically different, which justifies the need to obtain age-specific biochemical reference intervals. The aim of this research was to assess the potential effect of age, sex, body size, and their interaction on routine biochemical analytes and physiological constants (body temperature, heart rate, and respiratory rate). To carry out the research, we selected 197 healthy dogs of both sexes and different body sizes (small, medium and large) classified by age: group I (4-8 wk), group II (9-24 wk), group III (25-52 wk), and group IV (> 52 wk). The biochemical analysis included the measurement of the enzymatic activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and the concentrations of cholesterol, triglycerides, total proteins, albumin, globulins, glucose, urea, and creatinine. Statistical analyses used analysis of variance (ANOVA) and a general linear model (GLM), which allows the comparison of multiple factors at two or more levels (p < 0.05). RESULTS: The results of this study showed that ALT, total protein, albumin, globulin, urea, creatinine, and body temperature levels were lower in puppies than in adult dogs of group IV (p < 0.05), while the enzymatic activity of ALP, LDH, glucose concentration, and heart rate were higher. Whereas sex, body size and the interaction did not show a significant effect (p > 0.05). CONCLUSIONS: Some biochemical components are influenced by age. For this reason, this manuscript contributes with additional data for the clinical interpretation of blood biochemical results in puppies.


Assuntos
Envelhecimento/fisiologia , Análise Química do Sangue/veterinária , Tamanho Corporal/fisiologia , Cães/sangue , Envelhecimento/sangue , Animais , Cães/crescimento & desenvolvimento , Cães/fisiologia , Feminino , Testes Hematológicos/veterinária , Masculino , Valores de Referência
5.
Health Psychol ; 40(7): 459-467, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34435797

RESUMO

OBJECTIVE: Inflammation is one biological pathway through which marital dissolution and marital discord may increase risk for chronic disease. The present study was conducted to investigate the cross-sectional association between marital dissolution, marital discord, and C-reactive protein (CRP), an indicator of inflammation, in a probability sample of Irish adults aged 50 years or older. METHOD: Data were drawn from The Irish Longitudinal Study on Ageing. Linear regression analyses were conducted to examine (a) the association between marital dissolution and CRP values (N = 2,545), (b) the association between marital discord and CRP values (N = 1,949), and (c) whether these associations were moderated by gender. Subsequent models adjusted for demographic characteristics and health variables. RESULTS: With respect to marital dissolution, individuals who were separated or divorced had significantly higher CRP relative to married individuals. With respect to marital discord, gender significantly moderated the association between marital discord and CRP, such that marital discord was significantly and positively associated with CRP for men, whereas this association was not statistically significant for women. Results for marital dissolution and marital discord remained statistically significant when adjusting for demographic characteristics and health variables. CONCLUSIONS: This is one of the first studies to document a significant cross-sectional association between marital dissolution, marital discord, and CRP, incremental to demographic and health covariates, in a non-American probability sample. Results indicate that inflammation may be one pathway by which marital dissolution and marital discord contribute to risk for disease and early death. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Envelhecimento , Proteína C-Reativa/análise , Estado Civil/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Estudos Transversais , Suscetibilidade a Doenças , Feminino , Humanos , Inflamação/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
6.
Genes (Basel) ; 12(6)2021 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-34204075

RESUMO

In recent years, scientists have found a close correlation between DNA methylation and aging in epigenetics. With the in-depth research in the field of DNA methylation, researchers have established a quantitative statistical relationship to predict the individual ages. This work used human blood tissue samples to study the association between age and DNA methylation. We built two predictors based on healthy and disease data, respectively. For the health data, we retrieved a total of 1191 samples from four previous reports. By calculating the Pearson correlation coefficient between age and DNA methylation values, 111 age-related CpG sites were selected. Gradient boosting regression was utilized to build the predictive model and obtained the R2 value of 0.86 and MAD of 3.90 years on testing dataset, which were better than other four regression methods as well as Horvath's results. For the disease data, 354 rheumatoid arthritis samples were retrieved from a previous study. Then, 45 CpG sites were selected to build the predictor and the corresponded MAD and R2 were 3.11 years and 0.89 on the testing dataset respectively, which showed the robustness of our predictor. Our results were better than the ones from other four regression methods. Finally, we also analyzed the twenty-four common CpG sites in both healthy and disease datasets which illustrated the functional relevance of the selected CpG sites.


