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The onset and worsening of some diseases are related to the variation and instability of gut microbiota. However, studies examining the personal variation of gut microbiota in detail are limited. Here, we evaluated the yearly variation of individual gut microbiota in 218 Japanese subjects aged 66–91 years, using Jensen-Shannon distance (JSD) metrics. Approximately 9% of the subjects showed a substantial change, as their formerly predominant bacterial families were replaced over the year. These subjects consumed fermented milk products less frequently than their peers. The relationship between the intake frequencies of fermented milk products containing Lacticaseibacillus paracasei strain Shirota (LcS) and JSD values was also investigated. The intra-individual JSD of subjects ingesting LcS products ≥ 3 days/week over the past 10 years was statistically lower than the P = 0.045). Focusing on subjects with substantial gut microbiota changes, only 1.7% of the subjects were included in the LcS intake ≥ 3 days/week group whereas 11.3% were found in the P = 0.029). These results suggest that about one-tenth of the elderly Japanese could experience a substantial change in their gut microbiota during a 1-year period, and that the habitual intake of probiotics may stabilize their gut microbiota.

The onset and worsening of some diseases are related to the variation and instability of gut microbiota. However, studies examining the personal variation of gut microbiota in detail are limited. Here, we evaluated the yearly variation of individual gut microbiota in 218 Japanese subjects aged 66-91 years, using Jensen-Shannon distance (JSD) metrics. Approximately 9% of the subjects showed a substantial change, as their formerly predominant bacterial families were replaced over the year. These subjects consumed fermented milk products less frequently than their peers. The relationship between the intake frequencies of fermented milk products containing Lactocaseibacillus paracasei strain Shirota (LcS) and JSD values was also investigated. The intra-individual JSD of subjects ingesting LcS products ≥ 3 days/week over the past 10 years was statistically lower than the 3 days/week group (P = 0.045). Focusing on subjects with substantial gut microbiota changes, only 1.7% of the subjects were included in the LcS intake ≥ 3 days/week group whereas 11.3% were found in the 3 days/week group (P = 0.029). These results suggest that about one-tenth of the elderly Japanese could experience a substantial change in their gut microbiota during a 1-year period, and that the habitual intake of probiotics may stabilize their gut microbiota.

Background: An age-related decrease in functional capacity is consistently reported, but it is not consistently related to a worsening of health-related quality of life (HRQOL) or psychological adjustment. A poor functional capacity and HRQOL have been associated with anxiety or depression, but the possible causal nature and direction of the relationship remain to be explored using long-term longitudinal data. Objective: The purpose of this study was to examine age-related changes in functional capacity, HRQOL, and scores on the Hospital Anxiety and Depression Scale (HADS), and possible causal interrelationships between these variables. Methods: Study participants were 5,124 Japanese aged ≥65 years. After the baseline study (2003), annual follow-up observations continued for 10 years. Generalized linear mixed models examined age-related changes in Barthel index (BI), Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC), HRQOL, and HADS. Cross-lagged effects models tested possible causal interrelationships. Results: With age, functional capacity and HRQOL scores showed similar declines in both sexes. Changes in mental health, anxiety, and depression developed more slowly than decreases in physical health (BI, TMIG-IC, and physical functioning scores). Cross-lagged effects models demonstrated that functional capacity had positive effects on psychological adjustment, and that psychological adjustment had positive effects on functional capacity 5 years later. Interactions between functional capacity and psychological adjustment showed no sex differences. A decline in functional capacity negatively affected psychological adjustment, but reduced psychological adjustment had no significant impact on functional capacity 5 and 10 years later. Moreover, functional capacity and poor psychological adjustment showed no interactions in either sex. Conclusion: Functional capacity and mood state are interrelated. Greater function could sustain vitality and mental health, possibly reducing anxiety and depression.

Background Japan, like many developed countries, now faces fiscal problems from the escalating health-care expenditures associated with an aging population. Mental health problems such as depression contribute as much to these growing demands as physical disease, and measures to prevent depression are important to controlling costs. There are few longitudinal studies examining the relation between objectively measured physical activity and depressive symptoms. Therefore, the aims of our study were to explore the patterns of change of physical activity in older Japanese adults for 5 years through the use of trajectory analysis and to examine the relation between physical activity trajectories and depressive mood states. Main body Ninety-two male and 99 female volunteers aged 65–85 years were asked to equip themselves with an electronic accelerometer with a 60-day storage capacity for at least 5 years. The parameters calculated each July for the 5 years were the average daily step count and the average daily duration of activity > 3 METs (moderate to vigorous physical activity: MVPA). Hospital Anxiety and Depression Scale (HADS) assessed corresponding mood states (HADS-A and HADS-D). Trajectories of the accelerometer data were analyzed and fifth-year HADS-D and HADS-A scores were compared among trajectory groups using an analysis of covariance (ANCOVA) that controlled for baseline scores and for baseline scores and age. Six and five distinct trajectories were identified for daily step count and for daily duration of MVPA, respectively. Using ANCOVA controlling for baseline scores, HADS-D scores differed significantly among trajectory groups classed by daily duration of MVPA (p = 0.04), and Tukey’s multiple comparison tests showed significant differences between group 2, whose pattern was stable with the middle duration of MVPA, and group 1, whose pattern was stable with the lowest duration of MVPA (p = 0.02), while the results were not significant controlling for both baseline scores and age. Conclusions Older people with less MVPA continued to do less MVPA over the 5 years of study, which may be related to a future more depressive mood. Further clinical studies will be necessary to clarify these findings.

Infrequent bowel movements decrease the number of beneficial bacteria in the human intestines, thereby potentially increasing the individual’s risk of colorectal cancer. The correction of such bowel problems could therefore make an important contribution to improving population health and quality-adjusted lifespan. We examined independent and interactive effects upon the fecal microbiota of two potentially favorable determinants of intestinal motility: the intake frequency of a fermented milk product containing Lactobacillus casei strain Shirota (LcS) and the quantity/quality of habitual physical activity in 338 community-living Japanese aged 65–92 years. Subjects were arbitrarily grouped on the basis of questionnaire estimates of LcS intake (0–2, 3–5, and 6–7 days/week) and pedometer/accelerometer-determined patterns of physical activity [3 metabolic equivalents (METs)]. After adjustment for potential confounders, the respective numbers of various beneficial fecal bacteria tended to be larger in more frequent consumers of LcS-containing products, this trend being statistically significant (mostly P < 0.001) for total Lactobacillus, the Lactobacillus casei subgroup, and the Atopobium cluster; in contrast, there were no statistically significant differences in fecal bacterial counts between the physical activity groups. A multivariate-adjusted logistic regression analysis estimated that the risk of infrequent bowel movements (arbitrarily defined as defecating ≤3 days/week) was significantly lower (P < 0.05) in subjects who ingested LcS-containing products 6–7 rather than 0–2 days/week [odds ratio (95% confidence interval) 0.382 (0.149–0.974)] and was also lower in those who took ≥7000 rather than 3 METs [0.412 (0.183–0.929)]. The risk of infrequent bowel movements in subjects who combined 6–7 days/week of LcS with ≥7000 steps/day or ≥15 min/day of activity at >3 METs was only a tenth of that for individuals who combined 0–2 days/week of LcS with 3 METs. These results suggest that elderly individuals can usefully ingest LcS-containing supplements regularly (≥6 days/week) and also engage in moderate habitual physical activity (≥7000 steps/day and/or ≥15 min/day at >3 METs) in order to enhance their gastrointestinal health.

