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1.
Acta Cir Bras ; 34(8): e201900803, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618403

RESUMO

PURPOSE: To evaluate changes in the quantity of elastic fibers in the corpora cavernosa of rats during the natural aging process, and to assess the degree of this change by determining volumetric density (Vv) at different ages via stereological analysis. METHODS: Forty-eight rats, raised under similar conditions, were subjected to the natural aging process and divided into four groups (G1 to G4), according to age at the time of penectomy (6, 9, 12, and 24 months, respectively). Histological sections of the middle segment of the penis were stained with Weigert's resorcin-fuchsin, and the volumetric density (Vv) of elastic fibers of the corpora cavernosa were determined via stereological analysis. RESULTS: There were no statistically significant differences in Vv among groups G1, G2, and G3. These three groups were therefore considered as a single group. The mean Vv of this group showed a statistically significant reduction compared to that of G4 (0.16 vs. 0.11, p<0.05). CONCLUSION: Natural aging in rats was responsible for a reduction in volumetric density of elastic fibers of the corpora cavernosa (approximately 30% decrease in Vv) during senescence.


Assuntos
Envelhecimento/fisiologia , Tecido Elástico/ultraestrutura , Células Endoteliais/fisiologia , Pênis/citologia , Envelhecimento/patologia , Animais , Colágeno/fisiologia , Colágeno/ultraestrutura , Tecido Elástico/patologia , Tecido Elástico/fisiologia , Disfunção Erétil/fisiopatologia , Masculino , Modelos Animais , Pênis/fisiologia , Ratos , Ratos Wistar
2.
Prague Med Rep ; 120(2-3): 84-94, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31586507

RESUMO

Ageing is associated with the accumulation of damage to all the macromolecules within and outside cells leading to progressively more cellular and tissue defects and resulting in age-related frailty, disability and disease. As a result of the aging process the bone deteriorates in composition, structure and function. Age-related musculoskeletal losses are a major public health burden because they can cause physical disability and increased mortality. We tried to find out on a small set of old women, without risk factors for osteoporosis, what caused them the loss of bone minerals. All 492 women had just only one risk factor - the old age. Laboratory findings have shown a decreased serum C telopeptide and low serum alkaline phosphatase circulating markers, used to quantify bone resorption and formation, and very low level of vitamin D. Very low level of vitamin D that disrupted calcium absorption through the intestine, and decreased calcemia increased parathyroid hormone levels with resulting bone effect. The manifestation of physiological aging is worsening eyesight, peripheral neuropathy, depression, worsening of physical condition, skin aging, sarcopenia and bone mineral loss. Senile osteoporosis, which is not caused by known risk factors for osteoporosis, does not appear to be a separate disease, but is part of the physiological process of aging. Treatment of senile osteoporosis should be focused on the control of secondary hyperparathyroidism by administration of vitamin D and calcium. The risk of fractures in the advanced age is determined by a large number of factors ranging from hazards in the home environment to frailty and poor balance.


Assuntos
Envelhecimento/sangue , Envelhecimento/patologia , Fosfatase Alcalina/sangue , Densidade Óssea , Cálcio/metabolismo , Colágeno Tipo I/sangue , Feminino , Humanos , Osteogênese , Osteoporose/sangue , Hormônio Paratireóideo/sangue , Peptídeos/sangue , Vitamina D/sangue
3.
Wiad Lek ; 72(9 cz 1): 1655-1659, 2019.
Artigo em Polonês | MEDLINE | ID: mdl-31586978

RESUMO

In the elderly, there is a reduction of the efficiency in many organs, including muscles. The weight, strength and power reduction of elderly muscles is defined as sarcopenia. The pathophysiology of sarcopenia is multifactorial, it can be influenced by intrinsic and extrinsic factors such as reduced caloric intake, denervation of muscle fibers - in the course of various neurodegenerative diseases, intracellular oxidative stress, hormonal disorders and others. The European Working Group on sarcopenia in the elderly published diagnostic criteria for sarcopenia in 2010, which should increase the recognition of this disease and speed up the treatment process. The best-confirmed methods of treatment of sarcopenia are nutritional hyperalimentation and resistance training. Pharmacological agents, i.e. selective androgen receptor modulators, and myostatin inhibitors are not sufficiently tested to be approved, by the FDA as a treatment regimen of sarcopenia.


