Programming of cardiac metabolism by miR-15b-5p, a miRNA released in cardiac extracellular vesicles following ischemia-reperfusion injury.

OBJECTIVE: We investigated the potential involvement of miRNAs in the developmental programming of cardiovascular diseases (CVD) by maternal obesity. METHODS: Serum miRNAs were measured in individuals from the Helsinki Birth Cohort (with known maternal body mass index), and a mouse model was used to determine causative effects of maternal obesity during pregnancy and ischemia-reperfusion on offspring cardiac miRNA expression and release. RESULTS: miR-15b-5p levels were increased in the sera of males born to mothers with higher BMI and in the hearts of adult mice born to obese dams. In an ex-vivo model of perfused mouse hearts, we demonstrated that cardiac tissue releases miR-15b-5p, and that some of the released miR-15b-5p was contained within small extracellular vesicles (EVs). We also demonstrated that release was higher from hearts exposed to maternal obesity following ischaemia/reperfusion. Over-expression of miR-15b-5p in vitro led to loss of outer mitochondrial membrane stability and to repressed fatty acid oxidation in cardiomyocytes. CONCLUSIONS: These findings suggest that miR-15-b could play a mechanistic role in the dysregulation of cardiac metabolism following exposure to an in utero obesogenic environment and that its release in cardiac EVs following ischaemic damage may be a novel factor contributing to inter-organ communication between the programmed heart and peripheral tissues.

Healthy ageing from birth to age 84 years in the Helsinki Birth Cohort Study, Finland: a longitudinal study.

BACKGROUND: The true prevalence of healthy ageing on a population level is unknown. In this study we aimed to examine the upper limit for the prevalence of healthy ageing, by quantifying the probability of surviving and remaining free of chronic diseases that could impact functioning (ie, healthy survival) across adulthood. We also estimated the prevalence of clinically assessed healthy ageing, and the determinants of healthy survival and healthy ageing. METHODS: In this longitudinal study, we assessed men and women born in 1934-44 from the Helsinki Birth Cohort Study (Helsinki, Finland; n=13 140). We obtained information on chronic diseases, deaths, and early-to-midlife variables from national registers, databases, and health records for the period Jan 1, 1971, to Dec 31, 2017 (follow-up 951 088 person-years). We also collated data from clinical visits conducted in 2001-04 and 2017-18. Healthy ageing was defined on the basis of clinical data according to six criteria covering chronic diseases, cognitive function, physical performance, depressive symptoms, pain interference, and social functioning. We analysed the probability of healthy survival across adulthood using the Kaplan-Meier method, and the determinants of healthy survival using Cox regression models. We assessed the association of healthy ageing status in 2017-18 (n=813 with available data) with late-midlife factors collected in 2001-04 using age-adjusted logistic regression. FINDINGS: The probability of healthy survival was 42·8% (95% CI 41·6-44·0) in men and 40·1% (38·9-41·4) in women at age 65 years, and 22·5% (21·5-23·6%) in men and 24·4% (23·3-25·6) in women at age 75 years. Healthy survival was associated with socioeconomic position in childhood (adjusted hazard ratio [aHR], upper-middle class vs manual worker, men: 1·21 [1·11-1·31]; women: 1·15 [95% CI 1·05-1·26]) and years of education (aHR per 1 SD increase, men: 1·12 [1·08-1·16]; women: 1·03 [1·00-1·07]). In men, healthy survival was also associated with lower maternal BMI in late pregnancy (aHR per 1 SD increase 0·93 [0·90-0·96]), and in women, with shorter height at age 7 years (aHR per 1 SD increase 0·95 [0·91-0·99]). Among the 813 individuals with relevant clinical assessment data, 159 (19·6%) met all six criteria for healthy ageing at mean age 76 years (SD 3). In addition to age, we found that nutrition (Alternative Healthy Eating Index, age-adjusted odds ratio [aOR] per 1 point increase 1·03 [1·01-1·05]), former smoker status (vs non-smoker status, aOR 0·68 [0·47-0·98], and use of lipid-lowering medication (vs not used, aOR 0·60 [0·42-0·87]) in late midlife (mean age 61 years [SD 3]) were associated with healthy ageing. INTERPRETATION: The probability of healthy survival, as the upper limit for healthy ageing, was less than 50% from age 65 years. The probability of healthy survival and healthy ageing was influenced by several factors across the life course. Promotion of healthy ageing needs to take a life course approach. FUNDING: Signe and Ane Gyllenberg Foundation, Samfundet Folkhälsan, Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, European Commission Seventh Framework Programme, EU Horizon 2020, and the Academy of Finland.

