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Ten-Year Legacy Effects of Three Eight-Month Exercise Training Programs on Cardiometabolic Health Parameters.

ABSTRACT: Background: STRRIDE (Studies Targeting Risk Reduction Interventions through Defined Exercise) was an eight-month exercise study conducted from 1998-2003. Subjects were randomized to control or one of three exercise groups differing in intensity and amount. To determine if there were legacy effects, we invited 161 individuals who completed the intervention phase to return for a 10-year Reunion study. Methods: Subjects completed medical history and physical activity questionnaires. Height, body weight, blood pressure, waist circumference, and peak VO2 were measured. Fasting blood samples were analyzed for glucose, insulin and lipids. Of 161 original subjects, 153 were within 10 years of STRRIDE completion. Of these, 28 were lost to follow-up and 21 declined to participate in the Reunion study. Overall, 104 subjects (83% eligible) participated. Change over time was computed as the 10-year Reunion value minus the pre-intervention value. Significant within group changes were calculated using two-tailed t-tests. ANCOVA determined differences among groups with pre-intervention values as covariates. Bonferroni corrections were applied to account for multiple comparisons. Results: Ten years after completing STRRIDE, there were a number of group-specific health and fitness legacy effects. Original participation in either the moderate intensity exercise or control group resulted in a 10.5% decrease in peak VO2 over the ensuing 10 years. Conversely, both vigorous intensity groups experienced only a 4.7% decrement in cardiorespiratory fitness over that time period. As compared to controls, all three exercise groups experienced smaller increases in waist circumference. Those who participated in moderate intensity exercise experienced the greatest 10-year reduction in fasting insulin. Compared to all other groups, the moderate intensity subjects had greater reductions in mean arterial pressure at the Reunion timepoint. Summary: Ten years after completing a randomized eight-month exercise training intervention, previously sedentary individuals exhibited group-specific differences consistent with an intervention-based legacy effect on cardiorespiratory fitness and cardiometabolic parameters. These findings highlight the critical need to better understand the sustained legacy health effects of exercise training interventions.

SUBMITTER: Johnson JL

PROVIDER: S-EPMC6476955 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Ten-Year Legacy Effects of Three Eight-Month Exercise Training Programs on Cardiometabolic Health Parameters.

Johnson Johanna L JL Slentz Cris A CA Ross Leanna M LM Huffman Kim M KM Kraus William E WE

Frontiers in physiology 20190416

<b>Background:</b> STRRIDE (Studies Targeting Risk Reduction Interventions through Defined Exercise) was an eight-month exercise study conducted from 1998-2003. Subjects were randomized to control or one of three exercise groups differing in intensity and amount. To determine if there were legacy effects, we invited 161 individuals who completed the intervention phase to return for a 10-year Reunion study. <b>Methods:</b> Subjects completed medical history and physical activity questionnaires. H ...[more]

PMID: 31040797

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Project description:Abstract Objectives Obesity imposes risk to cardiometabolic health; however, intentional weight loss in obese older adults remains controversial. Using data from the CROSSROADS Study (clinicaltrials.gov #NCT00955903), this ancillary study investigated effects of exercise with and without intentional weight loss on changes in cardiometabolic risk assessed by four risk-scoring tools. Methods Participants (n = 134, 39% male, 23% African American, 70.2 ± 4.7 y) were randomized to exercise (n = 48), exercise + nutrient-dense weight maintenance diet (n = 44), or exercise + nutrient-dense caloric restriction of 500 kcals/day (n = 42). The following risk scores were calculated using baseline and 12-month data: Framingham risk assessment, Cardiometabolic Disease Staging (CMDS), metabolic syndrome classification by the International Diabetes Federation (IDF), and metabolic syndrome classification by the National Cholesterol Education Program's Adult Treatment Panel (ATP III). Generalized Estimating Equations were employed to determine differences between groups with ethnicity, sex, and age as covariates. Results Group-time interaction was not significant in application of IDF or ATPIII. Group-time interaction was significant for Framingham and CMDS (P = 0.005 and 0.041, respectively). Upon post-hoc analysis, significant within-group improvements in Framingham scores were observed for exercise + weight maintenance (P < 0.001, r = −1.682) and exercise + weight loss (P = 0.020, r = −0.881). In analysis of between-group differences in Framingham scores, a significant decrease was observed in the exercise + weight maintenance group (P = 0.001, r = −1.723) compared to the exercise group. For CMDS, the exercise + weight loss group had significant within-group improvements (P = 0.023, r = - 0.102). For between-group differences in CMDS, the exercise + weight loss group showed significant risk score reduction (P = 0.012, r = −0.142) compared to the exercise group. Conclusions Risk assessment by Framingham and CMDS showed greater sensitivity to change in cardiometabolic risk factors. Results suggest obese older adults can lower cardiometabolic risk by engaging in exercise + weight maintenance or exercise + weight loss by moderate caloric restriction. Funding Sources R01AG033094 NIA, K07AG043588 NIA, P30DK056336 NIDDK.