Assuntos
Envelhecimento/genética , Metilação de DNA , Genética Forense/métodos , Modelos Genéticos , Envelhecimento/sangue , Biomarcadores/sangue , Ilhas de CpG , Genética Forense/normas , Humanos , Especificidade de Órgãos , Sensibilidade e Especificidade
7.
Sci Rep ; 11(1): 14122, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34239023

RESUMO

Total testosterone levels decline with age, while prostate volume and the prevalence of benign prostatic hyperplasia increase with age. We sought to investigate the correlation of serum testosterone levels with prostate volume in aging men. We analyzed clinical data obtained from 416 ostensibly healthy men who underwent routine health check-ups and recruited and collected data from these subjects 4 years later. We analyzed the correlation between prostate volume and relevant factors, as well as the correlation between changes in prostate volume and low testosterone over a 4-year period. Men with low testosterone had significantly larger prostate volume than those in the normal testosterone group (26.86 ± 8.75 vs. 24.06 ± 6.77 P = 0.02), and subjects with low testosterone had significantly higher levels of obesity-related factors, including waist circumference, body mass index, and insulin (all P < 0.001). After adjustment for age, testosterone level was negatively correlated with prostate volume (P = 0.004), and prostate volume and 4-year changes in prostate volume were associated with low testosterone. With increased testosterone level, prostate volume showed a significant linear decreasing trend. These findings provide evidence of the relationship between testosterone and prostate volume. Additional large studies are needed to confirm these preliminary results.


Assuntos
Envelhecimento/sangue , Próstata/anatomia & histologia , Testosterona/sangue , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Análise de Regressão
8.
J Trauma Acute Care Surg ; 91(4): 692-699, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34252063

RESUMO

BACKGROUND: After severe trauma, the older host experiences more dysfunctional hematopoiesis of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs), and dysfunctional differentiation of circulating myeloid cells into effective innate immune cells. Our main objective was to compare BM HSPC microRNA (miR) responses of old and young mice in a clinically relevant model of severe trauma and shock. METHODS: C57BL/6 adult male mice aged 8 to 12 weeks (young) and 18 to 24 months (old) underwent multiple injuries and hemorrhagic shock (polytrauma [PT]) that engenders the equivalent of major trauma (Injury Severity Score, >15). Pseudomonas pneumonia (PNA) was induced in some young and old adult mice 24 hours after PT. MicroRNA expression patterns were determined from lineage-negative enriched BM HSPCs isolated from PT and PT-PNA mice at 24 and 48 hours postinjury, respectively. Genome-wide expression and pathway analyses were also performed on bronchoalveolar lavage (BAL) leukocytes from both mouse cohorts. RESULTS: MicroRNA expression significantly differed among all experimental conditions (p < 0.05), except for old-naive versus old-injured (PT or PT-PNA) mice, suggesting an inability of old mice to mount a robust early miR response to severe shock and injury. In addition, young adult mice had significantly more leukocytes obtained from their BAL, and there were greater numbers of polymorphonuclear cells compared with old mice (59.8% vs. 2.2%, p = 0.0069). Despite increased gene expression changes, BAL leukocytes from old mice demonstrated a more dysfunctional transcriptomic response to PT-PNA than young adult murine BAL leukocytes, as reflected in predicted upstream functional pathway analysis. CONCLUSION: The miR expression pattern in BM HSPCs after PT (+/-PNA) is dissimilar in old versus young adult mice. In the acute postinjury phase, old adult mice are unable to mount a robust miR HSPC response. Hematopoietic stem and progenitor cell miR expression in old PT mice reflects a diminished functional status and a blunted capacity for terminal differentiation of myeloid cells.


Assuntos
Medula Óssea/patologia , Hematopoese/genética , Células-Tronco Hematopoéticas/fisiologia , Traumatismo Múltiplo/complicações , Choque Hemorrágico/imunologia , Fatores Etários , Envelhecimento/sangue , Envelhecimento/genética , Envelhecimento/imunologia , Animais , Medula Óssea/fisiologia , Diferenciação Celular/imunologia , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/imunologia , Hematopoese/imunologia , Humanos , Imunidade Inata , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo Múltiplo/sangue , Traumatismo Múltiplo/imunologia , Choque Hemorrágico/sangue , Choque Hemorrágico/genética , Choque Hemorrágico/patologia
9.
J Clin Endocrinol Metab ; 106(10): 2890-2900, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34197576

