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.

Association of skeletal muscle function, quantity, and quality with gut microbiota in Japanese adults: A cross-sectional study.

AIM: The gut microbiota has emerged as a new intervention target for sarcopenia. Prior studies in humans have focused on the association between gut microbiota and skeletal muscle quantity, while the evidence on muscle function and quality is lacking. This study aimed to identify gut microbiota genera associated with skeletal muscle function, quantity, and quality in a general population of Japanese adults. METHODS: This cross-sectional study included 164 participants aged 35-80 years, women and men recruited from urban areas of Japan. Fecal samples were collected and analyzed using 16S rRNA gene amplicon sequencing. Skeletal muscle function was measured using handgrip strength and leg extension power (LEP), while skeletal muscle mass was estimated using bioelectrical impedance analysis. Phase angle was used as a measure of skeletal muscle quality. Multivariate linear regression analysis stratified by age group was used to examine the association between the dominant genera of the gut microbiota and skeletal muscle variables. RESULTS: A significant association was found between Bacteroides and Prevotella 9 with LEP only in the ≥60 years group. When both Bacteroides and Prevotella 9 were included in the same regression model, only Bacteroides remained consistently and significantly associated with LEP. No significant associations were observed between skeletal muscle mass, handgrip strength, and phase angle and major gut microbiota genera. CONCLUSIONS: In this study, we observed a significant positive association between Bacteroides and leg muscle function in older adults. Further studies are required to elucidate the underlying mechanisms linking Bacteroides to lower-extremity muscle function. Geriatr Gerontol Int 2024; 24: 53-60.

Association between physical activity and the prevalence of tumorigenic bacteria in the gut microbiota of Japanese adults: a cross-sectional study.

Escherichia coli harboring polyketide synthase (pks+ E. coli) has been suggested to contribute to colorectal cancer development. Physical activity is strongly associated with lower colorectal cancer risks, but its effects on pks+ E. coli remain unclear. The aim of this study was to investigate the association between pks+ E. coli prevalence and physical activity. A cross-sectional study was conducted on 222 Japanese adults (27-79-years-old, 73.9% female). Triaxial accelerometers were used to measure light-intensity physical activity, moderate-to-vigorous intensity physical activity, the physical activity level, step-count, and time spent inactive. Fecal samples collected from participants were used to determine the prevalence of pks+ E. coli. Multivariate logistic regression analysis and restricted cubic spline curves were used to examine the association between pks+ E. coli prevalence and physical activity. The prevalence of pks+ E. coli was 26.6% (59/222 participants). The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the highest tertile with reference to the lowest tertile of physical activity variables were as follows: light-intensity physical activity (OR 0.63; 95% CI 0.26-1.5), moderate-to-vigorous intensity physical activity (OR 0.85; 95% CI 0.39-1.87), physical activity level (OR 0.69; 95% CI 0.32-1.51), step-count (OR 0.92; 95% CI 0.42-2.00) and time spent inactive (OR 1.30; 95% CI 0.58-2.93). No significant dose-response relationship was found between all physical activity variables and pks+ E. coli prevalence. Our findings did not suggest that physical activity has beneficial effects on the prevalence of pks+ E. coli. Longitudinal studies targeting a large population are needed to clarify this association.

Association between green tea and coffee consumption and body iron storage in Japanese men and women: a cross-sectional study from the J-MICC Study Saga.