Assuntos
Envelhecimento/patologia , Sarcopenia/diagnóstico , Idoso , Ingestão de Energia , Humanos , Estresse Oxidativo
5.
Nat Neurosci ; 22(10): 1617-1623, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31551603

RESUMO

Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.


Assuntos
Envelhecimento/genética , Envelhecimento/patologia , Encefalopatias/diagnóstico por imagem , Encefalopatias/genética , Encéfalo/crescimento & desenvolvimento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Estudo de Associação Genômica Ampla , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/genética , Pessoa de Meia-Idade , Testes Neuropsicológicos , Esquizofrenia/genética , Esquizofrenia/patologia , Caracteres Sexuais , Adulto Jovem
6.
Adv Exp Med Biol ; 1178: 227-245, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31493230

RESUMO

The cytoskeleton consists of filamentous protein polymers that form organized structures, contributing to a multitude of cell life aspects. It includes three types of polymers: the actin microfilaments, the microtubules and the intermediate filaments. Decades of research have implicated the cytoskeleton in processes that regulate cellular and organismal aging, as well as neurodegeneration associated with injury or neurodegenerative disease, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, or Charcot Marie Tooth disease. Here, we provide a brief overview of cytoskeletal structure and function, and discuss experimental evidence linking cytoskeletal function and dynamics with aging and neurodegeneration.


Assuntos
Envelhecimento , Citoesqueleto , Doenças Neurodegenerativas , Envelhecimento/patologia , Citoesqueleto/química , Citoesqueleto/metabolismo , Humanos , Doenças Neurodegenerativas/patologia
7.
Vasc Health Risk Manag ; 15: 259-281, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496716

RESUMO

Background: Small vessels have the pivotal role for the brain's autoregulation. The arteriosclerosis-dependent alteration of the brain perfusion is one of the major determinants in small vessel disease. Endothelium distress can potentiate the flow dysregulation and lead to subcortical vascular dementia (sVAD). sVAD increases morbidity and disability. Epidemiological studies have shown that sVAD shares with cerebrovascular disease most of the common risk factors. The molecular basis of this pathology remains controversial. Purpose: To detect the possible mechanisms between small vessel disease and sVAD, giving a broad vision on the topic, including pathological aspects, clinical and laboratory findings, metabolic process and cholinergic dysfunction. Methods: We searched MEDLINE using different search terms ("vascular dementia", "subcortical vascular dementia", "small vessel disease", "cholinergic afferents", etc). Publications were selected from the past 20 years. Searches were extended to Embase, Cochrane Library, and LILIACS databases. All searches were done from January 1, 1998 up to January 31, 2018. Results: A total of 560 studies showed up, and appropriate studies were included. Associations between traditional vascular risk factors have been isolated. We remarked that SVD and white matter abnormalities are seen frequently with aging and also that vascular and endothelium changes are related with age; the changes can be accelerated by different vascular risk factors. Vascular function changes can be heavily influenced by genetic and epigenetic factors. Conclusion: Small vessel disease and the related dementia are two pathologies that deserve attention for their relevance and impact in clinical practice. Hypertension might be a historical problem for SVD and SVAD, but low pressure might be even more dangerous; CBF regional selective decrease seems to be a critical factor for small vessel disease-related dementia. In those patients, endothelium damage is a super-imposed condition. Several issues are still debatable, and more research is needed.


Assuntos
Envelhecimento , Artérias Cerebrais/inervação , Doenças de Pequenos Vasos Cerebrais/fisiopatologia , Circulação Cerebrovascular , Fibras Colinérgicas , Demência Vascular/fisiopatologia , Acoplamento Neurovascular , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Animais , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Doenças de Pequenos Vasos Cerebrais/patologia , Fibras Colinérgicas/patologia , Demência Vascular/epidemiologia , Demência Vascular/patologia , Progressão da Doença , Homeostase , Humanos , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Fatores de Risco
8.
Nat Med ; 25(9): 1385-1389, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501613

