Short sleep duration and smoking initiation in university students: a retrospective cohort study.

PURPOSE: The aim of this study was to clarify an association between short sleep duration and smoking initiation. METHODS: Participants eligible for this retrospective cohort study were university students who were admitted to a single national university in Japan between 2007 and 2015. Baseline sleep duration and smoking status were measured using general questionnaires at health checkups at admission. During a 6-year observation period, smoking initiation was assessed using general questionnaires at annual health checkups. Cox proportional hazards models adjusted for clinically relevant factors were used to assess the association between sleep duration and smoking initiation. RESULTS: Of 17,493 men, including 540, 5,568, 8,458, 2,507, and 420 men with sleep duration of < 5, 5-6, 6-7, 7-8, and ≥ 8 h, respectively, smoking initiation was observed in 16.1%, 12.5%, 11.2%, 10.0%, and 11.7%, respectively, during a median observation period of 3.0 years. Men with shorter sleep duration were at a higher risk of smoking initiation (adjusted hazard ratio 1.49 [95% confidence interval 1.19-1.85], 1.11 [1.01-1.22], 1.00 [reference], 0.92 [0.80-1.06], and 1.00 [0.75-1.34], respectively). Of 8,880 women, including 267, 3,163, 4,220, and 1,230 women with sleep duration of < 5, 5-6, 6-7, and ≥ 7 h, respectively, smoking initiation was observed in 4.9%, 2.3%, 2.0%, and 2.2%, respectively, during a median observation period of 3.0 years. A similar dose dependent association was ascertained in women (2.50 [1.39-4.49], 1.18 [0.86-1.62], 1.00 [reference], and 1.22 [0.79-1.89], respectively). CONCLUSION: This study clarified that university students with short sleep duration were vulnerable to smoking initiation.

Living Arrangements Predict Frequent Alcohol Consumption Among University Students: A Retrospective Cohort Study.

PURPOSE: This study aimed to confirm the clinical impact of living arrangements on incidence of frequent alcohol consumption in university students. DESIGN: A retrospective cohort study. SETTING: A national university in Japan. SUBJECTS: 17,774 university students. MEASURES: The association between living arrangements on admission and the incidence of frequent alcohol consumption (≥4 days/week) was assessed using multivariable-adjusted Cox proportional-hazards models. RESULTS: Among 5,685, 692, and 5,151 male students living with family, living in the dormitory, and living alone, 5.0%, 6.2%, and 5.8% reported frequent alcohol consumption during the median observational period of 3.0 years, respectively. Living in the dormitory and living alone were identified as significant predictors of frequent alcohol consumption (multivariable-adjusted hazard ratios: 1.00 [reference], 1.39 [1.01-1.92], and 1.21 [1.03-1.42], respectively). On the contrary, living arrangements were not associated with the incidence of frequent alcohol consumption among of 6,091 female students, partly because of low incidence of frequent alcohol consumption (2.3%, 1.4%, and 2.6%, respectively). CONCLUSIONS: Living arrangements predicted frequent alcohol consumption among male university students, whereas not among female university students.

Association of secondhand smoke exposure and health-related lifestyle behaviors among male university employees in Japan.

Secondhand smoke (SHS) exposure causes various health problems associated with an unhealthy lifestyle. However, the lifestyles of individuals exposed to SHS have not been characterized extensively. Therefore, this cross-sectional study aimed to investigate the association between SHS exposure and lifestyle behaviors. The participants were 2379 healthy male employees at Osaka University who underwent health examinations. Physical and biochemical parameters and lifestyle behavior data were obtained from all the participants. Participants with SHS exposure had significantly higher body mass index, waist circumference, and serum levels of triglycerides and uric acid than that of those without SHS exposure. SHS exposure was significantly correlated with several lifestyle behaviors, including TV time, frequency of breakfast consumption and fried food consumption, vegetable and fruit intake, alcohol consumption frequency and daily alcohol intake, and smoking status. Thus, SHS exposure may be associated with an unhealthy lifestyle. The lifestyle behaviors of the smoke-excluded population were assessed further; however, SHS exposure was still associated with dietary and drinking habits. Since participants with SHS exposure are likely to have an unhealthy life and combined unhealthy lifestyle behaviors, the confounding effect of these factors should be considered when assessing the impact of SHS exposure on health.

