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PURPOSE: Research on the concept of expressed emotion (EE) has expanded in recent years but its role in dementia still requires elucidation. Understanding the role of EE in the dementia context could help in the development of appropriate interventions. METHOD: The current review synthesized relevant literature to investigate the prevalence and correlates of EE status in families of people with dementia. A comprehensive search of four databases from inception to 2022 produced 2,683 papers; 18 studies met inclusion criteria. RESULTS: The use of EE criteria differed not only across cultural contexts, but even within the same cultural context. Overall, the prevalence of EE in families with dementia compared with other psychiatric conditions was not high. CONCLUSION: Specific changes in EE over time remain to be explored, and findings emphasize the need to carefully discriminate High EE status based on the cultural background of family members with dementia. [Journal of Gerontological Nursing, 50(2), 17-25.].
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Demência , Emoções Manifestas , Humanos , Cuidadores/psicologia , Família/psicologia , CulturaRESUMO
BACKGROUND: Family caregivers of dementia patients face significant challenges, including managing their own emotional responses. Understanding factors influencing expressed emotion (EE) is crucial for effective support interventions. The aim of this study was to explore and describe changes in EE among family caregivers of dementia and its associated factors at different time points over 3 months. METHODS: A 3-month observational study was conducted in Japan. We collected demographically detailed data on family caregivers currently providing care, including care burden, relationship closeness, and depression. We assessed EE using the validated Family Attitude Scale (FAS). After adjustment for multiple confounding factors, multivariate linear regression analysis was performed to assess factors affecting EE at various time points. Linear regression analysis with generalised estimating equations was used to assess associations between 3-month time-varying EE and burden, intimacy, and depression. RESULTS: Fifty-six family caregivers completed the study. Changes in FAS scores did not show statistical differences over 3 months. It is worth noting that the degree of relationship closeness and care burden are important influencing factors of EE in both cross-sectional analysis and longitudinal analysis. CONCLUSIONS: Early identification of risk factors can aid in developing interventions aimed at preventing high levels of EE in the dementia family, thereby mitigating their detrimental effects. Tailored interventions are essential to enhance caregiver well-being and cultivate positive caregiver-patient relationships.
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Although α-synuclein (SNCA) is a well-known pathological molecule involved in synucleinopathy in neurons, its physiological roles remain largely unknown. We reported that serum SNCA levels have a close inverse correlation with blood pressure and age, which indicates the involvement of SNCA in age-related endothelial dysfunction. Therefore, this study aimed to elucidate the molecular functions of SNCA in the endothelium. We confirmed that SNCA was expressed in and secreted from endothelial cells (ECs). Exogenous treatment with recombinant SNCA (rSNCA) activated the Akt-eNOS axis and increased nitric oxide production in ECs. Treatment with rSNCA also suppressed TNF-α- and palmitic acid-induced NF-κB activation, leading to the suppression of VCAM-1 upregulation and restoration of eNOS downregulation in ECs. As for endogenous SNCA expression, replicative senescence resulted in the attenuation of SNCA expression in cultured ECs, similar to the effects of physiological aging on mice aortas. The siRNA-mediated silencing of SNCA consistently resulted in senescent phenotypes, such as eNOS downregulation, increased ß-gal activity, decreased Sirt1 expression, and increased p53 expression, in ECs. Ex vivo assessment of endothelial functions using aortic rings revealed impaired endothelium-dependent acetylcholine-induced relaxation in SNCA knockout (KO) mice. Furthermore, SNCA KO mice, especially those on a high-fat diet, displayed elevated blood pressure compared with wild-type mice; this could be eNOS dysfunction-dependent because of the lower difference caused by L-NAME administration. These results indicate that exogenous and endogenous SNCA in ECs might physiologically maintain vascular integrity, and age-related endothelial dysfunction might be partially ascribed to loss-of-function of SNCA in ECs.