RESUMO

The worldwide obesity epidemic1 makes it important to understand how lipid turnover (the capacity to store and remove lipids) regulates adipose tissue mass. Cross-sectional studies have shown that excess body fat is associated with decreased adipose lipid removal rates2,3. Whether lipid turnover is constant over the life span or changes during long-term weight increase or loss is unknown. We determined the turnover of fat cell lipids in adults followed for up to 16 years, by measuring the incorporation of nuclear bomb test-derived 14C in adipose tissue triglycerides. Lipid removal rate decreases during aging, with a failure to reciprocally adjust the rate of lipid uptake resulting in weight gain. Substantial weight loss is not driven by changes in lipid removal but by the rate of lipid uptake in adipose tissue. Furthermore, individuals with a low baseline lipid removal rate are more likely to remain weight-stable after weight loss. Therefore, lipid turnover adaptation might be important for maintaining pronounced weight loss. Together these findings identify adipose lipid turnover as an important factor for the long-term development of overweight/obesity and weight loss maintenance in humans.


Assuntos
Envelhecimento/metabolismo , Peso Corporal/genética , Obesidade/metabolismo , Ganho de Peso/genética , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Adolescente , Adulto , Envelhecimento/genética , Envelhecimento/patologia , Peso Corporal/fisiologia , Radioisótopos de Carbono/química , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Metabolismo dos Lipídeos/genética , Lipídeos/genética , Masculino , Obesidade/genética , Obesidade/patologia , Sobrepeso/genética , Sobrepeso/metabolismo , Sobrepeso/patologia , Triglicerídeos/metabolismo , Perda de Peso/genética
9.
Nature ; 572(7767): 62-66, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31341278

RESUMO

Recent work has shown that meningeal lymphatic vessels (mLVs), mainly in the dorsal part of the skull, are involved in the clearance of cerebrospinal fluid (CSF), but the precise route of CSF drainage is still unknown. Here we reveal the importance of mLVs in the basal part of the skull for this process by visualizing their distinct anatomical location and characterizing their specialized morphological features, which facilitate the uptake and drainage of CSF. Unlike dorsal mLVs, basal mLVs have lymphatic valves and capillaries located adjacent to the subarachnoid space in mice. We also show that basal mLVs are hotspots for the clearance of CSF macromolecules and that both mLV integrity and CSF drainage are impaired with ageing. Our findings should increase the understanding of how mLVs contribute to the neuropathophysiological processes that are associated with ageing.


Assuntos
Líquido Cefalorraquidiano/metabolismo , Sistema Glinfático/anatomia & histologia , Sistema Glinfático/fisiologia , Vasos Linfáticos/anatomia & histologia , Vasos Linfáticos/fisiologia , Base do Crânio/anatomia & histologia , Envelhecimento/patologia , Envelhecimento/fisiologia , Animais , Células Endoteliais/citologia , Células Endoteliais/patologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Sistema Glinfático/citologia , Sistema Glinfático/patologia , Proteínas de Homeodomínio/metabolismo , Vasos Linfáticos/citologia , Vasos Linfáticos/patologia , Linfedema/metabolismo , Linfedema/patologia , Imagem por Ressonância Magnética , Masculino , Camundongos , Espaço Subaracnóideo/anatomia & histologia , Fatores de Tempo , Proteínas Supressoras de Tumor/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo
10.
High Blood Press Cardiovasc Prev ; 26(4): 321-329, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31325087

RESUMO

Cardiovascular disease (CVD) remains the leading cause of morbility and mortality worldwide. The identification of common cardiovascular risk factors has led to the development of effective treatments that enabled a significant reduction of the global cardiovascular disease burden. However, a significant proportion of cardiovascular risk remains unexplained by these risk factors leaving many individuals at risk of cardiovascular events despite good control of the risk factors. Recent randomized clinical trials and Mendelian randomization studies have suggested that inflammation explains a significant proportion of the residual cardiovascular risk in subjects with good control of risk factors. An accelerated process of vascular ageing is increasingly recognized as a potential mechanism by which inflammation might increase the risk of CVD. In turn, cellular ageing represents an important source of inflammation within the vascular wall, potentially creating a vicious cycle that might promote progression of atherosclerosis, independently from the individual cardiovascular risk factor burden. In this review, we summarise current evidence suggesting a role for biological ageing in CVD and how inflammation might act as a key mediator of this association.