Depressive symptoms and mortality-findings from Helsinki birth cohort study.

BACKGROUND: Individuals with depression and depressive symptoms have a higher mortality rate than non-depressed individuals. The increased comorbidity and mortality associated with depression has remained largely unexplained. The underlying pathophysiological differences between depressive subtypes, melancholic and non-melancholic, may provide some explanation to this phenomenon. METHODS: One thousand nine hundred and ninety five participants (mean age 61 years) from the Helsinki Birth Cohort Study were recruited for this prospective study and followed up for a mean of 14.1 years. Information regarding medical history, lifestyle, and biochemical parameters were obtained. Depressive symptoms were assessed using the Beck Depression Inventory. Standardized mortality ratios were calculated. RESULTS: Participants were followed up for a total of 28,044 person-years. The melancholic depressive group had an increased adjusted risk of mortality [HR 1.49 (95% CI: 1.02-2.20)] when compared to the non-depressive group. Comparing mortality to the whole population of Finland using standardized mortality ratios (SMR) both the non-melancholic [1.11 (95% CI: 0.85-1.44)] and melancholic depressive [1.26 (95% CI: 0.87-1.81)] groups had higher mortality than the non-depressive group [0.82 (95% CI: 0.73-0.93)]. CONCLUSIONS: Melancholic depressive symptoms are most strongly related to a higher mortality risk.

COX7A2L genetic variants determine cardiorespiratory fitness in mice and human.

Mitochondrial respiratory complexes form superassembled structures called supercomplexes. COX7A2L is a supercomplex-specific assembly factor in mammals, although its implication for supercomplex formation and cellular metabolism remains controversial. Here we identify a role for COX7A2L for mitochondrial supercomplex formation in humans. By using human cis-expression quantitative trait loci data, we highlight genetic variants in the COX7A2L gene that affect its skeletal muscle expression specifically. The most significant cis-expression quantitative trait locus is a 10-bp insertion in the COX7A2L 3' untranslated region that increases messenger RNA stability and expression. Human myotubes harboring this insertion have more supercomplexes and increased respiration. Notably, increased COX7A2L expression in the muscle is associated with lower body fat and improved cardiorespiratory fitness in humans. Accordingly, specific reconstitution of Cox7a2l expression in C57BL/6J mice leads to higher maximal oxygen consumption, increased lean mass and increased energy expenditure. Furthermore, Cox7a2l expression in mice is induced specifically in the muscle upon exercise. These findings elucidate the genetic basis of mitochondrial supercomplex formation and function in humans and show that COX7A2L plays an important role in cardiorespiratory fitness, which could have broad therapeutic implications in reducing cardiovascular mortality.

Adiposity-Related Predictors of Vascular Aging From a Life Course Perspective-Findings From the Helsinki Birth Cohort Study.

The main objective of this study was to study predictors of vascular health with focus on adiposity-related factors. Glucose metabolism, blood lipids, inflammatory markers and body composition were assessed 15 years before assessment of vascular health which was assessed with pulse wave velocity (PWV) in 660 subjects born 1934-44. In a univariate analysis in women the strongest association with PWV was seen for age, systolic blood pressure, dysglycemia, dyslipidemia, inflammatory markers and body fat percentage measured in late midlife and PWV measured 15 years later. In men age, body mass index (BMI), systolic blood pressure, dysglycemia, and body fat percentage in late midlife were associated with PWV. One novel finding was that adiposity-related factors were strong predictors of vascular health, something not fully encapsulated in BMI, lean body mass or body fat percentage alone. A higher fat mass index was associated with worse vascular health, which was not ameliorated by a higher lean mass index. Our findings stress the importance to study body composition and fat and lean body mass simultaneously because of their close interaction with each other also in relation to vascular health.

