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.

Resistance Training Increases White Matter Density in Frail Elderly Women.

We aimed to investigate the effects of maternal obesity on brain structure and metabolism in frail women, and their reversibility in response to exercise. We recruited 37 frail elderly women (20 offspring of lean/normal-weight mothers (OLM) and 17 offspring of obese/overweight mothers (OOM)) and nine non-frail controls to undergo magnetic resonance and diffusion tensor imaging (DTI), positron emission tomography with Fluorine-18-fluorodeoxyglucose (PET), and cognitive function tests (CERAD). Frail women were studied before and after a 4-month resistance training, and controls were studied once. White matter (WM) density (voxel-based morphometry) was higher in OLM than in OOM subjects. Exercise increased WM density in both OLM and OOM in the cerebellum in superior parietal regions in OLM and in cuneal and precuneal regions in OOM. OLM gained more WM density than OOM in response to intervention. No significant results were found from the Freesurfer analysis, nor from PET or DTI images. Exercise has an impact on brain morphology and cognition in elderly frail women.

Tannin-Based Microbicidal Coatings for Hospital Privacy Curtains.

The goal of this study was to develop a sustainable, tannin-based option for silver-based and other current antimicrobial solutions for hospital privacy curtains. Commercial tree-derived tannins were characterized and their in vitro antibacterial properties against Staphylococcus aureus and Escherichia coli were determined. Hydrolysable tannins showed greater antibacterial efficacy than condensed tannins but differences in antibacterial efficacy between any of the tannins could not be attributed to their functional group content or molar mass. Outer membrane disruption was not a significant factor in antibacterial efficacy of tannins against E. coli. In a hospital field study, draw patches coated with hydrolysable tannins and affixed to privacy curtains reduced total bacteria count by 60% over eight weeks compared to their matching uncoated reference sides. In a follow-up laboratory study with S. aureus, very light spraying with water improved contact between bacteria and coating, enhancing the antibacterial effect by several orders of magnitude.

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.

Early-Life Factors as Predictors of Age-Associated Deficit Accumulation Across 17 Years From Midlife Into Old Age.

BACKGROUND: Early-life exposures have been associated with the risk of frailty in old age. We investigated whether early-life exposures predict the level and rate of change in a frailty index (FI) from midlife into old age. METHODS: A linear mixed model analysis was performed using data from 3 measurement occasions over 17 years in participants from the Helsinki Birth Cohort Study (n = 2 000) aged 57-84 years. A 41-item FI was calculated on each occasion. Information on birth size, maternal body mass index (BMI), growth in infancy and childhood, childhood socioeconomic status (SES), and early-life stress (wartime separation from both parents) was obtained from registers and health care records. RESULTS: At age 57 years the mean FI level was 0.186 and the FI levels increased by 0.34%/year from midlife into old age. Larger body size at birth associated with a slower increase in FI levels from midlife into old age. Per 1 kg greater birth weight the increase in FI levels per year was -0.087 percentage points slower (95% confidence interval = -0.163, -0.011; p = 0.026). Higher maternal BMI was associated with a higher offspring FI level in midlife and a slower increase in FI levels into old age. Larger size, faster growth from infancy to childhood, and low SES in childhood were all associated with a lower FI level in midlife but not with its rate of change. CONCLUSIONS: Early-life factors seem to contribute to disparities in frailty from midlife into old age. Early-life factors may identify groups that could benefit from frailty prevention, optimally initiated early in life.

Sphingolipids accumulate in aged muscle, and their reduction counteracts sarcopenia.

Age-related muscle dysfunction and sarcopenia are major causes of physical incapacitation in older adults and currently lack viable treatment strategies. Here we find that sphingolipids accumulate in mouse skeletal muscle upon aging and that both genetic and pharmacological inhibition of sphingolipid synthesis prevent age-related decline in muscle mass while enhancing strength and exercise capacity. Inhibition of sphingolipid synthesis confers increased myogenic potential and promotes protein synthesis. Within the sphingolipid pathway, we show that accumulation of dihydroceramides is the culprit disturbing myofibrillar homeostasis. The relevance of sphingolipid pathways in human aging is demonstrated in two cohorts, the UK Biobank and Helsinki Birth Cohort Study in which gene expression-reducing variants of SPTLC1 and DEGS1 are associated with improved and reduced fitness of older individuals, respectively. These findings identify sphingolipid synthesis inhibition as an attractive therapeutic strategy for age-related sarcopenia and co-occurring pathologies.