A randomised, double-blind, placebo-controlled trial was performed to investigate the effects of enteric-coated lactoferrin (LF) supplementation on the immune function of healthy, elderly individuals. Sixty-two healthy men and women were randomly divided into LF (300 mg of bovine LF intake per day) and placebo groups, who consumed the assigned supplements once daily for 3 months. The blood cell count, peripheral blood lymphocyte subset ratios, neutrophil phagocytic function, natural killer (NK) cell cytotoxicity, and serum granulysin and lysozyme concentrations were measured every month. By the third month of treatment, significant inter-group differences were observed in peripheral blood lymphocyte subset ratios, neutrophil phagocytic function, and NK cell cytotoxicity. Our findings suggest that immune competent cells of the innate immune system in elderly individuals are specifically activated by LF intake; therefore, enteric LF supplementation may have beneficial effects on immune function in elderly individuals.

Objectives To examine dose/response relationships between habitual physical activity and bone health in the elderly. Design Longitudinal. Setting Community of Nakanojo. Participants Community-living Japanese aged 65 to 84 (212 men, 284 women). Measurements Daily 24-h pedometer/accelerometer data were collected continuously for 5 years. A quantitative calcaneal osteosonic index (OSI) was determined annually. Results Year-end OSI values were higher in those with greater daily step counts and especially a greater duration of activity >3 metabolic equivalents (METs). However, after controlling for baseline OSI, age and body mass, final OSI values were not significantly greater in the fourth than in the third activity quartile, where men and women, respectively, took means of 7,700 and 7,500 steps/day and/or exercised at an intensity >3 METs for means of 19 and 17 min/day. A multivariate-adjusted proportional hazards model predicted that the OSI values of men and women were, respectively, 2.6 (1.4–4.4) and 3.3 (2.1–5.2) and/or 2.8 (1.5–5.6) and 3.9 (2.4–6.7) times more likely to drop below the OSI fracture threshold over 5 years in the two lowest activity quartiles ( 3 METs) than in the highest quartile (>9,100 and >8,800 steps/day and/or >30 and >25 min/day at >3 METs). Conclusion After adjustment for potential confounders, the calcaneal health of seniors is associated with both the daily step count and the duration of activity at an intensity >3 METs. The bone health is optimal in elderly people who take at least 7,000-8,000 steps/day and/or spend at least 15–20 min/day at an intensity >3 METs.

To relate 5-year lean tissue loss to habitual physical activity of elderly adults.Longitudinal.Community of Nakanojo.Community-living Japanese aged 65 to 84 (200 men, 268 women).Daily 24-hour pedometer/accelerometer data, collected continuously for 5 years, were categorized into activity quartiles. Bioelectrical impedance measurements of lean body mass were taken annually. A sarcopenia threshold was defined arbitrarily as an appendicular lean mass/height(2) of more than 1 standard deviation below the mean for healthy young Japanese.Subjects with greater habitual physical activity retained a greater lean mass over the 5 years of observation. Controlling for baseline lean mass and age, final lean mass was greater for the third activity quartile (men and women with respective mean counts of 7,800 and 7,700 steps per day or mean duration of exercise at3 metabolic equivalents (METs) of 20 and 17 minutes per day) than for the first and second quartiles. A multivariate-adjusted proportional hazards model predicted that, over the 5 years, men and women in the two lowest activity quartiles (6,700 and6,800 steps per day) were 2.3 (95% confidence interval (CI) = 1.4-4.5) and 3.0 (95% CI = 1.9-3.4) times as likely, respectively, to be sarcopenic as those in the highest activity quartile (9,000 and8,400 steps per day). Likewise, men and women with less than 16 and less than 14 minutes per day, respectively, of activity of more than 3 METs were 3.0 (95% CI = 2.0-6.0) and 3.5 (95% CI = 2.1-6.3) times as likely to develop sarcopenia as those with more than 28 and more than 22 minutes per day.After adjustment for potential confounders, the risk of developing sarcopenia was substantially lower in elderly people taking at least 7,000 to 8,000 steps per day or exercising for at least 15 to 20 minutes per day at an intensity greater than 3 METs. Clinicians should encourage seniors to get at least this volume of regular daily exercise.

We previously showed that the C→T polymorphism (rs6929846) in butyrophilin, subfamily 2, member A1 gene (BTN2A1) was associated with myocardial infarction in Japanese individuals. Given that hypertension is a major risk factor for myocardial infarction, the association of rs6929846 of BTN2A1 with myocardial infarction might be attributable, at least in part, to its effect on susceptibility to hypertension. We have thus examined the relation of rs6929846 of BTN2A1 to hypertension in Japanese individuals.A total of 8,567 Japanese individuals from two independent subject panels were examined: Subject panels A and B comprised 2,317 hypertensive individuals and 1,933 controls, and 2,911 hypertensive individuals and 1,406 controls, respectively. The genotype of rs6929846 was determined by a method that combines the PCR and sequence-specific oligonucleotide probes with suspension array technology.Multivariable logistic regression analysis with adjustment for covariates revealed that rs6929846 of BTN2A1 was significantly associated with hypertension in subject panel A (P = 2.6 × 10(-6); odds ratio, 1.69) and in subject panel B (P = 0.0284; odds ratio, 1.24), with the T allele representing a risk factor for hypertension. The rs6929846 was associated with systolic blood pressure (BP) in subject panels A (P = 0.0063) and B (P = 0.0115) and with diastolic BP in subject panel B (P = 0.0323), with the T allele being related to high BP.BTN2A1 may be a susceptibility gene for hypertension in Japanese individuals. Determination of genotype for this polymorphism may prove informative for assessment of the genetic risk for hypertension.

