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1.
BMJ ; 371: m3485, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028588

RESUMO

OBJECTIVE: To evaluate the effect of five years of supervised exercise training compared with recommendations for physical activity on mortality in older adults (70-77 years). DESIGN: Randomised controlled trial. SETTING: General population of older adults in Trondheim, Norway. PARTICIPANTS: 1567 of 6966 individuals born between 1936 and 1942. INTERVENTION: Participants were randomised to two sessions weekly of high intensity interval training at about 90% of peak heart rate (HIIT, n=400), moderate intensity continuous training at about 70% of peak heart rate (MICT, n=387), or to follow the national guidelines for physical activity (n=780; control group); all for five years. MAIN OUTCOME MEASURE: All cause mortality. An exploratory hypothesis was that HIIT lowers mortality more than MICT. RESULTS: Mean age of the 1567 participants (790 women) was 72.8 (SD 2.1) years. Overall, 87.5% of participants reported to have overall good health, with 80% reporting medium or high physical activity levels at baseline. All cause mortality did not differ between the control group and combined MICT and HIIT group. When MICT and HIIT were analysed separately, with the control group as reference (observed mortality of 4.7%), an absolute risk reduction of 1.7 percentage points was observed after HIIT (hazard ratio 0.63, 95% confidence interval 0.33 to 1.20) and an absolute increased risk of 1.2 percentage points after MICT (1.24, 0.73 to 2.10). When HIIT was compared with MICT as reference group an absolute risk reduction of 2.9 percentage points was observed (0.51, 0.25 to 1.02) for all cause mortality. Control participants chose to perform more of their physical activity as HIIT than the physical activity undertaken by participants in the MICT group. This meant that the controls achieved an exercise dose at an intensity between the MICT and HIIT groups. CONCLUSION: This study suggests that combined MICT and HIIT has no effect on all cause mortality compared with recommended physical activity levels. However, we observed a lower all cause mortality trend after HIIT compared with controls and MICT. TRIAL REGISTRATION: ClinicalTrials.gov NCT01666340.


Assuntos
Envelhecimento , Exercício Físico , Frequência Cardíaca/fisiologia , Treinamento Intervalado de Alta Intensidade/métodos , Desempenho Físico Funcional , Idoso , Envelhecimento/fisiologia , Envelhecimento/psicologia , Causas de Morte , Exercício Físico/fisiologia , Exercício Físico/psicologia , Feminino , Humanos , Masculino , Mortalidade , Avaliação de Resultados em Cuidados de Saúde , Aptidão Física , Comportamento de Redução do Risco
4.
Emerg Med Clin North Am ; 38(4): 919-930, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32981626

RESUMO

The geriatric population is growing and is the largest utilizer of emergency and critical care services; the emergency clinician should be comfortable in the management of the acutely ill geriatric patient. There are important physiologic changes in geriatric patients, which alters their clinical presentation and management. Age alone should not determine the prognosis for elderly patients. Premorbid functional status, frailty, and severity of illness should be considered carefully for the geriatric population. Emergency clinicians should have honest conversations about goals of care based not only a patient's clinical presentation but also the patient's values.


Assuntos
Envelhecimento/fisiologia , Estado Terminal , Ressuscitação , Idoso , Cuidados Críticos , Tomada de Decisão Compartilhada , Delírio/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Serviço Hospitalar de Emergência , Fragilidade/classificação , Humanos , Farmacocinética , Polimedicação , Ordens quanto à Conduta (Ética Médica) , Assistência Terminal , Triagem
5.
Soins Gerontol ; 25(145): 12-13, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32988480

RESUMO

Normal aging can be defined as the result of the effects of genetic and environmental factors to which subjects are exposed throughout their lives. This process is slow and progressive and must be distinguished from disease. All organs are subject to aging in a physiological way.


Assuntos
Envelhecimento/fisiologia , Sensação/fisiologia , Idoso , Humanos
6.
Soins Gerontol ; 25(145): 18-21, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32988482

RESUMO

Compared with other sensory modalities, age-related alterations in taste and smell are less known and less investigated in clinical practice. In fact, the elderly with a loss of smell or taste may not always report it or be aware of it. In addition, the clinical evaluation of taste and smell by specific tests is rarely performed.


