Search

BackgroundAn overall healthy lifestyle may mitigate the risk of all-cause and cardiovascular disease (CVD) mortality despite the inherited risk for CVD. We assessed if similar phenomenon is observed independently with physical activity (PA).MethodsIn a prospective older Finnish Twin Cohort, genetic liability for coronary heart disease, systolic and diastolic blood pressure was estimated with polygenic risk scores (PRSs) derived from the Pan UK Biobank (N≈400,000) and >1,000,000 genetic variants, and leisure-time PA longitudinally with validated and structured questionnaires three times during 1975–1990 among 4,897 participants aged 33–60-years (54.3% women). Interactions of PRSs and PA with mortality and the independent main effects of different PA metrics with mortality were evaluated with Cox proportional hazards models. A co-twin control design with 180 monozygotic twin pairs discordant for physical activity was used for causal inference.ResultsDuring the 17.4-y (mean) follow-up (85,136 person-years), 1,195 participants died with 389 CVD deaths. Although the favorable associations of an overall healthy lifestyle with mortality risk reduction replicated in the cohort, no interactions or significant independent main effects were observed with any of the assessed PA metrics. Adherence to World Health Organizations PA guidelines or vigorous PA during the 15-year observational period did not decrease mortality in more active twins compared to their less active identical twin brother or sister. The findings did not vary with genetic CVD risk.ConclusionsNo evidence was found that PA mitigates inherited CVD risk or is causally associated with mortality challenging some of our current understanding.

BackgroundPhysical activity (PA), aerobic fitness, and cardiometabolic diseases (CMD) are highly heritable multifactorial phenotypes. Shared genetic factors may underlie the associations between higher levels of PA and better aerobic fitness and a lower risk for cardiometabolic CMDs. Our aim was first to validate PA genotype against self-reported leisure-time PA (LTPA) and second to study how PA genotype associates with aerobic fitness and CMD risk factors. Finally, we investigated if PA genotype predicts CMD endpoints. We expected that these analyses would provide evidence for pleiotropic effects (same gene variants explaining both phenotypes) of PA and CMDs.Methods and findingsPolygenic risk score (PRS) for PA was constructed in the Trøndelag Health Study (N=47,148) using UK Biobank single nucleotide polymorphism-specific weights (N=400,124). The results showed that genotypes predisposing to higher PA were associated with greater self-reported PA (Beta [B]=0.282 MET-h·wk-1per SD of PRS for PA, 95% confidence interval [CI]=0.211, 0.354) but not with aerobic fitness. These genotypes were also associated with healthier profile in CMD risk factors (waist circumference [B=-0.003 cm, 95% CI=-0.004, -0.002], body mass index [B=-0.002 kg·(m2)-1, 95% CI=-0.004, -0.001], high-density lipoprotein cholesterol [B=0.004 mmol·L-1, 95% CI=0.002, 0.006]) and lower incidence of hypertensive diseases (HR=0.97, 95% CI=0.951, 0.990), stroke (HR=0.94, 95% CI=0.903, 0.978) and type 2 diabetes (HR=0.94, 95% CI=0.902, 0.970). When accounting for self-reported PA, the associations between PA genotypes and CMD risk factors remained statistically significant.ConclusionsGenotypes predisposing to higher PA were associated with higher amount of PA. However, in general the predictive value of the PRS for PA in predicting self-reported PA was low, possibly because of the acknowledged inconsistencies in assessing PA in cohort studies. Genotypes predisposing to higher PA were also associated with better cardiometabolic health and lower incidence of CMDs, and the observed associations were independent of self-reported PA. These results support earlier findings suggesting small pleiotropic effects between PA and CMDs and provide new evidence about associations with polygenic inheritance of PA and intermediate CMD risk factors. The observed association were however small, and results do not suggest clinical relevance in health promotion.

BackgroundMeasures of biological aging range from DNA methylation (DNAm)-based estimates to measures of physical abilities. The purpose of this study was to compare DNAm- and physical functioning-based measures of biological aging in predicting mortality.MethodsWe studied 63- to 76-year-old women (N = 395) from the Finnish Twin Study on Aging (FITSA). Participants’ biological age (epigenetic clocks DNAm GrimAge and DunedinPACE) was estimated using blood DNAm data. Tests of physical functioning conducted under standardized laboratory conditions included the Timed Up and Go (TUG) test and 10-m walk test. Mortality hazard ratios were calculated per every 1 standard deviation (SD) increase in the predictor. Cox regression models were conducted for individuals and twin pairs, the latter controlling for underlying genetic effects. The models were adjusted for known lifestyle predictors of mortality.ResultsDuring the follow-up period (mean 17.0 years, range 0.2–20.3), 187 participants died. In both the individual-based and pairwise analyses, GrimAge and both functional biomarkers of aging were associated with mortality independent of family relatedness, chronological age, physical activity, body mass index, smoking, education, or chronic diseases. In a model including both the DNAm-based measures and functional biomarkers of aging, GrimAge and TUG remained predictive.ConclusionsThe findings suggest that DNAm GrimAge and the TUG test are strong predictors of mortality independent of each others and genetic influences. DNAm-based measures and functional tests capture different aspects of the aging process and thus complement each other as measures of biological aging in predicting mortality.