Case-Control Study of Long COVID, Sapporo, Japan.

We conducted a cross-sectional survey among SARS-CoV-2-positive persons and negative controls in Sapporo, Japan, to clarify symptoms of long COVID. We collected responses from 8,018 participants, 3,694 case-patients and 3,672 controls. We calculated symptom prevalence for case-patients at 2-3, 4-6, 7-9, 10-12, and 13-18 months after illness onset. We used logistic regression, adjusted for age and sex, to estimate the odds ratio (OR) for each symptom and control reference. We calculated symptom prevalence by stratifying for disease severity, age, and sex. At 4-18 months from illness onset, ORs for anosmia, ageusia, dyspnea, alopecia, and brain fog were consistently >1, whereas ORs for common cold-like, gastrointestinal, and dermatologic symptoms were <1. Time trend ORs increased for diminished ability to concentrate, brain fog, sleep disturbance, eye symptoms, and tinnitus. Clinicians should focus on systemic, respiratory, and neuropsychiatric symptoms among long COVID patients.

Living alone and prediction of weight gain and overweight/obesity in university students: a retrospective cohort study.

Objective:  To assess the clinical impact of living alone on weight gain in university students. Participants: This retrospective cohort study included 17540 male and 8854 female university students admitted to a national university in Japan. Methods: An association between living arrangement and the incidence of weight gain ≥10% and overweight/obesity (body mass index (BMI) ≥25 kg/m2) was assessed using multivariable-adjusted Poisson regression models. Results: Weight gain was observed in 1889 (10.8%) male and 1516 (17.1%) female students during 3.0 and 2.9 years of the mean observational period, respectively. Living alone was identified as a significant predictor of weight gain (adjusted incidence rate ratio of living alone vs. living with family: 1.24 [1.13-1.36] and 1.76 [1.58-1.95] in male and female students, respectively) and was also as a predictor of overweight/obesity. Conclusions: University students living alone were at a significantly higher risk of weight gain and overweight/obesity than those living with family.

Soluble angiotensin-converting enzyme 2 association with lipid metabolism.

Increased expression of angiotensin-converting enzyme 2 (ACE2) is one of the likely explanations for disease severity in patients with coronavirus disease 2019 (COVID-19). In this study, we aimed to test whether soluble ACE2 (sACE2) levels are correlated to known risk factors of severe COVID-19 including biochemical parameters, body mass index and smoking habits. We cross-sectionally evaluated serum sACE2 levels in obese or tobacco-smoking populations and compared them to those in non-obese and non-smoking healthy participants. Additionally, fibroblast growth factor-21 (FGF21) was investigated as a candidate regulator of sACE2. A total of 220 male participants aged 30-59 years undergoing an annual health checkup were enrolled in this study: 59 obese, 80 smokers, and 81 healthy. Serum sACE2 levels were significantly higher in obese participants but not in tobacco-smoking participants when compared to healthy participants. sACE2 levels were significantly correlated with total cholesterol and triglycerides but not with body mass index. Furthermore, no regulatory relationship was found between FGF21 and sACE2. Lipid metabolism disorders accompanied by upregulation of serum sACE2 may be underlying mechanisms of COVID-19 aggravation and might be a novel breakthrough treatment target.

Skipping Breakfast and Incidence of Frequent Alcohol Drinking in University Students in Japan: A Retrospective Cohort Study.

