Association Between the Appendicular Extracellular-to-Intracellular Water Ratio and All-Cause Mortality: A 10-Year Longitudinal Study.

The appendicular extracellular-to-intracellular water ratio (A-E/I) is a potential marker of skeletal muscle quality, reflecting the balance of water distribution between the extracellular and intracellular compartments of the appendicular limb regions. A-E/I has been increasingly used in recent studies; however, its association with adverse outcomes remains unclear. This study investigated the potential association between A-E/I and all-cause mortality. A prospective cohort study of 8 015 middle-aged and older adults (comprised of 4 755 women, aged 45-74 years) residing in a Japanese community was conducted. The baseline assessment was performed between 2010 and 2012, and the follow-up period lasted until July 2022. A-E/I and skeletal muscle mass were measured using segmental bioelectrical impedance spectroscopy. Handgrip strength (HGS) was measured using a Smedley-type dynamometer. Lifestyle, medical history, and physical activity were assessed by questionnaire and accelerometer. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for each quartile (Q) of A-E/I were estimated using the multivariable Cox regression model. During a 10.5-year median follow-up, the mortality rates were 8.9 and 3.6 per 1 000 person-years for men (292 deaths) and women (174 deaths), respectively. A-E/I quartiles were positively associated with all-cause mortality in both sexes (men: Q1, HR: 1.0 [95% CI: reference], Q4, HR: 1.8 [1.1-2.9], ptrend < .05; women, Q4, HR: 2.2 [1.3-3.8], ptrend < .01). This association remained significant after further adjustment for skeletal muscle mass and HGS (ptrend < .05). Our findings suggest that A-E/I serves as an early predictive marker for mortality in middle-aged and older Japanese adults.

Dose-response relationship between daily step count and prevalence of sarcopenia: A cross-sectional study.

OBJECTIVES: Daily step counts are an easy-to-understand indicator of physical activity; however, there is limited evidence regarding the optimal daily step count to prevent sarcopenia. This study examined the dose-response relationship between daily step count and the prevalence of sarcopenia and explored the optimal dose. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: The study included 7949 community-dwelling middle-aged and older adults (aged 45-74 years) from Japan. MEASUREMENTS: Skeletal muscle mass (SMM) was assessed using bioelectrical impedance spectroscopy, and muscle strength was quantified through handgrip strength (HGS) measurement. Participants who exhibited both low HGS (men: <28 kg, women: <18 kg) and low SMM (lowest quartile in each sex-specific category) were defined as having sarcopenia. Daily step counts were measured for 10 days using a waist-mounted accelerometer. To examine the association between daily step count and sarcopenia, a multivariate logistic regression analysis was performed, adjusting for potential confounding factors such as age, sex, body mass index, smoking status, alcohol consumption, protein intake, and medical history. The odds ratios (ORs) and confidence intervals (CIs) were calculated based on the daily step counts categorized into quartiles (Q1-Q4). Finally, a restricted cubic spline curve was fitted to further investigate the dose-response relationship between daily step count and sarcopenia. RESULTS: The prevalence of sarcopenia in the overall participants was 3.3 % (259/7949 participants), with a mean daily step count of 7292 ± 2966 steps. Expressed in quartiles, the mean daily step counts were 3873 ± 935 steps in Q1, 6025 ± 503 steps in Q2, 7942 ± 624 steps in Q3, and 11,328 ± 1912 steps in Q4. The prevalence of sarcopenia in each quartile of daily step count was 4.7 % (93/1987 participants) in Q1, 3.4 % (68/1987 participants) in Q2, 2.7 % (53/1988 participants) in Q3, and 2.3 % (45/1987 participants) in Q4. The ORs and 95 % CIs adjusted for covariates demonstrated a statistically significant inverse association between daily step count and sarcopenia prevalence (P for trend <0.01), as follows: Q1, reference; Q2, 0.79 (95 % CI: 0.55-1.11); Q3, 0.71 (95 % CI: 0.49-1.03); Q4, 0.61 (95 % CI: 0.41-0.90). The restricted cubic spline curve indicated that the ORs leveled off at approximately 8000 steps per day, and no statistically significant decrease in ORs was observed for daily step counts above this threshold. CONCLUSIONS: The study found a significant inverse association between daily step count and the prevalence of sarcopenia, with the association plateauing when the daily step count exceeded approximately 8000 steps. These findings suggest that 8000 steps per day may be the optimal dose to prevent sarcopenia. Further intervention and longitudinal studies are needed to validate the results.

Association of appendicular extracellular-to-intracellular water ratio with age, muscle strength, and physical activity in 8,018 community-dwelling middle-aged and older adults.