Purpose: This study examined the association between daily green tea and coffee consumption and body iron stores among Japanese middle-aged and older adults. Methods: This cross-sectional study used data obtained from 2005 to 2007. A total of 10,435 participants were recruited for this study. The participants completed a validated, self-administered food frequency questionnaire on green tea and coffee consumption. A multivariate linear regression analysis was conducted to assess the relationship between green tea and coffee consumption and serum ferritin levels. Additionally, logistic regression analysis was performed to ascertain whether excessive consumption of these beverages was linked to iron deficiency. Results: We observed that higher green tea and coffee consumption was associated with lower ferritin levels in men and postmenopausal women, even after adjusting for covariates (all P for trends <0.05). Among premenopausal women, we found an inverse association between green tea consumption and serum ferritin levels, while no significant association was observed for coffee consumption after adjusting for covariates (green tea, P for trend <0.05; coffee, P for trend = 0.08). Notably, the association between these beverages and iron deficiency was found only in postmenopausal women; the odds ratios (95% confidence intervals) for iron deficiency associated with almost None, <1 cup/day, 1-2 cups/day, and ≥ 3 cups/day were 1.00 (reference), 0.78 (0.26-2.49), 1.29 (0.49-3.39), and 1.59 (0.63-4.04) (P for trend = 0.05), respectively, for green tea and 1.00, 1.32 (0.64-2.73), 1.46 (0.68-3.13), and 2.20 (1.06-4.55) (P for trend <0.01), respectively, for coffee. Conclusion: Higher green tea and coffee consumption was associated with lower serum ferritin levels in men and postmenopausal women. In premenopausal women, consumption of green tea, but not coffee, was associated with lower serum ferritin levels. However, postmenopausal women who ≥3 cups of coffee demonstrated a higher prevalence of iron deficiency compared to those who consumed almost none.

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.

Variant Allele of ALDH2, rs671, Associates with Attenuated Post-Vaccination Response in Anti-SARS-CoV-2 Spike Protein IgG: A Prospective Study in the Japanese General Population.

Uncovering the predictors of vaccine immunogenicity is essential for infection control. We have reported that the most prevalent polymorphism of the aldehyde dehydrogenase 2 gene (ALDH2), rs671, may be associated with an attenuated immune system. To test the inverse relationship between rs671 and antibody production after COVID-19 vaccination, the levels of anti-SARS-CoV-2 Spike protein S1 subunit (S1) IgG were repeatedly measured for four months before and after vaccination with BNT162b2 or mRNA-1273, in 88 Japanese workers and students (including 45 females, aged 21-56 years, with an rs671 variant allele frequency of 0.3). The mixed model including fixed effects of the vaccine type, weeks post vaccination (categorical variable), sex, age, height, smoking status, ethanol intake, exercise habit, perceived stress, steroid use, allergic diseases, and dyslipidemia, indicated an inverse association between log-transformed anti-S1 IgG levels and the number of rs671 variant alleles (partial regression coefficient = -0.15, p = 0.002). Our study indicated for the first time that the variant allele of ALDH2, rs671, is associated with the attenuated immunogenicity of COVID-19 mRNA vaccines. Our finding may provide a basis for personalized disease prevention based on a genetic polymorphism that is prevalent among East Asians.

Effect of the interaction between physical activity and estimated macronutrient intake on HbA1c: population-based cross-sectional and longitudinal studies.

INTRODUCTION: Healthy diet and physical activity (PA) are essential for preventing type 2 diabetes, particularly, a combination of diet and PA. However, reports on interaction between PA and diet, especially from large epidemiological studies, are limited. We investigated the effect of interaction between PA and macronutrient intake on hemoglobin A1c (HbA1c) levels in the general population. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study of 55 469 men and women without diabetes who participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. A self-administered questionnaire ascertained PA and macronutrient intake (carbohydrate, fat, and protein). Multiple linear regression analyses were performed to adjust for confounding variables and examine the interactions. In addition, we conducted a longitudinal study during a 5-year period within a subcohort (n=6881) with accelerometer-assessed PA data. RESULTS: Overall, PA had a weak inverse association (ß=-0.00033, p=0.049) and carbohydrate intake had a strong positive association (ß=0.00393, p<0.001) with HbA1c. We observed a tendency of interactions between PA and carbohydrate or fat intake, but not protein intake, on HbA1c levels after adjusting for age, sex, study area, total energy intake, alcohol consumption, smoking, and medication for hypertension or hypercholesterolemia (Pinteraction=0.054, 0.006, and 0.156, respectively). The inverse associations between PA and HbA1c level were more evident in participants with high-carbohydrate (or low-fat) intake than in participants with low-carbohydrate (or high-fat) intake. Although further adjustment for body mass index slightly attenuated the above interactions (Pinteraction=0.098 for carbohydrate and 0.068 for fat), the associations between PA and HbA1c level in stratified analyses remained unchanged. Similar associations and interactions were reproduced in the longitudinal study. CONCLUSIONS: The present results suggest that the effect of PA on HbA1c levels is modified by intake of macronutrient composition.