Non-melancholic depressive symptoms are associated with above average fat mass index in the Helsinki birth cohort study.

There is an existing link between two of the most common diseases, obesity and depression. These are both of great public health concern, but little is known about the relationships between the subtypes of these conditions. We hypothesized that non-melancholic depressive symptoms have a stronger relationship with both body composition (lean mass and fat mass) and dysfunctional glucose metabolism than melancholic depression. For this cross-sectional study 1510 participants from the Helsinki Birth Cohort Study had their body composition evaluated as lean mass and fat mass (Lean Mass Index [LMI, kg/m2] + Fat Mass Index [FMI kg/m2] = Body Mass Index). Participants were evaluated for depressive symptoms utilizing the Beck depression inventory, and had laboratory assessments including an oral glucose tolerance test. Higher than average FMI was associated with a higher percentage (mean [%], 95% CI) of participants scoring in the depressive range of the Beck depression inventory (20.2, 17.2-23.2) compared to those with low FMI (16.3, 13.8-18.9; p = 0.048) when adjusted for age, sex, education, and fasting plasma glucose concentration. Higher FMI was associated with a higher likelihood of having depressive symptoms (OR per 1-SD FMI = 1.37, 95% CI 1.13-1.65), whereas higher LMI was associated with a lower likelihood of having depressive symptoms (OR per 1-SD LMI = 0.76, 95% CI 0.64-0.91). Participants with an above average FMI more frequently (mean [%], 95% CI) had non-melancholic depressive symptoms (14.7, 11.8-17.7) as compared to those with low FMI (9.7, 7.6-11.9; p = 0.008) regardless of LMI levels. There was no difference between the body composition groups in the likelihood of having melancholic depressive symptoms. The non-melancholic group had higher (mean [kg/m2], SD) FMI (9.6, 4.1) than either of the other groups (BDI < 10: 7.7, 3.1; melancholic: 7.9, 3.6; p < 0.001), and a higher (mean [mmol/l], SD) 2-h glucose concentration (7.21, 1.65) than the non-depressed group (6.71, 1.70; p = 0.005). As hypothesized, non-melancholic depressive symptoms are most closely related to high fat mass index and dysfunctional glucose metabolism.

Effect of childhood developmental coordination disorder on adulthood physical activity; Arvo Ylppö longitudinal study.

Individuals at risk of Developmental Coordination Disorder (DCD) have low levels of physical activity in childhood due to impaired motor competence; however, physical activity levels in adulthood have not been established. This study sought to determine the impact of DCD risk on physical activity levels in adults using accelerometry measurement. Participants (n = 656) from the Arvo Ylppö Longitudinal Study cohort had their motor competence assessed at the age of five years, and their physical activity quantified via device assessment at the age of 25 years. Between group differences were assessed to differentiate physical activity measures for individuals based on DCD risk status, with general linear modeling performed to control for the effects of sex, body mass index (BMI), and maternal education. Participants at risk of DCD were found to have a lower total number of steps (d = 0.3, p = 0.022) than those not at risk. Statistical modeling indicated that DCD risk status increased time spent in sedentary light activity (ß = 0.1, 95% CI 0.02 to 0.3, p = 0.026) and decreased time spent in vigorous physical activity via interaction with BMI (ß = 0.04, 95% CI 0.001 to 0.1, p = 0.025). Sensitivity analysis found that visuomotor impairment did not significantly impact physical activity but did increase the role of DCD risk status in some models. This 20-year-longitudinal study indicated that DCD risk status continues to negatively impact on levels of physical activity into early adulthood.

