Changes in and Interactions between Physical and Mental Health in Older Japanese: The Nakanojo Study.

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.

Identification of chromosome 3q28 and ALPK1 as susceptibility loci for chronic kidney disease in Japanese individuals by a genome-wide association study.

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<0.05) associated with CKD by the GWAS. The relation of these five SNPs and of an additional 22 SNPs at these loci to CKD was examined in subject panel B, revealing that rs9846911 at 3q28 was significantly associated with CKD in all individuals and that rs2074381 and rs2074380 in ALPK1 were associated with CKD in individuals with diabetes mellitus. These three SNPs were further examined in subject panel C, revealing that rs2074381 and rs2074380 were significantly associated with CKD. For subject panels B and C combined, rs9846911 was significantly associated with CKD in all individuals and rs2074381 and rs2074380 were associated with CKD in diabetic individuals. CONCLUSIONS: Chromosome 3q28 may be a susceptibility locus for CKD in Japanese individuals, and ALPK1 may be a susceptibility gene for CKD in such individuals with diabetes mellitus.

Association of psychosocial factors with physical activity among Japanese adults aged 65 and older: a 6-year repeated cross-sectional study from the Nakanojo Study.

BACKGROUND: Physical activity (PA) provides substantial mental and physical health benefits for individuals of all ages. A limited number of long-term or longitudinal studies have investigated the association between psychosocial factors and PA in healthy older adults aged 65 and above. This study aimed to determine the long-term relationship between psychosocial factors, such as vitality, mental health, anxiety, and depression, and objectively measure PA in older adults. METHODS: Healthy participants from Nakanojo, Japan, aged 65-90, capable of walking, were included in this study and were followed up from 2008 to 2013. Those diagnosed with dementia and depression were excluded. Using a repeated cross-sectional dataset, a multilevel model was developed with psychosocial variables as independent variables and an average daily duration of PA volume of > 3 metabolic equivalents (METs) as the outcome. The Akaike information criterion was used to select the final model. RESULTS: This study included 1108 records from 319 participants. In the multilevel model, age (coefficient = -0.106, 95% confidence interval [CI] = -0.127 to -0.086, p < 0.001) and the Hospital Anxiety and Depression Scale depression scores (coefficient = -0.019, 95% CI = -0.036 to -0.002, p = 0.026) were negatively associated with the duration of PA volume > 3 METs, whereas male sex (coefficient = 0.343, 95% CI = 0.115 to 0.571, p = 0.003) was positively associated with PA volume. CONCLUSION: Depressive symptoms were related to a reduced duration of PA volume of > 3 METs among these adults aged 65 and above.

Association of a genetic variant of BTN2A1 with metabolic syndrome in East Asian populations.

BACKGROUND: The authors 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 χ(2) test revealed that the genotype distributions and allele frequencies of rs6929846 were significantly (p<0.05) associated with MetS in Japanese subject panels A (T allele frequency: MetS, 0.091; controls, 0.054; p=6.1×10(-5)) and B (T allele frequency: MetS, 0.091; controls, 0.039; p=0013) but not in the Korean population samples (T allele frequency: MetS, 0.102; controls, 0.125; p=0.0997). Multivariable logistic regression analysis with adjustment for covariates revealed that the rs6929846 of BTN2A1 was significantly (p<0.017) associated with MetS in Japanese subject panel A (p=0.0055, OR 1.97) and in all individuals (p=0.0038, OR 1.38), with the T allele representing a risk factor for this condition. CONCLUSION: BTN2A1 may be a susceptible gene for MetS in Japanese individuals.

Measurement of human energy expenditure, with particular reference to field studies: an historical perspective.

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.

How many steps/day are enough? For older adults and special populations.