Background 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. Methods 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. Results 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. Conclusions 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.

Background 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. Method 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. Results 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. Conclusions 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.

Aims and methodsOur aim was to characterise the methylation level of a polymorphically imprinted gene, VTRNA2-1/nc886, in human populations and somatic tissues. We utilised 48 datasets, consisting of >30 different tissues and >30 000 individuals.ResultsWe show that the nc886 methylation status is associated with twin status and ethnic background, but the variation between populations is limited. Monozygotic twin pairs present concordant methylation, while ∼30% of dizygotic twin pairs present discordant methylation in the nc886 locus. The methylation levels of nc886 are uniform across somatic tissues, except in cerebellum and skeletal muscle.ConclusionWe hypothesize that the nc886 imprint is established in the oocyte and that after implantation, the methylation status is stable, excluding a few specific tissues.

Gait speed is a measure of health and functioning. Physical and cognitive determinants of gait are amenable to interventions, but best practices remain unclear. We investigated the effects of a 12-month physical and cognitive training (PTCT) on gait speed, dual-task cost in gait speed, and executive functions (EFs) compared with physical training (PT) (ISRCTN52388040). Community-dwelling older adults, who did not meet physical activity recommendations, were recruited (n = 314). PT included supervised walking/balance (once weekly) and resistance/balance training (once weekly), home exercises (2-3 times weekly), and moderate aerobic activity 150 min/week in bouts of >10 min. PTCT included the PT and computer training (CT) on EFs 15-20 min, 3-4 times weekly. The primary outcome was gait speed. Secondary outcomes were 6-min walking distance, dual-task cost in gait speed, and EF (Stroop and Trail Making B-A). The trial was completed by 93% of the participants (age 74.5 [SD3.8] years; 60% women). Mean adherence to supervised sessions was 59%-72% in PT and 62%-77% in PTCT. Home exercises and CT were performed on average 1.9 times/week. Weekly minutes spent in aerobic activities were 188 (median 169) in PT and 207 (median 180) in PTCT. No significant interactions were observed for gait speed (PTCT-PT, 0.02; 95%CI -0.03, 0.08), walking distance (-3.8; -16.9, 9.3) or dual-task cost (-0.22; -1.74, 1.30). Stroop improvement was greater after PTCT than PT (-6.9; -13.0, -0.8). Complementing physical training with EFs training is not essential for promotion of gait speed. For EF's, complementing physical training with targeted cognitive training provides additional benefit.

MicroRNAs (miRs) are non-coding RNA-molecules that regulate gene expression. Global circulating miR (c-miR) expression patterns (c-miRnome) change with carcinogenesis in various sporadic cancers. Therefore, aberrantly expressed c-miRs could have diagnostic, predictive and prognostic potential in molecular profiling of cancers. c-miR functions in carriers of inherited pathogenic mismatch-repair gene variants (path_MMR), also known as Lynch syndrome (LS), have remained understudied. LS cohort provides an ideal population for biomarker mining due to increased lifelong cancer risk and excessive cancer occurrence. Using high-throughput sequencing and bioinformatic approaches, we conducted an exploratory analysis to characterize systemic c-miRnomes of path_MMR carriers. Our discovery cohort included 81 healthy path_MMR carriers and 37 non-LS controls. Our analysis also included cancer cohort comprised of 13 path_MMR carriers with varying cancers and 24 sporadic rectal cancer patients. We showed for the first time that c-miRnome can discern healthy path_MMR carriers from non-LS controls but does not distinguish healthy path_MMR carriers from cancer patients with or without path_MMR. Our c-miR expression analysis combined with in silico tools suggest ongoing alterations of biological pathways shared in LS and sporadic carcinogenesis. We observed that these alterations can produce a c-miR signature which can be used to track oncogenic stress in cancer-free path_MMR carriers. Thus, c-miRs hold potential in monitoring which cancer patients would require more intensive surveillance or clinical management.SignificanceC-miRnome can discern between healthy persons with or without path_MMR but does not distinguish healthy path_MMR carriers from cancer patients with or without path_MMR, indicating an ongoing alteration of biological pathways that can be used to track oncogenic stress at cancer-free state.