Cardiovascular disease in people born to unmarried mothers in two historical periods: The Helsinki Birth Cohort Study 1934-1944.

Aims:Socio-economic conditions in early life are important contributors to cardiovascular disease - the leading cause of mortality globally - in later life. We studied coronary heart disease (CHD) and stroke in adulthood among people born out of wedlock in two historical periods: before and during World War II in Finland. Methods: We compared offspring born out of wedlock before (1934-1939) and during (1940-1944) World War II with the offspring of married mothers in the Helsinki Birth Cohort Study. The war affected the position of unmarried mothers in society. We followed the study subjects from 1971 to 2014 and identified deaths and hospital admissions from CHD and stroke. Data were analysed using a Cox regression, adjusting for other childhood and adulthood socio-economic circumstances. Results: The rate of out-of-wedlock births was 240/4052 (5.9%) before World War II and 397/9197 (4.3%) during World War II. Among those born before World War II, out-of-wedlock birth was associated with an increased risk of stroke (hazard ratio (HR)=1.44; 95% confidence interval (CI) 1.00-2.07) and CHD (HR=1.37; 95% CI 1.02-1.86). Among those born out of wedlock during World War II, the risks of stroke (HR=0.89; 95% CI 0.58-1.36) and CHD (HR=0.70; 95% CI 0.48=1.03) were similar to those observed for the offspring of married mothers. The p-values for interaction of unmarried×World War II were (p=0.015) for stroke and (p=0.003) for CHD. Conclusions: In a society in which marriage is normative, being born out of wedlock is an important predictor of lifelong health disadvantage. However, this may change rapidly when societal circumstances change, such as during a war.

The utilization of specialized healthcare services among frail older adults in the Helsinki Birth Cohort Study.

BACKGROUND: The association between frailty and specialized healthcare utilization is not well studied. We, therefore, examined the utilization of specialized healthcare services among frail Finnish older adults. METHODS: A sub-sample of 1060 participants of the Helsinki Birth Cohort Study were followed prospectively for specialized healthcare utilization from nationwide registers between the years 2013 and 2017. The participants' frailty status was assessed according to Fried's criteria at a mean age of 71.0 (2.7 SD) years between the years 2011 and 2013. A negative binomial regression model was used to examine the association between frailty and the total number of visits, emergency visits, outpatient appointments separating the first outpatient appointments and the follow-up appointments, inpatient care including elective and non-elective hospital admissions and the total number of hospital days. We also calculated average length of stay (ALOS) and used the Kruskal-Wallis test to examine the differences between the groups. RESULTS: After adjusting for covariates, frailty was significantly associated with the number of specialized healthcare visits (IRR 1.50, 95% CI = 1.04-2.15) and all subgroups of visits apart from follow-up outpatient appointments. Frailty was particularly strongly associated with the number of hospital days (IRR 5.24, 95% CI = 2.35-11.7) and notably with emergency visits (IRR = 2.26, 95% CI = 1.45-3.51) and hospital admissions (IRR 2.23, 95% CI = 1.39-3.56). Frail older adults had also higher ALOS compared to non-frail participants (p = .009). CONCLUSIONS: Frailty increases the use of most specialized healthcare services. Preventative interventions against frailty are needed to decrease the burden on specialized healthcare systems.KEY MESSAGEFrailty is associated with the utilization of most specialized healthcare services, the most expensive part of the healthcare in most high-income countries.The association of frailty with inpatient care is particularly strong.Preventative interventions against frailty are needed to decrease the burden on specialized healthcare systems.

Advanced glycation end products measured by skin autofluorescence are associated with melancholic depressive symptoms - Findings from Helsinki Birth Cohort Study.

