Does telomere length predict decline in physical functioning in older twin sisters during an 11-year follow-up?

Leukocyte telomere length (LTL) is known to be associated with mortality, but its association with age-related decline in physical functioning and the development of disability is less clear. This study examined the associations between LTL and physical functioning, and investigated whether LTL predicts level of physical functioning over an 11-year follow-up. Older mono-(MZ) and dizygotic (DZ) twin sisters (n = 386) participated in the study. Relative LTL was measured by qPCR at baseline. Physical functioning was measured by 6-min walking distance and level of physical activity (PA). Walking distance was measured at baseline and at 3-year follow-up. PA was assessed by questionnaire at baseline and at 3- and 11-year follow-ups. The baseline analysis was performed with path models, adjusted with age and within-pair dependence of twin pairs. The longitudinal analysis was performed with a repeated measures linear model adjusted for age and longitudinal within-pair dependence. A nonrandom missing data analysis was utilized. At baseline, in all individuals, LTL was associated with PA (est. 0.14, SE 0.06, p = 0.011), but not with walking distance. Over the follow-up, a borderline significant association was observed between LTL and walking distance (est. 0.14, SE 0.07, p = 0.060) and a significant association between LTL and PA (est. 0.19, SE 0.06, p = 0.001). The results suggest that LTL is associated with PA and may, therefore, serve as a biomarker predicting the development of disability. Longitudinal associations between LTL and PA were observed only when nonrandom data missingness was taken into account in the analysis.Peer reviewe

Polygenic Score for Physical Activity Is Associated with Multiple Common Diseases

Introduction Genetic pleiotropy, in which the same genes affect two or more traits, may partially explain the frequently observed associations between high physical activity (PA) and later reduced morbidity or mortality. This study investigated associations between PA polygenic risk scores (PRS) and cardiometabolic diseases among the Finnish population. Methods PRS for device-measured overall PA were adapted to a FinnGen study cohort of 218,792 individuals with genomewide genotyping and extensive digital longitudinal health register data. Associations between PA PRS and body mass index, diseases, and mortality were analyzed with linear and logistic regression models. Results A high PA PRS predicted a lower body mass index (beta = -0.025 kg center dot m(-2) per one SD change in PA PRS, SE = 0.013, P = 1.87 x 10(-80)). The PA PRS also predicted a lower risk for diseases that typically develop later in life or not at all among highly active individuals. A lower disease risk was systematically observed for cardiovascular diseases (odds ratio [OR] per 1 SD change in PA PRS = 0.95, P = 9.5 x 10(-19)) and, for example, hypertension [OR = 0.93, P = 2.7 x 10(-44)), type 2 diabetes (OR = 0.91, P = 4.1 x 10(-42)), and coronary heart disease (OR = 0.95, P = 1.2 x 10(-9)). Participants with high PA PRS had also lower mortality risk (OR = 0.97, P = 0.0003). Conclusions Genetically less active persons are at a higher risk of developing cardiometabolic diseases, which may partly explain the previously observed associations between low PA and higher disease and mortality risk. The same inherited physical fitness and metabolism-related mechanisms may be associated both with PA levels and with cardiometabolic disease risk.Peer reviewe

The role of adolescent lifestyle habits in biological aging : A prospective twin study

Background: Adolescence is a stage of fast growth and development. Exposures during puberty can have long -term effects on health in later life. This study aims to investigate the role of adolescent lifestyle in biological aging. Methods: The study participants originated from the longitudinal FinnTwin12 study (n = 5114). Adolescent lifestyle-related factors, including body mass index (BMI), leisure -time physical activity, smoking, and alcohol use, were based on self-reports and measured at ages 12, 14, and 17 years. For a subsample, blood -based DNA methylation (DNAm) was used to assess biological aging with six epigenetic aging measures in young adulthood (21-25 years, n = 824). A latent class analysis was conducted to identify patterns of lifestyle behaviors in adolescence, and differences between the subgroups in later biological aging were studied. Genetic and environmental influences on biological aging shared with lifestyle behavior patterns were estimated using quantitative genetic modeling. Results: We identified five subgroups of participants with different adolescent lifestyle behavior patterns. When DNAm GrimAge, DunedinPoAm, and DunedinPACE estimators were used, the class with the unhealthiest lifestyle and the class of participants with high BMI were biologically older than the classes with healthier lifestyle habits. The differences in lifestyle-related factors were maintained into young adulthood. Most of the variation in biological aging shared with adolescent lifestyle was explained by common genetic factors. Conclusions: These findings suggest that an unhealthy lifestyle during pubertal years is associated with accelerated biological aging in young adulthood. Genetic pleiotropy may largely explain the observed associations.Peer reviewe