Frequency of alcohol drinking is a potential predictor of binge drinking of alcohol, a serious social problem for university students. Although previous studies have identified skipping breakfast as a predictor of various health-compromising behaviors and cardiometabolic diseases, few studies have assessed the association between skipping breakfast and the incidence of frequent alcohol drinking. This retrospective cohort study included 17,380 male and 8799 female university students aged 18-22 years admitted to Osaka universities between 2004 and 2015. The association between breakfast frequency (eating every day, skipping occasionally, and skipping often/usually) and the incidence of frequent alcohol drinking, defined as drinking ≥4 days/week, was assessed using multivariable-adjusted Cox proportional hazards models. During the median observational period of 3.0 years, 878 (5.1%) men and 190 (2.2%) women engaged in frequent alcohol drinking. Skipping breakfast was significantly associated with the incidence of frequent alcohol drinking (adjusted hazard ratios [95% confidence interval] of eating every day, skipping occasionally, and skipping often/usually: 1.00 [reference], 1.02 [0.84-1.25], and 1.48 [1.17-1.88] in men; 1.00 [reference], 1.60 [1.03-2.49], and 3.14 [1.88-5.24] in women, respectively). University students who skipped breakfast were at a higher risk of frequent alcohol drinking than those who ate breakfast every day.

Singing Is a Risk Factor for Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Case-Control Study of Karaoke-Related Coronavirus Disease 2019 Outbreaks in 2 Cities in Hokkaido, Japan, Linked by Whole Genome Analysis.

Background: Singing in an indoor space may increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a case-control study of karaoke-related coronavirus disease 2019 (COVID-19) outbreaks to reveal the risk factors for SARS-CoV-2 infection among individuals who participate in karaoke. Methods: Cases were defined as people who enjoyed karaoke at a bar and who tested positive for SARS-CoV-2 by reverse-transcription polymerase chain reaction between 16 May and 3 July 2020. Controls were defined as people who enjoyed karaoke at the same bar during the same period as the cases and tested negative. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. ORs of key variables adjusted for each other were also estimated (aOR). Results: We identified 81 cases, the majority of whom were active elderly individuals (median age, 75 years). Six cases died (case fatality ratio, 7%). Among the cases, 68 (84%) were guests, 18 of whom had visited ≧2 karaoke bars. A genome analysis conducted in 30 cases showed 6 types of isolates within 4 single-nucleotide variation difference. The case-control study revealed that singing (aOR, 11.0 [95% CI, 1.2-101.0]), not wearing a mask (aOR, 3.7 [95% CI, 1.2-11.2]), and additional hour spent per visit (aOR, 1.7 [95% CI, 1.1-2.7]) were associated with COVID-19 infection. Conclusions: A karaoke-related COVID-19 outbreak that occurred in 2 different cities was confirmed by the results of genome analysis. Singing in less-ventilated, indoor and crowded environments increases the risk of acquiring SARS-CoV-2 infection. Wearing a mask and staying for only a short time can reduce the risk of infection during karaoke.

Serum FGF21 levels are altered by various factors including lifestyle behaviors in male subjects.

Fibroblast growth factor (FGF) 21 has various functions, including glucose and lipid metabolism. This cross-sectional study aimed to investigate specific conditions that might influence the functions of FGF21. 398 men who underwent a health examination were enrolled in this study. Physical and biochemical parameters and information on several lifestyle behaviors were obtained from all subjects. FGF21 levels correlated with age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), uric acid, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), fasting plasma glucose (FPG), and HbA1c. Moreover, FGF21 levels were significantly associated with lifestyle behaviors, including smoking status and breakfast and alcohol consumption frequency. Multivariable regression analysis showed that age, ALT, γ-GTP, smoking status, and breakfast and alcohol consumption frequency were independent variables for FGF21 levels. Assessment among the non-obese and obese groups showed that FGF21 levels correlated with WC, SBP, and TC only in the non-obese group. Thus, serum FGF21 levels were affected by several factors, including lifestyle behaviors, age, and liver function. To assess the functions of FGF21 in individuals, considering these factors would be essential.

Vegetable Preference and Prediction of Proteinuria: A Retrospective Cohort Study.

