Effect of Moderate Versus Vigorous Exercise Intensity on Body Composition in Young Untrained Adults: The Activating Brown Adipose Tissue Through Exercise (ACTIBATE) Randomized Controlled Trial.

The present study aimed to investigate the effect of a 24-week aerobic + resistance training programs at moderate versus vigorous intensity on body composition, and the persistence of the changes after a 10-month free-living period, in young untrained adults. This report is based on a secondary analysis from the activating brown adipose tissue through exercise (ACTIBATE) single-center unblinded randomized controlled trial. A total of 144 young adults (65.6% women) aged 18-25 years were randomly allocated to three different groups: (a) aerobic + resistance exercise training program based on the international physical activity recommendations at vigorous intensity (Ex-Vigorous group), (b) at moderate intensity (Ex-Moderate group), and (c) control group (no exercise). Body composition outcomes were determined by a dual-energy X-ray absorptiometry scanner. Both Ex-Vigorous and Ex-Moderate decreased body weight, fat mass, and visceral adipose tissue mass in a similar manner (all p < .04). After a 10-month free-living period, these parameters returned to baseline levels in both exercise groups (all ps < .03). No differences between the exercise groups and the control group were noted in lean mass changes (all ps > .1). A 24-week aerobic + resistance training intervention based on the international physical activity recommendations was enough to improve body weight, fat mass, and visceral adipose tissue mass in untrained young adults, independently of the exercise intensity (moderate vs. vigorous).

Activating brown adipose tissue through exercise (ACTIBATE) in young adults: Rationale, design and methodology.

AIMS: The energy expenditure capacity of brown adipose tissue (BAT) makes it an attractive target as a therapy against obesity and type 2 diabetes. BAT activators namely catecholamines, natriuretic peptides and certain myokines, are secreted in response to exercise. ACTIBATE will determine the effect of exercise on BAT activity and mass measured by positron emission tomography/computed tomography (PET/CT, primary outcome) in young adults. ACTIBATE will also investigate the physiological consequences of activating BAT (secondary outcomes). METHODS: ACTIBATE will recruit 150 sedentary, healthy, young adults (50% women) aged 18-25 years. Eligible participants will be randomly assigned to a non-exercise group (n ≈ 50) or one of two exercise groups (n=50 each). Participants in the exercise groups will perform aerobic and strength training 3-4 days/week at a heart rate equivalent to 60% of heart rate reserve (HRres), and at 50% of 1 repetition maximum (RM) for the moderate-intensity group, and at 80% of HRres and 70% RM for the vigorous-intensity group. Laboratory measures completed at baseline and 6 months include BAT activity and mass, resting energy expenditure, meal and cold-induced thermogenesis, body temperature regulation and shivering threshold, body composition and cardiovascular disease risk factors. We will also obtain biopsies from abdominal subcutaneous white adipose tissue and skeletal muscle to analyse the expression of genes encoding proteins involved in the thermogenic machinery. DISCUSSION: Findings from ACTIBATE will have significant implications for our understanding of exercise and its protective effects against the development of type 2 diabetes, obesity and related metabolic diseases. ClinicalTrials.gov ID: NCT02365129.

Are centenarians genetically predisposed to lower disease risk?

Our study purpose was to compare a disease-related polygenic profile that combined a total of 62 genetic variants among (i) people reaching exceptional longevity, i.e., centenarians (n = 54, 100-108 years, 48 women) and (ii) ethnically matched healthy controls (n = 87, 19-43 years, 47 women). We computed a 'global' genotype score (GS) for 62 genetic variants (mutations/polymorphisms) related to cardiometabolic diseases, cancer or exceptional longevity, and also specific GS for main disease categories (cardiometabolic risk and cancer risk, including 36 and 24 genetic variations, respectively) and for exceptional longevity (7 genetic variants). The 'global' GS was similar among groups (centenarians: 31.0 ± 0.6; controls 32.0 ± 0.5, P = 0.263). We observed that the GS for hypertension, cancer (global risk), and other types of cancer was lower in the centenarians group compared with the control group (all P < 0.05), yet the difference became non significant after adjusting for sex. We observed significant between-group differences in the frequency of GSTT1 and GSTM1 (presence/absence) genotypes after adjusting for multiple comparisons. The likelihood of having the GSTT1 low-risk (functional) allele was higher in centenarians (odds ratio [OR] 5.005; 95% confidence interval [CI], 1.810-13.839), whereas the likelihood of having the GSTMI low-risk (functional) allele was similar in both groups (OR 1.295; 95% CI, 0.868 -1.931). In conclusion, we found preliminary evidence that Spanish centenarians have a lower genetic predisposition for cancer risk. The wild-type (i.e., functional) genotype of GSTT1, which is associated with lower cancer risk, might be associated with exceptional longevity, yet further studies with larger sample sizes must confirm these findings.