RESUMO

AIMS: Prior studies have reported inconsistent results for the association between sex hormone-binding globulin (SHBG) and cardiovascular disease among men and women. Although it is suggested that SHBG levels change with aging, the exact trend of SHBG across age and cardiovascular risk and the underlying mechanisms of these changes remain to be elucidated. METHODS: Using data of 3264 men and women from a large population-based cohort study, we first visualized the distribution of serum SHBG levels across age. Second, we computed a cardiovascular risk factor sum score and investigated the mean SHBG levels across categories of the risk factor sum score and stratified per age-category. Next, linear regression models were used to investigate the associations between serum SHBG levels and age and potential regulators of SHBG, including body mass index (BMI), fasting insulin, sex steroids, thyroxine, and triglycerides. RESULTS: Among men, a linear increase in SHBG levels with age and among women a U-shaped pattern was observed. Participants with larger number of cardiovascular risk factors had lower SHBG levels. When stratified by age, older participants had higher SHBG levels. A multivariate model including total testosterone and triglyceride levels in men and total testosterone, triglycerides, BMI, and fasting insulin in women explained, respectively, 46.2% and 31.8% of the variance in SHBG levels. CONCLUSION: We observed a clear sex-specific pattern for SHBG levels with age. Our findings highlight the importance of taking into account the age-related changes in SHBG levels to avoid controversial results in the assessment of the cardiovascular risk associated with SHBG.


Assuntos
Fatores Etários , Envelhecimento/sangue , Doenças Cardiovasculares/etiologia , Fatores Sexuais , Globulina de Ligação a Hormônio Sexual/análise , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos Transversais , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Medição de Risco
10.
Front Immunol ; 12: 685344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211472

RESUMO

Vaccination is the best prophylaxis for the prevention of infectious diseases, including coronavirus disease 2019. However, the efficacy of vaccines and onset of adverse reactions vary among individuals. Circulating extracellular vesicles (EVs) regulate the immune responses after vaccination by delivering microRNAs (miRNAs) to myeloid and lymphoid cells. Among these, miR-192 levels in serum EVs increase with aging, in an IL-6-dependent manner, reducing excessive IL-6 expression in aged mice, creating a negative feedback loop. Excessive IL-6 expression reduces vaccination efficacy in aged mice, while EV miR-192 improves efficacy in these aged mice as well, making this miRNA an interesting focus of study. miR-21 levels in serum EVs also increase with aging, and regulates the expression of IL-12 required for Th1 responses; therefore, EV miR-21 is expected to regulate vaccine efficacy. miR-451a, another important miRNA, is abundant in serum EVs and controls the expression of cytokines, such as type I interferon and IL-6. However, levels differ among individuals and correlate with local inflammatory symptoms experienced after a seasonal flu vaccination. These findings suggest the importance of EV miRNAs as a tool to improve vaccine efficacy and also as biomarkers to predict the immune response and adverse reactions after vaccinations.


Assuntos
Vesículas Extracelulares/metabolismo , Interferon Tipo I/imunologia , Interleucina-6/imunologia , MicroRNAs/sangue , Envelhecimento/sangue , Envelhecimento/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Humanos , Interferon Tipo I/biossíntese , Subunidade p35 da Interleucina-12/biossíntese , Subunidade p35 da Interleucina-12/imunologia , Interleucina-6/biossíntese , MicroRNAs/genética , SARS-CoV-2/imunologia , Células Th1/imunologia , Vacinação
11.
Nutrients ; 13(7)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209930