BACKGROUND: Millions of people live with depression and its burden of disease. Depression has an increased comorbidity and mortality that has remained unexplained. Studies have reported connections between advanced glycation end products (AGEs) and various disease processes, including mental health. The present study evaluated associations between AGEs, depressive symptoms, and types of depressive symptoms. METHODS: From the Helsinki Birth Cohort Study, 815 participants with a mean age of 76 years were recruited for this cross-sectional study. Characteristics regarding self-reported lifestyle and medical history, as well as blood tests were obtained along with responses regarding depressive symptoms according to the Beck Depression Inventory (BDI) and Mental Health Inventory-5. Each participant had their AGE level measured non-invasively with skin autofluorescence (SAF). Statistical analyses looked at relationships between types of depressive symptoms and AGE levels by sex. RESULTS: Of women, 27% scored ≥10 on the BDI and 18% of men, respectively. Men had higher crude AGE levels (mean [standard deviation], arbitrary units) (2.49 [0.51]) compared to women (2.33 [0.46]) (p < 0.001). The highest crude AGE levels were found in those with melancholic depressive symptoms (2.61 [0.57]), followed by those with non-melancholic depressive symptoms (2.45 [0.45]) and those with no depressive symptoms (2.38 [0.49]) (p = 0.013). These findings remained significant in the fully adjusted model. CONCLUSIONS: The current study shows an association between depressive symptoms and higher AGE levels. The association is likely part of a multi-factorial effect, and hence no directionality, causality, or effect can be inferred solely based on the results of this study.

Higher carotid-radial pulse wave velocity is associated with non-melancholic depressive symptoms in men - findings from Helsinki Birth Cohort Study.

BACKGROUND: Depression and cardiovascular disease (CVD) are major causes of global disease burden that are interrelated through mostly unknown mechanisms. We studied the relationship of melancholic and non-melancholic depressive symptoms with arterial stiffness, an important underlying mechanism of CVD. METHODS: The Helsinki Birth Cohort Study recruited 683 previously extensively phenotyped subjects for this sub-study. Cross-sectional data along with responses regarding depressive symptoms were obtained for each participant. For evaluation of depressive symptoms, the Beck Depression Inventory (BDI)and subscales were used to measure melancholic and non-melancholic depressive symptoms. Arterial stiffness was assessed as pulse wave velocity (PWV) that was measured between the carotid and radial artery, and carotid and femoral artery. RESULTS: Of the participants, 532 scored <10 on the BDI and were classified as not having depressive symptoms. Of the 151 participants that scored ≥10 on the BDI, 122 were classified as having non-melancholic depressive symptoms and 29 as having melancholic depressive symptoms. Men had higher carotid-radial PWV (crPWV) values than women (p < .001). A positive relationship between BDI scores and crPWV (p < .001) was found in men. We also found higher crPWV in men with non-melancholic depressive symptoms compared to all others. No such differences were found in women. DISCUSSION: Arterial stiffness has a relationship with depressive symptoms and subtypes of depressive symptoms, at least in men. There is a significant relationship between higher PWV and non-melancholic depressive symptoms in men. Due to the intricate nature of the disease causality or directionality is impossible to infer solely based on this study. Further studies into the subtypes of depressive symptoms may be of benefit to understanding depression.KEY MESSAGESIt is known that arterial stiffness contributes to cardiovascular disease, and is associated with depression.Higher Beck Depression Inventory scores are associated with higher carotid-radial pulse wave velocity in men.Non-melancholic depressive symptoms are associated with higher carotid-radial pulse wave velocity in men.

Glucose regulation and pain in older people-The Helsinki Birth Cohort Study.