Project description:Many cancer survivors suffer from impairments in skeletal muscle (SkM), both in terms of reduced mass and function. Interestingly, human SkM possesses an epigenetic memory of earlier stimuli, such as exercise. Long-term retention of epigenetic changes in SkM following cancer survival and/or exercise training have not yet been studied. We therefore investigated genome-wide DNA methylation (the methylome) in SkM following a 5-month, 3/week treadmill-based aerobic training intervention in breast cancer survivors 10-14 years after diagnosis and treatment. These results were compared to breast cancer survivors who remained untrained and to age-matched controls with no history of cancer, who undertook the same training intervention. SkM biopsies were obtained before (pre) and after (post) the 5-month training period and DNA methylation was analysed using InfiniumEPIC 850K Arrays. The breast cancer survivors displayed a significant retention of increased DNA methylation (i.e., hypermethylation) at a larger number of differentially methylated positions (DMPs) compared with healthy age-matched controls pre-training. Training in cancer survivors led to an exaggerated number of DMPs with a hypermethylated signature occurring at more random non-regulatory regions across the DNA compared with training in healthy age-matched controls. However, the opposite occurred in important gene regulatory regions, where training in cancer survivors elicited a considerable reduction in methylation (i.e., hypomethylation) in 99% of the DMPs located specifically in CpG islands within promoter regions. Importantly, training was able to reverse the hypermethylation identified in cancer survivors back towards a hypomethylated signature that was observed pre-training in healthy age-matched controls at 300 (out of 881) of these island and promoter associated CpG sites. Pathway enrichment analysis identified that the training in cancer survivors evoked this predominantly hypomethylated signature in pathways associated with: Cell cycle, DNA replication and repair, transcription, translation, mTOR signalling and proteosome. Differentially methylated region (DMR) analysis also identified genes: BAG1, BTG2, CHP1, KIFC1, MKL2, MTR, PEX11B, POLD2, S100A6, SNORD104 and SPG7 as hypermethylated in breast cancer survivors with training reversing these CpG island / promoter associated DMRs towards a hypomethylated signature. Training also elicited a largely different epigenetic response in healthy individuals than that observed in cancer survivors, with very few overlapping changes. Only one gene, SIRT2, was identified as having altered methylation in cancer survivors at baseline as well as after training in both the cancer survivors and healthy controls. In conclusion, human SkM muscle retains a hypermethylated signature for as long as 10-14 years after breast cancer treatment and survival. Importantly, 5 months of aerobic training rejuvenated the SkM methylome towards signatures identified in healthy age-matched individuals in gene regulatory regions.