Older adults and special populations (living with disability and/or chronic illness that may limit mobility and/or physical endurance) can benefit from practicing a more physically active lifestyle, typically by increasing ambulatory activity. Step counting devices (accelerometers and pedometers) offer an opportunity to monitor daily ambulatory activity; however, an appropriate translation of public health guidelines in terms of steps/day is unknown. Therefore this review was conducted to translate public health recommendations in terms of steps/day. Normative data indicates that 1) healthy older adults average 2,000-9,000 steps/day, and 2) special populations average 1,200-8,800 steps/day. Pedometer-based interventions in older adults and special populations elicit a weighted increase of approximately 775 steps/day (or an effect size of 0.26) and 2,215 steps/day (or an effect size of 0.67), respectively. There is no evidence to inform a moderate intensity cadence (i.e., steps/minute) in older adults at this time. However, using the adult cadence of 100 steps/minute to demark the lower end of an absolutely-defined moderate intensity (i.e., 3 METs), and multiplying this by 30 minutes produces a reasonable heuristic (i.e., guiding) value of 3,000 steps. However, this cadence may be unattainable in some frail/diseased populations. Regardless, to truly translate public health guidelines, these steps should be taken over and above activities performed in the course of daily living, be of at least moderate intensity accumulated in minimally 10 minute bouts, and add up to at least 150 minutes over the week. Considering a daily background of 5,000 steps/day (which may actually be too high for some older adults and/or special populations), a computed translation approximates 8,000 steps on days that include a target of achieving 30 minutes of moderate-to-vigorous physical activity (MVPA), and approximately 7,100 steps/day if averaged over a week. Measured directly and including these background activities, the evidence suggests that 30 minutes of daily MVPA accumulated in addition to habitual daily activities in healthy older adults is equivalent to taking approximately 7,000-10,000 steps/day. Those living with disability and/or chronic illness (that limits mobility and or/physical endurance) display lower levels of background daily activity, and this will affect whole-day estimates of recommended physical activity.

Association of a genetic variant of BTN2A1 with chronic kidney disease in Japanese individuals.

AIM: Although recent genetic studies suggested that several genetic variants increase the risk for chronic kidney disease (CKD), the genes that underlie genetic susceptibility to this condition remain to be identified definitively. We showed that the C→T polymorphism (rs6929846) of BTN2A1 and A→G polymorphism (rs2569512) of ILF3 were significantly associated with myocardial infarction in Japanese individuals by a genome-wide association study. The purpose of the present study was to examine a possible association of these polymorphisms (rs6929846, rs2569512) with CKD in Japanese individuals. METHODS: A total of 7542 Japanese individuals from two independent populations were examined: Subject panel A comprised 971 individuals with CKD (estimated glomerular filtration rate (eGFR) <60 mL/min 1.73 m(-2)) ) and 2269 controls (eGFR ≥60 mL/min 1.73 m(-2) ); and subject panel B comprised 1318 individuals with CKD and 2984 controls. RESULTS: The χ(2) test revealed that rs6929846 of BTN2A1, but not rs2569512 of ILF3, was significantly related to the prevalence of CKD both in subject panels A (P = 0.0383) and B (P = 0.0477). Multivariable logistic regression analysis with adjustment for covariates revealed that the C→T polymorphism (rs6929846) of BTN2A1 was significantly associated with the prevalence of CKD in subject panels A (P = 0.0422; recessive model; odds ratio, 2.36) and B (P = 0.0386; dominant model; odds ratio, 1.21) with the T allele representing a risk for this condition. CONCLUSION: Our results suggest that BTN2A1 may be a susceptibility gene for CKD in Japanese individuals.

Trajectories of objectively measured physical activity and mood states in older Japanese adults: longitudinal data from the Nakanojo Study.

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.

Yearly changes in the composition of gut microbiota in the elderly, and the effect of lactobacilli intake on these changes.

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.

Habitual physical activity and health-related quality of life in older adults: interactions between the amount and intensity of activity (the Nakanojo Study).