Assuntos
Envelhecimento/metabolismo , Doenças Cardiovasculares/metabolismo , Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Telômero/metabolismo , Fatores Etários , Envelhecimento/genética , Envelhecimento/patologia , Animais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Senescência Celular , Humanos , Inflamação/genética , Inflamação/patologia , Inflamação/fisiopatologia , Medição de Risco , Fatores de Risco , Transdução de Sinais , Telômero/genética , Telômero/patologia , Homeostase do Telômero , Encurtamento do Telômero , Fatores de Tempo
11.
Int J Mol Sci ; 20(13)2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31261912

RESUMO

The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is one of the most important oxidative stress regulator in the human body. Once Nrf2 regulates the expression of a large number of cytoprotective genes, it plays a crucial role in the prevention of several diseases, including age-related disorders. However, the involvement of Nrf2 on these conditions is complex and needs to be clarified. Here, a brief compilation of the Nrf2 enrollment in the pathophysiology of the most common age-related diseases and bring insights for future research on the Nrf2 pathway is described. This review shows a controversial response of this transcriptional factor on the presented diseases. This reinforces the necessity of more studies to investigate modulation strategies for Nrf2, making it a possible therapeutic target in the treatment of age-related disorders.


Assuntos
Envelhecimento/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Envelhecimento/metabolismo , Doença de Alzheimer/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hipertensão/metabolismo , Fator 2 Relacionado a NF-E2/genética , Osteoporose/metabolismo , Doença de Parkinson/metabolismo
12.
Neuropsychology ; 33(5): 642-657, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31246073

RESUMO

OBJECTIVE: Mean speed of responding is the most commonly used measure in the assessment of reaction time (RT). An alternative measure is intraindividual variability (IIV): the inconsistency of responding across multiple trials of a test. IIV has been suggested as an important indicator of central nervous system functioning, and as such, there has been increasing interest in the associations between IIV and brain imaging metrics. Results however, have been inconsistent. The present seeks to provide a comprehensive evaluation of the associations between a variety of measures of brain white matter integrity and individual differences in choice RT (CRT) IIV. METHOD: MRI brain scans of members of the Lothian Birth Cohort 1936 were assessed to obtain measures of the volume and severity of white matter hyperintensities, and the integrity of brain white matter tracts. CRT was assessed with a 4 CRT task on a separate occasion. Data were analyzed using multiple regression (N range = 358-670). RESULTS: Greater volume of hyperintensities and more severe hyperintensities in frontal regions were associated with higher CRT IIV. White matter tract integrity, as assessed by both fractional anisotropy and mean diffusivity, showed the smallest effect sizes in associations with CRT IIV. Associations with hyperintensities were attenuated and no longer significant after controlling for M CRT. CONCLUSIONS: Taken together, the results of the present study suggested that IIV was not incrementally predictive of white matter integrity over mean speed. This is in contrast to previous reports, and highlights the need for further study. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Envelhecimento/patologia , Envelhecimento/fisiologia , Variação Biológica Individual , Lobo Frontal/patologia , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Substância Branca/patologia , Idoso , Envelhecimento Cognitivo/fisiologia , Estudos de Coortes , Imagem de Difusão por Ressonância Magnética , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Masculino , Substância Branca/diagnóstico por imagem
13.
Nat Commun ; 10(1): 2387, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160572

RESUMO

Senescent cells accumulate in human tissues during ageing and contribute to age-related pathologies. The mechanisms responsible for their accumulation are unclear. Here we show that senescent dermal fibroblasts express the non-classical MHC molecule HLA-E, which interacts with the inhibitory receptor NKG2A expressed by NK and highly differentiated CD8+ T cells to inhibit immune responses against senescent cells. HLA-E expression is induced by senescence-associated secretary phenotype-related pro-inflammatory cytokines, and is regulated by p38 MAP kinase signalling in vitro. Consistently, HLA-E expression is increased on senescent cells in human skin sections from old individuals, when compared with those from young, and in human melanocytic nevi relative to normal skin. Lastly, blocking the interaction between HLA-E and NKG2A boosts immune responses against senescent cells in vitro. We thus propose that increased HLA-E expression contributes to persistence of senescent cells in tissues, thereby suggesting a new strategy for eliminating senescent cells during ageing.