Background We previously showed that the C→T polymorphism (rs6929846) of butyrophilin, subfamily 2, member A1 gene ( BTN2A1 ) was significantly associated with myocardial infarction in Japanese individuals. Given that metabolic syndrome (MetS) is an important risk factor for myocardial infarction, the association of the rs6929846 of BTN2A1 with myocardial infarction might be attributable, at least in part, to its effect on susceptibility to MetS. Aim The aim of the present study was to examine the relation of the rs6929846 of BTN2A1 to MetS in East Asian populations. Methods The study population comprised 5210 Japanese or Korean individuals (3982 individuals with MetS, 1228 controls) from three independent subject panels. Japanese subject panels A and B comprised 1322 individuals with MetS and 654 controls, and 1909 individuals with MetS and 170 controls, respectively, whereas the Korean population samples comprised 751 individuals with MetS and 404 controls. Results Comparison of genotype distributions using the χ2 test revealed that the genotype distributions and allele frequencies of rs6929846 were significantly (p

We previously identified rs6929846 of the butyrophilin, subfamily 2, member A1 gene (BTN2A1) as a susceptibility locus for myocardial infarction in Japanese individuals by a genome-wide association study. The aim of the present study was to examine the relation of the rs6929846 polymorphism of BTN2A1 to dyslipidemia in Japanese and Korean populations, given that dyslipidemia is an important risk factor for myocardial infarction. A total of 10,953 individuals from three independent subject panels were examined. The relations of the rs6929846 polymorphism of BTN2A1 to serum concentrations of triglycerides, high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol were examined in each subject panel. The C→T polymorphism (rs6929846) of BTN2A1 was significantly associated with serum concentrations of triglycerides in Japanese subject panels A (P=0.0004) and B (P=0.0010), and in the Korean population (P=0.0095), with the minor T allele being related to an increased serum concentration of triglycerides. The rs6929846 was associated with serum concentrations of HDL-cholesterol in Japanese subject panels A (P=0.0047) and B (P=0.0015), with the T allele being related to a decreased serum concentration of HDL-cholesterol, but not in the Korean population. This polymorphism was associated with the serum concentration of LDL-cholesterol only in Japanese subject panel B (P=0.0059), with the T allele being related to an increased serum concentration of LDL-cholesterol. The results suggest that BTN2A1 may be a susceptibility gene for hypertriglyceridemia in East Asian populations and for low serum HDL-cholesterol in the Japanese population.

A 1-year randomized controlled trial examined effects of milk basic protein (MBP) supplementation (40 mg day −1 ) and daily physical activity (step count and duration of exercise > 3 metabolic equivalents [METs]) on bone metabolism, forearm bone mineral density (BMD) and a calcaneal osteosonic index (OSI) in 79 females aged 65–86 years. MBP did not affect osteocalcin or bone-specific alkaline phosphatase, but at 12 months, excretion of deoxypyridinoline and cross-linked N-teleopeptides of type I collagen (NTx) were significantly less than in controls. Experimental subjects also maintained BMD and had a 1.5% increase of OSI at 12 months. After adjustments for age and baseline bone parameters, osteocalcin, deoxypyridinoline, NTx and/or OSI at 12 months were significantly related to step count and/or duration of activity > 3 METs. MBP reduced markers of bone loss, particularly in the lower extremities. Reduced resorption of bone was also associated with moderate-intensity/duration exercise, MBP therapy interacting significantly with habitual physical activity.

Background: Recommendations on minimum exercise levels for the elderly have to date been based largely on extrapolation of epidemiological findings in middle-aged adults. Questionnaire assessments of physical activity in the latter age group have been correlated with health outcomes observed over 10 or more years. The reliability and construct validity of questionnaires have sometimes been reasonably high, but information on the volume of physical activity has been exaggerated as much as three- to five-fold, with corresponding uncertainties in health inferences. Objectives: To assess the contribution of inexpensive pedometer/accelerometers to objective determinations of physical activity needs in the elderly. Major findings: Pedometer/accelerometers work well in the elderly, whose main deliberate activity is walking. The steps taken on a treadmill or a walking course can be determined with considerable accuracy, but more tests are needed under free-living conditions. In elderly people, the relati...

The purpose of the present study was to identify genetic variants that confer susceptibility to myocardial infarction (MI) in Japanese individuals.The study population comprised 5014 Japanese individuals, including 1444 subjects with MI and 3570 controls. The 150 polymorphisms examined in the present study were selected by a genome-wide association study for ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix), and were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology.An initial screen by the chi-square test revealed that the A--G polymorphism of SEMA3F (rs12632110), the C--T polymorphism of CLEC16A (rs9925481), the A--G polymorphism of LAMA3 (rs12373237), and the C--G polymorphism of PCSK2 (rs6080699) were significantly (false discovery rate for allele frequencies of0.05) associated with MI. Subsequent multivariable logistic regression analysis with adjustment for covariates and a stepwise forward selection procedure revealed that the A--G polymorphism of SEMA3F (dominant model; P=0.0014; odds ratio, 0.76), the C--T polymorphism of CLEC16A (dominant model; P=0.0009; odds ratio, 0.75), the A--G polymorphism of LAMA3 (recessive model; P=0.0099; odds ratio, 0.80), and the C--G polymorphism of PCSK2 (recessive model; P=0.0155; odds ratio, 1.19) were significantly (P0.05) associated with the prevalence of MI.Determination of these genotypes may prove informative for assessment of the genetic risk for MI in Japanese individuals.

We tested the hypothesis that a low level of regular daily physical activity in elderly individuals would be associated with a clinically significant degree of sarcopenia. Subjects were 78 male and 97 female free-living Japanese, aged 65-84 years. A pedometer/accelerometer measured continuously the number of steps taken and the intensity of activity 24 h/day for 1 year. A whole-body dual X-ray absorptiometry scan assessed skeletal muscle mass in the upper and lower extremities at the end of the year. Sarcopenia was defined as a muscle mass/height(2) value1 SD below the mean for healthy young Japanese. Linear and exponential regressions showed that after controlling data for age and/or sex, muscle mass was associated with physical activity, more closely for the legs than for the arms, and for duration of moderate activity (3 METs) than for step count. Muscle mass increased progressively with daily activity, although when data were categorized into quartiles, muscle mass was not significantly greater in men and women who exceeded, respectively, 8,000 and 6,900 steps/day and/or 22 and 19 min/day at3 METs. All participants meeting such criteria exceeded our sarcopenia threshold. Multivariate-adjusted logistic regressions predicted that individuals who walked5,300 steps/day and/or spent15 min/day at3 METs were, respectively, 2.00-2.66 and/or 2.03-4.55 times more likely to show sarcopenia than those who walked7,800 steps/day and/or spent23 min/day at3 METs. Our hypothesis was proven correct: seniors who walked at least 7,000-8,000 steps/day and/or spent 15-20 min/day at an intensity of3 METs were likely to have a muscle mass above the sarcopenia threshold.

