Exercise-induced changes in plasma S-Klotho levels are associated with the obtained enhancements of heart rate variability in sedentary middle-aged adults: the FIT-AGEING study.

The shed form of the Klotho protein (S-Klotho) is considered a biomarker of longevity, but it is still unknown whether the levels are related to heart rate (HR) and heart rate variability (HRV); both of them greatly influenced by the ageing process, physical fitness, exercise, and health status. This study aimed (i) to investigate the association between S-Klotho plasma levels with HR and HRV parameters and (ii) to examine the association of exercise-induced changes in S-Klotho and those obtained in HR and HRV parameters after a 12-week exercise intervention in sedentary middle-aged adults. Sixty-six sedentary middle-aged adults participated in this study (50% women; 45-65 years old). Participants were randomized into 4 groups: (a) a control group (no exercise), (b) a physical activity recommendation from the World Health Organization group, (c) a high-intensity interval training group, and (d) a high-intensity interval training group adding whole-body electromyostimulation. S-Klotho plasma levels, HR, and HRV parameters (SDNN, RMSSD, high frequency, stress score, and sympathetic/parasympathetic ratio) were measured. At baseline, S-Klotho plasma levels were not related to HR and HRV parameters. After the intervention, exercise-induced changes in S-Klotho plasma levels were positively associated with changes in SDNN (ß=0.261; R2=0.102; p=0.014) and negatively related to changes in stress score and sympathetic/parasympathetic ratio (all ß=-0.257; R2 ranges between 0.092 and 0.131; all p<0.020). Our study suggests that higher S-Klotho plasma levels are related to increased vagal influence and reduced sympathetic tone in the autonomic nervous system in sedentary middle-aged adults after different training programs. ClinicalTrials.gov identifier: CT03334357.

Fit-Fat Index is better associated with heart rate variability compared to fitness and fatness alone as indicators of cardiometabolic human health.

OBJECTIVES: Cardiorespiratory fitness and fatness indicators have been related to heart rate variability (HRV) parameters. The Fit-Fat Index (FFI) is a single index combining cardiorespiratory fitness and fatness indicators. To the best of our knowledge, no studies have previously analyzed whether FFI are related to cardiac autonomic nervous system activity assessed through HRV parameters. This study aimed (i) to examine the association of cardiorespiratory fitness, fatness indicators, and FFI with HRV parameters; and (ii) to report what of the different fatness indicators included in FFI is better associated with HRV parameters in sedentary adults. METHODS: One hundred and fifty healthy adults (74 women; 76 men), aged between 18 and 65 years old, participated in this cross-sectional study. We measured cardiorespiratory fitness (maximal oxygen consumption) and fatness indicators (waist-to-height ratio [WHR], fat mass percentage [FM%] and visceral adipose tissue [VAT]). Three FFIs were calculated as the quotient between cardiorespiratory fitness and one out of three possible fatness indicators: Fit-Fat Index calculated waist-to-height ratio (FFIWHR ), Fit-Fat Index calculated with FM% (FFIFM% ), and Fit-Fat Index calculated with VAT (FFIVAT ). HRV parameters were measured in resting conditions using a Polar RS800CX. RESULTS: FFIWTHR , FFIFM% and FFIVAT were related to different HRV parameters (ß ranges between -0.507 and 0.529; R2 ranges between 0.096 and 0.275; all p < .001) and the association was stronger with HRV parameters than the isolated fitness or fatness indicators (ß ranges between -0.483 and 0.518; R2 ranges between 0.071 and 0.263; all p < .001). FFIVAT was the index more consistently associated with HRV parameters (ß ranges between -0.507 and 0.529; R2 ranges between 0.235 and 0.275; all p < .001). CONCLUSION: Our study suggests that compound FFIs are better predictors of HRV parameters than either cardiorespiratory fitness or fatness indicators alone. The FFIVAT was the best index in terms of its association to HRV.

Different exercise training modalities similarly improve heart rate variability in sedentary middle-aged adults: the FIT-AGEING randomized controlled trial.