Assuntos
Envelhecimento/imunologia , Linfócitos T CD8-Positivos/imunologia , Senescência Celular/imunologia , Fibroblastos/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Células Matadoras Naturais/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/imunologia , Adulto , Idoso , Envelhecimento/patologia , Citocinas/imunologia , Derme/citologia , Fibroblastos/patologia , Humanos , Técnicas In Vitro , Nevo Pigmentado/congênito , Nevo Pigmentado/imunologia , Nevo Pigmentado/patologia , Fenótipo , RNA Interferente Pequeno , Transdução de Sinais , Pele/imunologia , Pele/patologia , Adulto Jovem , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia
14.
Int J Mol Sci ; 20(11)2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31185614

RESUMO

Gangliosides are widely expressed in almost all tissues and cells and are also considered to be essential in the development and maintenance of various organs and tissues. However, little is known about their roles in bone metabolism. In this study, we investigated the effects of genetic deletion of ganglioside D3 (GD3) synthase, which is responsible for the generation of all b-series gangliosides, on bone metabolism. Although b-series gangliosides were not expressed in osteoblasts, these gangliosides were expressed in pre-osteoclasts. However, the expression of these gangliosides was decreased after induction of osteoclastogenesis by receptor activator of nuclear factor kappa-B ligand (RANKL). Three-dimensional micro-computed tomography (3D-µCT) analysis revealed that femoral cancellous bone mass in GD3 synthase-knockout (GD3S KO) mice was higher than that in wild type (WT) mice at the age of 40 weeks, although there were no differences in that between GD3S KO and WT mice at 15 weeks old. Whereas bone formation parameters (osteoblast numbers/bone surface and osteoblast surface/bone surface) in GD3S KO mice did not differ from WT mice, bone resorption parameters (osteoclast numbers/bone surface and osteoclast surface/bone surface) in GD3S KO mice became significantly lower than those in WT mice at 40 weeks of age. Collectively, this study demonstrates that deletion of GD3 synthase attenuates bone loss that emerges with aging.


Assuntos
Envelhecimento/patologia , Reabsorção Óssea/genética , Sialiltransferases/genética , Animais , Células Cultivadas , Gangliosídeos/metabolismo , Camundongos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteogênese , Ligante RANK/metabolismo , Células RAW 264.7 , Sialiltransferases/deficiência
15.
J Frailty Aging ; 8(3): 131-137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31237313

RESUMO

BACKGROUND: Prospective studies examining the potential association of vitamin D with age-related muscle loss have shown inconsistent results. OBJECTIVE: To examine the association between baseline serum 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and prospective change in lean mass with aging in African ancestry population. We also determined if associations were modulated by age and diabetes mellitus (DM). DESIGN: Prospective observational cohort study. SETTING: Data were collected from a random sub-sample of 574 men, participants of the Tobago Bone Health Study (TBHS). PARTICIPANTS: 574 Afro-Caribbean men, aged 43+ years (mean age: 59.1 ± 10.5), who were randomly selected as the participants in both the baseline and the follow-up visits. MEASUREMENTS: Baseline fasting serum 25(OH)D was measured using liquid chromatography mass spectrometry (LC-MS/MS), and and 1,25(OH)2D was measured using radioimmunosassay (RIA). Changes in dual-energy X-ray absorptiometry (DXA)-measured appendicular lean mass (ALM), and total body lean mass (TBLM) were measured over an average of 6.0 ± 0.5 years. The associations of 25(OH)D and 1,25(OH)2D with ALM and TBLM were assessed by multiple linear regression model after adjusting for potential confounders. RESULTS: When stratifying all men into two groups by age, greater baseline 25(OH)D and 1,25(OH)2D levels were associated with smaller losses of ALM and TBLM in older (age 60+ years) but not in younger (age 43 - 59 years) men. When stratifying by DM status, the associations of 25(OH)D and 1,25(OH)2D with declines in ALM and TBLM were statistically significant only in prediabetic, but not among normal glycemic or diabetic men. CONCLUSION: Higher endogenous vitamin D concentrations are associated with less lean mass loss with aging among older and prediabetic Afro-Caribbean men independent of potential confounders. Our findings raise a possibility that maintaining high serum vitamin D level might be important for musculoskeletal health in elderly and prediabetic African ancestry men.