BACKGROUND: The appendicular extracellular-to-intracellular water ratio (Ap ECW/ICW) has recently gained attention as a non-invasive measurable marker of muscle quality. However, there is a lack of basic evidence regarding age-related changes, sex differences, contribution to muscle strength independent of skeletal muscle mass (SMM), and potential improvement through physical activity (PA) in Ap ECW/ICW. METHODS: This cross-sectional study enrolled 8,018 middle-aged and older Japanese individuals (aged 45-75 years). The Ap ECW/ICW and SMM were measured using segmental bioelectrical impedance spectroscopy. Muscle strength was evaluated by measuring the handgrip strength (HGS) with a dynamometer, and the PA level (PAL) was measured with an accelerometer. We performed a linear regression analysis of the associations of the Ap ECW/ICW with age, HGS, and PAL. RESULTS: The Ap ECW/ICW increased by 0.019 for men and 0.014 for women per 5-year increase in age (p < 0.001), and the age-related increase was greater in men than in women (p for interaction <0.001). The Ap ECW/ICW was more strongly associated with the HGS than with the SMM in both men and women (p < 0.001). PAL showed a significant inverse association with the Ap ECW/ICW in both men and women (p < 0.001). CONCLUSIONS: Ap ECW/ICW is higher with age, and it varies by sex. The Ap ECW/ICW may reflect muscle strength more than the SMM, suggesting that the Ap ECW/ICW may be improved by PA. The findings from this study may provide a framework for further Ap ECW/ICW research.

Association between habitual coffee consumption and skeletal muscle mass in middle-aged and older Japanese people.

AIMS: Coffee consumption has been suggested, in animal studies, to inhibit the progression of sarcopenia, possibly through its anti-inflammatory effects; however, few studies have been carried out in humans. We aimed to examine whether coffee consumption was related to indicators of sarcopenia in a Japanese population, and whether the association was mediated by reduced inflammation. METHODS: This study was a cross-sectional design. Participants were community residents (n = 6369) aged 45-74 years. We measured skeletal muscle mass index (SMI; kg/m2 ) by a bioelectrical impedance method, and grip strength with a Smedley-type dynamometer. Habitual coffee consumption was assessed by a self-administered questionnaire. Serum high-sensitivity C-reactive protein was measured as an inflammatory marker. The association between habitual coffee consumption and SMI or grip strength was analyzed with a linear regression model adjusted for covariates. RESULTS: A significant positive association was found between coffee consumption and SMI (men: ß = 0.023; Ptrend  = 0.004, women: ß = 0.011; Ptrend  = 0.012). Further adjustment for high-sensitivity C-reactive protein did not materially alter the results (men: ß = 0.023; Ptrend  = 0.005, women: ß = 0.009; Ptrend  = 0.024). The relationship between coffee consumption and grip strength did not reach statistical significance; however, a positive trend was observed (men: ß = 0.208; Ptrend  = 0.085, women: ß = 0.092; Ptrend  = 0.167). CONCLUSIONS: We found that coffee consumption was positively associated with SMI independently of inflammation in middle-aged and older Japanese people. Reduced inflammation by coffee does not seem to be an important mediator, and further investigations are required to explore the mechanisms of this association. Geriatr Gerontol Int 2021; 21: 950-958.

Habitual Light-intensity Physical Activity and ASC Methylation in a Middle-aged Population.

Apoptosis-associated, speck-like protein containing a caspase recruitment domain (ASC) plays an important role in inflammatory cytokine synthesis in peripheral blood mononuclear cells (PBMCs), and the expression of ASC is suppressed by increased methylation of its CpG sites. The current study investigated the longitudinal association of replacing sedentary time with light-intensity physical activity (LPA) or moderate to vigorous-intensity physical activity (MVPA) on the ASC methylation in middle-aged people. We investigated 1 238 individuals who participated in baseline and 5-year follow-up surveys of a population-based cohort study. Sedentary, LPA and MVPA time were objectively measured using accelerometers. ASC methylation in PBMCs was measured by pyrosequencing. Using a multiple linear regression and employing an isotemporal substitution model, the longitudinal associations of changes in the sedentary time, LPA and MVPA on the changes in the ASC methylation were analyzed after adjusting for potential confounders. Substituting 60 min per day of LPA for sedentary time was associated with 1.17 times (95% confidence interval 1.07, 1.27) higher ASC methylation levels (mean of 7 CpG sites, P<0.001). However, such effects were not seen for MVPA. These results suggest that substituting LPA for sedentary time may be linked with increased (favorable) ASC methylation as a potential biomarker of systemic inflammation.

Coping strategy and social support modify the association between perceived stress and C-reactive protein: a longitudinal study of healthy men and women.

Inconsistent associations have been reported between perceived stress and C-reactive protein (CRP), a marker of systemic inflammation. We previously observed a male-specific inverse relationship between perceived stress and CRP in a cross-sectional study. In the present study, we examined the longitudinal association between changes in perceived stress and CRP, and further analyzed whether changes in coping strategies and social support modify this association. This study included 8454 participants in both a baseline survey and a follow-up survey 5 years later. Psychosocial measures (i.e. perceived stress, coping strategies, and social support) and CRP concentrations were measured by identical means in both surveys. Consistent with our previous findings, increased perceived stress was significantly associated with lower CRP in men (ptrend = .037), but not in women. Increased "emotional expression," a coping strategy, was also associated with lower CRP in women (ptrend = .024). Furthermore, interactions between perceived stress and a coping strategy (positive reappraisal) or social support on CRP were found in men (pinteraction = .007 and .038, respectively); the above inverse association between stress and CRP was not detected for participants with diminished positive reappraisal or social support. In conclusion, increases in perceived stress during a 5-year period were associated with decreases in CRP among healthy men, and the observed association was possibly modified by coping strategy or social support.

