Genes related to maintenance of autophagy and successful aging / Genes relacionados à manutenção da autofagia e envelhecimento bem-sucedido

ABSTRACT Considering aging as a phenomenon in which there is a decline in essential processes for cell survival, we investigated the autophagic and proteasome pathways in three different groups: young, older and oldest old male adults. The expression profile of autophagic pathway-related genes was carried out in peripheral blood, and the proteasome quantification was performed in plasma. No significant changes were found in plasma proteasome concentrations or in correlations between proteasome concentrations and ages. However, some autophagy- and/or apoptosis-related genes were differentially expressed. In addition, the network and enrichment analysis showed an interaction between four of the five differentially expressed genes and an association of these genes with the transcriptional process. Considering that the oldest old individuals maintained both the expression of genes linked to the autophagic machinery, and the proteasome levels, when compared with the older group, we concluded that these factors could be considered crucial for successful aging.

RESUMO Considerando o envelhecimento como um fenômeno em que há um declínio nos processos essenciais a sobrevivência celular, investigamos as vias autofágica e proteassômica em três grupos: jovens, idosos e longevos. O perfil de expressão dos genes relacionados à via autofágica foi analisado em sangue periférico, e a quantificação do proteassoma realizada em plasma. Não foram encontradas alterações significativas nas concentrações plasmáticas de proteassoma ou na correlação entre as concentrações de proteassoma e as idades. No entanto, alguns genes relacionados a autofagia e / ou apoptose foram expressos diferencialmente. Além disso, as análises de rede e de enriquecimento mostraram uma interação entre quatro dos cinco genes diferencialmente expressos e a associação desses ao processo transcricional. Considerando que os indivíduos longevos mantiveram tanto a expressão de genes ligados à maquinaria autofágica, quanto os níveis de proteassoma quando comparados aos idosos, concluímos que esses fatores poderiam ser considerados cruciais para o envelhecimento bem-sucedido.

Ventricular arrhythmias in Chagas disease

Sudden death is one of the most characteristic phenomena of Chagas disease, and approximately one-third of infected patients develop life-threatening heart disease, including malignant ventricular arrhythmias. Fibrotic lesions secondary to chronic cardiomyopathy produce arrhythmogenic substrates that lead to the appearance and maintenance of ventricular arrhythmias. The objective of this study is to discuss the main clinical and epidemiological aspects of ventricular arrhythmias in Chagas disease, the specific workups and treatments for these abnormalities, and the breakthroughs needed to determine a more effective approach to these arrhythmias. A literature review was performed via a search of the PubMed database from 1965 to May 31, 2014 for studies of patients with Chagas disease. Clinical management of patients with chronic Chagas disease begins with proper clinical stratification and the identification of individuals at a higher risk of sudden cardiac death. Once a patient develops malignant ventricular arrhythmia, the therapeutic approach aims to prevent the recurrence of arrhythmias and sudden cardiac death by the use of implantable cardioverter defibrillators, antiarrhythmic drugs, or both. In select cases, invasive ablation of the reentrant circuit causing tachycardia may be useful. Ventricular arrhythmias are important manifestations of Chagas cardiomyopathy. This review highlights the absence of high-quality evidence regarding the treatment of ventricular arrhythmias in Chagas disease. Recognizing high-risk patients who require specific therapies, especially invasive procedures such as the implantation of cardioverter defibrillators and ablative approaches, is a major challenge in clinical practice.

Análise genética de características de fertilidade, de crescimento e de produtividade em vacas da raça Canchim / Genetic analysis of fertility, growth and productivity traits of Canchim cows