Assuntos
Grupo com Ancestrais do Continente Africano/estatística & dados numéricos , Envelhecimento/etnologia , Atrofia Muscular/etnologia , Vitamina D/sangue , Adulto , Distribuição por Idade , Idoso , Envelhecimento/patologia , Diabetes Mellitus/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
16.
Anticancer Res ; 39(5): 2241-2249, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092415

RESUMO

Sarcopenia is a complex syndrome defined by progressive and generalized loss of skeletal muscle mass and strength. Although sarcopenia is mainly associated with aging, cancer is also one of its causes. Sarcopenia is now drawing attention as a poor prognostic factor in cancer. In patients with gastric cancer associated with eating disorders that often leads to loss of weight and muscle, sarcopenia is particularly important. Its definition and method of assessment, however, vary between studies, thus these need to be standardized. Nevertheless, emerging evidence suggests that sarcopenia contributes independently to postoperative complications and overall survival in gastric cancer. Interventions preventing sarcopenia with targeted nutrition and exercise are currently explored. This review aims to provide an understanding of sarcopenia, emphasizing its importance in the management of gastric cancer.


Assuntos
Envelhecimento/fisiologia , Músculo Esquelético/fisiopatologia , Sarcopenia/fisiopatologia , Neoplasias Gástricas/fisiopatologia , Envelhecimento/patologia , Gastrectomia , Humanos , Força Muscular/fisiologia , Estado Nutricional , Complicações Pós-Operatórias/fisiopatologia , Sarcopenia/etiologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia
17.
Anticancer Res ; 39(5): 2447-2451, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092438

RESUMO

BACKGROUND/AIM: The insulin-like growth factor 1 (IGF1) signaling pathway as an aging mechanism related to p53 in human melanogenesis remains unclear. The aim of this study was to investigate the relationship between p53 and IGF1 signaling pathway in young, senescent and H2O2-treated cells. MATERIALS AND METHODS: The protein and gene expression in young, senescent and H2O2-treated cells were analyzed using western blot and reverse transcription polymerase chain reaction (RT-PCR) assays, respectively. RESULTS: The expression levels of (phosphoinositide 3-kinases) PI3K, v-akt murine thymoma viral oncogene homolog 1 (AKT1), mammalian target of rapamycin, ß-catenin (CTNNB1), acetylated p53 (ac-p53), p53 and p-p21 proteins, related to IGF1 and p53 signaling pathways, were higher in senescent and H2O2-treated cells than those of young cells. Furthermore, AKT reduced melanogenesis through microphthalmia-associated transcription factor (MITF) inactivation by the inhibition of CTNNB1. The gene expression levels of PI3K, TP53 and catalase (CAT) in senescent and H2O2-treated cells were increased compared to young cells. CONCLUSION: p53 protein plays a key role in the aging of melanocytes via IGF1 signaling pathways.


Assuntos
Envelhecimento/genética , Proliferação de Células/genética , Fator de Crescimento Insulin-Like I/genética , Proteína Supressora de Tumor p53/genética , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Catalase/genética , Proliferação de Células/efeitos dos fármacos , Senescência Celular/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/toxicidade , Melanócitos/metabolismo , Melanócitos/patologia , Camundongos , Fator de Transcrição Associado à Microftalmia/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , beta Catenina/antagonistas & inibidores , beta Catenina/genética
18.
Invest Ophthalmol Vis Sci ; 60(6): 2208-2217, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31108551