PURPOSE: This study examined relationships between health-related quality of life (HRQOL) and objective assessments of habitual physical activity in older adults, focusing on interactions between the amount and intensity of activity. METHODS: Subjects were healthy Japanese aged 65-85 years (74 men and 109 women). Pedometer/accelerometers measured their step counts and the intensity of physical activity in metabolic equivalents (METs) continuously 24 h per day for 1 year. Each individual's final HRQOL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) instrument. RESULTS: The daily step count and the daily duration of physical activity at an intensity >3 METs were quite closely correlated (quadratic r2 = 0.93, P < 0.05). After controlling for age, sex, and daily step count, the overall SF-36 score and four constituent dimensions (physical functioning, freedom from pain, vitality, and mental health) were all significantly higher in individuals spending >25% of their total activity at an intensity >3 METs. However, engagement in activity >3 METs was not significantly associated with the remaining SF-36 components (physical limitations, general health, social functioning, and emotional limitations). CONCLUSIONS: Associations between moderate-intensity physical activity and HRQOL in older adults merit further evaluation by prospective studies and/or randomized controlled trials.

Yearlong physical activity and sarcopenia in older adults: the Nakanojo Study.

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) value >1 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 at >3 METs. All participants meeting such criteria exceeded our sarcopenia threshold. Multivariate-adjusted logistic regressions predicted that individuals who walked <5,300 steps/day and/or spent <15 min/day at >3 METs were, respectively, 2.00-2.66 and/or 2.03-4.55 times more likely to show sarcopenia than those who walked >7,800 steps/day and/or spent >23 min/day at >3 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 of >3 METs were likely to have a muscle mass above the sarcopenia threshold.

Yearlong physical activity and regional stiffness of arteries in older adults: the Nakanojo Study.

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.

Association of a polymorphism of the apolipoprotein E gene with chronic kidney disease in Japanese individuals with metabolic syndrome.

The purpose of the present study was to identify genetic variants that confer susceptibility to chronic kidney disease (CKD) in Japanese individuals with metabolic syndrome. The study population comprised 2150 Japanese individuals with metabolic syndrome, including 411 subjects with CKD [estimated glomerular filtration rate (eGFR) <50 mL/min/1.73m(2)] and 1739 controls (eGFR >/=60 mL/min/1.73m(2)). The genotypes for 100 polymorphisms of 80 candidate genes were determined. The chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that nine polymorphisms of APOE, ABCA1, PTGS1, TNF, CPB2, AGTR1, OR13G1, and GNB3 were associated (P<0.05) with the prevalence of CKD. Among these polymorphisms, the -219G-->T polymorphism of APOE (rs405509) was most significantly associated with CKD in Japanese individuals with metabolic syndrome.

Association of genetic variants with myocardial infarction in Japanese individuals with chronic kidney disease.

Chronic 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 <0.05) associated with the prevalence of MI in individuals with CKD. Subsequent multivariable logistic regression analysis with adjustment for covariates and a stepwise forward selection procedure also revealed that this polymorphism was significantly (p <0.005) associated with MI, with the variant A (Gln) allele protecting against this condition. Determination of genotype for the 11496G-->A (Arg353Gln) polymorphism of F7 may prove informative for assessment of the genetic risk for MI in individuals with CKD.

Steps per day: the road to senior health?

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 aged > or =65 years, physical activity has already been assessed continuously for 24 h/day for >8 years using a specially adapted pedometer/accelerometer. This device has a storage capacity of 36 days and can distinguish >10 intensities of physical activity (expressed in metabolic equivalents [METs]). Data have to date been summarized as daily step counts and daily durations of activity of <3 and >3 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 of >3 METs and the daily step count. In men, the extent of health is associated more closely with the daily duration of activity of >3 METs than with the daily step count, whereas in women, the association is closer for the step count than for the duration of activity >3 METs. In both sexes, the threshold amount of physical activity associated with better health is greater for physical than for mental benefits: >8000 versus >4000 steps/day and/or >20 versus >5 min/day at an intensity >3 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 further >60 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 of <3 and >3 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.

Association of genetic variants with chronic kidney disease in Japanese individuals with type 2 diabetes mellitus.