Supplemental digital content is available in the text., 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 (β = −0.025 kg·m−2 per one SD change in PA PRS, SE = 0.013, P = 1.87 × 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 × 10−19) and, for example, hypertension [OR = 0.93, P = 2.7 × 10−44), type 2 diabetes (OR = 0.91, P = 4.1 × 10−42), and coronary heart disease (OR = 0.95, P = 1.2 × 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.

Purpose Hand grip strength (HGS) is a widely used indicator of overall muscle strength and general health. We computed a polygenic risk score (PRS) for HGS, and examined, whether it predicted muscle strength, functional capacity and disability outcomes. Methods Genome-wide association study summary statistics for HGS from the Pan-UK Biobank was utilized. PRSs were calculated in the Finnish Twin Study on Aging (N = 429 women, 63–76 years). Strength tests included HGS, isometric knee extension, and ankle plantar flexion strength. Functional capacity was examined with the Timed Up and Go, six-minute and 10-meter walk tests, and dual-task tests. Disabilities in the basic (ADL) and instrumental activities of daily living (IADL) were investigated with questionnaires. The proportion of variation in outcomes accounted for by PRS HGS was examined using linear mixed models and extended logistic regression. Results The measured HGS increased linearly over increasing PRS (β 4.8, SE 0.93, P < 0.001). PRS HGS independently accounted for 6.1% of the variation in the measured HGS (β 14.2, SE 3.1, P < 0.001), 5.4% of the variation in knee extension strength (β 19.6, SE 4.7, P < 0.001), 1.2% of the variation in ankle plantar flexion strength (β 9.4, SE 4.2, P = 0.027), and 0.1%–1.5% of the variation in functional capacity tests (P range 0.016–0.133). Further, participants with higher PRS HGS were less likely to have ADL/IADL disabilities (OR range 0.74–076). Conclusions Older women with genetic risk for low muscle strength were significantly weaker than those with genetic susceptibility for high muscle strength. PRS HGS was also systematically associated with overall muscle strength and proximal and distal functional outcomes that require muscle strength. peerReviewed

Aims & methods: The aim of this study was to characterize the methylation level of a polymorphically imprinted gene, VTRNA2-1/nc886, in human populations and somatic tissues.48 datasets, consisting of more than 30 tissues and >30,000 individuals, were used. Results: nc886 methylation status is associated with twin status and ethnic background, but the variation between populations is limited. Monozygotic twin pairs present concordant methylation, whereas similar to 30% of dizygotic twin pairs present discordant methylation in the nc886 locus. The methylation levels of nc886 are uniform across somatic tissues, except in cerebellum and skeletal muscle. Conclusion: The nc886 imprint may be established in the oocyte, and, after implantation, the methylation status is stable, excluding a few specific tissues. Tweetable abstract Methylation status of a polymorphically imprinted gene, VTRNA2-1/nc886, is stable in human populations (48 cohorts, n > 30,000) and in somatic tissues, except in cerebellum and skeletal muscle. Twin data suggest it may already be established in the oocyte.

Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

The aim of this study was to investigate the correspondence of different biological ageing estimates (i.e. epigenetic age) in blood and muscle tissue and their associations with physical activity (PA), physical function and body composition. Two independent cohorts (N = 139 and N = 47) were included, whose age span covered adulthood (23–69 years). Whole blood and m. vastus lateralis samples were collected, and DNA methylation was analysed. Four different DNA methylation age (DNAmAge) estimates were calculated using genome-wide methylation data and publicly available online tools. A novel muscle-specific methylation age was estimated using the R-package ‘MEAT’. PA was measured with questionnaires and accelerometers. Several tests were conducted to estimate cardiorespiratory fitness and muscle strength. Body composition was estimated by dual-energy X-ray absorptiometry. DNAmAge estimates from blood and muscle were highly correlated with chronological age, but different age acceleration estimates were weakly associated with each other. The monozygotic twin within-pair similarity of ageing pace was higher in blood (r = 0.617–0.824) than in muscle (r = 0.523–0.585). Associations of age acceleration estimates with PA, physical function and body composition were weak in both tissues and mostly explained by smoking and sex. The muscle-specific epigenetic clock MEAT was developed to predict chronological age, which may explain why it did not associate with functional phenotypes. The Horvath’s clock and GrimAge were weakly associated with PA and related phenotypes, suggesting that higher PA would be linked to accelerated biological ageing in muscle. This may, however, be more reflective of the low capacity of epigenetic clock algorithms to measure functional muscle ageing than of actual age acceleration. Based on our results, the investigated epigenetic clocks have rather low value in estimating muscle ageing with respect to the physiological adaptations that typically occur due to ageing or PA. Thus, further development of methods is needed to gain insight into muscle tissue-specific ageing and the underlying biological pathways.