Leisure-time physical activity and DNA methylation agea twin study

BackgroundEpigenetic clocks may increase our understanding on human aging and how genetic and environmental factors regulate an individual aging process. One of the most promising clocks is Horvath's DNA methylation (DNAm) age. Age acceleration, i.e., discrepancy between DNAm age and chronological age, tells us whether the person is biologically young or old compared to his/her chronological age. Several environmental and lifestyle factors have been shown to affect life span. We investigated genetic and environmental predictors of DNAm age in young and older monozygotic (MZ) and dizygotic (DZ) twins with a focus on leisure time physical activity.ResultsQuantitative genetic modeling revealed that the relative contribution of non-shared environmental factors was larger among older compared with younger twin pairs [47% (95% CI 35, 63) vs. 26% (95% CI: 19, 35), pPeer reviewe

The Association Between Epigenetic Clocks and Physical Functioning in Older Women: A 3-Year Follow-up

Epigenetic clocks are composite markers developed to predict chronological age or mortality risk from DNA methylation (DNAm) data. The present study investigated the associations between 4 epigenetic clocks (Horvath’s and Hannum’s DNAmAge and DNAm GrimAge and PhenoAge) and physical functioning during a 3-year follow-up.We studied 63- to 76-year-old women (N = 413) from the Finnish Twin Study on Aging. DNAm was measured from blood samples at baseline. Age acceleration (AgeAccel), that is, discrepancy between chronological age and DNAm age, was determined as residuals from linear model. Physical functioning was assessed under standardized laboratory conditions at baseline and at follow-up. A cross-sectional analysis was performed with path models, and a longitudinal analysis was conducted with repeated measures linear models. A nonrandom missing data analysis was performed.In comparison to the other clocks, GrimAgeAccel was more strongly associated with physical functioning. At baseline, GrimAgeAccel was associated with lower performance in the Timed Up and Go (TUG) test and the 6-minute walk test. At follow-up, significant associations were observed between GrimAgeAccel and lowered performance in the TUG, 6-minute and 10-m walk tests, and knee extension and ankle plantar flexion strength tests.The DNAm GrimAge, a novel estimate of biological aging, associated with decline in physical functioning over the 3-year follow-up in older women. However, associations between chronological age and physical function phenotypes followed similar pattern. Current epigenetic clocks do not provide strong benefits in predicting the decline of physical functioning at least during a rather short follow-up period and restricted age range.Peer reviewe

Long-term physical activity modulates brain processing of somatosensory stimuli : Evidence from young male twins

Leisure-time physical activity is a key contributor to physical and mental health. Yet the role of physical activity in modulating cortical function is poorly known. We investigated whether precognitive sensory brain functions are associated with the level of physical activity. Physical activity history (3-yr-LTMET), physiological measures and somatosensory mismatch response (sMMR) in EEG were recorded in 32 young healthy twins. In all participants, 3-yr-LTMET correlated negatively with body fat%, r=0.77 and positively with VO2max, r=0.82. The fat% and VO2max differed between 15 physically active and 17 inactive participants. Trend toward larger sMMR was seen in inactive compared to active participants. This finding was significant in a pairwise comparison of 9 monozygotic twin pairs discordant for physical activity. Larger sMMR reflecting stronger synchronous neural activity may reveal diminished gating of precognitive somatosensory information in physically inactive healthy young men compared to the active ones possibly rendering them more vulnerable to somatosensory distractions from their surroundings. (C) 2016 Elsevier B.V. All rights reserved.Peer reviewe

Do Epigenetic Clocks Provide Explanations for Sex Differences in Life Span? A Cross-Sectional Twin Study

The sex gap in life expectancy has been narrowing in Finland over the past 4–5 decades; however, on average, women still live longer than men. Epigenetic clocks are markers for biological aging which predict life span. In this study, we examined the mediating role of lifestyle factors on the association between sex and biological aging in younger and older adults.Our sample consists of younger and older twins (21‒42 years, n = 1 477; 50‒76 years, n = 763) including 151 complete younger opposite-sex twin pairs (21‒30 years). Blood-based DNA methylation was used to compute epigenetic age acceleration by 4 epigenetic clocks as a measure of biological aging. Path modeling was used to study whether the association between sex and biological aging is mediated through lifestyle-related factors, that is, education, body mass index, smoking, alcohol use, and physical activity.In comparison to women, men were biologically older and, in general, they had unhealthier life habits. The effect of sex on biological aging was partly mediated by body mass index and, in older twins, by smoking. Sex was directly associated with biological aging and the association was stronger in older twins.Previously reported sex differences in life span are also evident in biological aging. Declining smoking prevalence among men is a plausible explanation for the narrowing of the difference in life expectancy between the sexes. Data generated by the epigenetic clocks may help in estimating the effects of lifestyle and environmental factors on aging and in predicting aging in future generations.Peer reviewe

