Relationship between plasma S-Klotho and cardiometabolic risk in sedentary adults.
ABSTRACT: This cross-sectional study investigates the relationship between the shed form of the Klotho protein (S-Klotho) in plasma, and cardiometabolic risk in healthy, sedentary adults. The study subjects were 214 healthy, sedentary adults (~64% women). Data were collected during the baseline assessments of two randomized controlled trials: The FIT-AGEING study (n=74 [~50% women] middle-aged adults aged 40-65 years) and the ACTIBATE study (n=140 [~70% women] young adults aged 18-25 years). A sex-specific cardiometabolic risk score was calculated for each subject based on waist circumference, systolic and diastolic blood pressure, and plasma glucose, high-density lipoprotein cholesterol and triglycerides. A significant inverse relationship was detected between S-Klotho and the cardiometabolic risk score of both the middle-aged men and women (?=-0.658, R2=0.433, P<0.001 and ?=-0.442, R2=0.195, P=0.007) which persisted after adjusting for actual age, energy intake, and VO2max. No significant association was found between S-Klotho and cardiometabolic risk score for the young, healthy adults (P>0.5), nor for the young, healthy men and women when analysed separately (all P>0.1). In conclusion, in healthy, sedentary, middle-aged adults, but not in young, healthy, sedentary adults, higher plasma S-Klotho concentrations are associated with a lower cardiometabolic risk score.
Project description:This 12-week randomized controlled trial investigates the effects of different training modalities on cardiometabolic risk in sedentary, middle-aged adults, and examines whether alterations in cardiometabolic risk are associated with changes in those health-related variables that are modifiable by exercise training. The study subjects were 71 middle-aged adults (~54 years old; ~50% women) who were randomly assigned to one of the following treatment groups: (1) no exercise (control group), (2) concurrent training based on international physical activity recommendations (PAR group), (3) high intensity interval training (HIIT) group, or (4) HIIT plus whole-body electromyostimulation (HIIT+EMS group). A cardiometabolic risk score was calculated based on the International Diabetes Federation's clinical criteria. A significant reduction in cardiometabolic risk was observed for all exercise training groups compared to the control group (all p < 0.05), which persisted after adjusting potential confounders (all p < 0.05). However, the HIIT+EMS group experienced the most significant reduction (p < 0.001). A significant inverse relationship was detected between the change in lean mass and the change in cardiometabolic risk (p = 0.045). A 12-week exercise training programs-especially the HIIT+EMS program-significantly reduced cardiometabolic risk in sedentary, middle-aged adults independent of sex, age, and cardiorespiratory fitness.
Project description:The aim of this study was to conduct a comprehensive investigation of the association between different types of leisure-time sedentary behavior (watching television, using a computer, reading and socializing) and clustered cardiometabolic risk in apparently healthy adults aged 40 to 65 years.One hundred seventy-three participants from the general population (64% women; mean age = 54.4 years) consented to attend a cardiovascular examination program and to complete a questionnaire on leisure-time sedentary behaviors. Waist circumference, blood pressure, glucose, triglycerides, and high-density lipoprotein cholesterol of non-fasting blood samples were assessed, and a clustered cardiometabolic risk score [CMRS] was calculated. Data were collected between February and July 2015. Associations between leisure-time sedentary behaviors and CMRS were analyzed using linear and quantile regression, adjusted for socio-demographic variables and other types of leisure-time sedentary behavior (model 1) and additionally, adjusted for leisure-time physical activity and traveling in motor vehicles (model 2).Linear regression revealed that there was a positive association between watching television and CMRS (model 1: b = 0.27 [CI: 0.03; 0.52]; model 2: b = 0.30 [CI: 0.05; 0.56]). In addition, quantile regression analysis revealed that using a computer was negatively associated with the 50th (model 1: b = - 0.43 [CI: -0.79; - 0.07]) and the 75th percentiles (model 1: b = - 0.71 [CI: -1.27; - 0.14]) of CMRS. Reading and socializing were not associated with CMRS.Watching television was positively associated with a clustered cardiometabolic risk score, while time spent using a computer revealed inconsistent findings. Our results give reason to consider different types of behaviors in which individuals are sedentary and the associations between these behaviors and cardiometabolic risk, supporting the need for behavior-specific assessments as well as public health recommendations to maintain or enhance adults' health.Clinical trial registration number: NCT02990039 , Retrospectively registered (December 12, 2016).