O objetivo deste trabalho foi estimar herdabilidades e correlações genéticas para idade (IPP), peso (PPP) e escore da condição corporal (EPP) ao primeiro parto, tempo de permanência no rebanho (TPR), número (ND10) e quilograma (QD10) de bezerros desmamados em até dez anos de idade, número (NDT) e quilograma (QDT) de bezerros desmamados durante a permanência no rebanho, quilograma de bezerros desmamados por ano de permanência no rebanho (QTPR), peso adulto (PAD) e parâmetros A e k da curva de crescimento de Bertalanffy de fêmeas de um rebanho da raça Canchim. As distribuições a posteriori dos componentes de (co)variância foram obtidas por inferência bayesiana, em análises bicaráter de IPP, PPP e EPP com as outras características. Os modelos estatísticos incluíram os efeitos aleatórios genético aditivo direto e residual e os efeitos fixos de ano e mês de nascimento ou do parto e idade da vaca ao parto, dependendo da característica. As médias a posteriori das herdabilidades foram 0,12 (IPP); 0,51 (PPP); 0,36 (EPP); 0,22 (TPR); 0,24 (ND10); 0,24 (QD10); 0,25 (NDT); 0,23 (QDT); 0,31 (QTPR); 0,56 (PAD); 0,60 (A) e 0,54 (k), indicando que as características possuem variação genética aditiva suficiente para apresentar boa resposta à seleção massal, com exceção de IPP. As correlações genéticas de TPR (-0,35; -0,23 e -0,02), ND10 (-0,33; -0,40 e -0,02), QD10 (-0,47; -0,29 e 0,00), NDT (-0,43; -0,41 e -0,02), QDT (-0,46; -0,28 e 0,00), QTPR (-0,52; -0,35 e 0,00), PAD (0,19; 0,86 e 0,40), A (0,07; 0,09 e -0,18) e k (-0,21; 0,08 e 0,04) com IPP, PPP e EPP, respectivamente, sugerem que a seleção para reduzir a IPP deve melhorar a longevidade e as características de produtividade das fêmeas; porém, o aumento do PPP poderá prejudicá-las...

The objective of this work was to estimate heritabilities and genetic correlations for age at first calving (AFC), weight at first calving (WFC), body condition score at first calving (SFC), culling age (DIH, days in herd), number (NW10) and kilograms (KW10) of calves weaned up to ten years of age, total number (TNW) and total kilograms (TQW) of calves weaned during herd life, kilograms of calves weaned per year in herd (KYH), adult body weight (ABW) and parameters A and k of the Bertalanffy growth curve of females of a Canchim (5/8 Charolais + 3/8 Zebu) beef cattle herd. The variance and covariance components were obtained by two-trait analyses of AFC, WFC and SFC with the other production traits, using the bayesian inference with statistical models that included the additive direct and residual random effects, and the fixed effects of year and month of birth or of calving and calving age, depending on the trait. The posteriori means of the heritability estimates were 0.12 (AFC), 0.51 (WFC), 0.36 (SFC), 0.22 (DIH), 0.24 (NW10), 0.24 (KW10), 0.25 (TNW), 0.23 (TKW), 0.31 (KYH), 0.56 (ABW), 0.60 (A) and 0.54 (k), indicating that these traits have enough additive genetic variation to show response to mass selection. The genetic correlations for DIH (-0.35, -0.23 and -0.02), NW10 (-0.33, -0.40 and -0.02), KW10 (-0.47, -0.29 and 0.00), TNW (-0.43, -0.41 and -0.02), TKW (-0.46, -0.28 and 0.00), KYH (-0.52, -0.35 and 0.00), ABW (0.19, 0.86 and 0.40), A (0.07, 0.09 and -0.18) and k (-0.21, 0.08 and 0.04) with AFC, WFC and SFC, suggest that selection to reduce age at first calving should improve longevity and productivity traits of females, but the increase in body weight at first calving should reduce these traits...

Y también la vejez tiene su historia / The old age has its history too

Desde el principio de los tiempos, la humanidad ha crecido, en términos generales, en distintas etapas: Infancia, Niñez, Adolescencia, Juventud, Edad adulta y Senectud.Lo interesante es que la longevidad, se ha convertido en nuestro siglo, en el destino de la mayoría, al menos en los países desarrollados. Vivir viejo está bien, pero lo importante es vivir plenamente disfrutando de esa etapa.El trabajo es una mirada histórica desde la lejana antigüedad hasta el presente, analizando los criterios en diferentes culturas, referidos a la magnífica legión de los viejos en aumento progresivo

Since time began mankind has grown, in general terms, in different stages: Infancy; Childhood, Adolescence, Youth, Adulthood and Old Age.The interesting point is that, in our century, longevity has become most people’s fate, at least in developed countries. Living old is good, but the important issue is living wholly, enjoying this stage. This work is a historical outlook from the ancient times up to the present, analyzing criteria in different cultures which refer to the marvelous and continuously increasing legion of the old

Electrolyzed-reduced water increases resistance to oxidative stress, fertility, and lifespan via insulin/IGF-1-like signal in C. elegans