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Doenças Vasculares , alfa-Sinucleína/metabolismo , Acetilcolina/metabolismo , Animais , Células Endoteliais/metabolismo , Camundongos , Camundongos Knockout , NF-kappa B/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Ácido Palmítico/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/metabolismo , Sirtuína 1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Doenças Vasculares/metabolismoRESUMO
INTRODUCTION: A rapidly increasing number of patients with dementia present a serious social problem. Recently, the incidence of epilepsy in patients with Alzheimer's disease (AD) is increasing, drawing attention to the pathological relationship between the two conditions. Clinical studies have suggested the protective action of antiepileptic agents on dementia; however, the underlying mechanism remains unknown. We evaluated the effects of multiple antiepileptic drugs using tau aggregation assay systems to determine the effects of antiepileptic agents on tau aggregation, a major neuropathological finding associated with AD. METHODS: We evaluated the effects of seven antiepileptic agents on intracellular tau aggregation using a tau-biosensor cell-based high-throughput assay. Next, we tested these agents in a cell-free tau aggregation assay using thioflavin T (ThT). RESULTS: The assay results revealed that phenobarbital inhibited tau aggregation, whereas sodium valproate, gabapentin, and piracetam promoted tau aggregation. In the cell-free tau aggregation assay using ThT, we confirmed that phenobarbital significantly inhibited tau aggregation. CONCLUSION: Antiepileptic drugs may modify the tau pathology in AD in a neural activity-independent manner. Our finding may provide an important insight into the optimization of antiepileptic drug therapy in older adults with dementia.
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Doença de Alzheimer , Anticonvulsivantes , Humanos , Idoso , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Proteínas tau , Ácido Valproico/farmacologia , Ácido Valproico/uso terapêutico , Fenobarbital/uso terapêuticoRESUMO
BACKGROUND: Factors associated with weight loss in community-dwelling older people have been reported in several studies, but few studies have examined factors associated with weight loss by age groups. The purpose of this study was to clarify factors associated with weight loss by age in community-dwelling older people through a longitudinal study. METHODS: Participants in the SONIC study (Longitudinal Epidemiological Study of the Elderly) were community-dwelling people aged 70 or older. The participants were divided into two groups: 5% weight loss and maintenance groups, and compared. In addition, we examined factors affecting weight loss by age. The analysis method used was the χ2 test, and the t-test was used for comparison of the two groups. Factors associated with 5% weight loss at 3 years were examined using logistic regression analysis with sex, age, married couple, cognitive function, grip strength, and the serum albumin level as explanatory variables. RESULTS: Of the 1157 subjects, the proportions showing 5% weight loss after 3 years among all subjects, those aged 70 years, 80 years, and 90 years, were 20.5, 13.8, 26.8, and 30.5%, respectively. In logistic regression analysis, factors associated with 5% weight loss at 3 years by age were influenced by BMI of 25 or higher (OR = 1.90, 95%CI = 1.08-3.34, p = 0.026), a married couple (OR = 0.49, 95% = 0.28-0.86, p = 0.013), serum albumin level below 3.8 g/dL (OR = 10.75, 95% = 1.90-60.73, p = 0.007) at age 70, and the grip strength at age 90 (OR = 1.24, 95%CI = 1.02-1.51, p = 0.034), respectively. CONCLUSIONS: The results suggest that factors associated with weight loss by age in community-dwelling older people through a longitudinal study differ by age. In the future, this study will be useful to propose effective interventions to prevent factors associated with weight loss by age in community-dwelling older people.
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Força da Mão , Vida Independente , Idoso , Humanos , Idoso de 80 Anos ou mais , Estudos Longitudinais , Albumina Sérica , Redução de PesoRESUMO
BACKGROUND: Semantic dementia (SD), a subtype of frontotemporal dementia, manifests as verbal symptoms, including social and behavioural deficits, associated with focal atrophy of the frontotemporal lobes. This study aimed to clarify the experiences of individuals with early-onset SD receiving speech and language rehabilitation (hereafter referred to as 'rehabilitation'), with the intent of making it routine, as well as the experiences of their families. METHODS: Individual interviews were conducted with nine families with members who had adopted rehabilitation. Verbatim transcripts were used as data, and analyzed inductively according to the content analysis process. RESULTS: The family members realised the changes in the personality and behaviour of the individual with SD early, to the extent that they thought the individual with SD was different from before and were distressed by the loss of verbal communication. Nevertheless, the family members found a way to communicate by maintaining residual functions through rehabilitation and utilising their unique relationship with the individual with SD. CONCLUSIONS: It is important to carefully explain the characteristics of the disease and the long-term significance of rehabilitation to individuals with SD and their families in the early stages of the disease.