Assuntos
Envelhecimento/fisiologia , Transtornos do Olfato/diagnóstico , Distúrbios do Paladar/diagnóstico , Idoso , Humanos , Olfato/fisiologia , Paladar/fisiologia
7.
J Frailty Aging ; 9(4): 191-196, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32996555

RESUMO

BACKGROUND: Aging results in adaptations which may affect the control of motor units. OBJECTIVE: We sought to determine if younger and older men recruit motor units at similar force levels. DESIGN: Cross-sectional, between-subjects design. SETTING: Controlled laboratory setting. PARTICIPANTS: Twelve younger (age = 25 ± 3 years) and twelve older (age = 75 ± 8 years) men. MEASUREMENTS: Participants performed isometric contractions of the dominant knee extensors at a force level corresponding to 50% maximal voluntary contraction (MVC). Bipolar surface electromyographic (EMG) signals were detected from the vastus lateralis. A surface EMG signal decomposition algorithm was used to quantify the recruitment threshold of each motor unit, which was defined as the force level corresponding to the first firing. Recruitment thresholds were expressed in both relative (% MVC) and absolute (N) terms. To further understand age-related differences in motor unit control, we examined the mean firing rate versus recruitment threshold relationship at steady force. RESULTS: MVC force was greater in younger men (p = 0.010, d = 1.15). Older men had lower median recruitment thresholds in both absolute (p = 0.005, d = 1.29) and relative (p = 0.001, d = 1.53) terms. The absolute recruitment threshold range was larger for younger men (p = 0.020; d = 1.02), though a smaller difference was noted in relative terms (p = 0.235, d = 0.50). These findings were complimented by a generally flatter slope (p = 0.070; d = 0.78) and lower y-intercept (p = 0.009; d = 1.17) of the mean firing rate versus recruitment threshold relationship in older men. CONCLUSION: Older men tend to recruit more motor units at lower force levels. We speculate that recruitment threshold compression may be a neural adaptation serving to compensate for lower motor unit firing rates and/or denervation and subsequent re-innervation in aged muscle.


Assuntos
Envelhecimento/fisiologia , Músculo Quadríceps/fisiologia , Recrutamento Neurofisiológico/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Eletromiografia , Humanos , Contração Isométrica , Masculino , Adulto Jovem
9.
Nat Commun ; 11(1): 4549, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917889

RESUMO

Arterial macrophages have different developmental origins, but the association of macrophage ontogeny with their phenotypes and functions in adulthood is still unclear. Here, we combine macrophage fate-mapping analysis with single-cell RNA sequencing to establish their cellular identity during homeostasis, and in response to angiotensin-II (AngII)-induced arterial inflammation. Yolk sac erythro-myeloid progenitors (EMP) contribute substantially to adventitial macrophages and give rise to a defined cluster of resident immune cells with homeostatic functions that is stable in adult mice, but declines in numbers during ageing and is not replenished by bone marrow (BM)-derived macrophages. In response to AngII inflammation, increase in adventitial macrophages is driven by recruitment of BM monocytes, while EMP-derived macrophages proliferate locally and provide a distinct transcriptional response that is linked to tissue regeneration. Our findings thus contribute to the understanding of macrophage heterogeneity, and associate macrophage ontogeny with distinct functions in health and disease.


Assuntos
Artérias/citologia , Arterite/imunologia , Diferenciação Celular/fisiologia , Homeostase/fisiologia , Macrófagos/fisiologia , Envelhecimento/fisiologia , Angiotensina II/administração & dosagem , Angiotensina II/imunologia , Animais , Artérias/fisiologia , Medula Óssea/fisiologia , Transplante de Medula Óssea , Linhagem da Célula , Modelos Animais de Doenças , Feminino , Células-Tronco Hematopoéticas/fisiologia , Humanos , Masculino , Camundongos , Camundongos Transgênicos , RNA-Seq , Regeneração/fisiologia , Análise de Célula Única , Quimeras de Transplante
10.
PLoS One ; 15(8): e0236986, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866198

RESUMO

White matter hyperintensities (WMHs) are among the most commonly observed marker of cerebrovascular disease. Age is a key risk factor for WMH development. Cardiorespiratory fitness (CRF) is associated with increased vessel compliance, but it remains unknown if high CRF affects WMH volume. This study explored the effects of CRF on WMH volume in community-dwelling older adults. We further tested the possibility of an interaction between CRF and age on WMH volume. Participants were 76 adults between the ages of 59 and 77 (mean age = 65.36 years, SD = 3.92) who underwent a maximal graded exercise test and structural brain imaging. Results indicated that age was a predictor of WMH volume (beta = .32, p = .015). However, an age-by-CRF interaction was observed such that higher CRF was associated with lower WMH volume in older participants (beta = -.25, p = .040). Our findings suggest that higher levels of aerobic fitness may protect cerebrovascular health in older adults.