Supplemental digital content is available in the text., Purpose Greater leisure-time physical activity (LTPA) associates with healthier lives, but knowledge regarding occupational physical activity (OPA) is more inconsistent. DNA methylation (DNAm) patterns capture age-related changes in different tissues. We aimed to assess how LTPA and OPA are associated with three DNAm-based epigenetic age estimates, namely, DNAm age, PhenoAge, and GrimAge. Methods The participants were young adult (21–25 yr, n = 285) and older (55–74 yr, n = 235) twin pairs, including 16 pairs with documented long-term LTPA discordance. Genome-wide DNAm from blood samples was used to compute DNAm age, PhenoAge, and GrimAge Age acceleration (Acc), which describes the difference between chronological and epigenetic ages. Physical activity was assessed with sport, leisure-time, and work indices based on the Baecke Questionnaire. Genetic and environmental variance components of epigenetic age Acc were estimated by quantitative genetic modeling. Results Epigenetic age Acc was highly heritable in young adult and older twin pairs (~60%). Sport index was associated with slower and OPA with faster DNAm GrimAge Acc after adjusting the model for sex. Genetic factors and nonshared environmental factors in common with sport index explained 1.5%–2.7% and 1.9%–3.5%, respectively, of the variation in GrimAge Acc. The corresponding proportions considering OPA were 0.4%–1.8% and 0.7%–1.8%, respectively. However, these proportions were minor (

BackgroundThe sex gap in life expectancy has been narrowing in Finland over the past four to five decades; however, on average, women still live longer than men. Epigenetic clocks are markers for biological aging that predict lifespan. In this study, we examined the mediating role of lifestyle factors on the association between sex and biological aging in younger and older adults.MethodsOur sample included same-sex younger and older twins (21-42-y, n = 1110; 50-76-y, n = 763) and younger opposite-sex twins (21-30-y, n = 302). Blood-based DNA methylation (DNAm) was used to compute epigenetic age acceleration by four epigenetic clocks as a measure of biological aging. Path modelling was used to study whether the association between sex and biological aging is mediated through lifestyle-related factors, i.e. education, body mass index, smoking, alcohol use, and physical activity.FindingsIn 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 smoking, but only in older twins. Sex was directly associated with biological aging and the association was stronger in older twins.InterpretationPreviously reported sex differences in lifespan 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.

PurposeIt has been suggested that 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. However, the evidence about pleiotropy from human studies is limited. This study investigated associations between PA polygenic risk scores (PRSs) and cardiometabolic diseases among the Finnish population.MethodsPRSs for device-measured overall PA were adapted to a FinnGen study cohort of 218,792 individuals with genome-wide genotyping and extensive digital longitudinal health register data. Associations between PA PRS and body mass index (BMI), diseases, and mortality were analysed with linear and logistic regression models. The number of different disease endpoints varied between 894 and 111,108 in FinnGen cohort.ResultsA high PA PRS predicted a lower BMI (β −0.025 kg/m2per one standard deviation (SD) change in PA PRS, SE 0.013, p=1.87×10−80). 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*10−19) and, for example, hypertension [OR 0.93, p=2.7*10−44), type 2 diabetes (OR 0.91, p=4.1*10−42), and coronary heart disease (OR 0.95 p=1.2*10−9). Participants with high PA PRS had also lower mortality risk (OR 0.97, p=0.0003). We did not observe statistically significant associations with hypothetical control conditions, such as osteoarthritis and osteoporosis.ConclusionsGenetically 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.

Biological ageing estimators derived from DNA methylation (DNAm) data are heritable and correlate with morbidity and mortality. Leveraging DNAm and SNP data from >41,000 individuals, we identify 137 genome-wide significant loci (113 novel) from meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We report strong genetic correlations with longevity and lifestyle factors such as smoking, education, and obesity. Significant associations are observed in polygenic risk score analysis and to a lesser extent in Mendelian randomization analyses. This study illuminates the genetic architecture underlying epigenetic ageing and its shared genetic contributions with lifestyle factors and longevity.

Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.

Background Whether increased life expectancy is accompanied by increased functional capacity in older people at specific ages is unclear. We compared similar validated measures of maximal physical performance in 2 population-based older cohorts born and assessed 28 years apart. Method Participants in the first cohort were born in 1910 and 1914 and were assessed at age 75 and 80 years, respectively (N = 500, participation rate 77%). Participants in the second cohort were born in 1938 or 1939 and 1942 or 1943 and were assessed at age 75 and 80 years, respectively (N = 726, participation rate 40%). Participants were recruited using a population register and all community-dwelling persons in the target area were eligible. Both cohorts were interviewed at home and were examined at the research center with identical protocols. Maximal walking speed, maximal isometric grip and knee extension strength, forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were assessed. Data on non-participation were systematically collected. Results Walking speed was on average 0.2–0.4 m/s faster in the later than earlier cohort. In grip strength, the improvements were 5%–25%, and in knee extension strength 20%–47%. In FVC, the improvements were 14–21% and in FEV1, 0–14%. Conclusions The later cohort showed markedly and meaningfully higher results in the maximal functional capacity tests, suggesting that currently 75- and 80-year-old people in Finland are living to older ages nowadays with better physical functioning.