Project description:Aims:The secreted form of the ?-Klotho gene (S-Klotho), which is considered a powerful biomarker of longevity, makes it an attractive target as an anti-ageing therapy against functional decline, sarcopenic obesity, metabolic and cardiovascular diseases, osteoporosis, and neurodegenerative disorders. The S-Klotho plasma levels could be related to physical exercise inasmuch physical exercise is involved in physiological pathways that regulate the S-Klotho plasma levels. FIT-AGEING will determine the effect of different training modalities on the S-Klotho plasma levels (primary outcome) in sedentary healthy adults. FIT-AGEING will also investigate the physiological consequences of activating the klotho gene (secondary outcomes). Methods:FIT-AGEING will recruit 80 sedentary, healthy adults (50% women) aged 45-65 years old. Eligible participants will be randomly assigned to a non-exercise group, i.e. the control group, (n?=?20), a physical activity recommendation from World Health Organization group (n?=?20), a high intensity interval training group (n?=?20), and a whole-body electromyostimulation group (n?=?20). The laboratory measurements will be taken at the baseline and 12 weeks later including the S-Klotho plasma levels, physical fitness (cardiorespiratory fitness, muscular strength), body composition, basal metabolic rate, heart rate variability, maximal fat oxidation, health blood biomarkers, free-living physical activity, sleep habits, reaction time, cognitive variables, and health-related questionnaires. We will also obtain dietary habits data and cardiovascular disease risk factors.
Project description:Evidence suggests that time spent engaging in sedentary behaviors is associated with a greater risk of adverse cardiometabolic outcomes. We investigated the cross-sectional associations of 6 unique sedentary tasks (watching television, using the computer, completing paperwork, reading, talking on the telephone, and sitting in a car) with cardiometabolic risk factors, and also examined the effect of replacing one type of sedentary behavior with another on the level of cardiometabolic risk. Participants consisted of 3,211 individuals from the Coronary Artery Risk Development in Young Adults Study who visited the clinic between 2010 and 2011. Linear regression models examined the independent and joint associations of sedentary tasks with a composite cardiometabolic risk score, as well as with individual cardiometabolic risk factors (waist circumference, blood pressure, fasting glucose, insulin, triglycerides, and high density lipoprotein cholesterol) after adjusting for physical activity and other covariates. Replacing 2 hours of television viewing with 2 hours spent performing any other sedentary activity was associated with a lower cardiometabolic risk score of 0.06-0.09 standard deviations (all 95% confidence intervals: -0.13, -0.02). No other replacements of one type of sedentary task for another were significant. Study findings indicate that television viewing has a more adverse association with cardiometabolic risk factors than other sedentary behaviors.
Project description:BACKGROUND:Soluble Klotho (S-Klotho) is an aging suppressor with a close link with inflammation. However, it is still unknown whether the dietary inflammatory potential is associated with S-Klotho plasma level. We aimed to investigate the association of the Dietary Inflammatory Index (DII) with S-Klotho plasma levels in middle-aged sedentary adults. METHODS:73 middle-aged sedentary adults (40-65 years old) participated in the present study. DII was determined from 28 dietary items obtained by 24 h recalls and food frequency questionnaires. The S-Klotho plasma levels were measured using a solid-phase sandwich enzyme-linked immunosorbent assay. RESULTS:a weak positive association was observed between DII and S-Klotho plasma levels (? = 52.223, R2 = 0.057, p = 0.043), which disappeared after controlling for body mass index (p = 0.057). CONCLUSIONS:A pro-inflammatory dietary pattern measured with the DII was slightly and positively associated with S-Klotho plasma levels in middle-aged sedentary adults.