Assuntos
Envelhecimento/patologia , Envelhecimento/fisiologia , Aptidão Cardiorrespiratória/fisiologia , Substância Branca/diagnóstico por imagem , Idoso , Circulação Cerebrovascular/fisiologia , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/patologia , Transtornos Cerebrovasculares/fisiopatologia , Teste de Esforço , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Fatores de Risco , Substância Branca/irrigação sanguínea , Substância Branca/patologia
11.
Nat Commun ; 11(1): 4510, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908143

RESUMO

With human median lifespan extending into the 80s in many developed countries, the societal burden of age-related muscle loss (sarcopenia) is increasing. mTORC1 promotes skeletal muscle hypertrophy, but also drives organismal aging. Here, we address the question of whether mTORC1 activation or suppression is beneficial for skeletal muscle aging. We demonstrate that chronic mTORC1 inhibition with rapamycin is overwhelmingly, but not entirely, positive for aging mouse skeletal muscle, while genetic, muscle fiber-specific activation of mTORC1 is sufficient to induce molecular signatures of sarcopenia. Through integration of comprehensive physiological and extensive gene expression profiling in young and old mice, and following genetic activation or pharmacological inhibition of mTORC1, we establish the phenotypically-backed, mTORC1-focused, multi-muscle gene expression atlas, SarcoAtlas (https://sarcoatlas.scicore.unibas.ch/), as a user-friendly gene discovery tool. We uncover inter-muscle divergence in the primary drivers of sarcopenia and identify the neuromuscular junction as a focal point of mTORC1-driven muscle aging.


Assuntos
Envelhecimento/fisiologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Fibras Musculares Esqueléticas/patologia , Junção Neuromuscular/patologia , Sarcopenia/patologia , Envelhecimento/efeitos dos fármacos , Animais , Linhagem Celular , Modelos Animais de Doenças , Eletromiografia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Humanos , Microdissecção e Captura a Laser , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Camundongos , Mioblastos , Junção Neuromuscular/efeitos dos fármacos , Técnicas de Patch-Clamp , RNA-Seq , Sarcopenia/genética , Sarcopenia/fisiopatologia , Sarcopenia/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sirolimo/administração & dosagem
12.
Cien Saude Colet ; 25(9): 3459-3464, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32876247

RESUMO

This article provides information about COVID-19, contextualizing the national and international scenario, with an emphasis on the health of the elderly. Perspectives and initiatives for this risk group are presented, reinforcing the need to consider the aging process and not just age as the main marker in the approach of this population.


Assuntos
Envelhecimento/fisiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Fatores Etários , Idoso , Brasil/epidemiologia , Humanos , Pandemias , Fatores de Risco
13.
J Int Med Res ; 48(8): 300060520949039, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32865077

RESUMO

OBJECTIVE: This study was performed to investigate the clinical characteristics of patients with coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We analyzed the electronic medical records of 405 hospitalized patients with laboratory-confirmed COVID-19 in the Third Hospital of Wuhan. RESULTS: The patients' median age was 56 years, 54.1% were female, 11.4% had a history of smoking, and 10.6% had a history of drinking. All cases of COVID-19 were community-acquired. Fever (76.8%) and cough (53.3%) were the most common clinical manifestations, and circulatory system diseases were the most common comorbidities. Gastrointestinal symptoms were present in 61.2% of the patients, and 2.9% of the patients were asymptomatic. Computed tomography showed ground-glass opacities in most patients (72.6%) and consolidation in 30.9%. Lymphopenia (72.3%) and hypoproteinemia (71.6%) were observed in most patients. About 20% of patients had abnormal liver function. Patients with severe disease had significantly more prominent laboratory abnormalities, including an abnormal lymphocyte count and abnormal C-reactive protein, procalcitonin, alanine aminotransferase, aspartate aminotransferase, D-dimer, and albumin levels. CONCLUSION: SARS-CoV-2 causes a variety of severe respiratory illnesses similar to those caused by SARS-CoV-1. Older age, chronic comorbidities, and laboratory abnormalities are associated with disease severity.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Gastroenteropatias/diagnóstico , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Betacoronavirus , Proteína C-Reativa/análise , China , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/patologia , Infecções Comunitárias Adquiridas/virologia , Comorbidade , Infecções por Coronavirus/transmissão , Feminino , Gastroenteropatias/patologia , Gastroenteropatias/virologia , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/transmissão , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem
14.
PLoS Biol ; 18(9): e3000852, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32931487