Intensity-specific effect of physical activity on urinary levels of 8-hydroxydeoxyguanosine in middle-aged Japanese.

Physical activity (PA) is recommended to both promote and maintain health and prevent cancer by improving the body's DNA repair system, which is considered a mechanism of cancer prevention. However, associations between PA and urinary levels of 8-hydroxydeoxyguanosine (8-OH-dG), which reflects DNA damage, are unclear. This cross-sectional study included 2370 men and 4052 women aged 45-74 years enrolled between 2010 and 2012. Habitual PA was assessed by single-axis accelerometer and urinary 8-OH-dG levels by automated HPLC. Multiple linear regression analysis was used to examine the relationship between log-transformed urinary 8-OH-dG and total PA (TPA) and PA of moderate/vigorous intensity (MVPA; ≥3 metabolic equivalents), with adjustment for age, body mass index, energy intake, alcohol consumption, smoking status, daily coffee drinking, menopause status (in women), and TPA (for MVPA). On multivariate adjustment, urinary 8-OH-dG levels were inversely correlated with TPA (ß = -0.020, P < 0.01) in women, and this correlation was not changed by PA intensity. Conversely, urinary 8-OH-dG levels were inversely correlated with MVPA (ß = -0.022, P < 0.05) in men, although the correlation with TPA was non-significant. This inverse correlation was clearer in current smokers than in never or former smokers, although the interaction between smoking status and MVPA on urinary 8-OH-dG levels was non-significant. In conclusion, greater TPA in women and greater MVPA in men were correlated with reduction in urinary 8-OH-dG, suggesting sex-specific effects of MVPA and TPA on protection from oxidative DNA damage. Increasing PA may mediate reduction in oxidative stress.

Factors associated with non-participation in a face-to-face second survey conducted 5 years after the baseline survey.

BACKGROUND: Non-participation in second surveys is reported to be associated with certain baseline characteristics; however, such data are unavailable for Japanese populations. Although disease incidence during follow-up might influence participation, few reports have addressed this possibility. This study sought to identify factors associated with non-participation in a second survey of a population-based cohort, and to evaluate the influence of self-reported disease incidence on non-participation. METHODS: After excluding participants who left the area (n = 423), died (n = 163), and withdrew from the study (n = 9) among 12 078 participants in a baseline survey for the Japan Multi-Institutional Collaborative Cohort Study in the Saga region between 2005 and 2007, 11 483 people were invited by mail to participate in a face-to-face second survey between 2010 and 2012. The 5-year clinical health history of non-participants was assessed by mail or telephone. Baseline characteristics and self-reported clinical outcomes of non-participants were compared with those of participants. RESULTS: Among 11 483 people, 8454 (73.6%) participated in the second survey, and 2608 out of 3029 non-participants answered mail or telephone health surveys. Female sex, youngest and oldest ages, lower education, lower occupational class, current smoking, lower physical activity level, shorter sleep time, obesity, and constipation were associated with non-participation. Light drinking (0.1-22.9 g ethanol/day) was associated with participation. Non-participants reported a significantly higher incidence of cancer and a significantly lower proportion of hypertension compared with participants. CONCLUSIONS: Both baseline characteristics and disease incidence during the follow-up period had significant associations with non-participation in the face-to-face second survey.

Estimation of thigh muscle cross-sectional area by single- and multifrequency segmental bioelectrical impedance analysis in the elderly.

Bioelectrical impedance analysis (BIA) has been used to estimate skeletal muscle mass, but its application in the elderly is not optimal. The accuracy of BIA may be influenced by the expansion of extracellular water (ECW) relative to muscle mass with aging. Multifrequency BIA (MFBIA) can evaluate the distribution between ECW and intracellular water (ICW), and thus may be superior to single-frequency BIA (SFBIA) to estimate muscle mass in the elderly. A total of 58 elderly participants aged 65-85 years were recruited. Muscle cross-sectional area (CSA) was obtained from computed tomography scans at the mid-thigh. Segmental SFBIA and MFBIA were measured for the upper legs. An index of the ratio of ECW and ICW was calculated using MFBIA. The correlation between muscle CSA and SFBIA was moderate (r = 0.68), but strong between muscle CSA and MFBIA (r = 0.85). ECW/ICW index was significantly and positively correlated with age (P < 0.001). SFBIA tends to significantly overestimate muscle CSA in subjects who had relative expansion of ECW in the thigh segment (P < 0.001). This trend was not observed for MFBIA (P = 0.42). Relative expansion of ECW was observed in older participants. The relative expansion of ECW affects the validity of traditional SFBIA, which is lowered when estimating muscle CSA in the elderly. By contrast, MFBIA was not affected by water distribution in thigh segments, thus rendering the validity of MFBIA for estimating thigh muscle CSA higher than SFBIA in the elderly.