Background-Long-term physical inactivity seems to cause many health problems. We studied whether persistent physical activity compared with inactivity has a global effect on serum metabolome toward reduced cardiometabolic disease risk. Methods and Results-Sixteen same-sex twin pairs (mean age, 60 years) were selected from a cohort of twin pairs on the basis of their >30-year discordance for physical activity. Persistently (≥5 years) active and inactive groups in 3 populationbased cohorts (mean ages, 31-52 years) were also studied (1037 age-and sex-matched pairs). Serum metabolome was quantified by nuclear magnetic resonance spectroscopy. We used permutation analysis to estimate the significance of the multivariate effect combined across all metabolic measures; univariate effects were estimated by paired testing in twins and in matched pairs in the cohorts, and by meta-analysis over all substudies. Persistent physical activity was associated with the multivariate metabolic profile in the twins (P=0.003), and a similar pattern was observed in all 3 population cohorts with differing mean ages. Isoleucine, α1-acid glycoprotein, and glucose were lower in the physically active than in the inactive individuals (P<0.001 in meta-analysis); serum fatty acid composition was shifted toward a less saturated profile; and lipoprotein subclasses were shifted toward lower very-low-density lipoprotein (P<0.001) and higher large and very large high-density lipoprotein (P<0.001) particle concentrations. The findings persisted after adjustment for body mass index. Conclusions-The numerous differences found between persistently physically active and inactive individuals in the circulating metabolome together indicate better metabolic health in the physically active than in inactive individuals. T he modern environment is conducive to a sedentary lifestyle with an increased propensity for obesity and adverse cardiometabolic risk. The current obesity epidemic is ultimately due to an imbalance between energy intake and energy expenditure.1 High leisure-time physical activity and high levels of physical fitness are associated with reduced levels of total and visceral fat; decreased cardiometabolic risk factors; reduced prevalence of metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease; and reduced mortality. 2 Editorial see p 317 Clinical Perspective on p 348Research on the specific effects of long-term physical activity is challenging because of the considerable difficulties in conducting randomized, controlled, long-term exercise trials. We combined 2 population-based approaches to address this issue. To control for childhood environments and partially for genetic factors possibly underlying the associations between physical activity and cardiometabolic risk factor levels, we selected same-sex twin pairs from a population-based cohort of baseline-healthy twin pairs 3,4 on the basis of their 32-year discordance for physical activity. To test our findings in the general population, we identified persistently active o...

The older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945–1957 in 2011–2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938–1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these are described briefly together with key results. We also review other projects based on the older FTC and provide information on the biobanking of biosamples and related phenotypes.

Background and Objective: Exercise is thought to reduce high-risk body fat, but intervention studies are frequently limited by short follow-ups and observational studies by genetic selection. Therefore, we studied the effects of a physically inactive vs active lifestyle on high-risk (visceral, liver and intramuscular) fat in twin pairs discordant for leisure-time physical activity habits for over 30 years. Design: A longitudinal population-based twin study. Subjects: Sixteen middle-aged (50-74 years) same-sex twin pairs (seven monozygotic (MZ), nine dizygotic (DZ)) with longterm discordance for physical activity habits were comprehensively identified from the Finnish Twin Cohort (TWINACTIVE study). Discordance was initially defined in 1975 and the same co-twin remained significantly more active during the 32-yearlong follow-up. Main Outcome Measures: Magnetic resonance imaging-assessed visceral, liver and intramuscular fat. Results: In within-pair analyses carried out after the adult life-long discordance in physical activity habits, the physically inactive co-twins had 50% greater visceral fat area compared with the active co-twins (mean difference 55.5 cm 2 , 95% confidence interval (CI) 7.0-104.1, P ¼ 0.010). The liver fat score was 170% higher (13.2, 95% CI 3.5-22.8, P ¼ 0.030) and the intramuscular fat area 54% higher (4.9 cm 2 , 95% CI 1.9-7.9, P ¼ 0.002) among the inactive co-twins. All the trends were similar for MZ and DZ pairs. Peak oxygen uptake was inversely associated with visceral (r ¼ À0.46, P ¼ 0.012) and intramuscular fat area (r ¼ À0.48, P ¼ 0.028), with similar trends in intrapair difference correlations (r ¼ À0.57, P ¼ 0.021 and r ¼ À0.50, P ¼ 0.056, respectively). The intrapair difference correlation between visceral and intramuscular fat was also high (r ¼ 0.65, P ¼ 0.009). Conclusion: Regular physical activity seems to be an important factor in preventing the accumulation of high-risk fat over time, even after controlling for genetic liability and childhood environment. Therefore, the prevention and treatment of obesity should emphasize the role of regular leisure-time physical activity.

T he physically active lifestyle is associated with low future morbidity and mortality, but the causality between physical activity and health is not always clear. As some inherited biological characteristics and childhood experiences may cause selection bias in observational studies, we sought to take them into account by identifying 16 twin pairs (7 MZ, 9 DZ, mean age 60 years) discordant for leisure time physical activity habits for thirty years. We conducted detailed health-related examinations among these twin pairs. Our main aims were to study the effects of physical activity and genes on fitness and body composition, with special reference to body fat compartments, metabolic syndrome components and related diseases and risk factor levels, status of arteries, structure and function of the heart, bone properties, and muscle and fat tissue-related mechanisms linked to physical activity and chronic disease development. Our physical activity assessments showed that inactive co-twins were on average 8.8 MET hours/day less active than their active co-twins through out their midlife (2.2 ± 2.3 vs. 11.0 ± 4.1 MET h/day, p < .001). Follow-up fitness tests showed that physically inactive co-twins were less fit than their active co-twins (estimated VO 2peak 26.4 ± 4.9 vs. 32.5 ± 5.5 ml/kg/min, p < .001). Similar differences were found in both MZ and DZ pairs. On the basis of earlier epidemiological observations on nonrelated individuals, these physical activity and fitness differences are large enough to cause differences in many mechanisms and risk factors related to the development of chronic diseases and to permit future analyses.