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 exercise-induced long noncoding RNA CYTOR promotes fast-twitch myogenesis in aging.

Skeletal muscle displays remarkable plasticity upon exercise and is also one of the organs most affected by aging. Despite robust evidence that aging is associated with loss of fast-twitch (type II) muscle fibers, the underlying mechanisms remain to be elucidated. Here, we identified an exercise-induced long noncoding RNA, CYTOR, whose exercise responsiveness was conserved in human and rodents. Cytor overexpression in mouse myogenic progenitor cells enhanced myogenic differentiation by promoting fast-twitch cell fate, whereas Cytor knockdown deteriorated expression of mature type II myotubes. Skeletal muscle Cytor expression was reduced upon mouse aging, and Cytor expression in young mice was required to maintain proper muscle morphology and function. In aged mice, rescuing endogenous Cytor expression using adeno-associated virus serotype 9 delivery of CRISPRa reversed the age-related decrease in type II fibers and improved muscle mass and function. In humans, CYTOR expression correlated with type II isoform expression and was decreased in aged myoblasts. Increased CYTOR expression, mediated by a causal cis­expression quantitative trait locus located within a CYTOR skeletal muscle enhancer element, was associated with improved 6-min walk performance in aged individuals from the Helsinki Birth Cohort Study. Direct CYTOR overexpression using CRISPRa in aged human donor myoblasts enhanced expression of type II myosin isoforms. Mechanistically, Cytor reduced chromatin accessibility and occupancy at binding motifs of the transcription factor Tead1 by binding, and hence sequestering, Tead1. In conclusion, the long noncoding RNA Cytor was found to be a regulator of fast-twitch myogenesis in aging.

Mental, Physical and Social Functioning in Independently Living Senior House Residents and Community-Dwelling Older Adults.

Senior houses provide social interaction and support, potentially supporting older people's physical and mental functioning. Few studies have investigated functioning of senior house residents. The aim was to compare functioning between senior house residents and community-dwelling older adults in Finland. We compared senior house residents (n = 336, 69% women, mean age 83 years) to community-dwelling older adults (n = 1139, 56% women, mean age 74 years). Physical and mental functioning were assessed using the SF 36-Item Health Survey. Loneliness and frequency of social contacts were self-reported. The analyses were adjusted for age, socioeconomic factors and diseases. Physical functioning was lower among men in senior houses compared to community-dwelling men (mean 41.1 vs. 46.4, p = 0.003). Mental functioning or the frequency of social contacts did not differ between type of residence in either sex. Loneliness was higher among women in senior houses compared to community-dwelling women (OR = 1.67, p = 0.027). This was not observed in men. Results suggest that women in senior houses had similar physical and mental functioning compared to community-dwelling women. Male senior house residents had poorer physical functioning compared to community-dwelling men. Women living in senior houses were lonelier than community-dwelling women despite the social environment.

The relationship between health-related quality of life and melancholic depressive symptoms is modified by brain insulin receptor gene network.

To investigate whether expression-based polygenic risk scores for the insulin receptor gene network (ePRS-IRs) modifiy the association between type of depressive symptoms and health-related quality of life (HRQoL). This cross-sectional study includes 1558 individuals from the Helsinki Birth Cohort Study. Between 2001 and 2004, the Short Form-36 questionnaire was employed to assess mental and physical components of HRQoL and Beck Depression Inventory (BDI) to assess depressive symptoms. Depressive symptoms were categorized into minimal (BDI < 10), non-melancholic and melancholic types of depression. The ePRS-IRs were calculated for the hippocampal (hePRS-IR) and the mesocorticolimbic (mePRS-IR) regions of the brain. General linear regression models adjusted for age, sex, population stratification, lifestyle factors and body mass index were applied to analyze the data. Both types of depressive symptoms were associated with lower HRQoL (p < 0.0001). HePRS-IR modified the association between the types of depression and mental HRQoL (p for interaction = 0.005). Melancholic type of depressive symptoms was associated with higher mental HRQoL compared to the non-melancholic symptoms among individuals with low hePRS-IR (adjusted mean 4.1, 95% CI 0.7-7.4, p = 0.018). However, no such difference was evident in moderate or high hePRS-IR groups as higher hePRS-IR was associated with lower mental HRQoL (B = - 3.4, 95% CI - 5.6 to - 1.2) in individuals with melancholic type of depressive symptoms. No direct associations were detected between the ePRS-IRs and type of depressive symptoms or HRQoL. Variations in the glucose-insulin metabolism can lower HRQoL in individuals with melancholic depressive symptoms.

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.