AIMS: To assess if individuals with diabetes or prediabetes report more pain or have increased use of pain medication compared to normoglycaemic individuals. METHODS: Using cross-sectional data, we studied 928 men and 1075 women from the Helsinki Birth Cohort Study in 2001-2004 at a mean age of 61.5 years. Glucose regulation was assessed with a 2-h 75 g oral glucose tolerance test, and applying World Health Organization criteria, participants were defined as having normoglycaemia, prediabetes (impaired fasting glucose or impaired glucose tolerance), newly diagnosed diabetes or previously diagnosed diabetes. Self-reported pain intensity and interference during the previous 4 weeks was estimated using the RAND 36-Item Health Survey 1.0. Information on use of pain medication during the past 12 months was obtained from the Social Insurance Institution of Finland. RESULTS: There was no difference in pain intensity or interference between glucose regulation groups for neither men nor women after adjusting for covariates (age, body mass index, education years, Beck Depression Inventory and physical activity). In addition, use of pain medication was similar between glucose regulation groups. CONCLUSIONS: Although pain is a common symptom in the general population, impairments in glucose regulation alone does not seem to increase pain among older individuals.

Glucose regulation and grip strength in adults: Findings from the Helsinki Birth Cohort Study.

AIM: This study aimed to assess the association between grip strength and glucose regulation in a cross-sectional setting. METHODS: Using data from the Helsinki Birth Cohort Study, 924 men and 953 women were studied at a mean age of 61.6 years. Grip strength was assessed in the dominant hand using a Newtest Grip Force dynamometer. A standard 2-h 75 g oral glucose tolerance test (OGTT) was used to define glucose regulation. The participants were classified into four groups: normoglycaemia, prediabetes (impaired fasting glucose or impaired glucose tolerance), newly diagnosed diabetes and previously known diabetes. The association between grip strength and glucose regulation was assessed using multiple linear regression models. RESULTS: Prediabetes was diagnosed in 32.2% and diabetes in 8.4% using the OGTT. A total of 7.8% of the individuals had previously known diabetes. Compared to individuals with normoglycaemia, grip strength was lower for those with newly diagnosed diabetes (-1.8 kg, 95% CI -3.2 to -0.5) as well as those with previously known diabetes (-1.8 kg, 95% CI -3.2 to -0.4) after adjusting for covariates (age, sex, body mass index, physical activity, education and smoking). No difference in grip strength was found when comparing those with prediabetes and normoglycaemia. CONCLUSION: In adults, grip strength was lower among those with known and newly diagnosed diabetes compared to those with normoglycaemia. Together with previous findings on associations between grip strength and chronic diseases, these results support the use of grip strength as an overall health marker in adults.

Maternal body mass index, change in weight status from childhood to late adulthood and physical activity in older age.

This study aimed to examine the longitudinal associations of maternal body mass index (BMI), weight status in childhood and late adulthood and device-measured total physical activity (TPA) in older age. The study involves 552 participants from Helsinki Birth Cohort Study who were born in Helsinki, Finland, in 1934-1944. TPA was measured with a multisensory body monitor at a mean age of 70 years and expressed in metabolic equivalent of task hours/day (METh/d). Childhood overweight (BMI > 85th percentile) was based on school health records at 6-7 years of age, and late adulthood overweight (BMI ≥ 25 kg/m2 ) was based on clinical measurements at the mean age of 61 years. Childhood overweight was associated with lower TPA, particularly in older women (mean difference -3.2 METh/d, 95% confidence interval (CI) -4.6 - -1.9), and late adulthood overweight was associated with lower TPA both in older women (mean difference -6.2, 95% CI (-7.2 - -5.1) and in older men (mean difference -2.6 METh/d, 95% CI -3.7 - -1.5). TPA in older age was highest in participants who were normal weight both in childhood and adulthood and lowest in participants who were overweight in childhood and adulthood. In participants with childhood overweight, TPA was lower in participants who were overweight both in childhood and adulthood compared to those who were overweight only in childhood. There was a U-shaped distribution of TPA according to maternal BMI in older women (P = .002), but not in older men. In conclusion, reaching normal weight after childhood predicted higher physical activity levels in older age.

Body composition and changes in health-related quality of life in older age: a 10-year follow-up of the Helsinki Birth Cohort Study.