RESUMO

High-density lipoproteins (HDL) maintain cholesterol homeostasis through the role they play in regulating reverse cholesterol transport (RCT), a process by which excess cholesterol is transported back to the liver for elimination. However, RCT can be altered in the presence of cardiovascular risk factors, such as aging, which contributes to the increase in the incidence of cardiovascular diseases (CVD). The present study was aimed at investigating the effect of extra virgin olive oil (EVOO) intake on the cholesterol efflux capacity (CEC) of HDL, and to elucidate on the mechanisms by which EVOO intake improves the anti-atherogenic activity of HDL. A total of 84 healthy women and men were enrolled and were distributed, according to age, into two groups: 27 young (31.81 ± 6.79 years) and 57 elderly (70.72 ± 5.6 years) subjects. The subjects in both groups were given 25 mL/d of extra virgin olive oil (EVOO) for 12 weeks. CEC was measured using J774 macrophages radiolabeled with tritiated cholesterol ((3H) cholesterol). HDL subclass distributions were analyzed using the Quantimetrix Lipoprint® system. The HDL from the elderly subjects exhibited a lower level of CEC, at 11.12% (p < 0.0001), than the HDL from the young subjects. The CEC of the elderly subjects returned to normal levels following 12 weeks of EVOO intake. An analysis of the distribution of HDL subclasses showed that HDL from the elderly subjects were composed of lower levels of large HDL (L-HDL) (p < 0.03) and higher levels of small HDL (S-HDL) (p < 0.002) compared to HDL from the young subjects. A multiple linear regression analysis revealed a positive correlation between CEC and L-HDL levels (r = 0.35 and p < 0.001) as well as an inverse correlation between CEC and S-HDL levels (r = -0.27 and p < 0.01). This correlation remained significant even when several variables, including age, sex, and BMI as well as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and glucose levels (ß = 0.28, p < 0.002, and ß = 0.24, p = 0.01) were accounted for. Consuming EVOO for 12 weeks modulated the age-related difference in the distribution of HDL subclasses by reducing the level of S-HDL and increasing the level of intermediate-HDL/large-HDL (I-HDL/L-HDL) in the elderly subjects. The age-related alteration of the CEC of HDL was due, in part, to an alteration in the distribution of HDL subclasses. A diet enriched in EVOO improved the functionality of HDL through an increase in I-HDL/L-HDL and a decrease in S-HDL.


Assuntos
Envelhecimento/sangue , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/prevenção & controle , Lipoproteínas HDL/sangue , Azeite de Oliva/administração & dosagem , Adulto , Idoso , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Voluntários Saudáveis , Humanos , Masculino
12.
Eur J Endocrinol ; 185(4): K1-K6, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34324429

RESUMO

Background: Many hormones display distinct circadian rhythms, driven by central regulators, hormonal bioavailability, and half-life. A set of 11-oxygenated C19 steroids (11-oxyandrogens) and pregnenolone sulfate (PregS) are elevated in congenital adrenal hyperplasia and other disorders, but their circadian patterns have not been characterized. Participants and methods: Peripheral blood was collected every 2 h over 24 h from healthy volunteer men (10 young, 18-30 years, and 10 older, 60-80 years). We used mass spectrometry to quantify 15 steroids, including androstenedione (A4), testosterone (T), 11ß-hydroxy- and 11-ketotestosterone (11OHT, 11KT),11ß-hydroxy- and 11-ketoandrostenedione (11OHA4, 11KA4), and 4 ∆5-steroid sulfates. Diurnal models including mesor (rhythm adjusted median), peak, and nadir concentrations, acrophase, and amplitude were computed. Results: 11OHA4 followed a rhythm similar to cortisol: acrophase 8:00 h, nadir 21:00 h and were similar in young and old men. 11KT had similar diurnal patterns, but the peak was lower in older than in young men, as was the case for A4. All four steroid sulfates were higher in young vs older men. PregS and 17-hydroxypregnenolone sulfate (17OHPregS) showed sustained elevations between 8:00 and 18:00 h, and nadirs around midnight, while DHEAS and AdiolS displayed minimal diurnal variations. All 4 11-oxyandrogens correlated tightly with cortisol (r from 0.54 for 11OHT to 0.81 for 11OHA4, P < 0.0001 for all), but very weakly with T, supporting their adrenal origin and ACTH governance. Conclusions: 11-Oxyandrogens, PregS, and 17OHPregS display distinct circadian and age variations, which should be accounted for when used as clinical biomarkers.