Electrolyzed-reduced water (ERW) scavenges reactive oxygen species and is a powerful anti-oxidant. A positive correlation between oxidative stress and aging has been proved in many model organisms. In Caenorhabditis elegans, many long-lived mutants showed reduced fertility as a trade off against longevity phenotype. We aimed to study the effect of ERW on oxidative stress, fertility and lifespan of C. elegans. We also investigated the genetic pathway involved in the effect of ERW on resistance to oxidative stress and lifespan. We compared lifespan and fertility of worms in media prepared with distilled water and ERW. ERW significantly extended lifespan and increased the number of progeny produced. Then the effect of ERW on resistance to oxidative stress and lifespan of long-lived mutants was determined. ERW increased resistance to oxidative stress and lifespan of eat-2, a genetic model of dietary restriction, but had no effect on those of age-1, which is involved in insulin/insulin-like growth factor (IGF)-1-like signal. In addition, knockdown of daf-16, the downstream mediator of insulin/IGF-1-like signal, completely prevented the effect of ERW on lifespan. These findings suggest that ERW can extend lifespan without accompanying reduced fertility and modulate resistance to oxidative stress and lifespan via insulin/IGF-1-like signal in C. elegans.

Caracterización clínica y genética de los adultos mayores centenarios del municipio Morón / Clinical and genetic characterization of centenarian greater adults from Morón municipality

Se realizó un estudio observacional descriptivo en el municipio Morón con el objetivo de caracterizar los adultos mayores centenarios desde el punto de vista clínico; se trabajó con el universo que fue de 10 pacientes donde predominó la edad de 100 a 104 años, sexo femenino, color de la piel blanca; entre los hábitos tóxicos sobresalió el consumo del café; la enfermedad crónica que prevaleció fue la hipertensión arterial; la mayoría de los longevos realizaron actividad física durante toda su vida y su alimentación fue buena; un mayor por ciento no tuvo riesgo de reacciones a drogas; en la evaluación funcional se analizaron las alteraciones en actividades básicas de la vida diaria, así como en las actividades instrumentadas. Todos los centenarios tenían antecedentes familiares de longevidad. Se realizó el árbol genealógico más representativo, que coincidió con el centenario más longevo del municipio Morón.

A descriptive observational study was carried out in Morón with the aim to characterize the centenarian greater adults from the clinical point of view; the universe was constituted by 10 patients predominating from 100 to 104 years, feminine sex, white skin, within the toxic habits of the coffee consumption; the chronic disease that prevailed was the arterial hypertension; most of the longevous made physical activity during their life and their feeding was good, a greater percent did not have risk of reactions to drugs. In the functional assessment prevailed instrumented alterations on daily life; in the affective sphere a great number of centenarians didn´t have alterations; all of them had longevity familiar antecedents. The genealogical tree more representative was carried out that agreed with the most longevous centenary from Morón municipality.

Candidate gene polymorphisms for diabetes mellitus, cardiovascular disease and cancer are associated with longevity in Koreans

Long-lived people may have a unique genetic makeup that makes them more resistant than the general population to prevalent age-related diseases; however, not much is known about genes involved in the longevity. To identify susceptibility variants controlling longevity, we performed a high-throughput candidate gene study using 137 Koreans over 90 yr old and 213 young healthy Koreans. We evaluated 463 informative markers located in 176 candidate genes mostly for diabetes mellitus, cardiovascular disease and cancer under five genetic models. We estimated the odds ratios for each allele, genotype, haplotype, and gene-gene interaction using logistic regression analysis. Associations between 13 genes and longevity were detected at a P-value less than 0.01. Particularly, the rs671 (A) allele of the aldehyde dehydrogenase 2 family (mitochondrial) (ALDH2) gene was associated with longevity only in men (OR 2.11, P = 0.008). Four genes, proprotein convertase subtilisin/kexin type 1 (PCSK1, P = 0.008), epidermal growth factor receptor (EGFR, P = 0.003), paired box 4 (PAX4, P = 0.008), and V-yes-1 Yamaguchi sarcoma viral related oncogene homolog (LYN, P = 0.002) consistently yielded statistical evidence for association with longevity. The findings of the current study may provide a starting point for future studies to unravel genetic factors controlling longevity in Koreans.