PURPOSE: Most studies examining the associations between body composition and health-related quality of life (HRQoL) in older age have been cross-sectional and analyzed only fat or lean mass. Hence, it is poorly known whether fat and lean mass are independently associated with subsequent changes in HRQoL. We investigated whether baseline lean and fat mass are associated with changes in HRQoL over a 10-year period in older adults. METHODS: We studied 1044 men and women from the Helsinki Birth Cohort Study (age 57-70 years at baseline). Bioelectrical impedance analysis was used to derive baseline fat mass index (FMI, fat mass/height2) and lean mass index (lean mass/height2), dichotomized at sex-specific medians. HRQoL was assessed using RAND 36-item Health Survey at baseline and follow-up 10 years later. RESULTS: When controlled for lean mass and adjusted for potential confounders, high baseline FMI was associated with a greater decline in general health (standardized regression coefficient [ß] = - 0.13, p = 0.001), physical functioning (ß = - 0.11, p = 0.002), role physical (ß = - 0.13, p = 0.003), vitality (ß = - 0.08, p = 0.027), role emotional (ß = - 0.12, p = 0.007), and physical component score (ß = - 0.14, p < 0.001). High baseline FMI was also associated with low HRQoL in all physical domains at baseline (ß: from - 0.38 to - 0.10). Lean mass was not strongly associated with HRQoL at baseline or change in HRQoL. CONCLUSION: In older community-dwelling adults, higher fat mass is, independent of lean mass, associated with lower physical HRQoL and greater decline in HRQoL. Prevention of adiposity may contribute to preservation of a good quality of life in older age.

Physical Activity and Telomeres in Old Age: A Longitudinal 10-Year Follow-Up Study.

BACKGROUND: Telomeres are crucial parts of chromosomes that protect the genome. They shorten every time the cell replicates, and shorter telomeres have been associated with increasing age and with many health behaviours. There is inconclusive evidence on the association between physical activity (PA) and telomere length. OBJECTIVES: To examine how leisure-time PA (LTPA) is associated with telomere length and telomere attrition during 10 years of follow-up in elderly people. DESIGN: This study is a 10-year prospective follow-up study. METHOD: For this prospective study, we examined 1,014 subjects (mean age at baseline 60.8 years) from the Helsinki Birth Cohort Study (HBCS). Relative leukocyte telomere length (LTL) was measured with a quantitative real-time PCR and LTPA with a validated questionnaire. Multiple linear regression analyses were used to assess the association between sex-specific LTPA quartiles and LTL at baseline and change in LTL over 10 years. The analyses were adjusted for age, educational attainment, smoking, body fat percentage, oestrogen exposure in women and for follow-up time when applicable. RESULTS: At baseline, volume of LTPA was not associated with LTL in men (p = 0.66) or in women (p = 0.33). Among women, however, higher volume of LTPA at baseline was associated with greater shortening of LTL (p for linearity 0.040) during the 10-year follow-up. No association was found among men (p for linearity 0.75). CONCLUSIONS: Our findings suggest that PA has a sex-specific role in regulation of telomere length in the aging process as in our study a high volume of LTPA in elderly women, but not in men, was associated with more rapid telomere attrition.

Associations of Fat and Lean Body Mass with Circulating Amino Acids in Older Men and Women.

Circulating amino acids are potential markers of body composition. Previous studies are mainly limited to middle age and focus on either fat or lean mass, thereby ignoring overall body composition. We investigated the associations of fat and lean body mass with circulating amino acids in older men and women. We studied 594 women and 476 men from the Helsinki Birth Cohort Study (age 62-74 years). Bioelectrical impedance analysis was used to indicate two main body compartments by fat (fat mass/height2) and lean mass indices (lean mass/height2), dichotomized based on sex-specific medians. Eight serum amino acids were quantified using nuclear magnetic resonance spectroscopy. General linear models were adjusted for age, smoking, and fasting glucose. Higher lean mass index (LMI) was associated with higher concentrations of branched-chain amino acids in both sexes (p ≤ .001). In men, LMI was also positively associated with tyrosine (p = .006) and inversely with glycine (p < .001). Higher fat mass index was associated with higher concentrations of all branched-chain amino acids, aromatic amino acids (phenylalanine and tyrosine), and alanine in both sexes (p ≤ .008). Associations between body composition and amino acids are largely similar in older men and women. The associations are largely similar to those previously observed in younger adults.