Project description:Low cardiorespiratory fitness is a powerful predictor of morbidity and cardiovascular mortality. In 473 sedentary adults, all whites, from 99 families of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, the heritability of gains in maximal O(2) uptake (VO(2max)) after exposure to a standardized 20-wk exercise program was estimated at 47%. A genome-wide association study based on 324,611 single-nucleotide polymorphisms (SNPs) was undertaken to identify SNPs associated with improvements in VO(2max) Based on single-SNP analysis, 39 SNPs were associated with the gains with P < 1.5 × 10(-4). Stepwise multiple regression analysis of the 39 SNPs identified a panel of 21 SNPs that accounted for 49% of the variance in VO(2max) trainability. Subjects who carried ≤9 favorable alleles at these 21 SNPs improved their VO(2max) by 221 ml/min, whereas those who carried ≥19 of these alleles gained, on average, 604 ml/min. The strongest association was with rs6552828, located in the acyl-CoA synthase long-chain member 1 (ACSL1) gene, which accounted by itself for ~6% of the training response of VO(2max). The genes nearest to the SNPs that were the strongest predictors were PR domain-containing 1 with ZNF domain (PRDM1); glutamate receptor, ionotropic, N-methyl-D-aspartate 3A (GRIN3A); K(+) channel, voltage gated, subfamily H, member 8 (KCNH8); and zinc finger protein of the cerebellum 4 (ZIC4). The association with the SNP nearest to ZIC4 was replicated in 40- to 65-yr-old, sedentary, overweight, and dyslipidemic subjects trained in Studies of a Targeted Risk Reduction Intervention Through Defined Exercise (STRRIDE; n = 183). Two SNPs were replicated in sedentary obese white women exercise trained in the Dose Response to Exercise (DREW) study (n = 112): rs1956197 near dishevelled associated activator of morphogenesis 1 (DAAM1) and rs17117533 in the vicinity of necdin (NDN). The association of SNPs rs884736 in the calmodulin-binding transcription activator 1 (CAMTA1) locus and rs17581162 ~68 kb upstream from regulator of G protein signaling 18 (RGS18) with the gains in VO(2max) in HERITAGE whites were replicated in HERITAGE blacks (n = 247). These genomic predictors of the response of Vo(2max) to regular exercise provide new targets for the study of the biology of fitness and its adaptation to regular exercise. Large-scale replication studies are warranted.

Project description:Parkinson's disease (PD) is the most common motor neurodegenerative disease, and neuromuscular function deficits associated with PD contribute to disability. Targeting these symptoms, our laboratory has previously evaluated 16-week high-intensity resistance exercise as rehabilitative training (RT) in individuals with PD. We reported significant improvements in muscle mass, neuromuscular function (strength, power, and motor unit activation), indices of neuromuscular junction integrity, total and motor scores on the unified Parkinson's disease rating scale (UPDRS), and total and sub-scores on the 39-item PD Quality of Life Questionnaire (PDQ-39), supporting the use of RT to reverse symptoms. Our objective was to identify transcriptional networks that may contribute to RT-induced neuromuscular remodeling in PD. We generated transcriptome-wide skeletal muscle RNA-sequencing in 5 participants with PD [4M/1F, 67 ± 2 years, Hoehn and Yahr stages 2 (n = 3) and 3 (n = 2)] before and after 16-week high intensity RT to identify transcriptional networks that may in part underpin RT-induced neuromuscular remodeling in PD. Following RT, 304 genes were significantly upregulated, notably related to remodeling and nervous system/muscle development. Additionally, 402 genes, primarily negative regulators of muscle adaptation, were downregulated. We applied the recently developed Pathway-Level Information ExtractoR (PLIER) method to reveal coordinated gene programs (as latent variables, LVs) that differed in skeletal muscle among young (YA) and old (OA) healthy adults and PD (n = 12 per cohort) at baseline and in PD pre- vs. post-RT. Notably, one LV associated with angiogenesis, axon guidance, and muscle remodeling was significantly lower in PD than YA at baseline and was significantly increased by exercise. A different LV annotated to denervation, autophagy, and apoptosis was increased in both PD and OA relative to YA and was also reduced by 16-week RT in PD. Thus, this analysis identified two novel skeletal muscle transcriptional programs that are dysregulated by PD and aging, respectively. Notably, RT has a normalizing effect on both programs in individuals with PD. These results identify potential molecular transducers of the RT-induced improvements in neuromuscular remodeling and motor function that may aid in optimizing exercise rehabilitation strategies for individuals with PD.

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Ten-Year Legacy Effects of Three Eight-Month Exercise Training Programs on Cardiometabolic Health Parameters.

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Ten-Year Legacy Effects of Three Eight-Month Exercise Training Programs on Cardiometabolic Health Parameters.

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