RESUMO

Purpose: To identify the factors associated with retinal vessel diameters in the population of the Thessaloniki Eye Study. Methods: Cross-sectional population-based study (age ≥ 60 years). Subjects with glaucoma, late age-related macular degeneration, and diabetic retinopathy were excluded from the analyses. Retinal vessel diameters were measured using the IVAN software, and measurements were summarized to central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole to venule ratio (AVR). Results: The analysis included 1614 subjects. The hypertensive group showed lower values of CRAE (P = 0.033) and AVR (P = 0.0351) compared to the normal blood pressure (BP) group. On the contrary, the group having normal BP under antihypertensive treatment did not have different values compared to the normal BP group. Diastolic BP (per mm Hg) was negatively associated with CRAE (P < 0.0001) and AVR (P < 0.0001), while systolic BP (per mm Hg) was positively associated with CRAE (P = 0.001) and AVR (P = 0.0096). Other factors significantly associated included age, sex, alcohol, smoking, cardiovascular disease history, ophthalmic medication, weight, and IOP; differences were observed in a stratified analysis based on BP medication use. Conclusions: Our study confirms previous reports about the association of age and BP with vessel diameters. The negative correlation between BP and CRAE seems to be guided by the effect of diastolic BP as higher systolic BP is independently associated with higher values of CRAE. The association of BP status with retinal vessel diameters is determined by diastolic BP status in our population. Multiple other factors are also independently associated with retinal vessel diameters.


Assuntos
Envelhecimento/patologia , Retinopatia Diabética/patologia , Glaucoma/patologia , Hipertensão/patologia , Degeneração Macular/patologia , Vasos Retinianos/patologia , Idoso , Arteríolas/patologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Vênulas/patologia
19.
Physiol Rev ; 99(3): 1381-1431, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31066630

RESUMO

Oligodendrocytes generate multiple layers of myelin membrane around axons of the central nervous system to enable fast and efficient nerve conduction. Until recently, saltatory nerve conduction was considered the only purpose of myelin, but it is now clear that myelin has more functions. In fact, myelinating oligodendrocytes are embedded in a vast network of interconnected glial and neuronal cells, and increasing evidence supports an active role of oligodendrocytes within this assembly, for example, by providing metabolic support to neurons, by regulating ion and water homeostasis, and by adapting to activity-dependent neuronal signals. The molecular complexity governing these interactions requires an in-depth molecular understanding of how oligodendrocytes and axons interact and how they generate, maintain, and remodel their myelin sheaths. This review deals with the biology of myelin, the expanded relationship of myelin with its underlying axons and the neighboring cells, and its disturbances in various diseases such as multiple sclerosis, acute disseminated encephalomyelitis, and neuromyelitis optica spectrum disorders. Furthermore, we will highlight how specific interactions between astrocytes, oligodendrocytes, and microglia contribute to demyelination in hereditary white matter pathologies.


Assuntos
Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiologia , Bainha de Mielina/fisiologia , Envelhecimento/patologia , Envelhecimento/fisiologia , Animais , Doenças Desmielinizantes/patologia , Humanos , Bainha de Mielina/ultraestrutura
20.
Nature ; 570(7761): 332-337, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31042697

RESUMO

Alzheimer's disease is a pervasive neurodegenerative disorder, the molecular complexity of which remains poorly understood. Here, we analysed 80,660 single-nucleus transcriptomes from the prefrontal cortex of 48 individuals with varying degrees of Alzheimer's disease pathology. Across six major brain cell types, we identified transcriptionally distinct subpopulations, including those associated with pathology and characterized by regulators of myelination, inflammation, and neuron survival. The strongest disease-associated changes appeared early in pathological progression and were highly cell-type specific, whereas genes upregulated at late stages were common across cell types and primarily involved in the global stress response. Notably, we found that female cells were overrepresented in disease-associated subpopulations, and that transcriptional responses were substantially different between sexes in several cell types, including oligodendrocytes. Overall, myelination-related processes were recurrently perturbed in multiple cell types, suggesting that myelination has a key role in Alzheimer's disease pathophysiology. Our single-cell transcriptomic resource provides a blueprint for interrogating the molecular and cellular basis of Alzheimer's disease.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Análise de Célula Única , Transcriptoma , Envelhecimento/genética , Envelhecimento/patologia , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Especificidade de Órgãos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , RNA Mensageiro/análise , RNA Mensageiro/genética , Análise de Sequência de RNA , Caracteres Sexuais
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