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Demência Frontotemporal , Humanos , Demência Frontotemporal/diagnóstico , Testes Neuropsicológicos , Idioma , Família , Pesquisa QualitativaRESUMO
BACKGROUND: This study evaluated the preliminary effect of an integrated novel intervention comprising visualised sleep report feedback using information and communication technology and periodic health guidance on improving sleep indicators among community-dwelling older people. METHODS: The intervention was implemented among 29 older people in Sakai City, Japan, in a 3 months pilot trial. Non-worn actigraph devices were placed under participants' bedding to continuously measure their sleep state, and they received monthly sleep reports in writing. Sleep efficiency, total sleep time, sleep latency, and the number of times away from bed were recorded. A trained nurse expertly interpreted participants' sleep data and provided telephone health guidance. The first month's data were used as the baseline (T1), the second month provided data for the first intervention (T2), and the third month provided data for the second intervention (T3). Friedman tests and Wilcoxon signed-rank tests were used to examine differences in sleep outcomes between different time points. RESULTS: Participants' mean age was 78.97 ± 5.15 years, and 51.72% (15/29) were female. Comparison of T2 and T1 showed the intervention decreased participants' sleep latency at T2 (P = 0.038). Compared with T1, the intervention significantly decreased sleep latency (P = 0.004), increased total sleep time (P < 0.001), and improved sleep efficiency (P < 0.001) at T3. When T3 was compared with T2, only total sleep time was significantly increased (P < 0.001). There were no significant differences in the number of times away from bed across the three time points (P > 0.05). CONCLUSIONS: This visualised sleep report feedback and periodic health guidance intervention for community-dwelling older people showed promising, albeit small preliminary effects on sleep. A fully powered randomised controlled trial is required to verify the significance of this effect.
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Vida Independente , Sono , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Retroalimentação , Projetos Piloto , Comunicação , TecnologiaRESUMO
In the early phase of the Coronavirus disease 2019 (COVID-19) pandemic, it was postulated that the renin-angiotensin-system inhibitors (RASi) increase the infection risk. This was primarily based on numerous reports, which stated that the RASi could increase the organ Angiotensin-converting enzyme 2 (ACE2), the receptor of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in rodents. RASi can theoretically antagonize the potential influence of angiotensin II (Ang II) on ACE2. However, while Ang II decreases the ACE2 levels in cultured cells, there is little evidence that supports this phenomenon in living animals. In this study, we tested whether Ang II or Ang II combined with its antagonist would alter the ACE2 and other molecules associated with the infection of SARS-CoV-2. Male C57BL6/J mice were administered vehicle, Ang II (400 ng/kg/min), or Ang II with losartan (10 mg/kg/min) for 2 weeks. ACE2 knockout mice were used as a negative control for the ACE2 assay. We found that both Ang II, which elevated blood pressure by 30 mm Hg, and Ang II with losartan, had no effect on the expression or protein activity of ACE2 in the lung, left ventricle, kidney, and ileum. Likewise, these interventions had no effect on the expression of Transmembrane Protease Serine 2 (TMPRSS2) and Furin, proteases that facilitate the virus-cell fusion, and the expression or activity of Tumor Necrosis Factor α-Convertase (TACE) that cleaves cell-surface ACE2. Collectively, physiological concentrations of Ang II do not modulate the molecules associated with SARS-CoV-2 infection. These results support the recent observational studies suggesting that the use of RASi is not a risk factor for COVID-19.