The polymorphism of the serotonin-2A receptor T102C is associated with age

Epidemiological investigations suggest that T102C polymorphism of gene 5-HT2A may be associated with mean life span because diseases and behaviors related to this polymorphism, such as schizophrenia, suicide, aggression, and addiction, may potentially shorten mean life span. A sample of 687 individuals without previous neuropsychiatric disease was genotyped and separated into 3 groups according to their gender and age: 14-45 years old, 46-64 years old and 65-100 years old. Molecular genotyping was performed using the technique of polymerase chain reaction followed by restriction fragment length polymorphism using HpaII restriction enzyme. 5-HT2A genotype frequencies were: TT = 21.5 percent (148), CC = 16.6 percent (114) and TC = 61.9 percent (425) and allele frequencies were T = 52.5 percent and C = 46.5 percent. Significant differences were found between mean age of the TT genotype carriers (60.27 ± 12.60 years) and TC genotype carriers (56.80 ± 13.18 years) of T102C polymorphism of gene 5-HT2A (P = 0.026) as well as the age groups (P = 0.012). Carriers of genotype TT were older than the other two genotypes, whereas carriers of genotype CC had an intermediate age compared with TT and CC subjects. The present results demonstrate an association between T102C polymorphism of gene 5-HT2A and age. Our results suggest that T102C polymorphism of gene 5-HT2A is associated with mean life span, and thus this gene becomes a possible candidate for the group of adaptive genes to meat consumption proposed in the literature. Further studies should be conducted in order to elucidate this association.

The effect of simulated censored data on estimates of heritability of longevity in the Thoroughbred racing industry

We examined the impact of censored data on estimates of heritability of longevity. Longevity, defined as the length of productive racing life of an individual, is influenced by many factors. A simulated data set, modelled on the Irish Thoroughbred industry, was used to estimate heritabilities of longevity. Several scenarios representing various levels of censoring of performance data were created. The heritability of longevity was estimated for each scenario and compared to the estimated heritability of 0.120 for the complete data set. It was found that the estimates of heritability (0.107, 0.106, 0.082) were biased downwards with (10, 20, and 25%, respectively) censoring of data from poor-performing animals. We found that for a complete reporting it is necessary to reduce bias in the estimation of heritability of longevity.

Ageing, gerontogenes, and hormesis.

Evolutionary theories of ageing and longevity argue against the existence of specific genes that cause ageing. However, genes whose altered activity influences ageing and longevity, may be termed gerontogenes. Several putative gerontogenes have been identified in various ageing systems, including the Drosophila, budding yeast, nematodes and cells in culture. Since ageing is characterized by a progressive failure of maintenance and repair, it is reasoned that genes involved in homeodynamic repair pathways are the most likely candidate gerontogenes. A promising approach for the identification of critical gerontogenic processes is hormesis-like positive effects of stress. Stimulation of various repair pathways by mild stress has significant effects on delaying the onset of various age-associated alterations in cells, tissues and organisms.

Mejoramiento genético de características de conformación en ganado Holstein / Genetic improvement of conformation traits in Holstein cattle

Actualmente se considera que en el ganado lechero los rasgos de conformación están asociados a mayor vida de hato y a una mayor producción de leche de por vida. El objetivo de este trabajo es presentar los resultados de las principales investigaciones que han analizado la relación entre los rasgos de conformación y productivos en ganado Holstein. Se presenta un resumen de los principales estimadores de parámetros genéticos generados por diversos autores. Además, se analizan las evaluaciones genéticas realizadas en México y se plantean algunas perspectivas del futuro mejoramiento genético para rasgos de conformación del ganado Holstein Mexicano

Estudios de la asociación genética de la apolipoproteína E con la longevidad, el deterioro cognoscitivo y la demencia / The association of apolipoprotein E with longevity, cognitive impairment and dementia

Las investigaciones recientes sugieren que el envejecimiento y el deterioro cognoscitivo son resultado de los cambios en la información a nivel molecular. Así, se han formulado teorías genéticas que han intentado explicar la pérdida neuronal que se produce con la edad. Sin embargo, un hallazgo reciente ha abierto un nuevo camino en esta área. Se trata de la asociación que hay entre el genotipo molecular de la apolipoproteína E (ApoE) y el aumento del riesgo de padecer demencia senil de tipo Alzheimer. La ApoE es una glicoproteína producida por una variedad de tejidos en el organismo, particularmente en el hígado y el cerebro, que interviene en el transporte y metabolismo de los lípidos, coordinando la movilización y redistribución del colesterol en los procesos de reparación de las membranas neuronales. Se ha estudiado cuál es su papel en el metabolismo de las lipoproteínas en el sistema nervioso y su importancia en la plasticidad cerebral. La presente revisión tiene por objeto describir la función de la ApoE en el metabolismo de los lípidos y por medio de su efecto biológico, profundizar en la relación de su genotipo molecular con la longevidad, el deterioro cognoscitivo y la demencia

Factors affecting longevity.

In view of the fact that hypercholesterolemia occurs in 31.4%, hypertension in 16.7% and the smoking rate is 58.8% in males (Table 8), risk factors are not low. Despite this, we Japanese preserve a leading position regarding longevity. I hope that I have provided some evidence supporting the proposal that apparently not only a low fat intake but other factors including genetic make up and a relatively high antioxidant intake contribute to our longevity.