INTRODUCTION: Little information is available about the association between vegetable preference and chronic kidney disease. METHODS: This retrospective cohort study included 10,819 university workers in Japan who underwent their annual health checkups between January 2005 and March 2013. According to a question "Do you like vegetables"? with 3 possible answers of "I like vegetables," "I like vegetables somewhat," or "I dislike vegetables," 2,831, 2,249, and 104 male workers and 3,902, 1,648, and 85 female workers were classified into the "like," "somewhat," and "dislike" groups, respectively. An association between vegetable preference and incidence of proteinuria (dipstick urinary protein ≥1+) was assessed using Cox proportional-hazards models adjusted for clinically relevant factors. RESULTS: During the median observational period of 5.0 years, the incidence of proteinuria was observed in 650 (12.7%) male and 789 (14.1%) female workers. Among male workers, the "dislike" group had a significantly higher risk of proteinuria (multivariable-adjusted hazard ratio of "like," "somewhat," and "dislike" groups: 1.00 [reference], 1.05 [0.90-1.23], and 1.59 [1.01-2.50], respectively). Among female workers, vegetable preference was associated with the incidence of proteinuria in a dose-dependent manner (1.00 [reference], 1.20 [1.04-1.40], 1.95 [1.26-3.02], respectively). CONCLUSION: "Do you like vegetables"? was a clinically useful tool to identify subjects vulnerable to proteinuria.

Proteomics of serum extracellular vesicles identifies a novel COPD biomarker, fibulin-3 from elastic fibres.

There is an unmet need for novel biomarkers in the diagnosis of multifactorial COPD. We applied next-generation proteomics to serum extracellular vesicles (EVs) to discover novel COPD biomarkers. EVs from 10 patients with COPD and six healthy controls were analysed by tandem mass tag-based non-targeted proteomics, and those from elastase-treated mouse models of emphysema were also analysed by non-targeted proteomics. For validation, EVs from 23 patients with COPD and 20 healthy controls were validated by targeted proteomics. Using non-targeted proteomics, we identified 406 proteins, 34 of which were significantly upregulated in patients with COPD. Of note, the EV protein signature from patients with COPD reflected inflammation and remodelling. We also identified 63 upregulated candidates from 1956 proteins by analysing EVs isolated from mouse models. Combining human and mouse biomarker candidates, we validated 45 proteins by targeted proteomics, selected reaction monitoring. Notably, levels of fibulin-3, tripeptidyl-peptidase 2, fibulin-1, and soluble scavenger receptor cysteine-rich domain-containing protein were significantly higher in patients with COPD. Moreover, six proteins; fibulin-3, tripeptidyl-peptidase 2, UTP-glucose-1-phosphate uridylyl transferase, CD81, CD177, and oncoprotein-induced transcript 3, were correlated with emphysema. Upregulation of fibulin-3 was confirmed by immunoblotting of EVs and immunohistochemistry in lungs. Strikingly, fibulin-3 knockout mice spontaneously developed emphysema with age, as evidenced by alveolar enlargement and elastin destruction. We discovered potential pathogenic biomarkers for COPD using next-generation proteomics of EVs. This is a novel strategy for biomarker discovery and precision medicine.

Serum Klotho Levels Contribute to the Prevention of Disease Progression.

BACKGROUND: Assessing the progression of a disorder from its pre-clinical state is important in the prevention of various diseases. In the present study, we evaluated the role of serum levels of αKlotho (αKl) in the progression of several pre-clinical disorders. METHODS: This cohort study included 80 males who underwent their annual health checkup during the entry period between April 2005 and March 2008. Physical and biochemical parameters were obtained from all subjects. The associations of baseline serum levels of soluble αKl (sαKl) with the progression of the disorders were assessed in the study. RESULTS: Baseline serum levels of sαKl were significantly lower in subjects developing a high fasting plasma glucose (FPG) level than in subjects not developing a high FPG level. Logistic multivariable analysis showed that baseline serum levels of sαKl and FPG levels significantly associated with a high FPG level progression. It is suggested that low sαKl levels are associated with the progression of hyperglycemia. Evaluation of serum levels of sαKl in subjects with multiple disorders revealed that those with more pre-clinical disorders progression tended to show lower sαKl levels. CONCLUSION: A decrease in serum levels of sαKl could be associated with the progression of pre-clinical disorders.

