Automated Dual-Mode Cell Monitoring To Simultaneously Explore Calcium Dynamics and Contraction-Relaxation Kinetics within Drug-Treated Stem Cell-Derived Cardiomyocytes.

This manuscript proposes a new dual-mode cell imaging system for studying the relationships between calcium dynamics and the contractility process of cardiomyocytes derived from human-induced pluripotent stem cells. Practically, this dual-mode cell imaging system provides simultaneously both live cell calcium imaging and quantitative phase imaging based on digital holographic microscopy. Specifically, thanks to the development of a robust automated image analysis, simultaneous measurements of both intracellular calcium, a key player of excitation-contraction coupling, and the quantitative phase image-derived dry mass redistribution, reflecting the effective contractility, namely, the contraction and relaxation processes, were achieved. Practically, the relationships between calcium dynamics and the contraction-relaxation kinetics were investigated in particular through the application of two drugs─namely, isoprenaline and E-4031─known to act precisely on calcium dynamics. Specifically, this new dual-mode cell imaging system enabled us to establish that calcium regulation can be divided into two phases, an early phase influencing the occurrence of the relaxation process followed by a late phase, which although not having a significant influence on the relaxation process affects significantly the beat frequency. In combination with cutting-edge technologies allowing the generation of human stem cell-derived cardiomyocytes, this dual-mode cell monitoring approach therefore represents a very promising technique, particularly in the fields of drug discovery and personalized medicine, to identify compounds likely to act more selectively on specific steps that compose the cardiomyocyte contractility.

Effects of Fisetin, a Plant-Derived Flavonoid, on Response to Oxidative Stress, Aging, and Age-Related Diseases in Caenorhabditis elegans.

Fisetin (3,3',4',7-tetrahydroxyflavone), a flavonoid abundant in various fruits and vegetables, including apple, strawberry, and onion, shows several beneficial effects such as anti-oxidant, anti-inflammatory, and anti-tumor effects. The free radical theory of aging suggests that age-related accumulation of oxidative damage is the major cause of aging and that decreasing cellular oxidative stress can regulate aging. Here, we investigated the effects of dietary supplementation with fisetin on the stress response, aging, and age-related diseases. Fisetin reduced the cellular ROS levels and increased the resistance to oxidative stress. However, the response to UV irradiation was not affected by fisetin. Both the mean and maximum lifespans were significantly extended by fisetin; lifespan extension by fisetin was accompanied by reduced fertility as a trade-off. Age-related decline in motility was also delayed by supplementation with fisetin. Amyloid beta-induced toxicity was markedly decreased by fisetin, which required DAF-16 and SKN-1. Reduced motility induced by a high-glucose diet was completely recovered by supplementation with fisetin, which was dependent on SKN-1. Using a Parkinson's disease model, we showed that degeneration of dopaminergic neurons was significantly inhibited by treatment with fisetin. Genetic analysis revealed that lifespan extension by fisetin was mediated by DAF-16-induced stress response and autophagy. These findings support the free radical theory of aging and suggest that fisetin can be a strong candidate for use in novel anti-aging anti-oxidant nutraceuticals.

Association between Disability and Edema Index Values in Rural Older Adult Osteosarcopenia Patients.