Assuntos
Androgênios/sangue , Ritmo Circadiano/fisiologia , Sulfatos/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Androgênios/química , Análise Química do Sangue/métodos , Voluntários Saudáveis , Humanos , Hidroxiesteroides/sangue , Cetosteroides/sangue , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Adulto Jovem
13.
Cancer Sci ; 112(10): 3962-3971, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34328684

RESUMO

Recent genome-wide studies have revealed that aging or chronic inflammation can cause clonal expansion of cells in normal tissues. Clonal hematopoiesis has been the most intensively studied form of clonal expansion in the last decade. Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related phenomenon observed in elderly individuals with no history of hematological malignancy. The most frequently mutated genes in CHIP are DNMT3A, TET2, and ASXL1, which are associated with initiation of leukemia. Importantly, CHIP has been the focus of a number of studies because it is an independent risk factor for myeloid malignancy, cardiovascular disease (CVD), and all-cause mortality. Animal models recapitulating human CHIP revealed that CHIP-associated mutations alter the number and function of hematopoietic stem and progenitor cells (HSPCs) and promote leukemic transformation. Moreover, chronic inflammation caused by infection or aging confers a fitness advantage to the CHIP-associated mutant HSPCs. Myeloid cells, such as macrophages with a CHIP-associated mutation, accelerate chronic inflammation and are associated with increased levels of inflammatory cytokines. This positive feedback loop between CHIP and chronic inflammation promotes development of atherosclerosis and chronic heart failure and thereby increases the risk for CVD. Notably, HSPCs with a CHIP-associated mutation may alter not only innate but also acquired immune cells. This suggests that CHIP is involved in the development of solid cancers or immune disorders, such as aplastic anemia. In this review, we provide an overview of recent findings on CHIP. We also discuss potential interventions for treating CHIP and preventing myeloid transformation and CVD progression.


Assuntos
Doenças Cardiovasculares/genética , Hematopoiese Clonal/genética , Mutação , Neoplasias/genética , Idoso , Envelhecimento/sangue , Animais , Aterosclerose/genética , Transformação Celular Neoplásica , Doença Crônica , Citocinas/sangue , DNA (Citosina-5-)-Metiltransferases/genética , Proteínas de Ligação a DNA/genética , Dioxigenases , Células-Tronco Hematopoéticas/fisiologia , Humanos , Inflamação/sangue , Inflamação/complicações , Inflamação/genética , Leucemia Mieloide/genética , Leucemia Mieloide/patologia , Macrófagos/patologia , Camundongos , Modelos Animais , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Fatores de Risco
14.
Sci Rep ; 11(1): 15167, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312416

RESUMO

ORIC ID: 0000-0002-3401-8191. It is unknown whether the interrelationship between diabetes and muscle loss is affected by ageing. Therefore, the serum creatinine levels, an indicator of muscle mass, were compared between older people with diabetes and those without diabetes, using a cross-sectional dataset from the Yuport Medical Checkup Center Study. We classified 6133 participants without kidney dysfunction into three age-groups: early-elderly (65-69 years), middle-elderly (70-74 years), and late-elderly (≥ 75 years). The association between diabetes and the lowest creatinine level, defined as less than or equal to the 25 percentile of serum creatinine, was evaluated in each age group, by calculating the odds ratio (OR) using logistic regression. Serum creatinine levels increased with ageing in the participants, and these trends were markedly observed in the non-diabetic group. Late-elderly people with diabetes were significantly more likely to have low creatinine levels than those without diabetes, with adjusted ORs 2.50 (95% CI 1.99-4.50) in men and 2.88 (95% CI 1.47-5.64) in women. Ageing modified the effect of their diabetes status towards a lower creatinine level (p for interactions between the diabetic status and age-groups were 0.01 in men and 0.05 in women, respectively). Ageing may thus accelerate the loss of muscle mass in people with diabetes.


Assuntos
Envelhecimento/sangue , Creatinina/sangue , Diabetes Mellitus Tipo 2/sangue , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Modelos Logísticos , Masculino , Músculo Esquelético/patologia , Razão de Chances , Sarcopenia/sangue , Sarcopenia/complicações , Sarcopenia/patologia , Tóquio
15.
Sci Rep ; 11(1): 15160, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312421

RESUMO

Mosaic loss of chromosome Y (LOY) in immune cells is a male-specific mutation associated with increased risk for morbidity and mortality. The CD99 gene, positioned in the pseudoautosomal regions of chromosomes X and Y, encodes a cell surface protein essential for several key properties of leukocytes and immune system functions. Here we used CITE-seq for simultaneous quantification of CD99 derived mRNA and cell surface CD99 protein abundance in relation to LOY in single cells. The abundance of CD99 molecules was lower on the surfaces of LOY cells compared with cells without this aneuploidy in all six types of leukocytes studied, while the abundance of CD proteins encoded by genes located on autosomal chromosomes were independent from LOY. These results connect LOY in single cells with immune related cellular properties at the protein level, providing mechanistic insight regarding disease vulnerability in men affected with mosaic chromosome Y loss in blood leukocytes.