RESUMO

Olfaction in most animals is mediated by neurons bearing cilia that are accessible to the environment. Olfactory sensory neurons (OSNs) in chordates usually have multiple cilia, each with a centriole at its base. OSNs differentiate from stem cells in the olfactory epithelium, and how the epithelium generates cells with many centrioles is not yet understood. We show that centrioles are amplified via centriole rosette formation in both embryonic development and turnover of the olfactory epithelium in adult mice, and rosette-bearing cells often have free centrioles in addition. Cells with amplified centrioles can go on to divide, with centrioles clustered at each pole. Additionally, we found that centrioles are amplified in immediate neuronal precursors (INPs) concomitant with elevation of mRNA for polo-like kinase 4 (Plk4) and SCL/Tal1-interrupting locus gene (Stil), key regulators of centriole duplication. These results support a model in which centriole amplification occurs during a transient state characterized by elevated Plk4 and Stil in early INP cells. These cells then go on to divide at least once to become OSNs, demonstrating that cell division with amplified centrioles, known to be tolerated in disease states, can occur as part of a normal developmental program.


Assuntos
Divisão Celular/fisiologia , Centríolos/fisiologia , Células-Tronco Neurais/citologia , Células-Tronco Neurais/fisiologia , Neurônios Receptores Olfatórios/fisiologia , Envelhecimento/fisiologia , Animais , Ciclo Celular/fisiologia , Células Cultivadas , Embrião de Mamíferos , Desenvolvimento Embrionário/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Córtex Olfatório/citologia , Córtex Olfatório/embriologia , Mucosa Olfatória/citologia , Mucosa Olfatória/embriologia , Mucosa Olfatória/ultraestrutura , Neurônios Receptores Olfatórios/citologia , Neurônios Receptores Olfatórios/ultraestrutura
15.
Nat Commun ; 11(1): 4618, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32934233

RESUMO

The identification of genes and interventions that slow or reverse aging is hampered by the lack of non-invasive metrics that can predict the life expectancy of pre-clinical models. Frailty Indices (FIs) in mice are composite measures of health that are cost-effective and non-invasive, but whether they can accurately predict health and lifespan is not known. Here, mouse FIs are scored longitudinally until death and machine learning is employed to develop two clocks. A random forest regression is trained on FI components for chronological age to generate the FRIGHT (Frailty Inferred Geriatric Health Timeline) clock, a strong predictor of chronological age. A second model is trained on remaining lifespan to generate the AFRAID (Analysis of Frailty and Death) clock, which accurately predicts life expectancy and the efficacy of a lifespan-extending intervention up to a year in advance. Adoption of these clocks should accelerate the identification of longevity genes and aging interventions.


Assuntos
Envelhecimento/fisiologia , Camundongos/fisiologia , Envelhecimento/genética , Animais , Relógios Biológicos , Feminino , Fragilidade , Humanos , Expectativa de Vida , Aprendizado de Máquina , Masculino , Camundongos/genética , Camundongos/crescimento & desenvolvimento , Camundongos Endogâmicos C57BL
16.
Eur Respir J ; 56(3)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32747391

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has elicited a swift response by the scientific community to elucidate the pathogenesis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced lung injury and develop effective therapeutics. Clinical data indicate that severe COVID-19 most commonly manifests as viral pneumonia-induced acute respiratory distress syndrome (ARDS), a clinical entity mechanistically understood best in the context of influenza A virus-induced pneumonia. Similar to influenza, advanced age has emerged as the leading host risk factor for developing severe COVID-19. In this review we connect the current understanding of the SARS-CoV-2 replication cycle and host response to the clinical presentation of COVID-19, borrowing concepts from influenza A virus-induced ARDS pathogenesis and discussing how these ideas inform our evolving understanding of COVID-19-induced ARDS. We also consider important differences between COVID-19 and influenza, mainly the protean clinical presentation and associated lymphopenia of COVID-19, the contrasting role of interferon-γ in mediating the host immune response to these viruses, and the tropism for vascular endothelial cells of SARS-CoV-2, commenting on the potential limitations of influenza as a model for COVID-19. Finally, we explore hallmarks of ageing that could explain the association between advanced age and susceptibility to severe COVID-19.