Our objectives were to test the hypothesis that the habitual physical activity of elderly individuals is associated with less arterial stiffening, to explore characteristics of any dose/response relationship, and to determine those segments of the arterial tree where associations are most apparent. Participants (89 men and 109 women, aged 65-84) wore a pedometer/accelerometer continuously for 1 year. The daily step count and the duration of moderate-intensity activity (>3 metabolic equivalents, METs) were recorded. At year's end, an automatic waveform analyzer determined the pulse wave velocity between five recording sites: the aortic root, and the carotid, brachial, femoral and tibial arteries. After appropriate adjustments for sex, age, and mean arterial pressure, overall (delta brachio-tibial "velocity") and central arterial stiffness (cardio-femoral velocity) showed small but statistically significant negative correlations with daily step count and the duration of activity >3 METs. Cardio-carotid velocity was also associated with step count. In contrast, cardio-brachial and femoro-tibial velocities were not significantly related to either estimate of habitual activity. Cardio-femoral and delta brachio-tibial velocities were significantly lower in physically active individuals, apparently reaching a minimum in subjects who exceeded counts of about 6,600 steps/day and/or exercised for more than 16 min/day at an intensity >3 METs. The data support our hypothesis, showing weak but statistically significant associations between habitual physical activity and pulse wave assessments of arterial stiffness in elderly adults. Further studies are recommended to test the causality of these associations and to explore why relationships seem more marked for central than for peripheral arterial segments.

Hypertension and diabetes mellitus are important risk factors for chronic kidney disease (CKD). The purpose of the present study was to identify genetic variants that confer susceptibility to CKD in individuals with or without hypertension or diabetes mellitus, thereby contributing to the personalized prevention of CKD in such individuals separately. The study population comprised 5835 unrelated Japanese individuals, including 1763 subjects with CKD and 4072 controls. The 150 polymorphisms were selected by genome-wide association studies of ischemic stroke and myocardial infarction with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix). The genotypes for these polymorphisms were determined by a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. The χ(2) test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that two different polymorphisms were significantly (P

The purpose of the present study was to identify genetic variants that confer susceptibility to myocardial infarction (MI) in individuals with metabolic syndrome (MetS).The study population comprised 1887 Japanese individuals with MetS, including 773 subjects with MI and 1114 controls. The genotypes for 136 polymorphisms of 97 candidate genes were determined.An initial screen by the chi-square test revealed that seven polymorphisms were significantly (false discovery rate0.05) associated with the prevalence of MI in individuals with MetS. Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the G--A (Ser89Asn) polymorphism of UTS2 [odds ratio (OR), 1.90; 95% confidence interval (CI), 1.18-3.08], the 2445G--A (Ala54Thr) polymorphism of FABP2 (OR, 1.72; 95% CI, 1.23-2.40), the -11377C--G polymorphism of ADIPOQ (OR, 1.43; 95% CI, 1.15-1.79), the -231A--G polymorphism of EDNRA (OR, 0.65; 95% CI, 0.48-0.89), and the -108/3G--4G polymorphism of PDX1 (OR, 0.64; 95% CI, 0.48-0.87) were significantly (P0.05) associated with MI. The variant alleles of UTS2, FABP2, and ADIPOQ were risk factors for MI, whereas the variant alleles of EDNRA and PDX1 were protective against this condition. A stepwise forward selection procedure demonstrated that UTS2, FABP2, ADIPOQ, EDNRA, and PDX1 genotypes were significant (P0.05) and independent determinants of MI.Determination of genotypes for these polymorphisms of UTS2, FABP2, ADIPOQ, EDNRA, and PDX1 may prove informative for assessment of the genetic risk for MI in Japanese individuals with MetS.

In older adults, as in younger individuals, habitual moderate-intensity physical activity is associated with a reduced risk of various chronic health conditions, including certain types of cardiovascular and musculoskeletal disease and certain forms of cancer. However, the pattern of physical activity associated with such benefits remains unclear. One problem is that most investigators have examined patterns of physical activity using either subjective questionnaires or accelerometer or pedometer measurements limited to a single week, despite clear evidence of both the unreliability/invalidity of questionnaires and seasonal changes in activity patterns. Since 2000, we have thus conducted an interdisciplinary study examining the habitual physical activity and health of elderly people living in a medium-sized Japanese town (the Nakanojo Study). In about one-tenth of some 5000 available subjects agedor =65 years, physical activity has already been assessed continuously for 24 h/day for8 years using a specially adapted pedometer/accelerometer. This device has a storage capacity of 36 days and can distinguish10 intensities of physical activity (expressed in metabolic equivalents [METs]). Data have to date been summarized as daily step counts and daily durations of activity of3 and3 METs, averaged over a 1-year period. This article provides a detailed overview of both factors influencing habitual physical activity and relationships between such activity and health in an elderly population. To date, analyses have been cross-sectional in type. Substantial associations have been noted between the overall health of participants and both the daily duration of effort undertaken at an intensity of3 METs and the daily step count. In men, the extent of health is associated more closely with the daily duration of activity of3 METs than with the daily step count, whereas in women, the association is closer for the step count than for the duration of activity3 METs. In both sexes, the threshold amount of physical activity associated with better health is greater for physical than for mental benefits:8000 versus4000 steps/day and/or20 versus5 min/day at an intensity3 METs, respectively. In other words, better physical health is seen in those spending at least 20 min/day in moderate walking (at a pace of around 1.4 m/s [5 km/h]) and a further60 min of light activity per day. In contrast, better mental health is associated with much smaller amounts of deliberate physical activity. The daily step count and the daily durations of activity of3 and3 METs are all influenced by meteorological factors, particularly precipitation and mean ambient temperature. Activity decreases exponentially to about 4000 steps/day as precipitation increases. Excluding the influence of rainfall, the daily step count peaks at a mean outdoor temperature of around 17 degrees C; above and especially below such readings, physical activity decreases as a quadratic function of temperature. Seasonal changes in microclimate should thus be considered when designing interventions intended to increase the habitual physical activity of elderly people. The observed associations between physical activity and health outcomes point to a need for longitudinal analyses; these should examine potential causal interpretations of the current findings and elucidate possible additional mediating variables.