Although diabetes mellitus has been recognized as a risk factor for chronic kidney disease (CKD), genetic factors for predisposition to CKD in individuals with diabetes mellitus remain elucidated. The purpose of the present study was to identify genetic variants that confer susceptibility to CKD among individuals with type 2 diabetes mellitus. The study population comprised 1742 Japanese individuals, including 636 subjects with CKD [estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2] and 1106 controls (eGFR>or=60 ml/min/1.73 m2). The genotypes for 24 polymorphisms of 22 candidate genes were determined. An initial screen of allele frequencies by the Chi-square test revealed that four polymorphisms were significantly (false discovery rate<0.05) associated with the prevalence of CKD in individuals with type 2 diabetes mellitus. Subsequent multivariable logistic regression analysis with adjustment for covariates as well as a stepwise forward selection procedure revealed that the 8733T-->C polymorphism of ALOX5AP (rs3803278), the C-->T (Ser532Leu) polymorphism of IRAK1 (rs1059703), and the 2445G-->A (Ala54Thr) polymorphism of FABP2 (rs1799883) were significantly (P<0.05) associated with the prevalence of CKD. Our results suggest that ALOX5AP, IRAK1, and FABP2 are susceptibility loci for CKD among Japanese individuals with type 2 diabetes mellitus.

Association of gene polymorphisms with chronic kidney disease in high- or low-risk subjects defined by conventional risk factors.

The purpose of the present study was to identify genetic variants which confer susceptibility to chronic kidney disease (CKD) in high- or low-risk subjects defined by conventional risk factors separately. The study population comprised 2828 Japanese individuals, including 434 subjects with CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)] and 2394 controls (eGFR > or =60 ml/min/ 1.73 m(2)). The 1012 high-risk subjects had both hypertension and diabetes mellitus, and the 1816 low-risk subjects had none of these conditions. The genotypes for 296 polymorphisms of 202 candidate genes were determined. The Chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that ten different polymorphisms were associated (P<0.05) with the prevalence of CKD in high- or low-risk subjects: the -519Aright curved arrow G polymorphism of MMP1, the 1061Aright curved arrow G (Ile405Val) polymorphism of CETP, the Aright curved arrow G (Lys45Glu) polymorphism of MMP3, the -219Gright curved arrow T polymorphism of APOE, the Aright curved arrow G (Ile1205Val) polymorphism of COL3A1, the -863Cright curved arrow A polymorphism of TNF, and the 1454Cright curved arrow G (Leu125Val) polymorphism of PECAM1 in high-risk subjects; and the 1167Cright curved arrow T (Asn389Asn) polymorphism of TGFBR2, the 2386Aright curved arrow G (Ile796Val) polymorphism of SCAP, and the TAAAright curved arrow del polymorphism of PDE4D in low-risk subjects. Among these polymorphisms, the -519Aright curved arrow G polymorphism of MMP1 and the 1167Cright curved arrow T (Asn389Asn) polymorphism of TGFBR2 were most significantly associated with CKD in high- or low-risk individuals, respectively. These results suggest that polymorphisms associated with CKD may differ among high- or low-risk subjects. Stratification of subjects according to conventional risk factors may thus be important for personalized prevention of CKD based on genetic information.

Association of genetic variants with chronic kidney disease in individuals with different lipid profiles.

The purpose of the present study was to identify genetic variants that confer susceptibility to chronic kidney disease (CKD) in individuals with low or high serum concentrations of triglycerides (TG), high-density lipoprotein (HDL)-cholesterol, or low-density lipoprotein (LDL)-cholesterol, thereby contributing to the personalized prevention of CKD in such individuals. The study population comprised 5944 Japanese individuals, including 1706 subjects with CKD [estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2] and 4238 controls (eGFR>or=60 ml/min/1.73 m2). The genotypes for 296 polymorphisms of 202 candidate genes were determined. The Chi-square test, multivariable logistic regression analysis with adjustment for covariates, and a stepwise forward selection procedure revealed that seven different polymorphisms were significantly (P<0.005) associated with the prevalence of CKD in individuals with low or high serum concentrations of TG or HDL- or LDL-cholesterol: the Aright curved arrow G (Glu23Lys) polymorphism of KCNJ11 and the 125592Cright curved arrow A (Thr431Asn) polymorphism of ROCK2 in individuals with low serum TG; the 734Cright curved arrow T (Thr254Ile) polymorphism of ACAT2 and the Cright curved arrow G (Gln27Glu) polymorphism of ADRB2 in individuals with high serum TG; the -1607/1Gright curved arrow 2G polymorphism of MMP1 in individuals with low serum HDL-cholesterol; the Gright curved arrow A (Val158Met) polymorphism of COMT in individuals with low serum LDL-cholesterol; the 584Gright curved arrow A (Gln192Arg) polymorphism of PON1 in individuals with high serum LDL-cholesterol. No polymorphism was associated with CKD in individuals with high serum HDL-cholesterol. These results suggest that polymorphisms associated with CKD may differ among individuals with different lipid profiles. Stratification of subjects according to lipid profiles may thus be important for personalized prevention of CKD based on genetic information.