PURPOSE: This study analyzed the relationship between degree of disability and edema index [extracellular water/total body water (ECW/TBW) ratio] values in a rural population of older adult patients with osteopenia, sarcopenia, or osteosarcopenia (OS). MATERIALS AND METHODS: This study used data from the Namgaram-2 cohort. The degree of disability was measured using the World Health Organization Disability Assessment Schedule (WHODAS) 12, and ECW/TBW ratio was calculated using bioelectrical impedance analysis. Based on ECW/TBW ratio, the participants were stratified into normal (<0.391) and abnormal (≥0.391) groups, and the mean WHODAS 12 scores were compared between the two groups. Multiple regression analysis corrected for demographic factors, smoking history, hypertension, diabetes, and serological test results was also conducted. RESULTS: Significant differences in mean WHODAS 12 scores were observed in the healthy group (5.8±7.4 vs. 9.2±9.7, p=0.008), the osteopenia only group (7.4±8.7 vs. 12.9±12.0, p<0.001), and the OS group (16.0±13.2 vs. 23.1±17.1, p=0.004). However, no significant difference in mean WHODAS 12 score was observed in the sarcopenia only group (14.9±13.4 vs. 20.7±14.8, p= 0.051). There were significant differences in ECW/TBW ratio values between the abnormal and normal groups in the osteopenia only group (B=4.646 and p=0.001), the sarcopenia only group (B=5.097 and p=0.016), and the OS group (B=5.653 and p=0.043). CONCLUSION: This study found that the degree of disability is related to the edema index in older patients with osteopenia, sarcopenia, or OS. Since the edema index indicates the nutritional status of an individual, proper nutrition and fluid intake are important to reduce disability.

Factors Associated with Gastrointestinal Symptoms among Rotating Shift Nurses in South Korea: A Cross-Sectional Study.

Rotating shift work places a serious burden on nurses' physical and psychological health. Gastrointestinal (GI) symptoms are a common complaint among shift workers. This study assessed GI symptoms and identified the associations between dietary habits, psychological status, and sleep quality among rotating shift nurses. Data from 125 female nurses in rotating shifts who worked at two tertiary hospitals in South Korea were collected using a questionnaire that included the Gastrointestinal Symptoms Questionnaire; the Dietary Habit Questionnaire; the Depression, Anxiety, Stress Scale (DASS)-21; and the Pittsburgh Sleep Quality Index (PSQI). All participants experienced various GI symptoms, and 47% of them complained of at least one severe GI symptom. There were significant differences in GI symptom scores according to the status of depression, anxiety, stress, and sleep quality. In multiple linear regression analysis, the factors associated with an increase in the occurrence and severity of GI symptoms were poor sleep quality and morbid anxiety and stress. The model explained power at 43.2%. As most nurses in rotating shifts experience GI symptoms, they should receive counseling and training programs at work to alleviate psychological symptoms, improve sleep quality, and pay more attention to their health status as well as GI symptom management.

The EEF1AKMT3/MAP2K7/TP53 axis suppresses tumor invasiveness and metastasis in gastric cancer.

The importance of methylation in the tumorigenic responses of nonhistone proteins, such as TP53, PTEN, RB1, AKT, and STAT3, has been emphasized in numerous studies. In parallel, the corresponding nonhistone protein methyltransferases have been acknowledged in the pathophysiology of cancer. Thus, this study aimed to explore the pathological role of a nonhistone methyltransferase in gastric cancer (GC), identify nonhistone substrate protein, and understand the underlying mechanism. Interestingly, among the 24 methyltransferases and methyltransferase family 16 (MTF16) proteins, EEF1AKMT3 (METTL21B) expression was prominently lower in GC tissues than in normal adjacent tissues and was associated with a worse prognosis. In addition, EEF1AKMT3-knockdown induced gastric tumor invasiveness and migration. Through gain and loss-of-function studies, mass spectrometry analysis, RNA-seq, and phospho-antibody array, we identified EEF1AKMT3 as a novel tumor-suppressive methyltransferase that catalyzes the monomethylation of MAP2K7 (MKK7) at K296, thereby decreasing the phosphorylation, ubiquitination, and degradation of TP53. Furthermore, EEF1AKMT3, p-MAP2K7, and TP53 protein levels were positively correlated in GC tissues. Collectively, our results delineate the tumor-suppressive function of the EEF1AKMT3/MAP2K7/TP53 signaling axis and suggest the dysregulation of the signaling axis as potential targeted therapy in GC.

Psychometric Properties and Effects on Health Outcomes of the Patient Assessment of Chronic Illness Care (PACIC) in Korean Hemodialysis Patients.