Associations of Skipping Breakfast, Lunch, and Dinner with Weight Gain and Overweight/Obesity in University Students: A Retrospective Cohort Study.

Although multiple studies have identified skipping breakfast as a risk factor for weight gain, there is limited evidence on the clinical impact of skipping lunch and dinner on weight gain. This retrospective cohort study including 17,573 male and 8860 female university students at a national university in Japan, assessed the association of the frequency of breakfast, lunch, and dinner with the incidence of weight gain (≥10%) and overweight/obesity (body mass index ≥ 25 kg/m2), using annual participant health checkup data. Within the observation period of 3.0 ± 0.9 years, the incidence of ≥10% weight gain was observed in 1896 (10.8%) men and 1518 (17.1%) women, respectively. Skipping dinner was identified as a significant predictor of weight gain in multivariable-adjusted Poisson regression models for both men and women (skipping ≥ occasionally vs. eating every day, adjusted incidence rate ratios, 1.45 (95% confidence interval: 1.04-2.01) and 1.67 (1.33-2.09) in male and female students, respectively), whereas skipping breakfast and lunch were not. Similarly, skipping dinner, not breakfast or lunch, was associated with overweight/obesity (1.74 (1.07-2.84) and 1.68 (1.02-2.78) in men and women, respectively). In conclusion, skipping dinner predicted the incidence of weight gain and overweight/obesity in university students.

Alpha-Klotho is a novel predictor of treatment responsiveness in patients with heart failure.

Heart failure is a major cause of death with an increasing population of elderly individuals. Several studies have demonstrated the involvement of soluble alpha-Klotho (sαKl) in various diseases. However, the correlation between sαKl and heart failure remains to be understood. The aim of this study is to investigate the levels and role of sαKl in patients with heart failure. Twenty-eight consecutive patients with acute heart failure (19 male, 9 female), admitted to the Osaka University Hospital from 2010 to 2018, were enrolled in this study. Mean NYHA score, left ventricular ejection fraction and BNP were 3.3, 17.0% and 588 pg/mL, respectively. SαKl significantly increased in heart failure patients. SαKl on admission were significantly higher in patients with heart failure who showed improvement after intensive treatment than that in patients who did not show improvement after the treatment. SαKl levels decreased significantly in patients who showed improvement. Interestingly, sαKl levels increased in male patients with heart failure, but not in female patients. Our data suggest that soluble αKl may be a novel biomarker for the responsiveness against treatment in patients with heart failure with reduced ejection fraction. Our findings may help developing a personalized therapy for different patients with heart failure.

Occupational sedentary behavior and prediction of proteinuria in young to middle-aged adults: a retrospective cohort study.

BACKGROUND: Although sedentary behavior is a risk factor of cardiometabolic diseases and mortality, little information is available about a clinical impact of occupational sedentary behavior on chronic kidney disease (CKD). METHODS: The present retrospective cohort study included 10,212 workers of a national university in Japan who underwent annual health checkups between April 2006 and March 2013. Main exposure of interest was self-reported occupational sedentary behavior at the baseline visit. The outcome was the incidence of proteinuria defined as dipstick urinary protein of 1 + or more. The association between sedentary workers and the incidence of proteinuria was assessed using Cox proportional hazards models adjusting for clinically relevant factors, including television viewing time, the major home sedentary behavior. RESULTS: During median 4.8 years (interquartile range 2.1-7.9) of the observational period, the incidence of proteinuria was observed in 597 (12.0%) males and 697 (13.3%) females. In males, sedentary workers were identified as a significant predictor of proteinuria (multivariable-adjusted hazard ratio of non-sedentary and sedentary workers: 1.00 [reference] and 1.35 [1.11-1.63]), along with longer television viewing time (< 30 min, 30-60 min, 1-2 h, 2-3 h, and > 3 h/day: 1.15 [0.93-1.42], 1.00 [reference], 1.24 [1.00-1.53], 1.41 [1.03-1.93], and 1.77 [1.13-2.76]), whereas not daily exercise time. In females, neither sedentary workers nor television viewing time was associated with the incidence of proteinuria. CONCLUSIONS: In conclusion, male sedentary workers were at high risk of proteinuria. Occupational sedentary behavior may be a potentially modifiable target for the prevention of CKD.