Although hypertension has been recognized as a risk factor for chronic kidney disease (CKD), the genetic factors for predisposition to CKD in individuals with hypertension remain largely unknown. The purpose of this study was to identify the genetic variants that confer susceptibility to CKD among individuals with hypertension. The study population comprised 3696 Japanese individuals with hypertension (2265 men, 1431 women), including 1257 individuals (789 men, 468 women) with CKD (estimated glomerular filtration rate (eGFR)60 ml min(-1) per 1.73 m(2)) and 2439 controls (1476 men, 963 women; eGFRor=60 ml min(-1) per 1.73 m(2)). The genotypes for 30 polymorphisms of 26 candidate genes were determined. An initial screening of allele frequencies by the chi(2)-test revealed that eight polymorphisms were significantly (false discovery rate0.05) associated with the prevalence of CKD in hypertensive individuals. Subsequent multivariable logistic regression analysis with adjustment for covariates as well as a stepwise forward selection procedure revealed that the T --C (Val591Ala) polymorphism of APOB (rs679899), the -681C --G polymorphism of PPARG (rs10865710), the T --C (Cys1367Arg) polymorphism of WRN (rs1346044), the -850C --T polymorphism of TNF (rs1799724), the -219G --T polymorphism of APOE (rs405509), the C --T polymorphism of PTGS1 (rs883484) and the 41A --G (Glu14Gly) polymorphism of ACAT2 (rs9658625) were significantly (P0.05) associated with the prevalence of CKD. Our results suggest that APOB, WRN, ACAT2, APOE, PPARG, TNF and PTGS1 are susceptibility loci for CKD among Japanese individuals with hypertension. Determination of the genotypes for these polymorphisms may prove informative for the assessment of genetic risk for CKD among such individuals.

SummaryChronic kidney disease (CKD) is a serious clinical condition that is associated with a high incidence of cardiovascular disease and end-stage renal disease. Although CKD has been recognised as a risk factor for myocardial infarction (MI), genetic factors for predisposition to MI in individuals with CKD have remained largely unknown. The purpose of the present study was to identify genetic variants that confer susceptibility to MI in Japanese individuals with CKD. The study subjects comprised 1,339 Japanese individuals with CKD, including 496 subjects with MI and 843 controls. The genotypes for 248 polymorphisms of 181 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. An initial screen of allele frequencies by the chi-square test revealed that the 11496G→A (Arg353Gln) polymorphism of F7 (rs6046) was significantly (false discovery rate

Background and Purpose— Although genetic epidemiologic studies have implicated several genetic variants as risk factors for ischemic or hemorrhagic stroke, the genetic determinants of these conditions remain largely unknown. We performed an association study to identify gene polymorphisms that confer susceptibility to atherothrombotic cerebral infarction, intracerebral hemorrhage, or subarachnoid hemorrhage. Methods— The study population comprised 3432 unrelated Japanese individuals: 1362 stroke patients (822 with atherothrombotic cerebral infarction, 333 with intracerebral hemorrhage, and 207 with subarachnoid hemorrhage) and 2070 controls. The genotypes for 50 polymorphisms of 38 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Results— An initial χ 2 test (false discovery rate P ABCA1 , the A→C (rs3027898) and C→T (Ser532Leu, rs1059703) polymorphisms of IRAK1 , and the G→C (Cys2229Ser) polymorphism (rs619203) of ROS1 were significantly associated with atherothrombotic cerebral infarction; that the −428G→A polymorphism (rs710968) of LIMK1 was significantly associated with intracerebral hemorrhage; and that the 13989A→G (Ile118Val) polymorphism (NC_000007.12) of CYP3A4 was significantly associated with subarachnoid hemorrhage. Conclusions— Genotypes for ABCA1 , IRAK1 , and ROS1 may prove useful for assessment of the genetic risk for atherothrombotic cerebral infarction, whereas those for LIMK1 and CYP3A4 may be similarly beneficial in assessment of the genetic risk for intracerebral hemorrhage and subarachnoid hemorrhage, respectively. Validation of these findings will require additional studies with independent subject panels.

The interactions of sex, age, season, and habitual physical activity were examined in 41 male and 54 female Japanese age 65–83 yr, using a pedometer/accelerometer that determined step counts and amounts of physical activity (3 metabolic equivalents [METs]) throughout each 24-hr period for an entire year. All 3 measures were greater in men than in women. In women, age was negatively correlated with step count and activity 3 METs. Irrespective of sex or age, all 3 activity variables were low in the winter, peaking in spring or autumn. In the summer, step counts matched the annual average, but durations of activity 3 METs were, respectively, longer and shorter than in other seasons. These findings have practical implications for those promoting physical activity for older adults.

Purpose: Daily variations of physical activity in the elderly remain unclear. We thus used a uniaxial accelerometer/pedometer to examine the variability of step counts for 1 yr, determining the minimum number of days observation needed to obtain reliable estimates of annual physical activity. Methods: Subjects were 37 males and 44 females, healthy Japanese, aged 65-83 yr. The pedometer was worn on the waistband throughout 1 yr, accumulating information on the individual's daily step count. Results: The step count spectrum showed peaks with periods of 2.3, 3.5, and 7.0 d and an aperiodic component that had a greater power at low frequencies (i.e., non-white noise). These characteristics were absent in randomly resequenced data. To ensure that 80% of total variance was attributable to between-subjects variance, 25 and 8 consecutive days of observation were needed in male and female subjects, respectively. To achieve 90% on this same measure of reliability, 105 and 37 consecutive days of observation were required. In contrast, 4 d of randomly timed observations yielded 80% reliability for both men and women, and 11 and 9 d gave 90% reliability in men and women, respectively. If sampling also took account of season and day of the week, the respective observation periods for men and women were reduced to 8 and 4 d (i.e., 2 and 1 consecutive days of sampling every 89 d) for 80% and to 16 and 12 d (i.e., 4 and 3 consecutive days every 89 d) for 90% reliability. Conclusion: When estimating annual step counts, seasonal and/or random sampling of data allows collection of reliable data during substantially fewer days than needed for consecutive observations.

The aim of the present study was to identify gene polymorphisms that confer susceptibility to obesity. A total of 5448 unrelated Japanese individuals from two independent populations were examined: subject panel A comprised 4252 individuals who visited participating hospitals; subject panel B comprised 1196 community-dwelling elderly individuals. The genotypes for 95 polymorphisms of 67 candidate genes were determined. The χ2 test revealed that six polymorphisms were related (p

Background: Although several environmental factors influence the development of myocardial infarction, genetic factors have been shown to contribute to individual susceptibility to this condition. The aim of the present study was to identify gene polymorphisms that confer susceptibility to myocardial infarction in order to allow assessment of genetic risk for this condition. Methods: The study population comprised 3433 unrelated Japanese individuals (1931 men, 1502 women), including 1328 subjects with myocardial infarction (1036 men, 292 women) and 2105 controls (895 men, 1210 women). The genotypes for 40 polymorphisms of 31 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Results: The chi-square test revealed that six polymorphisms were significantly (false discovery rate < 0.05) related to the prevalence of myocardial infarction. Further examination by multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of hypertension, diabetes mellitus, and hypercholesterolemia as well as by a stepwise forward selection procedure revealed that the A→C (Gln1334His) polymorphism (rs3742207) of the collagen, type IV, alpha-1 gene (COL4A1) and the A→G polymorphism (rs4804611) of the zinc finger protein 627 gene (ZNF627) were significantly (P < 0.05) associated with the prevalence of myocardial infarction. The variant C allele of COL4A1 was protective against myocardial infarction, whereas the variant G allele of ZNF627 represented a risk factor for this condition. Conclusions: Determination of genotypes for COL4A1 and ZNF627 may prove informative for assessment of the genetic risk for myocardial infarction.