Assuntos
Envelhecimento/fisiologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Síndrome do Desconforto Respiratório do Adulto/virologia , Suscetibilidade a Doenças , Humanos , Pandemias , Replicação Viral
17.
PLoS One ; 15(8): e0236147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32797082

RESUMO

PURPOSE: A variety of visual and psychometric tests have been developed for assessing on-road driving performance and fitness to drive. The diagnostic power of a state of the art psychometric test battery (Vienna Test System) combined with a set of standard visual parameters recommended for assessing fitness to drive is investigated using an on-road driving test. The study aimed to determine whether a psychometric test battery could predict older adults' on-road driving performance. The relevance of visual standards required by law is discussed. METHODS: Vision impairment is more prevalent in later adulthood and many studies on visual and cognitive impact on driving safety and performance therefore focus on adults above 60 years of age. We therefore acquired an extensive set of driving-related visual and psychometric performance parameters in a group of elderly drivers (N = 84, median age 69, SD 6.6 years). Visual assessment included foveal acuity, perimetric field size, and dynamic aspects of peripheral vision (termed "PP") in the computer-based Vienna Test System (VTS; Schuhfried), as well as letter contrast thresholds in foveal and parafoveal vision in a separate setup. A selection of psychometric driving-aptitude tests that demonstrated the battery's capacity to predict aspects of driving performance and safety were further conducted on the VTS. Driving performance was assessed in a standardized on-road driving test. Two independent observers rated driving performance using a fixed scoring system assessing the number of driving errors in pre-defined traffic situations. In addition, globalized driving competence scores were assigned on a 6-point scale. RESULTS: The test battery performed excellent in identification of good drivers but failed in the prediction of bad driving performance. Visual performance indicators required by German law were less indicative of driving ability than psychometric assessment. Selective and divided attention turned out to be much more important for predicting fitness to drive than either visual acuity, size of the visual field, or contrast sensitivity. CONCLUSION: Predicting fitness to drive by means of visual and psychometric tests is an ambitious challenge. On the one hand sensitivity of a multi-disciplinary test-battery is too low to predict reliable driving ability in diagnostic settings which require an unambiguous interpretation of test results for individual drivers. Low sensitivity and low predictive values are incompatible with that objective. On the other hand, the results are valuable for a routine screening of fitness to drive. For that case, the assessment of attentional abilities in particular appears to be promising. Performance measures of divided and selective attention showed themselves to be the most predictive for fitness to drive in a sample pre-screened for clear visual deficits. Visual performance parameters required by law, in contrast, had no meaningful impact on driving performance, indicating a gap between mandatory regulations of state authorities and research results. Our results suggest that visual acuity tests designed for clinical diagnosis and monitoring of eye diseases should not at all be the choice for a screening of fitness to drive.


Assuntos
Acidentes de Trânsito/prevenção & controle , Atenção/fisiologia , Condução de Veículo/legislação & jurisprudência , Psicometria/métodos , Campos Visuais/fisiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Condução de Veículo/psicologia , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Referência , Testes Visuais/normas , Pessoas com Deficiência Visual/legislação & jurisprudência , Pessoas com Deficiência Visual/psicologia
18.
Life Sci ; 259: 118187, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32781061

RESUMO

AIMS: Voluntary exercise training has cardioprotective effects in humans, but the underlying mechanism is unknown. This research was done to estimate the effect of voluntary exercise training to attenuate middle-aged maturity-induced cardiac apoptosis. MATERIALS AND METHODS: The study was designed to divide 64 male mice randomly into four groups, consisting of a 9-month sedentary pre-middle-aged group (9M), 15-month sedentary middle-aged group (15M), and two exercise groups using a voluntary wheel running respectively (9M+EX, 15M+EX). After 3 months, the condition of cardiac apoptosis in different groups was measured by HE dying, TUNEL and DAPI staining, and Western Blot analysis. KEY FINDINGS: TUNEL-positive cells were increased in 15M group compared with 9M group, while decreased in 9M+EX and 15M+EX groups compared with their control groups respectively. Protein levels of AIF, Endo G, TNF-α, TNFR1, TRAF2, TRADD, Fas, FasL, FADD, activated caspase 8, 3, 9, Bax/Bcl2, Bak/BclxL, and tBid were decreased in 9M+EX and 15M+EX groups compared with their control groups respectively. The protein levels of pBad/Bad, 14-3-3, IGF1, IGFR1, pPI3K/PI3K, and pAKT/AKT were more activated in the 9M+EX and 15M+EX groups than those in their control groups respectively. Significant differences were found between 9M group and 15M group for the protein levels of TRAF2, FADD, Bax/Bcl2, tBid and pAKT/AKT. SIGNIFICANCE: Voluntary exercise training as an important lifestyle modification may prevent cardiac widely dispersed apoptosis and enhance cardiac survival at middle-aged maturity.