Project description:In this study, we investigate the associations of objectively measured waking (sedentary, light physical activity [LPA] and moderate-to-vigorous physical activity [MVPA]) and sleep duration and quality characteristics with cardiometabolic risk among older women. Participants from the Healthy Women Study 2010-11 follow-up visit (n = 136, age = 73 ± 2 years, white = 91.9%) concurrently wore an ActiGraph GT1M accelerometer and Actiwatch-2 for seven days. A composite cardiometabolic risk score was calculated by transforming metabolic syndrome (MetS) components and summing z-scores. Multivariable regression models were fitted to relate waking and sleep estimates with the MetS z-score after adjustment for covariates. Compositional data analysis was used to predict the MetS z-score when fixed durations of time were reallocated from one characteristic to another. MVPA (per 10 min/day increase; ? = -7.80, P < 0.01), LPA (per 30 min/day increase; ? = -0.29, P = 0.04), and sleep efficiency (? = -0.10, P = 0.04) were inversely associated with MetS z-score, while sedentary time (per 30 min/day increase; ? = 0.34, P = 0.01) was positively associated with MetS z-score. Reallocation of 5 min from MVPA to sleep, sedentary, or LPA resulted in the greatest predicted change in MetS z-score. On average, the reallocation of 5 min from MVPA to other characteristics predicted an 11% increase in triglycerides, 6% decrease in HDL-C, and 5% increase in waist circumference. Lastly, reallocating 30 min of sedentary time to LPA was associated with a modestly lower predicted MetS z-score. This study suggests that MVPA is the most important contributor of MetS and that maintaining MVPA and increasing LPA may be beneficial for reducing cardiometabolic risk among older women.
Project description:Sleep and Klotho have both been closely related to the ageing process, both playing a substantial role in the endocrine and immune systems and, thereby, in oxidative stress and chronic inflammation. However, there are no studies elucidating the relationship between sleep and Klotho. Therefore, this study investigated the association of sleep quantity and quality with the shed form of the ?-Klotho gene (S-Klotho plasma levels) in sedentary middle-aged adults. A total of 74 volunteers (52.7% women; aged 53.7 ± 5.1) were recruited for the present study. Objective sleep quality parameters (total sleep time (TST), wake after sleep onset (WASO), and sleep efficiency (SE)) were determined using a wrist-worn accelerometer over seven consecutive days, and the subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI; higher scores indicate worse sleep quality). The S-Klotho plasma levels were measured in the ethylenediaminetetraacetic acid plasma using a solid-phase sandwich enzyme-linked immunosorbent assay. Objective sleep parameters were associated with the S-Klotho plasma levels only after including the age, fat mass percentage, and lean mass index as covariates. A direct relationship was observed between the subjective sleep quality (inverse of PSQI scores) and the S-Klotho plasma levels in sedentary middle-aged adults. Improving sleep quantity and quality could be considered an anti-aging therapeutic approach for the prevention, slowing, and even reversal of the physiological decline and degenerative pathologies that are certainly related to the aging process.
Project description:S-klotho, the shed form of ?-klotho, is thought to be an ageing suppressor with functions related to the physiology of energy metabolism. However, it remains unknown whether ageing biomarkers such as S-klotho and/or chronological ageing are associated in any way with basal metabolic rate (BMR) and fuel oxidation in basal conditions and during exercise. The present work investigates the association of BMR and fuel oxidation in basal conditions and during exercise, with plasma S-klotho in middle-aged, sedentary adults. BMR was measured by indirect calorimetry in 74 such subjects (53% women; age 53.7±5.1 years) following standard procedures, and their fuel oxidation estimated via stoichiometric equations. The maximal fat oxidation during exercise (MFO) and the intensity of exercise that elicits MFO (Fatmax) were determined using a walking graded exercise test. No relationship was seen between BMR and plasma S-klotho (P>0.1), although both basal fat oxidation and MFO showed positive associations with this protein (both P<0.001); these relationships persisted after controlling for age, sex and fat mass. However, no significant associations were seen between BMR, basal fat oxidation or MFO and chronological age (all P>0.1). The present findings suggest that basal fat oxidation and MFO are strongly associated with plasma S-klotho in middle-aged sedentary adults. These results support the idea that metabolic flexibility is a powerful predictor of biological ageing.