BACKGROUND: The satisfaction of patients receiving integrated care with End-Stage Renal Disease (ESRD) is widely advocated and patients with ESRD have special health needs, but few studies have investigated whether integrated care was associated with health outcomes. Our aims were to evaluate the psychometric properties of the Korean-translated patient assessment of chronic illness care (PACIC) in patients with ESRD, and to evaluate whether PACIC evaluated by patients was associated with health outcomes. METHODS: ESRD patients on hemodialysis (n = 172) at 2 dialysis centers. Data quality, internal consistency and correlation between items and scales were assessed. To test the external validity, the association between PACIC and the health behaviour and outcomes of hemodialysis patients was analyzed. RESULTS: The mean score of the PACIC items was 3.0. The item-scale correlation (0.67-0.85) and test-retest correlation (0.72-0.82) regarding scales for internal consistency showed excellent consistency. Total PACIC score was significantly associated with dietary self-efficacy (ß = 0.22) and serum potassium (Exp(B) = 1.65). Higher overall PACIC score was significantly associated with higher physical health status (ß = 3.52). CONCLUSIONS: The Korean-translated PACIC questionnaire is a tool with reliability and validity. Comprehensive treatment strategies for ESRD patients may improve their health behaviors and outcomes.

Predictors of Burnout in Hospital Health Workers during the COVID-19 Outbreak in South Korea.

This study aimed to identify the factors that influence the components of burnout-emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA)-among hospital health workers, including doctors and nurses, during the COVID-19 pandemic. We analyzed 200 healthcare workers' responses to the Employee Health Promotion Survey conducted at a general hospital in Seoul with over 200 hospital beds. The questionnaire included items about COVID-19-related burnout and its influencing factors. We performed three different multiple regression analyses using EE, DP, and PA as the dependent variables. The results show that sex, marital status, workload of treating suspected COVID-19 patients, fear of COVID-19 infection, anxiety, and depression predicted EE. The predictors of DP were job category, consecutive months of work in the current department, satisfaction with work environment, anxiety, and depression. The predictors of PA were the workload of directly interacting with patients, socioeconomic status, and job stress. For EE and DP, burnout was found to be worse in doctors and nurses than in other health workers; moreover, burnout was worse among nurses than among doctors across all three aspects of burnout. The findings can be used to establish tailored policies to address each burnout component.

Supplementation with phosphatidylethanolamine confers anti-oxidant and anti-aging effects via hormesis and reduced insulin/IGF-1-like signaling in C. elegans.

Phosphatidylethanolamine is a major component of phospholipids with both structural and metabolic functions in cells. Previous studies have revealed that phosphatidylethanolamine can modulate autophagy with a protective effect against age-related diseases. We examined the effect of dietary supplementation with phosphatidylethanolamine on stress response and aging in Caenorhabditis elegans. Phosphatidylethanolamine increased resistance to oxidative stress without effect on heat stress or ultraviolet irradiation. Both mean and maximum lifespans were significantly increased by phosphatidylethanolamine while fertility was reduced as a trade-off. Age-related decline of muscle function was delayed in animals treated with phosphatidylethanolamine. Supplementation with phosphatidylethanolamine suppressed toxic effect of amyloid ß and high-glucose diet. Increased ROS levels and induction of stress-responsive genes after dietary supplementation with phosphatidylethanolamine suggest that anti-oxidative stress and anti-aging effects of phosphatidylethanolamine might be though hormesis. Genetic analysis using long-lived mutants and knockdown by RNAi revealed that the lifespan-extending effect of phosphatidylethanolamine overlapped with that of reduced insulin/IGF-1-like signaling and required DAF-16, a downstream transcription factor known to regulate the expression of many stress-responsive genes. These findings indicate that phosphatidylethanolamine has anti-oxidative stress and anti-aging activities with its underlying mechanisms involving hormesis and reduced insulin/IGF-1-like signaling in C. elegans.

Behavioural and psychological symptoms of dementia in patients with Alzheimer's disease and family caregiver burden: a path analysis.