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Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Angiotensina II/farmacologia , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/metabolismo , Losartan/farmacologia , SARS-CoV-2 , Proteína ADAM17/genética , Proteína ADAM17/metabolismo , Angiotensina II/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Enzima de Conversão de Angiotensina 2/genética , Animais , Furina/genética , Furina/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Losartan/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Vasoconstritores/farmacologiaRESUMO
BACKGROUND: The relationship between moderate alcohol drinking or other alcohol drinking patterns such as frequency, beverage type, and situation of drinking and cognitive function is not sufficiently clear in older people. The purpose of this study was to investigate the association between alcohol drinking patterns and cognitive function in community-dwelling Japanese people aged 75 and over. METHODS: This study was a cross-sectional design based on a prospective cohort study called the SONIC study. Subjects were older people aged 75-77 or 85-87 who voluntarily participated in 2016-2017. Drinking information was collected for daily drinking frequency, daily drinking intake, beverage type, and non-daily drinking opportunity. Cognitive function was measured using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Other potential confounding factors evaluated were age, sex, medical factors, and psychosocial factors. An analysis of covariance was performed to evaluate the MoCA-J score relative to drinking frequency or alcohol intake. Multiple regression analysis was performed to investigate the association between beverage type or non-daily drinking opportunity and the MoCA-J score. RESULTS: The final number of participants analyzed was 1,226. The MoCA-J score for participants who reported drinking alcohol 1-6 days/week was significantly higher than that for those who reported drinking none or every day. No significant difference in the MoCA-J score was observed relative to daily alcohol intake. In terms of beverage type, wine was associated positively with the MoCA-J score. Non-daily drinking opportunity was also associated positively with the MoCA-J score. CONCLUSIONS: Moderate-frequency drinking, wine consumption, and non-daily drinking opportunities were associated with higher cognitive function in community-dwelling Japanese aged 75 and over. Further longitudinal studies are needed to clarify the causal relationships.
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Cognição , Disfunção Cognitiva , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos Transversais , Humanos , Testes de Estado Mental e Demência , Estudos ProspectivosRESUMO
AIMS: The purpose of this study was to objectively quantify the sleep of elderly patients with dementia at home using a device and to investigate the factors associated with its identification. METHODS: Sixteen patients (6 males [37.5%], 84.1±4.7 years old; and 10 patients with mild dementia [62.5%]) and their family caregivers who were using outpatient memory clinics and home-visiting nursing station in Japan were included. Demographic and clinical data of the patients and their family caregivers, subjective perceptions of patients' sleep, family caregivers' Zarit care burden, and whether or not they were aware of patients' sleep problems were determined. Nighttime sleep parameters were collected for one week using a non-wearable actigraph. Sleep parameters were compared with patients' subjective views and family caregivers' observations to investigate factors indicative of sleep disturbance. RESULTS: Nighttime sleep parameters for 1 week (mean) were follows: sleep efficiency, 77.2%±9.3%; asleep time, 442.3±99.9 minutes; sleep latency, 18.2±15.8 minutes; awake time, 105.1±69.7 minutes; and number of times leaving the bed, 4.6±3.8 (maximum of 29/night). A significant positive correlation was found between sleep efficiency and duration of dementia (r=0.53, p=0.046), while no correlation was found with dementia severity or Zarit care burden score. The agreement between the patients' complaints about sleep and sleep efficiency (75%) was 30.7%, and family caregivers' awareness of patients' nighttime awakening and bed-leaving was significantly associated with patients' incontinence (p=0.024) and a greater dementia severity (p=0.027). CONCLUSIONS: Elderly dementia patients experienced sleep disturbance at home, such as nighttime awakening and associated bed-leaving; however, it might be difficult to identify these patients at an early stage based on their own complaints and observations by family caregivers. Identifying sleep problems at an early stage may thus require the use of objective measurement devices.
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Demência , Transtornos do Sono-Vigília , Idoso , Idoso de 80 Anos ou mais , Cuidadores , Demência/complicações , Humanos , Japão , Masculino , Sono , Transtornos do Sono-Vigília/etiologiaRESUMO
While adipose tissue is required to maintain glucose metabolism, excessive calorie intake induces obesity via mechanisms including accelerated proliferation and differentiation of preadipocytes, leading to insulin resistance. Here, we investigated the role of myoferlin (MYOF), a ferlin family protein, in regulating glucose metabolism by mainly focusing on its unknown role in adipose tissue. Whereas young MYOF knockout (KO) mice on a normal diet showed aggravated glucose tolerance and insulin sensitivity, those on a high-fat diet (HFD) showed preserved glucose tolerance with an attenuated gain of body weight, reduced visceral fat deposits, and less severe fatty liver. The Adipose MYOF expression was reduced by aging but was restored by an HFD along with the retained expression of NFAT transcription factors. Loss-of-function of MYOF in preadipocytes suppressed proliferation and differentiation into mature adipocytes along with the decreased expression of genes involved in adipogenesis. The MYOF expression in preadipocytes was reduced with differentiation. Attenuated obesity in MYOF KO mice on an HFD was also accompanied with increased oxygen consumption by an unidentified mechanism and with reduced adipose inflammation due to less inflammatory macrophages. These insights suggest that the multifunctional roles of MYOF involve the regulation of preadipocyte function and affect glucose metabolism bidirectionally depending on consumed calories.