The purpose of the present study was to identify genetic variants that confer susceptibility to dyslipidemia. A total of 5213 individuals from two independent populations were examined: Subject panel A comprised 3794 individuals who visited participating hospitals; subject panel B comprised 1419 community-dwelling elderly individuals. The genotypes for 100 polymorphisms of 65 candidate genes were determined. The χ 2 test and multivariable logistic regression analysis revealed that seven polymorphisms of APOA5, APOC3, APOA1, ACAT2, and LPL were significantly associated with hypertriglyceridemia, six polymorphisms of APOA5, LIPC , and CYP3A4 with low HDL-cholesterol, and three polymorphisms of APOE and CCR2 with high LDL-cholesterol in subject panel A. For validation of these associations, the same polymorphisms were examined in subject panel B. Six polymorphisms of APOA5, APOC3, APOA1, and LPL were again significantly associated with hypertriglyceridemia, three polymorphisms of APOA5 with low HDL-cholesterol, and two polymorphisms of APOE with high LDL-cholesterol. Serum triglyceride, HDL-cholesterol, and LDL-cholesterol concentrations differed significantly among genotypes of these corresponding polymorphisms in both subject panels. These results indicate that polymorphisms of APOA5, APOC3, APOA1, and LPL are determinants of hypertriglyceridemia and that those of APOA5 and APOE are determinants of low HDL-cholesterol and high LDL-cholesterol, respectively, in Japanese individuals.

The Physical Activity Questionnaire for Elderly Japanese (PAQ-EJ) is a self-administered physical activity questionnaire for elderly Japanese; the authors report here on its repeatability and direct and indirect validity. Reliability was assessed by repeat administration after 1 month. Direct validation was based on accelerometer data collected every 4 s for 1 month in 147 individuals age 65–85 years. Indirect validation against a 10-item Barthel index (activities of daily living [ADL]) was completed in 3,084 individuals age 65–99 years. The test–retest coefficient was high (r = .64–.71). Total and subtotal scores for lower (transportation, housework, and labor) and higher intensity activities (exercise/sports) were significantly correlated with step counts and durations of physical activity r = .41, .28, .53), respectively. Controlling for age and ADL, scores for transportation, exercise/sports, and labor were greater in men, but women performed more housework. Sex- and ADL- or age-adjusted PAQ-EJ scores were significantly lower in older and dependent people. PAQ-EJ repeatability and validity seem comparable to those of instruments used in Western epidemiological studies.

We determined associations between bone health and the quantity and quality of habitual physical activity in a cohort of 172 free-living Japanese aged 65-83 years (76 men, 96 women).The number of steps taken and the intensity of physical activity were measured every 4 s throughout each 24-h period for 1 year, using a specially adapted accelerometer that distinguished up to 11 levels of physical activity (expressed in metabolic equivalents, METs). At the end of the year, a quantitative ultrasonic technique assessed each participant's osteosonic index (OSI, reflecting bone stiffness in the calcaneus).The data were significantly described by linear and exponential regression models which showed that in both sexes the OSI score increased with increasing daily physical activity, up to the observed maximum values of approximately 14,000 steps/day and 50 min/day at an intensity3 METs. However, when data were categorized into quartiles of physical activity, OSI scores were not significantly greater in persons exceeding recommended minimum standards of habitual physical activity (corresponding to counts of around 6,900 and 6,800 steps/day and durations3 METs of around 18 and 16 min/day in men and women, respectively). All who met such criteria (with the exception of a few women) had OSI scores above the threshold for a clinical diagnosis of osteoporosis. Multivariate-adjusted logistic regression analyses predicted that men and especially women who engaged in6,800 steps/day and16 min/day of moderate-intensity physical activity were, respectively, 4.9-8.4 and 2.2-3.5 times more likely to sustain fractures than those participating in8,200 steps/day and25 min/day of activity3 METs.Causation cannot be inferred from a cross-sectional study. Nevertheless, we suggest that from the viewpoint of bone health, elderly people should be encouraged to engage in low- and moderate-intensity habitual physical activity, taking7,000 steps/day with a duration15 min/day at3 METs.

Seasonal changes in ambient temperature and day length are thought to modify habitual physical activity. However, relationships between such environmental factors and the daily physical activity of older populations remain unclear. The present study thus examined associations between meteorological variables and the number of steps taken per day by elderly Japanese. Continuous pedometer counts over a 450-day period were collected from 41 healthy subjects (age 71+/-4 years), none of whom engaged in any specific occupational activity or exercise programs. An electronic physical activity monitor was attached to a belt worn on the left side of the body throughout the day. Daily values for mean ambient temperature, duration of bright sunshine, mean wind speed, mean relative humidity, and precipitation were obtained from local meteorological stations. The day length was calculated from times of sunrise and sunset. Based on the entire group of 41 subjects (ensemble average), a subject's step count per day decreased exponentially with increasing precipitation (r2=0.19, P

Moderate-intensity physical activity is recommended to promote health, and augment peak oxygen transport, thus reducing the risk of chronic disease, and delaying functional loss in the elderly. The optimal method of prescribing the recommended intensity of effort [approximately 50% of oxygen intake reserve ( V(.)O(2reserve)) or heart rate reserve (HR(reserve))] remains unclear for this age group. Our aim was to develop a new field-method of prescribing exercise for the elderly, based on walking velocity measured over a 5-m distance. Walking velocities were calculated from the time taken to move from the 3-m to the 8-m mark on an 11-m, straight, flat walkway. Interrelationships of preferred and maximal walking velocities with traditional laboratory measurements [peak isometric knee-extension strength and maximal oxygen intake ( V(.)O(2max))] were examined in 10 healthy male and 13 healthy female volunteers, aged 65-74 years. Percentages of oxygen intake reserve (% V(.)O(2reserve)) and heart rate reserve (%HR(reserve)) were also determined when walking at 30-70% of maximal velocity. Preferred and maximal walking velocities were significantly correlated ( r0.60; P0.05), the former corresponding to an average of 53-54% of the latter in both men and women. Maximal walking velocity was significantly correlated with both peak knee-extension torque ( r0.90; P0.05) and V(.)O(2max) ( r0.80; P0.05). As a result, the % V(.)O(2reserve) and %HR(reserve) showed a regular and linear relationship to various submaximal walking velocities. For both men and women, 40-60% of the maximal walking velocity corresponded to about 30-50% of V(.)O(2reserve) and HR(reserve). Approximately 60% of the maximal walking velocity (or 110-115% of the preferred walking velocity) represents an appropriate intensity of moderate exercise for the typical elderly person. Our preliminary data suggest that a prescription based on walking velocity over the 5-m distance allows the healthy elderly to exercise simply, safely, and effectively.