The impact of maternal weight in pregnancy on glucose metabolism in non-diabetic offspring in late adulthood.

AIMS: We aimed to examine the association between maternal adiposity and glucose metabolism in adult offspring without diabetes, simultaneous taking offspring own adiposity into account. METHODS: This longitudinal birth cohort study (Helsinki Birth Cohort Study) included 1,440 non-diabetic subjects examined at a mean age of 62 years. Subjects were divided into quartiles according to maternal body mass index (BMI). The impact of maternal BMI on offspring body composition was also studied. RESULTS: There were no differences in fasting glucose between the groups. In men, maternal BMI was inversely associated with mean 2-hour glucose concentration after a 75 g oral glucose tolerance test (p < 0.001) and mean homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.049). According to the subjects' own BMI, high maternal BMI was associated with lower 2-hour glucose concentrations only in non-obese men and with lower HOMA-IR only in obese men. Maternal BMI was not associated with glucose concentrations nor with HOMA-IR in women. In addition, maternal BMI was positively associated with a higher offspring lean body mass in men. CONCLUSIONS: High maternal BMI was associated with lower 2-hour plasma glucose concentration, especially in non-obese men. Offspring lean body mass may be a mediating factor for the association.

Telomere length and physical performance among older people-The Helsinki Birth Cohort Study.

Telomere length has been suggested a biomarker of aging and is associated with several chronic diseases. However, the association between telomere length and physical performance is not well known. Using both cross-sectional and longitudinal data, we studied 582 women and 453 men from the Helsinki Birth Cohort Study at two time-points; a baseline examination in 2001-2004 at a mean age of 61 years and a follow-up examination approximately 10 years later in 2011-2013. Telomere length was measured both at baseline and at follow-up using real-time quantitative polymerase chain reaction. Physical performance was evaluated only at follow-up using the Senior Fitness Test (SFT), which assesses strength, flexibility and endurance. In women, shorter telomere length at follow-up (p = 0.044) and greater telomere attrition during follow-up time (p = 0.022) were associated with poorer physical performance after adjusting for covariates (age at baseline, smoking status, body mass index at baseline, follow-up time and educational attainment). No similar associations were found for men. This indicates that, at least in women, telomere length could potentially be used as a biomarker for physical performance, however, more longitudinal studies are needed to confirm this association.

Change in physical activity and health-related quality of life in old age-A 10-year follow-up study.

The aim of the study was to examine the association between change in leisure-time physical activity (LTPA) and change in health-related quality of life (HRQoL) and symptoms of depression during a 10-year follow-up. This prospective study included 1036 men and women (mean age at baseline = 61.2 years) from the Helsinki Birth Cohort Study. Leisure-time physical activity was measured with a questionnaire, HRQoL with SF36 and depression symptoms with Beck's depression inventory (BDI). The association between the change in LTPA and change in HRQoL and BDI were investigated with sex-stratified general linear models adjusted for age, smoking, educational attainment, comorbidity score, and baseline value of outcomes. One standard deviation (SD) increase in LTPA was associated with increase in physical summary component of HRQoL in women (B = 0.7 unit, 95% CI = 0.1-1.3, P = 0.032) and in men (B = 0.8 unit, 95% CI = 0.2-1.5, P = 0.014). In women, the 1SD increase in LTPA was also associated with an increase in mental summary component score (B = 1.0, 95% CI = 0.3-1.7, P = 0.005) and a reduction in depressive symptoms (B = -0.7, 95% CI = -1.1 to -0.2, P = 0.003). In conclusion, increase in the volume of LTPA over a 10-year period in late adulthood was associated with improved HRQoL in both men and women, and also diminished depressive symptoms in women. The findings support the promotion of physical activity in later years to enhance HRQoL and mental well-being.