BACKGROUND: Studies reported the relationship between behavioural and psychological symptoms of dementia (BPSD), cognitive function, caregiver burden, and therapeutic effects. However, the causal relationship between BPSD in community-dwelling patients with Alzheimer's disease (AD) and caregiver burden is yet to be established. This study aimed to classify BPSD in patients with AD and identify the relationship between BPSD and the factors affecting family caregiver burden. METHODS: Path analysis was conducted at a neurology outpatient clinic of a tertiary general hospital in South Korea. The medical records of 170 patients, aged ≥50 years, diagnosed with or suspected for AD were retrospectively reviewed. We investigated cognitive function (Korean version of the Mini-Mental-State Exam), dementia stages (Korean version of the Expanded Clinical Dementia Rating scale), depression (Short-form Geriatric Depression Scale-Korea), activities of daily living (ADL; Korean version of the Barthel Activities of Daily Living index), instrumental activities of daily living (IADL; Seoul-Instrumental Activities of Daily Living), and BPSD and caregiver burden (Korean Neuropsychiatric Inventory). Considering the characteristic features of BPSD with various symptoms, BPSD was classified using factor analysis. Factor extraction was performed using principal component analysis, followed by Varimax factor rotation. RESULTS: Mean total BPSD score was 17.66 ± 20.67, and the mean score for family caregiver burden was 9.65 ± 11.12. Symptom cluster-1 (hyperactivity symptoms) included disinhibition, irritability, and agitation/aggression. Symptom cluster-2 (psychosis symptoms) included hallucinations, anxiety, elation/euphoria, delusions, and depression/dysphoria. Symptom cluster-3 (physical behaviour symptoms) included appetite and eating abnormalities, apathy/indifference, aberrant motor behaviour, sleep, and night-time behaviour disturbances. Dementia stages, ADL, and IADL had indirect effects on family caregiver burden through hyperactivity, psychosis, and physical behaviour symptoms, indicating that BPSD exerted a complete mediating effect. CONCLUSIONS: Unlike previous studies, we classified BPSD symptoms into similar symptom clusters to evaluate its effect on caregiver burden, rather than collectively investigating the 12 symptoms of BPSD. As the dementia stage worsens, symptom clusters in BPSD serve as a medium between ADL and IADL degradation and for the increase in caregivers' burden. The development and implementation of therapeutic, nursing interventions, and policies focusing on dementia stages, ADL, and IADL, delaying and preventing BPSD can alleviate family caregivers' burden.

Associations between Frailty in Older Adults and Malnutrition in Rural Areas: 2019 Updated Version of the Asian Working Group for Sarcopenia.

PURPOSE: The purpose of this study was to evaluate the prevalence of frailty among an older adult population living in rural communities and to determine if frailty is associated with nutritional status after adjusting for sarcopenia and depression. MATERIALS AND METHODS: This research used baseline data from the Namgaram-2 study. Frailty was evaluated using the Kaigo-Yobo checklist in an older Korean population. The nutritional statuses of older people were measured using the Korean version of the mini nutritional assessment (MNA). The recent criteria of the Asian Working Group for Sarcopenia were applied for diagnosis of sarcopenia, and depression was assessed using the Geriatric Depression Scale-Short Form. RESULTS: The prevalence of frailty was 18.8% (male: 9.6%; female: 23.4%) and was significantly higher in individuals in their 80s [male, 35.3% (p<0.001); female, 42.3% (p<0.001)], those of poor economic status [male, 18.2% (p=0.012); female, 34.9% (p<0.001)], those with hypertension [female, 27.7% (p=0.008)], those with sarcopenia [male, 34.1% (p<0.001); female, 37.2% (p<0.001)], those with depression [male, 46.4% (p<0.001); female, 51.7% (p<0.001)], and those at high risk of malnutrition [male, 44.4% (p<0.001); female, 51.7% (p<0.001)]. After adjusting for demographic variables, including hypertension, diabetes, sarcopenia and depression, frailty was significantly associated with nutritional status [male: odds ratio (OR)=6.73, 95% confidence interval (CI), 1.84-24.65; female: OR=4.83, 95% CI, 2.88-8.11]. CONCLUSION: For older adults, MNA is a suitable tool of use in assessing both nutritional status and frailty. Moreover, the nutritional status of older adults appears to be associated with frailty, even after corrections for physical and psychological function.