PURPOSE: This study aimed to investigate the influence of different exercise training modalities on heart rate variability (HRV) in sedentary middle-aged adults; and to study whether changes in health-related outcomes (i.e., body composition and cardiometabolic risk) are associated with those hypothetical HRV changes in sedentary middle-aged adults. METHODS: A total of 66 middle-aged adults (53.6 ± 4.4 years old; 50% women) were enrolled in the FIT-AGEING study. We conducted a 12-week randomized controlled trial. The participants were randomly assigned to 4 groups: (a) a control group (no exercise); (b) a physical activity recommendation from the World Health Organization group (PAR); (c) a high-intensity interval training group (HIIT); and (d) a high-intensity interval training group adding whole-body electromyostimulation (HIIT + EMS). RESULTS: All exercise training modalities induced changes in HRV parameters (all P ≤ 0.001) without statistical differences between them (all P > 0.05). We found associations between changes in body composition and cardiometabolic risk and exercise-related changes in HRV. CONCLUSION: Our results suggest that different exercise interventions (i.e., PAR, HIIT and HIIT + EMS) induced an enhancement of HRV in sedentary middle-aged adults. Our findings support the notion that exercise-related changes in HRV are associated with changes in body composition and cardiometabolic risk after the intervention program CLINICAL TRIAL REGISTRY: NCT03334357 (ClinicalTrials.gov). November 7, 2017 retrospectively registered.

Assessment of autonomous nerve system through non-linear heart rate variability outcomes in sedentary healthy adults.

BACKGROUND: Heart rate variability (HRV) is a psycho-physiological phenomenon with broad health implications. Different data analysis methods have been used to assess the autonomic nervous system activity, but the validation of new indexes that accurately describe its balance through non-invasive methods (i.e., HRV analysis) is of clinical interest. This study aimed: (i) to evaluate the association of the Stress Score (SS) and the Sympathetic/Parasympathetic Ratio (S/PS) with time domain and frequency domain analysis of HRV, and (ii) to set reference values of SS and S/PS in sedentary healthy adults. METHODS: A total of 156 sedentary healthy adults (38.4 ± 15.57 years old, 81 women), aged were involved in this study. HRV was measured for 15 min in a supine position at rest. SS and S/PS were calculated from the non-linear HRV analyses based on Poincare Plot. RESULTS: Stress Score showed a non-linear negative power-law relationship with SDNN (ß = -0.969; R 2 = 0.963; P < 0.001), RMSSD (ß = -0.867; R 2 = 0.722; P < 0.001), high frequency (ß = -0.834; R 2 = 0.752; P =< 0.001), low frequency (ß = -0.627; R 2 = 0.330; P < 0.001), SD1 (ß = -0.867; R 2 = 0.722; P < 0.001) and SD2 (ß = -1.000; R 2 > 0.999; P < 0.001). There was observed a negative cubic relationship between SS with PNN50 (ß = -1.972; R 2 = 0.644; P < 0.001). A linear regression model was conducted between SS with Ratio Low/High Frequency (ß = 0.026; R 2 < 0.001; P = 0.750). Non-linear power-law regression models were built between S/PS and SDNN (ß = -0.990; R 2 = 0.981; P < 0.001), RMSSD (ß = -0.973; R 2 = 0.939; P < 0.001), high frequency (ß = -0.928; R 2 = 0.970; P < 0.001), low frequency (ß = -2.344; R 2 = 0.557; P < 0.001), SD1 (ß = -0.973; R 2 = 0.939; P < 0.001) and SD2 (ß = -0.611; R 2 = 0.908; P < 0.001). A non-linear negative regression model was built between S/PS and PNN50 (ß = -3.412; R 2 = 0.868; P < 0.001). A linear regression model was conducted between S/PS and SD2/SD1 (ß = 0.075; R 2 = 0.006; P < 0.001). CONCLUSION: Our results support the use of SS as a sympathetic activity marker, and S/PS as an indicator of the sympathetic and parasympathetic activity of the autonomic nervous system in sedentary healthy adults.

Exercise training as S-Klotho protein stimulator in sedentary healthy adults: Rationale, design, and methodology.

AIMS: The secreted form of the α-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.