Assuntos
Antígeno 12E7/sangue , Cromossomos Humanos Y/genética , Leucócitos/imunologia , Mosaicismo , Antígeno 12E7/deficiência , Antígeno 12E7/genética , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Envelhecimento/genética , Envelhecimento/imunologia , Doença de Alzheimer/sangue , Doença de Alzheimer/genética , Doença de Alzheimer/imunologia , Cromossomos Humanos Y/imunologia , Cromossomos Humanos Y/metabolismo , Humanos , Leucócitos/metabolismo , Masculino , Mutação , RNA Mensageiro/sangue , RNA Mensageiro/genética , Análise de Célula Única
16.
Nutrients ; 13(5)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067821

RESUMO

Biological aging, or the discrepancy between biological and chronological age of a subject (Δage), has been associated with a polyphenol-rich Mediterranean diet and represents a new, robust indicator of cardiovascular disease risk. We aimed to disentangle the relationship of dietary polyphenols and total antioxidant capacity with Δage in a cohort of Italians. A cross-sectional analysis was performed on a sub-cohort of 4592 subjects (aged ≥ 35 y; 51.8% women) from the Moli-sani Study (2005-2010). Food intake was recorded by a 188-item food-frequency questionnaire. The polyphenol antioxidant content (PAC)-score was constructed to assess the total dietary content of polyphenols. Total antioxidant capacity was measured in foods by these assays: trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP) and ferric reducing-antioxidant power (FRAP). A deep neural network, based on 36 circulating biomarkers, was used to compute biological age and the resulting Δage, which was tested as outcome in multivariable-adjusted linear regressions. Δage was inversely associated with the PAC-score (ß = -0.31; 95%CI -0.39, -0.24) but not with total antioxidant capacity of the diet. A diet rich in polyphenols, by positively contributing to deceleration of the biological aging process, may exert beneficial effects on the long-term risk of cardiovascular disease and possibly of bone health.


Assuntos
Envelhecimento/fisiologia , Antioxidantes/análise , Doenças Cardiovasculares/etiologia , Ingestão de Alimentos/fisiologia , Polifenóis/análise , Adulto , Envelhecimento/sangue , Biomarcadores/sangue , Fenômenos Cronobiológicos , Estudos de Coortes , Estudos Transversais , Dieta/efeitos adversos , Inquéritos sobre Dietas , Dieta Mediterrânea/estatística & dados numéricos , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Itália , Modelos Lineares , Masculino , Redes Neurais de Computação , Medição de Risco
17.
Aging (Albany NY) ; 13(12): 16229-16247, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34139672

RESUMO

Brain mitochondrial dysfunction and reduced testosterone levels are common features of aging in men. Although evidence suggests that the two phenomena are interrelated, it is unclear whether testosterone supplementation ameliorates mitochondrial dysfunction in the aging male brain. Here, we show that testosterone supplementation significantly alleviates exploratory behavioral deficits and oxidative damage in the substantia nigra and hippocampus of aging male rats. These effects were consistent with improved mitochondrial function, reflected by testosterone-induced increases in mitochondrial membrane potential (MMP), antioxidant enzyme (GSH-PX, catalase, and Mn-SOD) expression/activity, and mitochondrial respiratory complex activities in both brain regions. Furthermore, elevated PGC-1α, NRF-1, and TFAM expression (suggestive of enhanced mitochondrial biogenesis), increased citrate synthase activity, mtDNA copy number, and ND1, COX1, and ATP6 expression (indicative of increased mitochondrial content), as well as increased PINK1/Parkin and decreased P62 expression (suggesting mitophagy activation), were detected in the substantial nigra and hippocampus of aged male rats after testosterone supplementation. These findings suggest that testosterone supplementation may be a viable approach to ameliorating brain mitochondrial dysfunction and thus prevent or treat cognitive-behavioral deficits and neurodegenerative conditions associated with aging.