GABAB-Receptor Agonist-Based Immunotherapy for Type 1 Diabetes in NOD Mice.

Some immune system cells express type A and/or type B γ-aminobutyric acid receptors (GABAA-Rs and/or GABAB-Rs). Treatment with GABA, which activates both GABAA-Rs and GABAB-Rs), and/or a GABAA-R-specific agonist inhibits disease progression in mouse models of type 1 diabetes (T1D), multiple sclerosis, rheumatoid arthritis, and COVID-19. Little is known about the clinical potential of specifically modulating GABAB-Rs. Here, we tested lesogaberan, a peripherally restricted GABAB-R agonist, as an interventive therapy in diabetic NOD mice. Lesogaberan treatment temporarily restored normoglycemia in most newly diabetic NOD mice. Combined treatment with a suboptimal dose of lesogaberan and proinsulin/alum immunization in newly diabetic NOD mice or a low-dose anti-CD3 in severely hyperglycemic NOD mice greatly increased T1D remission rates relative to each monotherapy. Mice receiving combined lesogaberan and anti-CD3 displayed improved glucose tolerance and, unlike mice that received anti-CD3 alone, had some islets with many insulin+ cells, suggesting that lesogaberan helped to rapidly inhibit ß-cell destruction. Hence, GABAB-R-specific agonists may provide adjunct therapies for T1D. Finally, the analysis of microarray and RNA-Seq databases suggested that the expression of GABAB-Rs and GABAA-Rs, as well as GABA production/secretion-related genes, may be a more common feature of immune cells than currently recognized.

Statin Supply and Polydrug Use in Older Adults: A Focus on Drug Combinations that Reduce Bone Density.

BACKGROUND: We investigated the comorbidities of individuals who were prescribed statins to identify the use of bone mineral density (BMD)-reducing drugs, examine polydrug use trends involving these drugs, and explore their relationship with osteoporosis. METHODS: We analyzed claims data from the Korean National Health Insurance Service (January 2014-December 2018). We sampled 20% of 8,379,419 patients aged ≥50 years who were prescribed statins. Among them, we analyzed the data of those who were administered two or more prescriptions for 14 days or longer within 6 months of the initial date of statin prescription. Data on comorbidities and drugs that can potentially reduce BMD were obtained. Osteoporosis-related diagnoses were obtained as an outcome measure. The relationship between statins and BMD-reducing drugs was analyzed using logistic regression. RESULTS: Among the 4,138 statin users aged 50 years or older, 552 were diagnosed with osteoporosis. The most common comorbidity in statin users was hypertension, followed by ischemic heart disease, diabetes mellitus, and stroke. The most frequently administered BMD-reducing drugs were proton pump inhibitors (PPIs). The osteoporosis diagnosis rate was higher in patients who were prescribed both statins and PPIs or both statins and levothyroxine than in those using only a statin. CONCLUSION: PPIs and levothyroxine should be prescribed cautiously in statin users and bone densitometry should be proactively performed considering the increased risk of osteoporosis.

The Association between Omega-3 Fatty Acid Intake and Human Brain Connectivity in Middle-Aged Depressed Women.

Omega-3 fatty acid (n-3 FA) intake is known to have a preventive effect on depressive symptoms in a general population. This study assessed the effects of n-3 FA intake on depressive symptoms and brain function in middle-aged women. Depressive symptoms were screened using the Beck Depression Inventory-II (BDI-II) and Center for Epidemiologic Studies-Depression scale (CES-D) assessment questionnaires, and n-3 FA intakes were assessed using semiquantitative food frequency questionnaire. We found that n-3 FA intakes were negatively associated with depressive symptoms in middle-aged women. Psychiatrists diagnosed the presence of depressive disorders using the 5th edition of the Mental Disorder Diagnosis and Statistics Manual (DSM-5). Resting-state functional magnetic resonance imaging (rs-fMRI) was performed to investigate the association between n-3 FA intake and brain functional connectivity. Functional connectivity of the right middle frontal cortex (default mode network) and the right middle temporal pole (frontoparietal network) was positively associated with depressive symptom scores and negatively associated with n-3 FA intakes. In conclusion, high n-3 FA intake decreases the risk of depressive symptoms and modifies the brain functional connectivity in middle-aged women.