Habitual physical activity and physical fitness in older Japanese adults: the Nakanojo Study.

BACKGROUND: Optimal patterns of habitual physical activity to ensure healthy aging remain unclear because of measurement limitations; most investigators have used either subjective questionnaires, or accelerometer or pedometer measurements limited to a single week, despite evidence of both the limited reliability/validity of questionnaires and seasonal changes in activity patterns. OBJECTIVE: This study explored possible associations between indicators of physical fitness (walking ability, upper- and lower-extremity isometric strength, and static and dynamic balance) and yearlong pedometer/accelerometer assessments of the quantity and quality of habitual physical activity in ostensibly healthy older adults. METHODS: Subjects were 76 male and 94 female Japanese aged 65-84 years. Each participant wore a pedometer/accelerometer for 1 year; measurements included the average number of steps taken each day and the duration of activity at an intensity of >3 metabolic equivalents (METs). Compliance was good, the instrument being removed for intervals of >3 h on <5% of days; data for such intervals were excluded from analysis. At the year's end, traditional laboratory techniques assessed preferred and maximal walking speeds, peak handgrip force, peak knee extension torque, total body sway, and maximal functional reach. RESULTS: After controlling data for age and/or sex, lower-extremity function (walking speeds and knee extension torque) showed significant positive relationships with the daily step count and daily duration of activity at >3 METs, especially in individuals > or = 75 years of age. On the other hand, handgrip force and body sway were unrelated to pedometer/accelerometer measurements. Linear and exponential regressions showed positive associations between walking speeds and pedometer/accelerometer scores up to the observed maxima of 13,700 steps/day and 62 min/day at >3 METs. However, when data were categorized into quartiles, walking speeds were not significantly greater in persons exceeding 7,000-8,000 steps/day and/or 15-20 min/day at >3 METs. With a few exceptions, subjects meeting these levels of habitual activity had walking speeds above the threshold predicting the development of functional dependence. CONCLUSION: The present data suggest that fitness is well maintained in elderly people who take >7,000-8,000 steps/day and/or spend >15-20 min/day at >3 METs. Nevertheless, the direction of this association merits exploration by longitudinal prospective studies and/or randomized controlled trials.

Seasonal variations in physical activity and implications for human health.

This review explores the implications of seasonal changes in physical activity for fitness and human health. Photosensitivity and nutrient shortages mediate animal hibernation via the hypothalamus and changes in leptin and ghrelin concentrations. Opportunities for hunting and crop cultivation determine seasonal activity in under-developed human societies, but in developed societies temperature and rainfall are dominant influences, usually over-riding innate rhythms. Both questionnaire data and objective measurements show that many groups from children to the elderly increase their physical activity from winter to spring or summer. Measurements of maximal oxygen intake and muscle strength commonly show parallel seasonal changes. However, potential effects upon body mass and body fat may be counteracted by changes of food intake; subsistence agriculturists sometimes maintain or increase physical activity at the expense of a decrease in body mass. In developed societies, body fat commonly increases during the winter, with parallel changes in blood lipids, blood pressure and blood coagulability; moreover, these changes are not always fully reversed the following summer. Most developed societies show increased all-cause and cardiac mortalities in the winter. Health consequences of seasonal variations in physical activity including an increased vulnerability to cardiac catastrophe and a year-by-year increase in total body fat seem most likely if the average level of physical activity for the year is low. Public health recommendations should underline the importance of maintaining physical activity during adverse environmental conditions by adapting clothing, modifying behaviour and exploiting any available air-conditioned indoor facilities.