Assuntos
Envelhecimento/patologia , Encéfalo/metabolismo , Mitocôndrias/patologia , Testosterona/farmacologia , Envelhecimento/sangue , Animais , Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Transporte de Elétrons/efeitos dos fármacos , Comportamento Exploratório/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Proteínas Quinases/metabolismo , Ratos Sprague-Dawley , Substância Negra/metabolismo , Testosterona/sangue , Tirosina 3-Mono-Oxigenase/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
18.
Int J Mol Sci ; 22(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066870

RESUMO

The gut microflora is a vital component of the gastrointestinal (GI) system that regulates local and systemic immunity, inflammatory response, the digestive system, and overall health. Older people commonly suffer from inadequate nutrition or poor diets, which could potentially alter the gut microbiota. The essential amino acid (AA) tryptophan (TRP) is a vital diet component that plays a critical role in physiological stress responses, neuropsychiatric health, oxidative systems, inflammatory responses, and GI health. The present study investigates the relationship between varied TRP diets, the gut microbiome, and inflammatory responses in an aged mouse model. We fed aged mice either a TRP-deficient (0.1%), TRP-recommended (0.2%), or high-TRP (1.25%) diet for eight weeks and observed changes in the gut bacterial environment and the inflammatory responses via cytokine analysis (IL-1a, IL-6, IL-17A, and IL-27). The mice on the TRP-deficient diets showed changes in their bacterial abundance of Coriobacteriia class, Acetatifactor genus, Lachnospiraceae family, Enterococcus faecalis species, Clostridium sp genus, and Oscillibacter genus. Further, these mice showed significant increases in IL-6, IL-17A, and IL-1a and decreased IL-27 levels. These data suggest a direct association between dietary TRP content, the gut microbiota microenvironment, and inflammatory responses in aged mice models.


Assuntos
Envelhecimento/patologia , Dieta , Microbioma Gastrointestinal , Inflamação/patologia , Triptofano/deficiência , Envelhecimento/sangue , Animais , Bactérias/classificação , Biodiversidade , Citocinas/sangue , Fezes/microbiologia , Inflamação/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Filogenia
19.
Nature ; 596(7872): 417-422, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34192737

RESUMO

Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating.


Assuntos
Envelhecimento/imunologia , Vacinas contra COVID-19/imunologia , Imunidade , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Autoanticorpos/imunologia , Linfócitos B/citologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Vacinas contra COVID-19/administração & dosagem , Feminino , Pessoal de Saúde , Humanos , Imunidade/genética , Imunização Secundária , Imunoglobulina A/imunologia , Switching de Imunoglobulina , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Memória Imunológica/imunologia , Inflamação/sangue , Inflamação/imunologia , Interferon gama/imunologia , Interleucina-2/imunologia , Masculino , Pessoa de Meia-Idade , Hipermutação Somática de Imunoglobulina , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/imunologia , Vacinação , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia
20.
Sci Rep ; 11(1): 12317, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112891

RESUMO

Aging is associated with widespread physiological changes, including skeletal muscle weakening, neuron system degeneration, hair loss, and skin wrinkling. Previous studies have identified numerous molecular biomarkers involved in these changes, but their regulatory mechanisms and functional repercussions remain elusive. In this study, we conducted next-generation sequencing of DNA methylation and RNA sequencing of blood samples from 51 healthy adults between 20 and 74 years of age and identified aging-related epigenetic and transcriptomic biomarkers. We also identified candidate molecular targets that can reversely regulate the transcriptomic biomarkers of aging by reconstructing a gene regulatory network model and performing signal flow analysis. For validation, we screened public experimental data including gene expression profiles in response to thousands of chemical perturbagens. Despite insufficient data on the binding targets of perturbagens and their modes of action, curcumin, which reversely regulated the biomarkers in the experimental dataset, was found to bind and inhibit JUN, which was identified as a candidate target via signal flow analysis. Collectively, our results demonstrate the utility of a network model for integrative analysis of omics data, which can help elucidate inter-omics regulatory mechanisms and develop therapeutic strategies against aging.


Assuntos
Envelhecimento/genética , Metilação de DNA/genética , Epigenoma/genética , Transcriptoma/genética , Adulto , Idoso , Envelhecimento/sangue , Envelhecimento/patologia , Alopecia/sangue , Alopecia/genética , Alopecia/patologia , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/sangue , Debilidade Muscular/genética , Debilidade Muscular/patologia , Músculo Esquelético/patologia , Neurônios/metabolismo , Neurônios/patologia , Envelhecimento da Pele/genética
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