Association of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) with Muscle Strength in Community-Dwelling Elderly with Knee Osteoarthritis.

PURPOSE: The purpose of this study was to evaluate the correlation between muscle strength and knee symptoms (pain, stiffness, and functional limitation) regardless of the presence of radiologic knee osteoarthritis (RKOA) in community-dwelling elderly. PATIENTS AND METHODS: This cross-sectional study used data from the Namgaram-2 cohort. The Namgaram-2 cohort consisted of participants living in three rural communities. Such participants were included for studies on activity limitation due to age-related musculoskeletal disorders including knee osteoarthritis, osteoporosis, and sarcopenia. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), a health assessment tool for patients with arthritis in lower extremities, was used to assess health-related quality of life (HRQOL). Muscle strengths were measured by knee strength (by using the isokinetic dynamometer) and hand grip strength. RESULTS: The WOMAC pain of Kallgren-Lawrence (K/L) grade < 2 was correlated with age, grip strength, nutrition status, and knee extension 180 peak torque. The WOMAC pain of K/L grade ≥ 2 was correlated with age, nutrition status, and knee extension 60 peak torque. The WOMAC stiffness of K/L grade < 2 was correlated with having a spouse, nutrition status, and knee extension 60 peak torque. The WOMAC stiffness of K/L grade ≥ 2 was correlated with knee extension 60 peak torque. The WOMAC function of K/L grade < 2 was correlated with age, grip strength, osteoporosis, nutrition status, and knee extension 180 peak torque. The WOMAC function of K/L grade ≥ 2 was correlated with age, nutrition status, and knee extension 60 peak torque. CONCLUSION: Muscle strength as measured by grip strength and knee extension was statistically significantly correlated with the WOMAC scores in patients with knee symptoms regardless of whether radiologic signs of knee osteoarthritis were observed.

Validation of the Western Ontario and McMaster Universities Arthritis Index Short Form (WOMAC-SF) and Its Relevance to Disability and Frailty.

PURPOSE: This study aimed to evaluate the validity of the Western Ontario and McMaster Universities Arthritis Index Short Form (WOMAC-SF) for the assessment of musculoskeletal disorders. We evaluated whether WOMAC-SF correlated with the World Health Organization Disability Assessment Schedule 12 (WHODAS-12) and Kaigo-Yobo questionnaires for assessing health-outcomes in Korea. MATERIALS AND METHODS: This cross-sectional study used data from the Namgaram-2 cohort. WOMAC, WOMAC-SF, WHODAS-12, and Kaigo-Yobo questionnaires were administered to patients with musculoskeletal disorders, including radiology-confirmed knee osteoarthritis (RKOA), sarcopenia, and osteoporosis. The relationships among WOMAC-SF, WHODAS-12, and Kaigo-Yobo scores were analyzed by stepwise multiple regression analysis. RESULTS: WOMAC-SF was associated with the WOMAC questionnaire. The results of confirmatory factor analysis for the hypothesized model with two latent factors, pain and function, provided satisfactory fit indices. WOMAC-SF pain and function were associated with RKOA. Kaigo-Yobo was associated with WOMAC-SF pain (B=0.140, p=0.001) and WOMAC-SF function (B=0.042, p=0.004). WHODAS-12 was associated with WOMAC-SF pain (B=0.679, p=0.003) and WOMAC-SF function (B=0.804, p<0.001). CONCLUSION: WOMAC-SF was validated for the evaluation of low extremity musculoskeletal disorders and health-related quality of life in a community-based population. Furthermore, we confirmed that WOMAC-SF were reflective of disability and frailty, which affect health outcomes.

Phosphatidylserine modulates response to oxidative stress through hormesis and increases lifespan via DAF-16 in Caenorhabditis elegans.