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Adipócitos/metabolismo , Adipogenia/fisiologia , Adiposidade/fisiologia , Glucose/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Musculares/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Diferenciação Celular , Inflamação/metabolismo , Resistência à Insulina/fisiologia , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BLRESUMO
We hypothesized that pre-exercise may effectively prevent cancer cachexia-induced muscle atrophy in both fast- and slow-twitch muscle types. Additionally, the fast-twitch muscle may be more affected by cancer cachexia than slow-twitch muscle. This study aimed to evaluate the effects of pre-exercise on cancer cachexia-induced atrophy and on atrophy in fast- and slow-twitch muscles. Twelve male Wistar rats were randomly divided into sedentary and exercise groups, and another 24 rats were randomly divided into control, pre-exercise, cancer cachexia induced by intraperitoneal injections of ascites hepatoma AH130 cells, and pre-exercise plus cancer cachexia groups. We analyzed changes in muscle mass and in gene and protein expression levels of major regulators and indicators of muscle protein degradation and synthesis pathways, angiogenic factors, and mitochondrial function in both the plantaris and soleus muscles. Pre-exercise inhibited muscle mass loss, rescued protein synthesis, prevented capillary regression, and suppressed hypoxia in the plantaris and soleus muscles. Pre-exercise inhibited mitochondrial dysfunction differently in fast- and slow-twitch muscles. These results suggested that pre-exercise has the potential to inhibit cancer-cachexia-induced muscle atrophy in both fast- and slow-twitch muscles. Furthermore, the different progressions of cancer-cachexia-induced muscle atrophy in fast- and slow-twitch muscles are related to differences in mitochondrial function.
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Caquexia/prevenção & controle , Fibras Musculares de Contração Rápida/fisiologia , Fibras Musculares de Contração Lenta/fisiologia , Atrofia Muscular/prevenção & controle , Condicionamento Físico Animal/métodos , Animais , Caquexia/etiologia , Linhagem Celular Tumoral , Masculino , Mitocôndrias Musculares/metabolismo , Fibras Musculares de Contração Rápida/metabolismo , Fibras Musculares de Contração Lenta/metabolismo , Atrofia Muscular/etiologia , Neoplasias Experimentais/complicações , Neovascularização Fisiológica , Biossíntese de Proteínas , Ratos , Ratos WistarRESUMO
Periodontal disease and arteriosclerotic disease are greatly affected by aging. In this study, the association of conventional risk factors and periodontal disease with atherosclerosis was longitudinally examined in Japanese older adults. Subjects in this study were 490 community-dwelling septuagenarians (69-71 years) randomly recruited from the Basic Resident Registry of urban or rural areas in Japan. At the baseline examination, all subjects underwent socioeconomic and medical interviews; medical examinations, including examinations for carotid atherosclerosis, hypertension, diabetes mellitus, and dyslipidemia; and conventional dental examinations, including a tooth count and measurement of probing pocket depth (PPD). After 3 years, 182 septuagenarians who had no atherosclerosis at the baseline examination were registered and received the same examination as at the baseline. In the re-examination conducted 3 years after the baseline survey, 131 (72.0%) of the 182 participants who had no atherosclerosis at the baseline examination were diagnosed with carotid atherosclerosis. Adjusting and analyzing the mutual relationships of the conventional risk factors for atherosclerosis by multiple logistic regression analysis for the 171 septuagenarians with a full set of data, the proportion of teeth with PPD ≥ 4 mm was independently related to the prevalence of atherosclerosis (odds ratio: 1.029, P < 0.022). This longitudinal study of Japanese older adults suggests that periodontal disease is associated with the onset/progression of atherosclerosis. Maintaining a healthy periodontal condition may be an important factor in preventing the development and progression of atherosclerosis.