We investigated progressive telomere shortening in normal human epidermis and lingual epithelium during aging, and attempted, in particular, to ascertain whether the telomere shortening that accompanies aging occurs at the same rate in different tissues. We studied telomeric DNA integrity, and estimated annual telomere loss, in 52 specimens of epidermis and 48 specimens of lingual epithelium collected at autopsy from subjects who had died at ages between 0 and 101 y. Most of the DNA samples were measured twice by southern blot hybridization. In addition, the correlation between telomere lengths in the two types of tissues was examined. The telomere reduction rates in epidermis and lingual epithelium were 36 bp and 30 bp per y, respectively, and these were significantly different. The rates obtained by the second measurements in epidermis and lingual epithelium were 39 and 32 bp per y, respectively, and these were also significantly different. The mean telomere lengths in the epidermis of eight neonates and the lingual epithelium of seven neonates were 13.2+/-1.0 and 13.8+/-1.0 kb, respectively. Comparison of telomere lengths in the two tissues for 41 paired samples showed that the mean telomere length in the epidermis (10.7+/-2.3 kb) was less than that in the lingual epithelium (12.4+/-2.5 kb); however, statistical analysis revealed a very significant relationship between epidermal and lingual epithelial telomere length (r=0.842, p0.0001). These results indicate that the telomeres in epidermis and lingual epithelium are characterized by tissue-specific loss rates.

Previous information on exercise recommendations for an elderly population, based mainly on self-reports of habitual physical activity, are reviewed in the context of the Nakanojo study, where accurate objective information on a group of 5200 independently living men and women aged 65–84 years from a small Japanese town has been obtained by continuous pedometer/accelerometer monitoring over periods of 1–5 years. Measures of physical fitness, metabolic risk factors and cardiovascular health all show correlations with habitual physical activity. Some health benefits are associated with quite low levels of activity (counts of around 6000 steps/day and/or 9–10 minutes of activity at an intensity >3 METs), but health increases progressively with activity level to step counts of 7000–8000/day, with 15–20 minutes at an intensity >3 METs. Benefit is associated more closely with habitual activity than with aerobic fitness, and there is no evidence of the activity threshold suggested in some earlier research. A smaller proportion of health costs is attributable to cardio-metabolic disease than would be the case in younger individuals. A large proportion of total health-care costs is attributable to those people in the lowest category of physical activity, but the gradation of costs from low to high activity categories is less steep for cardio-metabolic conditions than for other forms of chronic ill-health. Substantial financial benefits might accrue if at least a proportion of those in each activity category could be persuaded to increase their habitual activity by at least one category, a change of activity pattern showing the largest cost-benefit ratio for those in the lowest activity category.

Background:We examined the relative contributions of habitual physical activity and aerobic fitness to the prevention of arteriosclerosis.Methods:Elderly individuals (97 men and 109 women, aged > 65 y) each wore a uniaxial activity monitor continuously for 1 year, with activity data summarized as an average daily step count and duration of activity > 3 metabolic equivalents (METs). Aerobic fitness was assessed by a standardized 5-m walking test measure of maximal walking speed. Central arterial stiffness was determined using an automatic waveform analyzer measure of cardio-femoral pulse wave velocity (cfPWV).Results:The cfPWV was negatively associated with daily step count, duration of activity > 3 METs, and maximal walking speed (P < .05). Multiple stepwise regression analysis revealed that the step count, duration of activity > 3 METs, and maximal walking speed were all significant predictors of cfPWV, accounting for 11%, 7%, and 4% of total variance, respectively.Conclusions:In contrast to findings from studies using potentially fallible questionnaires, our data suggest that a measure of health (arterial stiffness) is more closely related to objective measures of physical activity than to an estimate of aerobic fitness.

Objectives Stressful life events may have an indirect effect on health by reducing a person's habitual physical activity. The literature supports a negative association between stressful life events and the self-reported physical activity of younger adults, but further evidence is needed for older individuals, using objective measurements of physical activity. We have therefore investigated this issue in a healthy sample of seniors. Methods The subjects were 83 men and 101 women, aged 65–85 years. An accelerometer measured their step counts and the intensity of physical activity in metabolic equivalents (METs) on a 24-h basis for an entire year. At the year's end, subjects reported stressful life events that had occurred during the year. Pearson's partial correlation coefficients between these events and physical activity were calculated after controlling for inter-individual differences in age. Results The age-adjusted number of events was negatively correlated with both average daily step count and average daily duration of activity > 3 METs in males ( r = −0.27, p = 0.02; r = −0.37, p = 0.001, respectively). The self-reported age-adjusted total severity of events showed significant negative correlations with both step count and duration of activity > 3 METs, both in males ( r = −0.29, p = 0.01; r = −0.37, p = 0.001, respectively) and in females ( r = −0.21, p = 0.03; r = −0.25, p = 0.01, respectively). Conclusion Stressful life events in the elderly are associated with a low level of habitual physical activity (particularly in men who take little exercise of moderate intensity).

Background Although genome-wide association studies (GWASs) have implicated several genes in the predisposition to chronic kidney disease (CKD) in Caucasian or African American populations, the genes that confer susceptibility to CKD in Asian populations remain to be identified definitively. We performed a GWAS to identify genetic variants that confer susceptibility to CKD in Japanese individuals. Methods 3851 Japanese individuals from three independent subject panels were examined. Subject panels A, B, and C comprised 252, 910, and 190 individuals with CKD and 249, 838, and 1412 controls, respectively. A GWAS for CKD was performed in subject panel A. Results Five single nucleotide polymorphisms (SNPs) at chromosome 3q28, ALPK1 , FAM78B , and UMODL1 were significantly (false discovery rate

The purpose of the present study was to compare the heat strain while wearing nuclear, biological, and chemical (NBC) protective clothing following a hot-wet (HW) or hot-dry (HD) heat acclimation protocol. Twenty-two males were assigned to groups HW (n = 7), HD (n = 8), or control (C, n = 7). Subjects were evaluated during continuous treadmill walking while wearing lightweight combat clothing and during intermittent exercise while wearing the NBC protective clothing. While wearing Combat clothing, greater decreases in rectal temperature (Tre), mean skin temperature [Formula: see text], and heart rate were observed for both acclimation groups. For the NBC clothing trials, lower Tre, [Formula: see text], and heart rates were observed only for group HW. The time required for Tre to increase 1.0 °C and 1.5 °C was significantly delayed for groups HW and HD. Sweat evaporation increased for HW, whereas no change was found for HD. The most significant changes in Tre, [Formula: see text], and heart rate while wearing the NBC protective clothing occur following heat acclimation that involves wearing the clothing during exercise. Key words: rectal temperature, mean skin temperature, heart rate, sweat rate