Phosphatidylserine is one of the phospholipids present in cell membranes, especially in brain and nervous system. The phosphatidylserine content is reduced with aging and age-related decrease in phosphatidylserine is known to contribute to cognitive impairment and Alzheimer's disease in the elderly. In the present study, we examined the effect of supplementation with phosphatidylserine on the response to oxidative stress and aging using C. elegans as a model system. Dietary supplementation with phosphatidylserine significantly increased resistance to oxidative stress and extended lifespan accompanying reduced fertility as a trade-off. Age-related decline in motility was also delayed by supplementation with phosphatidylserine. The cellular levels of reactive oxygen species and the expression of stress-responsive genes were increased by phosphatidylserine treatment, suggesting a hormetic effect. The extension of lifespan by phosphatidylserine overlaps with reduced insulin/IGF-1-like signaling and requires DAF-16. The effect of phosphatidylserine on age-related diseases was examined using animal model of disease. Supplementation with phosphatidylserine significantly suppressed amyloid beta-induced toxicity in Alzheimer's disease model. Reduced survival in diabetes mellitus due to high-glucose diet was reversed by supplementation with phosphatidylserine. This study reports the anti-oxidative stress and anti-aging effect of phosphatidylserine for the first time at the organismal level and proposes possible underlying mechanisms.

The Association of Perceived Neighborhood Walkability and Environmental Pollution With Frailty Among Community-dwelling Older Adults in Korean Rural Areas: A Cross-sectional Study.

OBJECTIVES: The aim of this study was to evaluate the associations of frailty with perceived neighborhood walkability and environmental pollution among community-dwelling older adults in rural areas. METHODS: The participants were 808 community-dwelling men and women aged 65 years and older in 2 rural towns. Comprehensive information, including demographics, socioeconomic status, grip strength, polypharmacy, perceived neighborhood environment (specifically, walkability and environmental pollution), and frailty, was collected from participants using face-to-face interviews conducted between June and August 2018. Perceived neighborhood walkability was measured using 20 items that were selected and revised from the Neighborhood Environment Walkability Scale, the Neighborhood Walkability Checklist from the National Heart Foundation of Australia, and the Physical Activity Neighborhood Environment Survey. The Kaigo-Yobo Checklist was used to assess participants' frailty. RESULTS: The overall prevalence of frailty in this community-dwelling population was 35.5%. Sex, age, cohabitation status, educational attainment, employment status, grip strength, and polypharmacy were significantly associated with frailty. In the logistic regression analysis, frailty was associated with low perceived neighborhood walkability (adjusted odds ratio [aOR], 0.881; 95% confidence interval [CI], 0.833 to 0.932; p<0.001) and severe perceived neighborhood environmental pollution (aOR, 1.052; 95% CI, 1.017 to 1.087; p=0.003) after adjusting for sex, age, cohabitation status, educational attainment, employment status, monthly income, grip strength, and polypharmacy. CONCLUSIONS: More studies are warranted to establish causal relationships between walkability and environmental pollution and frailty.

Cur2004-8, a synthetic curcumin derivative, extends lifespan and modulates age-related physiological changes in Caenorhabditis elegans.

Curcumin, a compound found in Indian yellow curry, is known to possess various biological activities, including anti-oxidant, anti-inflammatory, and anti-cancer activities. Cur2004-8 is a synthetic curcumin derivative having symmetrical bis-alkynyl pyridines that shows a strong anti-angiogenic activity. In the present study, we examined the effect of dietary supplementation with Cur2004-8 on response to environmental stresses and aging using Caenorhabditis elegans as a model system. Dietary intervention with Cur2004-8 significantly increased resistance of C. elegans to oxidative stress. Its anti-oxidative-stress effect was greater than curcumin. However, response of C. elegans to heat stress or ultraviolet irradiation was not significantly affected by Cur2004-8. Next, we examined the effect of Cur2004-8 on aging. Cur2004-8 significantly extended both mean and maximum lifespan, accompanying a shift in time-course distribution of progeny production. Age-related decline in motility was also delayed by supplementation with Cur2004-8. In addition, Cur2004-8 prevented amyloid-beta-induced toxicity in Alzheimer's disease model animals which required a forkhead box (FOXO) transcription factor DAF-16. Dietary supplementation with Cur2004-8 also reversed the increase of mortality observed in worms treated with high-glucose-diet. These results suggest that Cur2004-8 has higher anti-oxidant and anti-aging activities than curcumin. It can be used for the development of novel anti-aging product.