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Aterosclerose , Doenças Periodontais , Idoso , Aterosclerose/epidemiologia , Humanos , Japão/epidemiologia , Estudos Longitudinais , Doenças Periodontais/complicações , Doenças Periodontais/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Cognitive impairment is a major health concern among older and oldest people. Moreover, stroke is a relevant contributor for cognitive decline and development of dementia. The study of cognitive decline focused on stroke as the important risk factor by recruiting older and oldest is still lagging behind. Therefore, the aim of this study was to investigate the importance of stroke as a risk factor of cognitive decline during 3 years in community dwelling older and oldest people. METHODS: This study was longitudinal study with a 3-year follow-up in Japan. The participants were 1333 community dwelling older and oldest people (70 years old = 675, 80 years old = 589, and 90 years old = 69). Data collected included basic data (age, sex, and history of stroke), vascular risk factors (hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, and current smoking), and social factors (educational level, frequency of going outdoors, long-term care (LTC) service used, and residential area). The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was decline of ≥2 points was defined as cognitive decline. Multiple logistic regression analysis was used to investigate the association between stroke and other risk factors with cognitive decline during a 3-year follow-up. RESULTS: The fit of the hypothesized model by multiple logistic regression showed that a history of stroke, advanced age, and greater MoCA-J score at the baseline were important risk factors, while the presence of dyslipidemia and a higher educational level were protective factors that were significantly correlated with cognitive decline during the 3-year follow-up. CONCLUSIONS: The cognitive decline after the 3-year follow-up was influenced by the history of stroke and advanced age, while greater MoCA-J score at the baseline was positively associated with subsequent 3 years cognitive decline. The protective factors were the presence of dyslipidemia and a higher educational level. Therefore, these factors are considered important and should be taken into consideration when searching for creative solutions to prevent cognitive decline after stroke in community dwelling older and oldest people.
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Disfunção Cognitiva , Acidente Vascular Cerebral , Idoso , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Feminino , Humanos , Vida Independente , Japão/epidemiologia , Estudos Longitudinais , Masculino , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND: Preventing the need for long-term care (LTC) by identifying physical function risk factors are important to decrease the LTC burden. The objective of this study was to investigate whether grip strength and/or walking speed, which are components of the frailty definition, are associated with LTC in community-dwelling older and oldest people. METHODS: The participants were 1098 community-dwelling older and oldest people who had not received LTC at the baseline. The endpoint was receiving LTC after the baseline survey. The independent variables were grip strength and walking speed, and participants were divided into two groups based on these variables. The confounding factors were age, sex, the Japanese version of the Montreal Cognitive Assessment (MoCA-J), hypertension, diabetes mellitus, stroke, joint diseases, living alone, body mass index, and serum albumin. We calculated the hazard ratio of receiving LTC using the Cox proportional hazard model. RESULTS: Among the 1098 participants, 107 (9.7%) newly received LTC during the follow-up. Regarding the physical function, only slow walking speed was significantly correlated with LTC after adjusting for all confounding factors except the MoCA-J score (HR = 1.74, 95% CI = 1.10-2.75, P = .018). However, slow walking speed was still a risk factor for LTC after adjusting for the MoCA-J score and other confounding factors (HR = 1.64, 95% CI = 1.03-2.60, P = .037). CONCLUSIONS: The findings from this study may contribute to a better understanding of slow walking speed as a factor related to LTC, which might be a criterion for disability prevention and could serve as an outcome measure for physical function in older people.