Are mitochondrial haplogroups associated with extreme longevity? A study on a Spanish cohort.

Mitochondrial haplogroups could influence individual susceptibility to mitochondrial DNA (mtDNA) damage, and human longevity, as indicated by previous studies with Caucasian (European) or Asian cohorts. Here, we compared the frequency of mtDNA haplogroups in a group of Spanish (Caucasian) centenarians (n = 65, aged 100-108 years, 58 women, most from the central part of Spain) and a group of healthy young adults (n = 138, 62 women, aged 20-40 years) of the same ethnic origin. We did not find significant differences between centenarians and the control group (P > 0.2). Only two centenarians (both women) had the haplogroup J, which hampered comparison with the control group (n = 15, five women). Our data confirm that the potential effects of mitochondrial haplogroups on human longevity might be population/geographic specific, with important differences between studies (notably, with regard to the previously reported potential benefit brought about by the haplogroup J) arising from the different living environment and ethnic background of the study cohorts.

Are 'endurance' alleles 'survival' alleles? Insights from the ACTN3 R577X polymorphism.

Exercise phenotypes have played a key role for ensuring survival over human evolution. We speculated that some genetic variants that influence exercise phenotypes could be associated with exceptional survival (i.e. reaching ≥100 years of age). Owing to its effects on muscle structure/function, a potential candidate is the Arg(R)577Ter(X) polymorphism (rs1815739) in ACTN3, the structural gene encoding the skeletal muscle protein α-actinin-3. We compared the ACTN3 R577X genotype/allele frequencies between the following groups of ethnically-matched (Spanish) individuals: centenarians (cases, n = 64; 57 female; age range: 100-108 years), young healthy controls (n = 283, 67 females, 216 males; 21±2 years), and humans who are at the two end-points of exercise capacity phenotypes, i.e. muscle endurance (50 male professional road cyclists) and muscle power (63 male jumpers/sprinters). Although there were no differences in genotype/allele frequencies between centenarians (RR:28.8%; RX:47.5%; XX:23.7%), and controls (RR:31.8%; RX:49.8%; XX:18.4%) or endurance athletes (RR:28.0%; RX:46%; XX:26.0%), we observed a significantly higher frequency of the X allele (P = 0.019) and XX genotype (P = 0.011) in centenarians compared with power athletes (RR:47.6%; RX:36.5%;XX:15.9%). Notably, the frequency of the null XX (α-actinin-3 deficient) genotype in centenarians was the highest ever reported in non-athletic Caucasian populations. In conclusion, despite there were no significant differences with the younger, control population, overall the ACTN3 genotype of centenarians resembles that of world-class elite endurance athletes and differs from that of elite power athletes. Our preliminary data would suggest a certain 'survival' advantage brought about by α-actinin-3 deficiency and the 'endurance'/oxidative muscle phenotype that is commonly associated with this condition.

Is the ACE I/D polymorphism associated with extreme longevity? A study on a Spanish cohort.

The 287 bp Ins(I)/Del(D) polymorphism [rs1799752] in intron 16 of the angiotensin-converting enzyme (ACE) gene has been associated with extreme longevity (≥ 100 years) in some Caucasian and Asian cohorts, but this finding was not corroborated in other reports. We compared the allelic/genotypic frequency of the ACE I/D polymorphism among centenarians (N = 64, 100-108 years, 89.1% female) and nonagenarians (N = 47, 90-97 years, 76.6% female), and a control group of healthy young adults (n = 434, age 20-40 years, 50% female). All participants were of the same Caucasian (Spanish) descent. The ACE I/D genotype met Hardy-Weinberg expectations in all the cohorts. Allelic and genotypic frequencies did not differ by sex in any of the study groups (all p > 0.2). There were no differences in allelic or genotypic frequencies between groups, for example the frequency of the D allele was 62.3% in controls vs. 65.3% in the elderly (64.8% in centenarians). In summary, the ACE I/D polymorphism is not significantly associated with extreme longevity in the Spanish population. Further research is, however, necessary using other approaches. It also remains to be determined if the interaction of ACE genotypes with some other genetic variants exerts a potential effect on longevity.