Phosphatidylcholine Extends Lifespan via DAF-16 and Reduces Amyloid-Beta-Induced Toxicity in Caenorhabditis elegans.

Phosphatidylcholine is one of the major phospholipids comprising cellular membrane and is known to have several health-promoting activities, including the improvement of brain function and liver repair. In this paper, we examine the in vivo effect of dietary supplementation with phosphatidylcholine on the response to environmental stressors and aging in C. elegans. Treatment with phosphatidylcholine significantly increased the survival of worms under oxidative stress conditions. However, there was no significant difference in response to stresses caused by heat shock or ultraviolet irradiation. Oxidative stress is believed to be one of the major causal factors of aging. Then, we examined the effect of phosphatidylcholine on lifespan and age-related physiological changes. Phosphatidylcholine showed a lifespan-extending effect and a reduction in fertility, possibly as a tradeoff for long lifespan. Age-related decline of motility was also significantly delayed by supplementation with phosphatidylcholine. Interestingly, the expressions of well-known longevity-assuring genes, hsp-16.2 and sod-3, were significantly upregulated by dietary intervention with phosphatidylcholine. DAF-16, a transcription factor modulating stress response genes, was accumulated in the nucleus by phosphatidylcholine treatment. Increase of the ROS level with phosphatidylcholine suggests that the antioxidant and lifespan-extending effects are due to the hormetic effect of phosphatidylcholine. Phosphatidylcholine also showed a protective effect against amyloid beta-induced toxicity in Alzheimer's disease model animals. Experiments with long-lived mutants revealed that the lifespan-extending effect of phosphatidylcholine specifically overlapped with that of reduced insulin/IGF-1-like signaling and required DAF-16. These findings showed the antioxidant and antiaging activities of phosphatidylcholine for the first time in vivo. Further studies focusing on the identification of underlying cellular mechanisms involved in the antiaging effect will increase the possibility of using phosphatidylcholine for the development of antiaging therapeutics.

The Association between Frailty and Disability among the Elderly in Rural Areas of Korea.

BACKGROUND: The rapid increase in the elderly population in Korea is associated with an expanded burden of health problems. The purpose of this study was to investigate the association between frailty and physical disability among Koreans using the frailty index, which was developed to assess health conditions in elderly people. METHODS: We included 503 elderly people from the Namgaram-II cohort. We used the Korean version of the Kaigo-Yobo checklist as our frailty assessment tool. For the disability assessment tool, we used the Korean version of the 12-item World Health Organization Disability Assessment Schedule (WHODAS-12). We fit multiple linear regression models for men and women for each section. Our models also included variables for musculoskeletal diseases that are known to be associated with frailty, such as sarcopenia, osteoporosis, and radiologic knee osteoarthritis. RESULTS: After correcting for social demographic characteristics, blood profiles, high blood pressure, and diabetes, the Kaigo-Yobo results showed a significant difference in frailty between men (1.53 ± 0.74) and women (2.60 ± 0.77), and WHODAS-12 also showed a significant difference between men (6.59 ± 5.08) and women (15.99 ± 5.70). After correcting for social demographic characteristics, blood profiles, high blood pressure, and diabetes, Kaigo-Yobo and WHODAS-12 were significantly associated with each other among both men (ß = 2.667) and women (ß = 3.200) (p < 0.001). CONCLUSIONS: The study results show an association between frailty and disability among elderly people in rural areas. Therefore, prevention should occur at the pre-frailty stage of a person's life to prevent further disability. Also, disability welfare programs should be provided to elderly people who present with frailty.