Assuntos
Envelhecimento/fisiologia , Apoptose/fisiologia , Coração/fisiologia , Condicionamento Físico Animal/fisiologia , Animais , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias Cardíacas/fisiologia , Músculo Esquelético/citologia , Músculo Esquelético/fisiologia , Corrida/fisiologia , Comportamento Sedentário
19.
PLoS One ; 15(8): e0236919, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845910

RESUMO

Mount Everest is an extreme environment for humans. Nevertheless, hundreds of mountaineers attempt to summit Everest each year. In a previous study we analyzed interview data for all climbers (2,211) making their first attempt on Everest during 1990-2005. Probabilities of summiting were similar for men and women, declined progressively for climbers about 40 and older, but were elevated for climbers with experience climbing in Nepal. Probabilities of dying were also similar for men and women, increased for climbers about 60 and older (especially for the few that had summited), and were independent of experience. Since 2005, many more climbers (3,620) have attempted Everest. Here our primary goal is to quantify recent patterns of success and death and to evaluate changes over time. Also, we investigate whether patterns relate to key socio-demographic covariates (age, sex, host country, prior experience). Recent climbers were more diverse both in gender (women = 14.6% vs. 9.1% for 1990-2005) and in age (climbers ≥ 40 = 54.1% vs. 38.7%). Strikingly, recent climbers of both sexes were almost twice as likely to summit-and slightly less likely to die-than were comparable climbers in the previous survey. Temporal shifts may reflect improved weather forecasting, installation of fixed ropes on much of the route, and accumulative logistic equipment and experience. We add two new analyses. The probability of dying from illness or non-traumas (e.g., high-altitude illness, hypothermia), relative to dying from falling or from 'objective hazards' (avalanche, rock or ice fall), increased marginally with age. Recent crowding during summit bids was four-fold greater than in the prior sample, but surprisingly crowding has no evident effect on success or death during summit bids. Our results inform prospective climbers as to their current odds of success and of death, as well as inform governments of Nepal and China of the safety consequences and economic impacts of periodically debated restrictions based on climber age and experience.


Assuntos
Envelhecimento/fisiologia , Mortalidade , Montanhismo/fisiologia , Montanhismo/estatística & dados numéricos , Caracteres Sexuais , Adulto , Doença da Altitude/fisiopatologia , Desempenho Atlético , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos
20.
Nat Commun ; 11(1): 4289, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855397

RESUMO

Older organs represent an untapped potential to close the gap between demand and supply in organ transplantation but are associated with age-specific responses to injury and increased immunogenicity, thereby aggravating transplant outcomes. Here we show that cell-free mitochondrial DNA (cf-mt-DNA) released by senescent cells accumulates with aging and augments immunogenicity. Ischemia reperfusion injury induces a systemic increase of cf-mt-DNA that promotes dendritic cell-mediated, age-specific inflammatory responses. Comparable events are observed clinically, with the levels of cf-mt-DNA elevated in older deceased organ donors, and with the isolated cf-mt-DNA capable of activating human dendritic cells. In experimental models, treatment of old donor animals with senolytics clear senescent cells and diminish cf-mt-DNA release, thereby dampening age-specific immune responses and prolonging the survival of old cardiac allografts comparable to young donor organs. Collectively, we identify accumulating cf-mt-DNA as a key factor in inflamm-aging and present senolytics as a potential approach to improve transplant outcomes and availability.


Assuntos
DNA Mitocondrial/efeitos adversos , Dasatinibe/farmacologia , Inflamação/prevenção & controle , Transplante de Órgãos/métodos , Quercetina/farmacologia , Adulto , Envelhecimento/fisiologia , Animais , Diferenciação Celular , Ácidos Nucleicos Livres , Senescência Celular/efeitos dos fármacos , Senescência Celular/fisiologia , Citocinas/metabolismo , DNA Mitocondrial/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/fisiologia , Transplante de Coração/efeitos adversos , Transplante de Coração/métodos , Humanos , Inflamação/etiologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , Transplante de Órgãos/efeitos adversos , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/imunologia , Doadores de Tecidos
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