Frequency of Breakfast, Lunch, and Dinner and Incidence of Proteinuria: A Retrospective Cohort Study.

Although multiple studies have revealed a close association of skipping breakfast with cardiometabolic diseases, few studies have reported its association with chronic kidney disease (CKD). Furthermore, there is scant reporting on the clinical impacts that skipping lunch and dinner has on cardiometabolic diseases and CKD. This retrospective cohort study, including 5439 female and 4674 male workers of a national university in Japan who underwent annual health checkups between January 2005 and March 2013, aimed to assess an association of frequencies of breakfast, lunch, and dinner with incidence of proteinuria (dipstick urinary protein ≥1+). The incidence of proteinuria was observed in 763 (14.0%) females and 617 (13.2%) males during the median 4.3 and 5.9 years of the observational period, respectively. In females, skipping breakfast as well as skipping dinner, but not lunch, were associated with the incidence of proteinuria (adjusted hazard ratios of breakfast frequency of "every day", "sometimes", and "rarely": 1.00 (reference), 1.35 (1.09-1.66), and 1.54 (1.22-1.94), respectively; those of dinner frequency of "every day" and "≤sometimes": 1.00 (reference) and 1.31 (1.00-1.72), respectively). However, no association was observed in male workers. Skipping breakfast and skipping dinner were identified as risk factors of proteinuria in females, but not in males.

Body mass index modifies the association between frequency of alcohol consumption and incidence of hypertension in men but not in women: a retrospective cohort study.

Alcohol consumption is one of the major modifiable risk factors of hypertension. The aim of the present retrospective study was to assess the clinical impact of obesity on the association between alcohol consumption and the incidence of hypertension. The present study included 5116 male and 6077 female university employees with a median age of 32 (interquartile range 27-39) who underwent annual health checkups between January 2005 and March 2013. Self-reported drinking frequency was recorded at their first checkup and categorized into rarely and 1-3, 4-6, and 7 days/week. During the median observational period of 4.9 years (interquartile range 2.1-8.3), hypertension, defined as systolic/diastolic blood pressure of ≥140/90 mmHg and/or self-reported treatment for hypertension, was observed in 1067 (20.9%) men and 384 (6.3%) women. Poisson regression models adjusted for clinically relevant factors revealed a dose-dependent association between drinking frequency and the incidence of hypertension in men (adjusted incidence rate ratio [95% confidence interval] of men who drank rarely, 1-3, 4-6, and 7 days/week was 1.00 [reference], 1.12 [0.97-1.30], 1.42 [1.19-1.70], and 1.35 [1.14-1.59], respectively; Ptrend < 0.001). However, this association was not observed in women. The dose-dependent association was significant in nonobese men (body mass index (BMI) < 25 kg/m2), but not in obese men (BMI ≥25 kg/m2) (P for interaction between drinking frequency and BMI = 0.072). The present study provides clinically useful evidence to identify the drinkers who may reap the health benefits of abstinence from alcohol consumption.

Sleep debt and prevalence of proteinuria in subjects with short sleep duration on weekdays: a cross-sectional study.