Estrogen-based hormone replacement therapy (HRT) may be associated with deceleration of cellular aging. We investigated whether long-term HRT has effects on leukocyte (LTL) or mean and minimum skeletal muscle telomere length (SMTL) in a design that controls for genotype and childhood environment. Associations between telomeres, body composition, and physical performance were also examined. Eleven monozygotic twin pairs (age 57.6 ± 1.8 years) discordant for HRT were studied. Mean duration of HRT use was 7.3 ± 3.7 years in the user sister, while their co-twins had never used HRT. LTL was measured by qPCR and SMTLs by southern blot. Body and muscle composition were estimated by bioimpedance and computed tomography, respectively. Physical performance was measured by jumping height and grip strength. HRT users and non-users did not differ in LTL or mean or minimum SMTL. Within-pair correlations were high in LTL (r= 0.69,p= .020) and in mean (r= 0.74,p= .014) and minimum SMTL (r= 0.88,p= .001). Body composition and performance were better in users than non-users. In analyses of individuals, LTL was associated with BMI (r2= 0.30,p= .030), percentage total body (r2= 0.43,p= .014), and thigh (r2= 0.55,p= .004) fat, while minimum SMTL was associated with fat-free mass (r2= 0.27,p= .020) and thigh muscle area (r2= 0.42,p= .016). We found no associations between HRT use and telomere length. Longer LTLs were associated with lower total and regional fat, while longer minimum SMTLs were associated with higher fat-free mass and greater thigh muscle area. This suggests that telomeres measured from different tissues may have different associations with measures of body composition.

Resistance training (RT) may improve metabolic health; however, the extent of its effectiveness is constantly evaluated to assess improvements in the group means, thus obscuring the heterogeneous individual effects. This study investigated inter-individual variation in response to RT as reflected in metabolic health indicators and how age, sex, nutrition, and pre-training phenotypes are associated with such variabilities. Methods Previously collected data of men and women (39-73 years, 135 trained, 73 non-trained controls) were pooled for analysis. Measurements were taken twice before training to estimate individual day-to-day variations and measurement errors (n = 208). The individual responsiveness to the 21-week RT in cardiometabolic health indicators (ie, systolic blood pressure, high-density lipoprotein cholesterol (HDL-C), cholesterol and triglycerides) was determined. Body composition was estimated by bioimpedance and dietary intake according to 4-day food diaries. Results Metabolic responses to RT seemed to be highly individual, and both beneficial and unfavorable changes were observed. Large inter-individual variations in training response were not explained by a subject's age, sex, body composition, or nutritional status, with the exception of improvements in HDL-C, which were associated with simultaneous decreases in body fat in older women. The incidence of metabolic syndrome diminished following RT. Conclusion This study showed that RT could improve some specific metabolic health indicators beyond normal day-to-day variations, especially in blood lipid profile. Further studies are needed to elucidate genetic and other mechanisms underlining the heterogeneity of RT responses. This knowledge may be useful in providing individually tailored exercise prescriptions as part of personalized preventative health care.

Background Women experience drastic hormonal changes during midlife due to the menopausal transition. Menopausal hormonal changes are known to lead to bone loss and potentially also to loss of lean mass. The loss of muscle and bone tissue coincide due to the functional relationship and interaction between these tissues. If and how physical activity counteracts deterioration in muscle and bone during the menopausal transition remains partly unresolved. This study investigated differences between premenopausal, early perimenopausal, late perimenopausal, and postmenopausal women in appendicular lean mass (ALM), appendicular lean mass index (ALMI), femoral neck bone mineral density (BMD) and T score. Furthermore, we investigated the simultaneous associations of ALM and BMD with physical activity in the above‐mentioned menopausal groups. Methods Data from the Estrogen Regulation of Muscle Apoptosis study were utilized. In total, 1393 women aged 47–55 years were assigned to premenopausal, early perimenopausal, late perimenopausal, and postmenopausal groups based on follicle‐stimulating hormone concentration and bleeding diaries. Of them, 897 were scanned for ALM and femoral neck BMD by dual‐energy X‐ray absorptiometry and ALMI (ALM/height2) and neck T scores calculated. Current level of leisure‐time physical activity was estimated by a validated self‐report questionnaire and categorized as sedentary, low, medium, and high. Results Appendicular lean mass, appendicular lean mass index, femoral neck bone mineral density, and and T score showed a significant linear declining trend across all four menopausal groups. Compared with the postmenopausal women, the premenopausal women showed greater ALM (18.2, SD 2.2 vs. 17.8, SD 2.1, P < 0.001), ALMI (6.73, SD 0.64 vs. 6.52, SD 0.62, P < 0.001), neck BMD (0.969, SD 0.117 vs. 0.925, SD 0.108, P < 0.001), and T score (−0.093, SD 0.977 vs −0.459, SD 0.902, P < 0.001). After adjusting for potential confounding pathways, a higher level of physical activity was associated with greater ALM among the premenopausal [β = 0.171; confidence interval (CI) 95% 0.063–0.280], late perimenopausal (β = 0.289; CI 95% 0.174–0.403), and postmenopausal (β=0.278; CI 95% 0.179–0.376) women. The positive association between femoral neck BMD and level of physical activity was significant only among the late perimenopausal women (β = 0.227; CI 95% 0.097–0.356). Conclusions Skeletal muscle and bone losses were associated with the menopausal transition. A higher level of physical activity during the different menopausal phases was beneficial, especially for skeletal muscle. Menopause‐related hormonal changes predispose women to sarcopenia and osteoporosis and further to mobility disability and fall‐related fractures in later life. New strategies are needed to promote physical activity among middle‐aged women. Longitudinal studies are needed to confirm these results.

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.

Reliable and good suppliers are an important competitive advantage for a customer and that is why the development of suppliers, improvement of performance and enhancement of customership are also in the interest of the customer. The purpose of this study is to clarify a customer’s possibilities to increase the performance of a service provider and to develop the service process in FM services and thus help to improve partnership development. This research is a qualitative research. The research complements the existing generic model of supplier development towards partnership development by customer and clarifies the special features that facility management services bring to this model. The data has been gathered from interviews of customers and service providers in the facility management service sector. The result is a model of customers’ possibilities to develop the performance of service providers from the viewpoint of value addition and relationship development and in that way ensure added value to the customer and the development of a long-term relationship. The results can be beneficial to customers when they develop the cooperation between the customer and the service provider toward being more strategic and more partnership focused.

In today’s dynamic business environment, firms are required to utilize efficiently and effectively all the useful resources to gain competitive advantage. Supplier development has evolved as an important strategic instrument to improve buyer supplier relationships. For that reason, this study focuses on providing the strategic significance of supplier development approaches to improve business relationships. By using qualitative research method, an integrated framework of supplier development and buyer-supplier relationship development has been tested and validated in a Finnish case company to provide empirical evidence. It particularly investigates how supplier development approaches can develop buyer-supplier relationships. The study present a set of propositions that identify significant supplier development approaches critical for the development of buyer-supplier relationships and develop a theoretical framework that specifies how these different supplier development approaches support in order to strengthen the relationships. The results are produced from an in-depth case study by implementing the proposed research framework. The findings reveal that supplier development strategies i.e., supplier incentives and direct involvements strongly effect in developing buyer-supplier relationships. Further research may focus on considering in-depth investigation of trust and communication factors along with propositions developed in the study to find out general applicability in dynamic business environment. Proposed integrated framework along with propositions is a unique combination of useful solutions for tactical and strategic management’s decision making and also valid for academic researchers to develop supplier development theories.

Background Epigenetic 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. Results Quantitative 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), p

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 (β = − 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. Electronic supplementary material The online version of this article (10.1186/s12877-018-0775-6) contains supplementary material, which is available to authorized users.

Purpose – The purpose of the study is to formulate a model for the information integration development. The service supply chain is managed with information; therefore, the functionality of the flow of information is an essential part of service business. The aim of this study is to address this issue by looking into the meaning and development of the elements of information integration in real estate and user services. Design/methodology/approach – This paper is a qualitative research into elements of information integration and developing them in real estate and user services. Collecting the data for the study consisted of three stages: a workshop and two rounds of interviews. Findings – The finding of the study is a model for developing information integration in a real estate and user services. The model presents the meanings of the six elements which integration consists of and which need to be developed to increase information integration. Research limitations/implications – In services, the supply chain is typically shorter than in production. This study is limited to analyse the supply chain between a customer and a service provider since these are the most significant and often the only parties in the supply chain of real estate and user services. Practical implications – The results can be utilized when developing information integration in the service supply chain and developing service providers operations. Originality/value – The research results bring additional value to the previous studies regarding elements of information integration by developing a model for the sequence of development of these elements.

Academic and corporate interest in supplier development and buyer-supplier relationship has increased substantially in recent years. This paper provides a framework for analysing the current understanding of supplier development strategies, its impact on performance, and buyer-supplier relationship approaches. There is an increased need for buyers and suppliers to strategically collaborate to build a stronger and long-term relationship. The goal is to get extended understanding in buyer-supplier relationship and supplier development strategies. Supplier development is a process of understanding including four steps: 1) supplier assessment; 2) competitive pressure; 3) supplier incentives; 4) direct involvement. Future research can be more empirically focused including multiple case study in global environment to validate the supplier development strategy approaches and help the organisation to develop their supplier’s strategies. The presented literature review offers supplier development strategies for empirical case studies and a systematic way to build buyer-supplier relationships to improve the performance.

BACKGROUND: Muscle mass, strength, and power are known determinants of mobility in older adults but there is limited knowledge on the influence of muscle architecture or tendon properties on mobility. The purpose of this study was to examine the relationship between mobility and plantarflexor muscle-tendon properties in healthy older adults.METHODS: A total of 52 subjects (age 70-81 years) were measured for 6-minute walk test (6MWT), timed "up and go"-test (TUG), isometric plantarflexion strength, Achilles tendon stiffness, triceps surae muscle architecture, lower extremity lean mass, isometric leg extension strength, and leg extension power. Partial correlations and multivariate regression models adjusted for sex, age, body mass, and height were used to examine the relationship between mobility (6MWT and TUG) and lower limb muscle-tendon properties.RESULTS: Multivariate regression models revealed that Achilles tendon stiffness (p = .020), plantarflexion strength (p = .022), and medial gastrocnemius fascicle length (p = .046) were independently associated with 6MWT. Plantarflexion strength (p = .037) and soleus fascicle length (p = .031) were independently associated with TUG.CONCLUSIONS: Plantarflexor muscle-tendon properties were associated with mobility in older adults independent of lower extremity lean mass, leg extension strength, or power. Plantarflexion strength was a stronger predictor of mobility than leg extension strength or power. The novel finding of this study was that muscle architecture and tendon properties explained interindividual differences in mobility. This study highlights the importance of the plantarflexors for mobility in older adults and provides understanding of possible mechanisms of age-related decline in mobility.

DNA methylation (DNAm) age, a novel marker of biological aging, has been shown to predict mortality and to be associated with physiological aging. However, the relative contribution of genetic and environmental factors to DNAm age over life span is not fully known. We estimated the magnitude of genetic and environmental factors in DNAm based age acceleration.

Objective This study compared bioimpedance analysis (BIA) in the assessment of body composition with dual-energy X-ray absorptiometry (DXA) in 18- to 88-year-old adults. Design and Methods Body composition of 882 adults was estimated by eight-polar BIA and DXA. In addition, estimates of lean mass, fat mass, and percentage of fat were investigated across a range of age and leisure time physical activity (LTPA) groups. Results Compared to DXA, larger lean masses (mean difference 2.9 and 1.6 kg) and smaller fat masses (3.1 and 2.6 kg) were estimated by BIA in both women and men, respectively. Differences between the methods' mean values were evident in all age and LTPA groups, except in the oldest men (over 70 years). Age, waist circumference, grip strength, and LTPA explained 21% or less of the variance observed in the differences between methods. Conclusions Compared to DXA, BIA provided systematically different body composition estimates throughout the adult age span with considerable amount of intraindividual variation. The differences between estimates may be related to the BIAs' algorithm or body geometry or composition of the population used in this study. Knowledge about the methodological limitations and device comparability is essential for researchers, clinicians, and persons working in rehabilitation and sport centers.

Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in is (FEV1), forced vital capacity (PVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (beta= -0.0452, p= 0.024) as well as COPD (beta= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07 x 10(-7)), FVC (p=2.07 x 10(-5)), and FEV1/FVC (p =5.27 x 10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.

Few studies have examined responsiveness of bioimpedance (BIA) to detect changes over time in body composition using a longitudinal design. Accuracy of BIA and skinfold thickness in estimating body composition among 39–64 year-old women was investigated using dual-energy X-ray absorptiometry (DXA) as a criterion method both cross-sectionally and during a training intervention. 97 women had percentage of fat assessed using DXA, skinfolds and eight-polar BIA using multi-frequency current. Fat mass and lean mass were estimated by DXA and BIA. Measurements were performed before and after the 21-week training intervention. At baseline relative to DXA, BIA under predicted percentage of fat (−6.50 %) and fat mass (−3.42 kg) and overestimated lean mass (3.18 kg) considerably. Also skinfold measurement under predicted percentage of fat compared to DXA, but the difference was smaller (−1.69 % units). Skinfold measurement overestimated percentage of fat at low values and underestimated at high values (r 2 = 0.535). A significant bias was detected between DXA and BIA’s estimate of change in percentage of fat, fat mass and lean mass. Compared to DXA, BIA and skinfolds underestimated the training-induced positive changes in body composition. BIA and skinfold methods compared to DXA are not interchangeable to quantify the percentage of fat, fat mass and lean mass at the cross-sectional design in middle-aged women. Moreover, exercise training-induced small changes in body composition cannot be detected with BIA or skinfold method, even though DXA was able to measure statistically significant within-group changes in body composition after training.

Background: Leucocyte 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. Methods: 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 non-random missing data analysis was utilized. Results: 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). Conclusions: 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. peerReviewed

Physical activity recommendations for public health include typically muscle-strengthening activities for a minimum of 2 days a week. The range of inter-individual variation in responses to resistance training (RT) aiming to improve health and well-being requires to be investigated. The purpose of this study was to quantify high and low responders for RT-induced changes in muscle size and strength and to examine possible effects of age and sex on these responses. Previously collected data of untrained healthy men and women (age 19 to 78 years, n = 287 with 72 controls) were pooled for the present study. Muscle size and strength changed during RT are 4.8 ± 6.1 % (range from −11 to 30 %) and 21.1 ± 11.5 % (range from −8 to 60 %) compared to pre-RT, respectively. Age and sex did not affect to the RT responses. Fourteen percent and 12 % of the subjects were defined as high responders (>1 standard deviation (SD) from the group mean) for the RT-induced changes in muscle size and strength, respectively. When taking into account the results of non-training controls (upper 95 % CI), 29 and 7 % of the subjects were defined as low responders for the RT-induced changes in muscle size and strength, respectively. The muscle size and strength responses varied extensively between the subjects regardless of subject’s age and sex. Whether these changes are associated with, e.g., functional capacity and metabolic health improvements due to RT requires further studies.

PurposeThe purpose is to clarify the concept of service innovation in the context of FM service and to map the factors that are critical for service innovations in the FM service sector. The research questions are: how can service innovations be classified in the FM service sector and what are the factors that create requirements and barriers to the service innovations in the FM service sector?Design/methodology/approachThe nature of this study is qualitative. The data were gathered from two specialist workshops and from semi‐structured interviews. The people interviewed worked for the largest service provider companies in Finland and their customers.FindingsResults yielded by this study comprise the classification of service innovations and the factors that create requirements and barriers for the service innovations in the FM service sector.Research limitations/implicationsThis study focuses on examining the innovation process and its development and on developing innovation activity in large‐scale service provider companies in Finland.Practical implicationsThis study promotes innovation activity in the FM service sector. It helps a service provider to minimize the barriers of service innovation and maximize the related requirements.Originality/valueThis study promotes innovation activity in the FM service sector. It helps a service provider to minimize the barriers of service innovation and maximize the related requirements.

The purpose of this study was to evaluate the effects of 21 weeks of strength and/or endurance training on health related quality of life (HRQoL) in 39-77 year-old healthy subjects. 108 men and 96 women were randomized into endurance, strength, or combined training groups and controls. Strength-group performed high-intensity strength training while endurance-group performed cycle training. Combined-group completed both training protocols. Leg extension strength and maximal oxygen uptake were measured. HRQoL was assessed with a Finnish version of SF-36 questionnaire. A significant training-induced difference was observed between groups (p=0.038) in the vitality dimension of HRQoL, which was characterized by a 6.6 ± 1.5 unit increase in the combined group and no change in the other groups. Both endurance and combined training showed small improvements in certain dimensions of HRQoL. Dimensions of general (4.6 ± 1.9) and mental health (3.9 ± 1.4) improved in combined-group while general health (4.4 ± 2.0), bodily pain (5.5 ± 2.5) and role physical (6.0 ± 2.4) improved in endurance-group. Strength-group experienced increased pain ( -5.4 ± 1.8) during the experimental period. However, increased perception of pain was not observed during combined training. According to the present results both endurance and especially combined training may have potential to promote or maintain certain dimensions of HRQoL even in middle-aged and older adults.

Both strength and endurance training have several positive effects on aging muscle and physical performance of middle-aged and older adults, but their combination may compromise optimal adaptation. This study examined the possible interference of combined strength and endurance training on neuromuscular performance and skeletal muscle hypertrophy in previously untrained 40-67-year-old men. Maximal strength and muscle activation in the upper and lower extremities, maximal concentric power, aerobic capacity and muscle fiber size and distribution in the vastus lateralis muscle were measured before and after a 21-week training period. Ninety-six men [mean age 56 (SD 7) years] completed high-intensity strength training (S) twice a week, endurance training (E) twice a week, combined training (SE) four times per week or served as controls (C). SE and S led to similar gains in one repetition maximum strength of the lower extremities [22 (9)% and 21 (8)%, P