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Exercício Físico , Vida Independente/estatística & dados numéricos , Assistência de Longa Duração/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão , Masculino , Modelos de Riscos ProporcionaisRESUMO
Skeletal muscle performs 80% of the glucose metabolism in the body. Improvement of insulin resistance and prevention of diabetes by habitual exercise is considered beneficial due to the improved glucose uptake in skeletal muscles. Investigation of the mechanism by which skeletal muscles regulate glucose uptake can contribute to the prevention and treatment of diabetes. Myokines are a kind of cytokine secreted from skeletal muscle, which are expected to regulate muscle metabolism. Interleukin-15 (IL-15) is one such myokine that has been reported to improve glucose metabolism in vitro, although the mechanism remains unclear. In this study, we examined the glucose metabolism of skeletal muscle-specific IL-15 transgenic mice (IL-15TG), and investigated how IL-15 affects glucose metabolism in skeletal muscles. Although High Fat Diet-fed IL-15TG did not exhibit obvious difference in intraperitoneal insulin tolerance test, they had less impaired glucose tolerance compared to wild-type C57BL/6. Phosphorylation of AMP-activated protein kinase (AMPK), Akt substrate of 160â¯kDa (AS160), tre-2/USP6, BUB2, and cdc16 domain family member 1 (TBC1D1), and translocation of Glucose transporter type 4 (GLUT4) were accelerated in the skeletal muscle of IL-15TG. Our study demonstrated that overexpression of IL-15 in skeletal muscle improves glucose metabolism in skeletal muscle via AMPK pathway. We report the first in-vivo study that describes the signaling pathway of IL-15 in muscle glucose metabolism, and thereby contributes to the elucidation of the regulatory mechanism of muscle glucose metabolism by myokines.
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Proteínas Quinases Ativadas por AMP/metabolismo , Intolerância à Glucose/tratamento farmacológico , Transportador de Glucose Tipo 4/metabolismo , Interleucina-15/metabolismo , Músculo Esquelético/metabolismo , Animais , Transporte Biológico , Glucose/metabolismo , Glucose/farmacocinética , Resistência à Insulina , Interleucina-15/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Transdução de SinaisRESUMO
Cardiovascular disease is one of the leading causes of death in the elderly, and novel therapeutic targets against atherogenesis are urgent. The initiation of atherosclerotic changes of monocyte adhesion on the vascular endothelium and subsequent foam cell formation are noteworthy pathophysiologies when searching for strategies to prevent the progression of age-related atherosclerosis. We report the significance of the deubiquitinating enzyme cylindromatosis (CYLD) in vascular remodeling by interference with inflammatory responses regulated by NF-κB signaling. The purpose of this study was to elucidate the pathological functions of CYLD in the early phase of atherogenesis associated with aging. Treatment with inflammatory cytokines induced endogenous CYLD in aortic endothelial cells (HAECs) and THP-1â¯cells. siRNA-mediated CYLD silencing led to enhanced monocyte adhesion along with increased adhesion molecules in HAECs treated with TNFα. In siRNA-mediated CYLD silenced RAW 264.7 macrophages treated with oxidized LDL (oxLDL), augmented lipid accumulation was observed, along with increased expression of the class A macrophage scavenger receptor (SR-A), lectin-like oxidized LDL receptor-1 (LOX-1), CD36, fatty acid binding protein 4 (FABP4), the cholesterol ester synthase acyl-CoA cholesterol acyltransferase (ACAT1), MCP-1, and IL-1ß and decreased expression of scavenger receptor class B type I (SR-BI). Intriguingly, CYLD gene expression was significantly reduced in bone marrow-derived macrophages of aged mice compared that of young mice, as well as in senescent HAECs compared with young cells. These findings suggest that age-related attenuation of CYLD expression in endothelial cells (ECs) and macrophages triggers the initiation of age-related atherogenesis by exacerbating monocyte adhesion on the endothelium and foam cell formation. CYLD in the vasculature may be a novel therapeutic target, especially in the early preventive intervention against the initiation of age-related atherogenesis.