STUDY OBJECTIVE: Short sleep duration is a risk factor of chronic kidney disease, along with cardiovascular diseases and all-cause mortality. Several studies reported that many people sleep longer on weekends than on weekdays, suggesting that they should be compensated for their sleep debt on weekdays on the weekends. Few studies have reported the clinical impact of sleep debt on the kidney. METHODS: This cross-sectional study included 5799 employees of Osaka University who visited its Health Care Center for their annual health examinations and answered ≤ 6 h of sleep duration on weekdays. The independent variable was the sleep debt index defined as a gap in self-reported sleep duration (≤ 5, 5-6, 6-7, 7-8, 8-9, and ≥ 9 h) between weekdays and weekends, which was categorized into ≤ 0, + 1, + 2, + 3 and ≥+4. An association between the sleep debt index and a prevalence of proteinuria defined as dipstick proteinuria of ≥ 1 + was assessed using logistic regression models adjusting for clinically relevant factors. RESULTS: More than four-fifths of the subjects had a positive sleep debt index (≤ 0, + 1, + 2, + 3, and ≥+4 recorded for 19%, 36%, 28%, 11%, and 6%, respectively). The multivariable-adjusted logistic regression models showed the sleep debt index ≥ 3 + was significantly associated with the prevalence of proteinuria (sleep debt index ≤ 0, adjusted odds ratio 1.13 [0.77, 1.65]; + 1, 1.00 [reference]; + 2, 1.29 [0.93, 1.79]; + 3, 1.54 [1.02, 2.33]; ≥ + 4, 1.87 [1.15, 3.05]). CONCLUSIONS: Sleep debt was associated with the prevalence of proteinuria in a dose-dependent manner.

Implication of alpha-Klotho as the predictive factor of stress.

Stress is known as a risk factor for both mental and physical health problems. While stress is known as one of the major health problems in modern society, a biomarker of stress has not yet been well established. In the present study, we focused on the serum levels of α-Klotho (αKl) as a possible objective biomarker of stress. Subjects included apparently healthy individuals who underwent a health examination in the Osaka University Health and Counseling Center. Physical and biochemical parameters were obtained from all subjects. Information regarding the lifestyle of each individual was obtained via questionnaires. Among male subjects, serum levels of soluble αKl (sαKl) were significantly elevated in subjects who had poor stress management and unsatisfactory sleep, suggesting that stress management and sleeping conditions influenced the serum levels of sαKl. The total Kessler Screening Scale for Psychological Distress (K6) score was significantly increased in subjects who reported experiencing considerable stress, had poor stress management and unsatisfactory sleep. Since serum levels of sαKl showed the same tendency as the K6 score in terms of the relationship between stress management and sleeping conditions in male subjects, increased sαKl levels could be associated with considerable psychological stress in healthy men.

Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated aging.

Chronic obstructive pulmonary disease (COPD) has been recently characterized as a disease of accelerated lung aging, but the mechanism remains unclear. Tetraspanins have emerged as key players in malignancy and inflammatory diseases. Here, we found that CD9/CD81 double knockout (DKO) mice with a COPD-like phenotype progressively developed a syndrome resembling human aging, including cataracts, hair loss, and atrophy of various organs, including thymus, muscle, and testis, resulting in shorter survival than wild-type (WT) mice. Consistent with this, DNA microarray analysis of DKO mouse lungs revealed differential expression of genes involved in cell death, inflammation, and the sirtuin-1 (SIRT1) pathway. Accordingly, expression of SIRT1 was reduced in DKO mouse lungs. Importantly, siRNA knockdown of CD9 and CD81 in lung epithelial cells additively decreased SIRT1 and Foxo3a expression, but reciprocally upregulated the expression of p21 and p53, leading to reduced cell proliferation and elevated apoptosis. Furthermore, deletion of these tetraspanins increased the expression of pro-inflammatory genes and IL-8. Hence, CD9 and CD81 might coordinately prevent senescence and inflammation, partly by maintaining SIRT1 expression. Altogether, CD9/CD81 DKO mice represent a novel model for both COPD and accelerated senescence.