Two methods of estimating body heat storage were compared under differing conditions of clothing, training, and acclimation to heat. Six male subjects underwent 8 weeks of physical training [60–80% of maximal aerobic power (\(\dot VO_{2\max } \)) for 30–45 min · day–, 3–4 days · week−1 at < 25 °C dry bulb (db)] followed by 6 consecutive days of heat acclimation (45–55%\(\dot VO_{2\max } \) for 60 min · day−1 at 40°C db, 30% relative humidity)]. Nine other male subjects underwent corresponding periods of control observation followed by heat acclimation. Before and after each treatment, subjects walked continuously on a treadmill (1.34 m · s−1, 2% grade) in a climatic chamber (40°C db, 30% relative humidity) for an average of 118 min (range 92–120 min) when wearing normal light combat clothing and for an average of 50 min (range 32–68 min) when wearing protective clothing resistant to nuclear, biological, and chemical agents. The heat storage was determined calorimetrically (by the balance of heat gains and losses) and thermometrically [by the conventional equations, using one or two set(s) of relative weightings for the rectal temperature (Tre) to mean skin temperature\(\bar T\)sk of 4:1 and 4:1, 2:1 and 4:1, or 2:1 and 9:1 in thermoneutral and hot environments, respectively].\(\bar T\)sk was calculated from 12-site measurements, weighted according to the regional distribution of body surface area and the first eigenvectors of principal component analysis. There were only minor differences (< 5%) between the heat storage values calculated by given weighting factors forTre and\(\bar T\)sk, whether the individual coefficients were derived from estimates of regional surface area or principal component methodologies. When wearing normal clothing, no significant differences were found between the two estimates of heat storage (calorimetry vs thermometry with an invariant relative weighting of 4:1) in any experimental condition, with one specific exception: when wearing protective clothing, thermometry underestimated the heat storage by 24–31%. This underestimation was attenuated by using two sets of relative weightings of 2: 1 and 4: 1 or 2: 1 and 9: 1. The results suggest that when subjects wearing protective clothing are transferred from thermoneutral to hot environments, the accuracy of thermometric estimates of heat storage can be improved by using two sets of weighting factors forTre and\(\bar T\)sk

We review sex differences in the relationship between habitual physical activity and health in the elderly, with particular reference to pedometer/accelerometer data from the Nakanojo Study. Maximal aerobic power, walking speed and habitual physical activity are 10-30% greater in men than in women. This reflects not only biological but also socio-cultural and environmental factors, with the latter becoming dominant as age advances. It implies a need for sex-specific thresholds of moderate activity. Overall health is associated with both the year-averaged daily step count (the best indicator in women) and the year-averaged daily duration of physical activity >3 metabolic equivalents (METs) (the best indicator in men). In both sexes, the threshold ranges of step count and/or duration of activity >3 METs associated with a reduced prevalence of health problems are: 4000-5000 steps/day and/or 5-7.5 min/day for impaired mental and psychosocial health, such as a depressed mood state and a poor health-related quality of life; 7000-8000 steps/day and/or 15-20 min/day for markers of aortic arteriosclerosis, osteoporosis, sarcopenia and poor physical fitness; and 8000-10,000 steps/day and/or 20-30 min/day for components of the metabolic syndrome, especially hypertension and hyperglycemia. Irrespective of sex, both the intensity and the total volume of physical activity are influenced by stressful life events, such as a partner's death, and immediate meteorological factors, particularly precipitation and mean ambient temperature, underlining the need for long-term measurement of activity patterns. These findings have practical implications for those who engage in epidemiological studies and/or design health promotional programs for the elderly.

We previously showed that the -1131T→C polymorphism (rs662799) of the apolipoprotein A-V gene (APOA5) and the C→T polymorphism (rs6929846) of the butyrophilin, subfamily 2, member A1 gene (BTN2A1) were significantly associated with an increased serum concentration of triglycerides, a decreased serum concentration of high density lipoprotein (HDL)-cholesterol, and the prevalence of metabolic syndrome (MetS) in Japanese individuals. The purpose of the present study was to examine whether these polymorphisms synergistically affect the prevalence of dyslipidemia and MetS in East Asian populations. The study populations comprised 7471 Japanese and 3529 Korean individuals in the dyslipidemia study, and 3474 Japanese and 1671 Korean individuals in the MetS study. Multivariable logistic regression analysis of combined genotypes with adjustment for age, gender and diabetes mellitus revealed that rs662799 and rs6929846 significantly and synergistically affected dyslipidemia. Japanese or Korean individuals with the C allele of APOA5 and the T allele of BTN2A1 had a 2.05- or 1.92-fold increased risk for hypertriglyceridemia and a 1.82- or 1.56-fold increased risk for hypo-HDL-cholesterolemia, respectively, compared to those with the TT genotype of APOA5 and the CC genotype of BTN2A1. Similar analysis with adjustment for age and gender revealed that Japanese individuals, but not Korean individuals, with the C allele of APOA5 and the T allele of BTN2A1 had a 2.87-fold increased risk for MetS compared to those with the TT genotype of APOA5 and the CC genotype of BTN2A1. Genetic variants of APOA5 and BTN2A1 may synergistically affect the prevalence of dyslipidemia in East Asian populations and of MetS in Japanese individuals.

Over the years, techniques for the study of human movement have ranged in complexity and precision from direct observation of the subject through activity diaries, questionnaires, and recordings of body movement, to the measurement of physiological responses, studies of metabolism and indirect and direct calorimetry. This article reviews developments in each of these domains. Particular reference is made to their impact upon the continuing search for valid field estimates of activity patterns and energy expenditures, as required by the applied physiologist, ergonomist, sports scientist, nutritionist and epidemiologist. Early observers sought to improve productivity in demanding employment. Direct observation and filming of workers were supplemented by monitoring of heart rates, ventilation and oxygen consumption. Such methods still find application in ergonomics and sport, but many investigators are now interested in relationships between habitual physical activity and chronic disease. Even sophisticated questionnaires still do not provide valid information on the absolute energy expenditures associated with good health. Emphasis has thus shifted to use of sophisticated pedometer/accelerometers, sometimes combining their output with GPS and other data. Some modern pedometer/accelerometers perform well in the laboratory, but show substantial systematic errors relative to laboratory reference criteria such as the metabolism of doubly labeled water when assessing the varied activities of daily life. The challenge remains to develop activity monitors that are sufficiently inexpensive for field use, yet meet required accuracy standards. Possibly, measurements of oxygen consumption by portable respirometers may soon satisfy part of this need, although a need for valid longer term monitoring will remain.