Assuntos
Envelhecimento/patologia , Aterosclerose/fisiopatologia , Cisteína Endopeptidases/metabolismo , Enzima Desubiquitinante CYLD/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Macrófagos/metabolismo , Envelhecimento/genética , Animais , Aterosclerose/genética , Aterosclerose/patologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Adesão Celular/efeitos dos fármacos , Citocinas/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/efeitos dos fármacos , Células Espumosas/efeitos dos fármacos , Células Espumosas/metabolismo , Inativação Gênica/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Lipoproteínas LDL/farmacologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Células RAW 264.7 , RNA Interferente Pequeno/metabolismo , Células THP-1 , Regulação para Cima/efeitos dos fármacosRESUMO
The angiotensin-converting enzyme 2 (ACE2)-angiotensin 1-7 (A1-7)-A1-7 receptor (Mas) axis plays a protective role in the renin-angiotensin system (RAS). We recently found that ACE2 knockout (ACE2KO) mice exhibit earlier aging-associated muscle weakness, and that A1-7 alleviates muscle weakness in aging mice. In the present study, we investigated the role of the A1-7-Mas pathway in the effect of ACE2 on physiological aging. Male wild-type, ACE2KO, and Mas knockout (MasKO) mice were subjected to periodical grip strength measurement, followed by administration of A1-7 or vehicle for 4 weeks at 24 months of age. ACE2KO mice exhibited decreased grip strength after 6 months of age, while grip strength of MasKO mice was similar to that of wild-type mice. A1-7 improved grip strength in ACE2KO and wild-type mice, but not in MasKO mice. Muscle fibre size was smaller in ACE2KO mice than that in wild-type and MasKO mice, and increased with A1-7 in ACE2KO and WT mice, but not in MasKO mice. Centrally nucleated fibres (CNFs) and expression of the senescence-associated gene p16INK4a in skeletal muscles were enhanced only in ACE2KO mice and were not altered by A1-7. ACE2KO mice, but not MasKO mice, exhibited thinning of peripheral fat along with increased adipose expression of p16INK4a A1-7 significantly increased bone volume in wild-type and ACE2KO mice, but not in MasKO mice. Our findings suggest that the impact of ACE2 on physiological aging does not depend on the endogenous production of A1-7 by ACE2, while overactivation of the A1-7-Mas pathway could alleviate sarcopenia and osteoporosis in aged mice.
Assuntos
Envelhecimento/patologia , Angiotensina I/uso terapêutico , Reabsorção Óssea/tratamento farmacológico , Debilidade Muscular/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Peptidil Dipeptidase A/deficiência , Tecido Adiposo/patologia , Angiotensina I/farmacologia , Enzima de Conversão de Angiotensina 2 , Animais , Peso Corporal/efeitos dos fármacos , Reabsorção Óssea/complicações , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Membro Anterior/fisiopatologia , Deleção de Genes , Força da Mão , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Debilidade Muscular/complicações , Debilidade Muscular/diagnóstico por imagem , Músculos/diagnóstico por imagem , Músculos/efeitos dos fármacos , Músculos/patologia , Tamanho do Órgão/efeitos dos fármacos , Fator de Transcrição PAX3/metabolismo , Fragmentos de Peptídeos/farmacologia , Peptidil Dipeptidase A/metabolismo , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas G/deficiência , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Fatores de TempoRESUMO
The angiotensin II type 1 receptor (AT1) is a 7-transmembrane domain GPCR that when activated by its ligand angiotensin II, generates signaling events promoting vascular dysfunction and the development of cardiovascular disease. Here, we show that the single-transmembrane oxidized LDL (oxLDL) receptor (LOX-1) resides in proximity to AT1 on cell-surface membranes and that binding of oxLDL to LOX-1 can allosterically activate AT1-dependent signaling events. oxLDL-induced signaling events in human vascular endothelial cells were abolished by knockdown of AT1 and inhibited by AT1 blockade (ARB). oxLDL increased cytosolic G protein by 350% in Chinese hamster ovary (CHO) cells with genetically induced expression of AT1 and LOX-1, whereas little increase was observed in CHO cells expressing only LOX-1. Immunoprecipitation and in situ proximity ligation assay (PLA) assays in CHO cells revealed the presence of cell-surface complexes involving LOX-1 and AT1. Chimeric analysis showed that oxLDL-induced AT1 signaling events are mediated via interactions between the intracellular domain of LOX-1 and AT1 that activate AT1. oxLDL-induced impairment of endothelium-dependent vascular relaxation of vascular ring from mouse thoracic aorta was abolished by ARB or genetic deletion of AT1. These findings reveal a novel pathway for AT1 activation and suggest a new mechanism whereby oxLDL may be promoting risk for cardiovascular disease.