Early-onset tobacco use and suicide-related behavior - A prospective study from adolescence to young adulthood

Background: Developmental relationships between tobacco use and suicide-related behaviors (SRB) remain unclear. Our objective was to investigate the longitudinal associations of tobacco use in adolescence and SRB in adulthood. Methods: Using a prospective design, we examined whether tobacco use in adolescence is associated with SRB (intentional self-injury, suicide ideation) in young adulthood in a population-based sample of 1330 twins (626 males, 704 females). The baseline and follow-up data were collected by professionally administered semi-structured poly-diagnostic interviews at ages 14 and 22, respectively. Results: After adjusting for multiple potential confounders, those who reported early-onset of regular tobacco use had a significantly increased risk for intentional self-injury, such as cutting or burning, at age 22 (adjusted odds ratio[AOR] 4.57, 95% CI 1.93-10.8) in comparison to those who had not at all initiated tobacco use. Also, daily cigarette smoking at baseline was associated with future intentional self-injury (AOR 4.45, 95% CI 2.04-9.70). Early-onset tobacco use was associated with suicidal ideation in females (AOR 3.69, 95% CI 1.56-8.72) but not in males. Considering any SRB, baseline daily smokers (AOR 2.13, 95% CI 1.12-4.07) and females with early onset of regular tobacco use (AOR 3.97, 95% CI 1.73-9.13) had an increased likelihood. Within-family analyses among twin pairs discordant for exposure and outcome controlling for familial confounds showed similar, albeit statistically non-significant, associations. Conclusion: Early-onset tobacco use in adolescence is longitudinally associated with SRB (intentional self-injury and/or suicide ideation) in young adulthood, particularly among females. Further investigation may reveal whether this association has implications for prevention of SRB in adolescence and young adulthood.Peer reviewe

Biological clocks and physical functioning in monozygotic female twins

Background: Biomarkers of biological aging - DNA methylation age (DNAm age) and leukocyte telomere length (LTL)-correlate strongly with chronological age across the life course. It is, however, unclear how these measures of cellular wear and tear are associated with muscle strength and functional capacity, which are known to decline with older age and are associated with mortality. We investigated if DNAm age and LTL were associated with body composition and physical functioning by examining 48 monozygotic twin sisters. Methods: White blood cell DNAm age (predicted years) was calculated from Illumina 450 k BeadChip methylation data using an online calculator. DNAm age acceleration was defined from the residuals derived from a linear regression model of DNAm age on chronological age. LTL was measured by qPCR. Total body percentage of fat and lean mass were estimated using bioimpedance. Physical functioning was measured by grip strength, knee extension strength and by 10 m maximal walking speed test. Results: In all participants, DNAm age (58.4 +/- 6.6) was lower than chronological age (61.3 +/- 5.9 years). Pairwise correlations of monozygotic co-twins were high for DNAm age (0.88, 95% CI 0.79, 0.97), age acceleration (0.68, 95% CI 0.30, 0.85) and LTL (0.77, 95% CI 0.60, 0.94). Increased age acceleration i.e. faster epigenetic aging compared to chronological age was associated with lower grip strength (beta = -5.3 SE 1.9 p = 0.011), but not with other measures of physical functioning or body composition. LTL was not associated with body composition or physical functioning. Conclusions: To conclude, accelerated DNAm age is associated with lower grip strength, a biomarker known to be associated with physiological aging, and which predicts decline in physical functioning and mortality. Further studies may clarify whether epigenetic aging explains the decline in muscle strength with aging or whether DNAm age just illustrates the progress of aging.Peer reviewe

Impact of central nervous system (CNS) prophylaxis on the incidence of CNS relapse in patients with high-risk diffuse large B cell/follicular grade 3B lymphoma

Although overall survival in diffuse large B cell lymphomas (DLBCL) has improved, central nervous system (CNS) relapse is still a fatal complication of DLBCL. For this reason, CNS prophylaxis is recommended for patients at high risk of CNS disease. However, no consensus exists on definition of high-risk patient and optimal CNS prophylaxis. Systemic high-dose methotrexate in combination with R-CHOP has been suggested as a potential prophylactic method, since methotrexate penetrates the blood-brain barrier and achieves high concentration in the CNS. In this retrospective analysis, we report treatment outcome of 95 high-risk DLBCL/FL grade 3B patients treated with R-CHOP or its derivatives with (N = 57) or without (N = 38) CNS prophylaxis. At a median follow-up time (51 months), CNS relapses were detected in twelve patients (12.6%). Ten out of twelve (83%) of CNS events were confined to CNS system only. Median overall survival after CNS relapse was 9 months. Five-year isolated CNS relapse rates were 5% in the prophylaxis group and 26% in the group without prophylaxis. These findings suggest that high-dose methotrexate-containing prophylaxis decreases the risk of CNS failure.Peer reviewe