How Does the Experience of Loneliness Change Across the Adult Life Span? An Examination of Age-Related Changes in the Level, Antecedents and Consequences of Loneliness

Loneliness is defined as the feeling that one’s social relationships are deficient in some important way, either quantitatively or qualitatively. Results from previous research suggest that loneliness is both a consequence and an antecedent of social relationships and relationship goals. It is still an open question, however, to what extent the experience of loneliness remains stable as people grow older. The aim of the present dissertation is to combine previous research on loneliness and adult development by examining how the average level, social antecedents and social consequences of loneliness change with increasing age. Specifically, I address three major research questions in this dissertation (1) Does the average level of loneliness change between midlife and old age?; (2) Do the social antecedents of loneliness change with age?; and (3) Do the socio-motivational consequences of loneliness change with age? To answer research questions 1 and 2 I used data from the German Ageing Survey (DEAS), a cohort-sequential and nationally representative study of community-dwelling adults in the second half of life (40 years and older) living in Germany. To analyze the socio-motivational consequences of loneliness (research question 3) I used data from a diary study and two experimental studies with young, middle-aged and older adults in Germany. The results of this dissertation show that the average level of loneliness remains relatively stable between midlife and old age. Moreover, the findings suggest that age-related changes in emotional qualities of the social network include both gains (e.g. a reduced number of distressing relationships) and losses (e.g. a reduced satisfaction with friendships). While poor emotional quality of social relationships was equally predictive of loneliness between midlife and old age, the absence of a romantic partner appeared to be less straining and less relevant as an antecedent of loneliness as people grew older. The results regarding the socio-motivational consequences of loneliness indicate that a temporarily heightened level of loneliness may amplify people’s motivation to avoid negative social experiences. There was no indication that the immediate socio-motivational consequences of loneliness differ between young, middle-aged and older adults. Taken together, the findings of this dissertation suggest that age-related stability in loneliness from midlife into old age may reflect changed relationship goals rather than improved relationship quality. Moreover, the results provide first evidence suggesting that the immediate socio-motivational consequences of loneliness may be relatively stable across the adult life span. Further studies are needed to understand how both stable inter-individual differences and intra-individual changes in a person’s relationship goals contribute to the development of loneliness across the adult life span. Specifically, it is an important open question to what extent a flexible adaption of relationship goals may be both beneficial and damaging to a person’s social well-being. It can be concluded that both researchers and practitioners dealing with loneliness should pay greater attention to the opportunity that factors in the emergence and maintenance of loneliness may vary over persons and time

Wahlverwandtschaften: Sind Freundschaften für die soziale Integration wichtiger geworden?

Im Jahr 2014 haben die 40- bis 85-Jährigen mehr Personen in ihrem engen Netzwerk als im Jahr 1996. Mehr Menschen haben im Jahr 2014 Freundinnen oder Freunde im engen Netzwerk als 1996 - diese können auch von mehr Menschen um Rat oder Trost gefragt werden. Altersunterschiede in der emotionalen Unterstützung durch Freundinnen oder Freunde sind im Jahr 2014 größer als noch im Jahr 1996. Altersunterschiede bei Freizeitaktivitäten mit Freundinnen oder Freunden werden zwischen 1996 und 2014 geringer. Bildungsunterschiede bei Freizeitaktivitäten mit Freundinnen und Freunden nehmen zwischen 1996 und 2014 zu

Validation of T-Track® CMV to assess the functionality of cytomegalovirus-reactive cell-mediated immunity in hemodialysis patients

Background: Uncontrolled cytomegalovirus (CMV) replication in immunocompromised solid-organ transplant recipients is a clinically relevant issue and an indication of impaired CMV-specific cell-mediated immunity (CMI). Primary aim of this study was to assess the suitability of the immune monitoring tool T-Track (R) CMV to determine CMV-reactive CMI in a cohort of hemodialysis patients representative of patients eligible for renal transplantation. Positive and negative agreement of T-Track (R) CMV with CMV serology was examined in 124 hemodialysis patients, of whom 67 (54%) revealed a positive CMV serostatus. Secondary aim of the study was to evaluate T-Track (R) CMV performance against two unrelated CMV-specific CMI monitoring assays, QuantiFERON (R)-CMV and a cocktail of six class I iTAg (TM) MHC Tetramers. Results: Positive T-Track (R) CMV results were obtained in 90% (60/67) of CMV-seropositive hemodialysis patients. In comparison, 73% (45/62) and 77% (40/52) positive agreement with CMV serology was achieved using QuantiFERON (R)-CMV and iTAg (TM) MHC Tetramer. Positive T-Track (R) CMV responses in CMV-seropositive patients were dominated by pp65-reactive cells (58/67 [ 87%]), while IE-1-responsive cells contributed to an improved (87% to 90%) positive agreement of T-Track (R) CMV with CMV serology. Interestingly, T-Track (R) CMV, QuantiFERON (R)-CMV and iTAg (TM) MHC Tetramers showed 79% (45/57), 87% (48/55) and 93% (42/45) negative agreement with serology, respectively, and a strong inter-assay variability. Notably, T-Track (R) CMV was able to detect IE-1-reactive cells in blood samples of patients with a negative CMV serology, suggesting either a previous exposure to CMV that yielded a cellular but no humoral immune response, or TCR cross-reactivity with foreign antigens, both suggesting a possible protective immunity against CMV in these patients. Conclusion: T-Track (R) CMV is a highly sensitive assay, enabling the functional assessment of CMV-responsive cells in hemodialysis patients prior to renal transplantation. T-Track (R) CMV thus represents a valuable immune monitoring tool to identify candidate transplant recipients potentially at increased risk for CMV-related clinical complications

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention