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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.

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.

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

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 (

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.

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.

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.

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.

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.

Background The purpose of the study was to estimate the heritability of leukocyte telomere length (LTL) and lung function and to examine whether LTL and lung function share genetic or environmental effects in common. Methods 386 monozygotic and dizygotic Finnish twin sisters (age 68.4±3.4 years) were included. Relative LTL was determined from peripheral blood DNA by qPCR. Lung function measures of FEV1, FVC, FEV1/FVC, and PEF were derived from spirometry. Genetic modeling was performed with MPlus statistical software. Results Univariate analysis revealed that in LTL, 62% (95% confidence interval 50-72) of the variance was explained by additive genetic and 38% (28-50) by unique environmental factors. For FEV1, FVC, and PEF, the corresponding estimates were 65%-67% for additive genetic and 33%-35% for unique environmental factors. Across the sample, the phenotypic correlation between LTL and FEV1 was modest (r = .104, p = .041). Bivariate correlated factors model revealed that the genetic correlation between LTL and FEV1 was .18 (-0.19 to 0.64) and environmental correlation was -.10 (-0.84 to 0.55). Conclusions Both LTL and lung function variables are moderately to highly genetically determined. The associations between LTL and the lung function variables were weak. However, the positive genetic correlation point estimate gave minor suggestions that, in a larger sample, genetic factors in common might play a role in the phenotypic correlation between LTL and FEV1. Future studies with larger samples are needed to confirm these preliminary findings.

Background: A consensus on the diagnostic criteria for sarcopenia, a common syndrome in the elderly, has not been reached yet. Prevalence rates vary between studies due to the use of different criteria encompassing different measures, correction factors and cutoff points. Objective: This study compared prevalence rates of sarcopenia using nine sets of diagnostic criteria applied in two different elderly populations. Methods: The study population encompassed 308 healthy elderly participants (152 males, 156 females; mean age 74 years) and 123 geriatric outpatients (54 males, 69 females; mean age 81 years). Diagnostic criteria included relative muscle mass, absolute muscle mass, muscle strength and physical performance. Results: Prevalence rates of sarcopenia varied between 0 and 15% in healthy elderly participants and between 2 and 34% in geriatric outpatients. Conclusion: This study clearly demonstrates the dependency of sarcopenia prevalence rates on the applied diagnostic criteria.

Pathological obstruction in lungs leads to severe decreases in muscle strength and mobility in patients suffering from chronic obstructive pulmonary disease. The purpose of this study was to investigate the interdependency between muscle strength, spirometric pulmonary functions and mobility outcomes in healthy older men and women, where skeletal muscle and pulmonary function decline without interference of overt disease. A total of 135 69- to 81-year-old participants were recruited into the cross-sectional study, which was performed as a part of European study MyoAge. Full, partial and no mediation models were constructed to assess the interdependency between muscle strength (handgrip strength, knee extension torque, lower extremity muscle power), spirometric pulmonary function (FVC, FEV1 and FEF50) and mobility (6-min walk and Timed Up and Go tests). The models were adjusted for age, sex, total fat mass, body height and site of enrolment. Partial mediation models, indicating both direct and pulmonary function mediated associations between muscle strength and mobility, fitted best to the data. Greater handgrip strength was significantly associated with higher FVC, FEV1 and FEF50 (p < 0.05). Greater muscle power was significantly associated with better performance in mobility tests. Results suggest that decline in mobility with aging may be caused by decreases in both muscle strength and power but also mediated through decreases in spirometric pulmonary function. Future longitudinal studies are warranted to better understand how loss of function and mass of the respiratory muscles will affect pulmonary function among older people and how these changes are linked to mobility decline.

SUMMARY: Currently used diagnostic measures for sarcopenia utilize different measures of muscle mass, muscle strength, and physical performance. These diagnostic measures associate differently to bone mineral density (BMD), as an example of muscle-related clinical outcome. These differences should be taken into account when studying sarcopenia.INTRODUCTION: Diagnostic measures for sarcopenia utilize different measures of muscle mass, muscle strength, and physical performance. To understand differences between these measures, we determined the association with respect to whole body BMD, as an example of muscle-related clinical outcome.METHODS: In the European cross-sectional study MYOAGE, 178 young (18-30 years) and 274 healthy old participants (69-81 years) were recruited. Body composition and BMD were evaluated using dual-energy X-ray densitometry. Diagnostic measures for sarcopenia were composed of lean mass as percentage of body mass, appendicular lean mass (ALM) as percentage of body mass, ALM divided by height squared (ALM/height(2)), knee extension torque, grip strength, walking speed, and Timed Up and Go test (TUG). Linear regression models were stratified for sex and age and adjusted for age and country, and body composition in separate models.RESULTS: Lean mass and ALM/height(2) were positively associated with BMD (P CONCLUSIONS: The associations between diagnostic measures of sarcopenia and BMD as an example of muscle-related outcome vary widely. Differences between diagnostic measures should be taken into account when studying sarcopenia.

Within the European multi-centre MyoAge project, one workpackage was designed to investigate the contribution of age-related changes to muscle mass, contractile characteristics and neural control in relation to reductions in mobility in older age. The methodology has been described here. Test centres were located in Manchester, UK; Paris, France; Leiden, The Netherlands; Tartu, Estonia and Jyväskylä, Finland. In total, 182 young (18-30 years old, 52.2 % female) and 322 older adults (69-81 years old, 50 % female) have been examined. The participants were independent living, socially active and free from disease that impaired mobility levels. The older participants were selected based on physical activity levels, such that half exceeded current recommended physical activity levels and the other half had lower physical activity levels than is recommended to maintain health. Measurements consisted of blood pressure; anthropometry and body composition (dual-energy X-ray absorptiometry and magnetic resonance imaging); lung function; standing balance and cognitive function (CANTAB). Mobility was assessed using the Timed Up and Go, a 6 min walk, activity questionnaires and accelerometers to monitor habitual daily activities. Muscle strength, power, fatigue and neural activation were assessed using a combination of voluntary and electrically stimulated contractions. Fasting blood samples and skeletal muscle biopsies were collected for detailed examination of cell and molecular differences between young and older individuals. The results from this study will provide a detailed insight into "normal, healthy" ageing, linking whole-body function to the structure and function of the neuromuscular system and the molecular characteristics of skeletal muscle.

Purpose: A combination of endurance and strength training is generally used to seek further health benefits or enhanced physical performance in older adults compared with either of the training modes alone. The mean change within a training group, however, may conceal a wide range of individual differences in the responses. The purpose, therefore, was to examine the individual trainability of aerobic capacity and maximal strength, when endurance and strength training are performed separately or concurrently. Methods: For this study, 175 previously untrained volunteers, 89 men and 86 women between the ages of 40 and 67 yr, completed a 21-wk period of either strength training (S) twice a week, endurance training (E) twice a week, combined training (ES) four times per week, or served as controls. Training adaptations were quantified as peak oxygen uptake (V?O2peak) in a bicycle ergometer test to exhaustion and maximal isometric bilateral leg extension force (MVC) in a dynamometer. Results: A large range in training responses, similar to endurance or strength training alone, was also observed with combined endurance and strength training in both ?V?O2peak (from -8% to 42%) and ?MVC (from -12% to 87%). There were no significant correlations between the training responses in V?O2peak and MVC in the E, S, or especially in the ES group, suggesting that the same subjects did not systematically increase both aerobic capacity and maximal strength. Conclusions: The goal of combined endurance and strength training-increasing both aerobic capacity and maximal strength simultaneously-was only achieved by some of the older subjects. New means are needed to personalize endurance, strength, and especially combined endurance and strength training programs for optimal individual adaptations.

We examined effects of 21 weeks of strength and/or endurance training and nutrition on serum hormones and physical fitness in 39-64-year-old women. Subjects (n=79) were randomized into the endurance group (E), strength group (S), combined group (SE) and controls (C). Total body strength training and high-intensity bicycle training were used. Average energy and nutrient intake remained the same in all groups. Body fat (dual energy X-ray absorptiometry) decreased significantly in all training groups and body mass index in E, SE and C. Only SE increased total body lean mass (2.2%, p=0.001), between groups p=0.044. Maximal cycling power increased more in E (16%) and SE (17%) than in S (8%)(all p

In this study adaptations in body composition, physical fitness and metabolic health were examined during 21 weeks of endurance and/or strength training in 39- to 64-year-old healthy women. Subjects (n = 62) were randomized into endurance training (E), strength training (S), combined strength and endurance training (SE), or control groups (C). S and E trained 2 and SE 2 + 2 times in a week. Muscle strength and maximal oxygen uptake (VO(2)max) were measured. Leg extension strength increased 9 +/- 8% in S (P0.001), 12 +/- 8% in SE (P0.001) and 3 +/- 4% in E (P = 0.036), and isometric bench press 20% only in both S and SE (P0.001). VO(2)max increased 23 +/- 18% in E and 16 +/- 12% in SE (both P0.001). The changes in the total body fat (dual X-ray absorptiometry) did not differ between groups, but significant decreases were observed in E (-5.9%, P = 0.022) and SE (-4.8%, P = 0.005). Lean mass of the legs increased 2.2-2.9% (P = 0.004-0.010) in S, SE and E. There were no differences between the groups in the changes in blood lipids, blood pressure or serum glucose and insulin. Total cholesterol and low-density lipoprotein cholesterol decreased and high-density lipoprotein cholesterol increased in E. Both S and SE showed small decreases in serum fasting insulin. Both endurance and strength training and their combination led to expected training-specific improvements in physical fitness, without interference in fitness or muscle mass development. All training methods led to increases in lean body mass, but decreases in body fat and modest improvements in metabolic risk factors were more evident with aerobic training than strength training.

Background Living alone is a risk factor for health decline in old age, especially when facing adverse events increasing vulnerability. Aim We examined whether living alone is associated with higher post-fracture mortality risk. Methods Participants were 190 men and 409 women aged 75 or 80 years at baseline. Subsequent fracture incidence and mortality were followed up for 15 years. Extended Cox regression analysis was used to compare the associations between living arrangements and mortality risk during the first post-fracture year and during the non-fracture time. All participants contributed to the non-fracture state until a fracture occurred or until death/end of follow-up if they did not sustain a fracture. Participants who sustained a fracture during the follow-up returned to the non-fracture state 1 year after the fracture unless they died or were censored due to end of follow-up. Results Altogether, 22% of men and 40% of women sustained a fracture. During the first post-fracture year, mortality risk was over threefold compared to non-fracture time but did not differ by living arrangement. In women, living alone was associated with lower mortality risk during non-fracture time, but the association attenuated after adjustment for self-rated health. In men, living alone was associated with increased mortality risk during non-fracture time, although not significantly. Conclusion The results suggest that living alone is not associated with pronounced mortality risk after a fracture compared to living with someone.

This study examined the effects of strength training and diet on serum basal hormone concentrations and muscle mass in aging women. Fifty-one women age 49 to 74 y were divided into two groups: strength training and nutritional counseling (n = 25), and strength training (n = 26). Both groups performed strength training twice a week for 21 wk. Nutritional counseling was given to attain sufficient energy and protein intake and recommended intake of fat and fiber. We found that the cross-sectional area of the quadriceps femoris increased by 9.5 ± 4.1% in the nutritional counseling group versus 6.8 ± 3.5% in the strength training only group after training (P < 0.052). Nutritional counseling evoked dietary changes such as increases in the proportion of energy from protein and the ratio of poly-unsaturated and saturated fatty acids. Strength training increased testosterone and testosterone/sex hormone-binding globulin ratio after the first half of training, but these returned to baseline values at the end of the entire training period. Changes in serum basal hormone concentrations did not differ between the groups. Our results support the conclusion that nutritional counseling can contribute to the increase in the muscle cross-sectional area during prolonged strength training in aging women.