Association of perceived stress and coping strategies with the renal function in middle-aged and older Japanese men and women.

Elucidating the risk factors for chronic kidney disease is important for preventing end-stage renal disease and reducing mortality. However, little is known about the roles of psychosocial stress and stress coping behaviors in deterioration of the renal function, as measured by the estimated glomerular filtration rate (eGFR). This cross-sectional study of middle-aged and older Japanese men (n = 31,703) and women (n = 38,939) investigated whether perceived stress and coping strategies (emotional expression, emotional support seeking, positive reappraisal, problem solving, and disengagement) were related to the eGFR, with mutual interactions. In multiple linear regression analyses adjusted for age, area, lifestyle factors, and psychosocial variables, we found a significant inverse association between perceived stress and the eGFR in men (Ptrend = 0.02), but not women. This male-specific inverse association was slightly attenuated after adjustment for the history of hypertension and diabetes and was more evident in lower levels of emotional expression (Pinteraction = 0.003). Unexpectedly, problem solving in men (Ptrend < 0.001) and positive reappraisal in women (Ptrend = 0.002) also showed an inverse association with the eGFR. Perceived stress may affect the eGFR, partly through the development of hypertension and diabetes. The unexpected findings regarding coping strategies require the clarification of the underlying mechanisms, including the hormonal and immunological aspects.

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.

The Independent Relationship Between Leg Skeletal Muscle Mass Asymmetry and Gait Speed in Community-Dwelling Older Adults.

OBJECTIVES: To investigate the relationship between leg skeletal muscle mass asymmetry and usual gait speed in older adults. METHODS: The subjects were 139 community-dwelling older adults. The asymmetry index was calculated using the leg skeletal muscle mass index (LSMI) values of both legs. The subjects were divided into "large" and "small" asymmetry groups based on the asymmetry index. The relationship between asymmetry and gait speed was analyzed using a linear regression model. The appendicular skeletal muscle mass index and LSMI were included as adjustment variables in the analysis. RESULTS: The asymmetry index and having a "large" asymmetry were independently related to gait speed, even after adjusting for covariates such as appendicular skeletal muscle mass index and LSMI. DISCUSSION: Leg skeletal muscle mass asymmetry was related to gait speed independently of the appendicular skeletal muscle mass index and LSMI values. A skeletal muscle mass evaluation among older adults should include an assessment of the total skeletal muscle mass and its asymmetry.

Effects of a water-based exercise program on disability prevention in older Japanese adults.

AIM: This study aimed to evaluate the potential preventive effects of a water-based exercise program on disability in community-dwelling older adults. METHODS: The study design was a propensity score-matched retrospective study. Older adults were contacted through a mail survey carried out by City Hall, and those who scored ≥3 points on the physical domain of the Kihon Checklist were encouraged to participate in the water-based exercise program. The program consisted of aerobic and walking exercises in the water for 1 h, once a week for 6 months. Propensity scores were used to match individuals who participated in the exercise program with control individuals based on age, sex, height, weight, body mass index and Kihon Checklist score. Among matched pairs, the study included 278 participants (control group 139, intervention group 139). The main outcome was the number of participants who received a new long-term care insurance certification during the first follow-up year, which was used to indicate disability. RESULTS: Of the 278, 13 participants (5.5%) required long-term care insurance certification. A significantly smaller proportion of intervention group members required long-term care insurance certification (intervention group 0.7% [1/139 participants] vs control group 8.6% [12/139 participants], P = 0.003). CONCLUSIONS: Water-based exercise program appears to effectively prevent disability in community-dwelling older adults. Because water-based exercise program is associated with a minimal burden on joints and lower risk of falling, it might particularly enable the prevention of disability in older adults with chronic pain and restricted mobility. Geriatr Gerontol Int 2019; 19: 1282-1288.