Project description:OBJECTIVE:The aim of this study was to examine the associations between sedentary behavior and different intensities of physical activity with cardiometabolic risk, and to analyze the simultaneous effect of excess sedentary behavior and recommended levels of physical activity on cardiometabolic risk markers in older adults. METHODS:We conducted a population-based cross-sectional study on a sample of older adults (60+) living in Florianopolis, Brazil. The objectively measured predictors were sedentary time, light physical activity and moderate to vigorous physical activity, and the outcomes were markers of cardiometabolic risk. Data were considered valid when the participant had used the accelerometer for at least four days per week. RESULTS:The sample included 425 older adults (59.8% women), with a mean age of 73.9 years (95%CI: 73.5-74.4). Sedentary behavior was associated with lower systolic blood pressure levels (? = -0.03; 95%CI: -0.05; -0.01) and lower HDL cholesterol (? = -0.02; 95%CI: -0.02; -0.01). Light physical activity was not associated with any cardiovascular risk markers after adjustment. Each minute spent in moderate to vigorous physical activity was associated with lower waist circumference (? = -0.15; 95%CI: -0.24; -0.05), systolic blood pressure (? = -0.18; 95%CI: -0.32; -0.04) and plasma glucose (? = -0.18; 95%CI: -0.33;-0.02), and with higher HDL cholesterol (? = 0.10; 95%CI: 0.01; 0.18). Moreover, physically inactive and sedentary individuals had a greater mean waist circumference and lower HDL cholesterol than physically active and non-sedentary subjects. CONCLUSION:The results suggest that moderate to vigorous physical activity have a positive impact on cardiometabolic risk markers in older adults. Light physical activity does not appear to have a beneficial effect on the cardiometabolic markers, and despite the benefits provided by the different intensities of physical activity, the simultaneous presence of sedentary behavior and low physical activity level was associated with poor cardiometabolic risk markers.
Project description:BACKGROUND:For several cardiometabolic risk factors, values considered within normal range are associated with an increased risk of cardiovascular morbidity and mortality. We aimed to investigate the short-term and long-term effects of calorie restriction with adequate nutrition on these risk factors in healthy, lean, or slightly overweight young and middle-aged individuals. METHODS:CALERIE was a phase 2, multicentre, randomised controlled trial in young and middle-aged (21-50 years), healthy non-obese (BMI 22·0-27·9 kg/m2) men and women done in three clinical centres in the USA. Participants were randomly assigned (2:1) to a 25% calorie restriction diet or an ad libitum control diet. Exploratory cardiometabolic risk factor responses to a prescribed 25% calorie restriction diet for 2 years were evaluated (systolic, diastolic, and mean blood pressure; plasma lipids; high-sensitivity C-reactive protein; metabolic syndrome score; and glucose homoeostasis measures of fasting insulin, glucose, insulin resistance, and 2-h glucose, area-under-the curve for glucose, and insulin from an oral glucose tolerance test) analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00427193. FINDINGS:From May 8, 2007, to Feb 26, 2010, of 238 participants that were assessed, 218 were randomly assigned to and started a 25% calorie restriction diet (n=143, 66%) or an ad libitum control diet (n=75, 34%). Individuals in the calorie restriction group achieved a mean reduction in calorie intake of 11·9% (SE 0·7; from 2467 kcal to 2170 kcal) versus 0·8% (1·0) in the control group, and a sustained mean weight reduction of 7·5 kg (SE 0·4) versus an increase of 0·1 kg (0·5) in the control group, of which 71% (mean change in fat mass 5·3 kg [SE 0·3] divided by mean change in weight 7·5 kg [0·4]) was fat mass loss. Calorie restriction caused a persistent and significant reduction from baseline to 2 years of all measured conventional cardiometabolic risk factors, including change scores for LDL-cholesterol (p<0·0001), total cholesterol to HDL-cholesterol ratio (p<0·0001), and systolic (p<0·0011) and diastolic (p<0·0001) blood pressure. In addition, calorie restriction resulted in a significant improvement at 2 years in C-reactive protein (p=0·012), insulin sensitivity index (p<0·0001), and metabolic syndrome score (p<0·0001) relative to control. A sensitivity analysis revealed the responses to be robust after controlling for relative weight loss changes. INTERPRETATION:2 years of moderate calorie restriction significantly reduced multiple cardiometabolic risk factors in young, non-obese adults. These findings suggest the potential for a substantial advantage for cardiovascular health of practicing moderate calorie restriction in young and middle-aged healthy individuals, and they offer promise for pronounced long-term population health benefits. FUNDING:National Institute on Aging and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.