Sex differences in mental health among older adults: investigating time trends and possible risk groups with regard to age, educational level and ethnicity

Objectives: Older women report lower mental health compared to men, yet little is known about the nature of this sex difference. Therefore, this study investigates time trends and possible risk groups. Method: Data from the Doetinchem Cohort Study (DCS) and the Longitudinal Aging Study Amsterdam (LASA) were used. General mental health was assessed every 5 years, from 1995 to 1998 onwards (DCS, n = 1412, 20-year follow-up, baseline age 55–64 years). Depressive and anxiety symptoms were assessed for two birth cohorts, from 1992/1993 onwards (LASA cohort 1, n = 967, 24-year follow-up, age 55-65 years,) and 2002/2003 onwards (LASA cohort 2, n = 1002, 12-year follow-up, age 55–65 years) with follow-up measurements every 3–4 years. Results: Mixed model analyses showed that older women had a worse general mental health (−6.95; −8.36 to 5.53; range 0–100, ∼10% lower), more depressive symptoms (2.09; 1.53–2.63; range 0-60, ∼30% more) and more anxiety symptoms (0.86; 0.54–1.18; range 0–11, ∼30% more) compared to men. These sex differences remained stable until the age of 75 years, where after they decreased due to an accelerated decline in mental health for men compared to women. Sex differences and their course by age were consistent over successive birth cohorts, educational levels and ethnic groups (Caucasian vs. Turkish/Moroccan). Conclusion: There is a consistent female disadvantage in mental health across different sociodemographic groups and over decennia (1992 vs. 2002) with no specific risk groups

Homeostatic Imbalance between Apoptosis and Cell Renewal in the Liver of Premature Aging XpdTTD Mice

Unrepaired or misrepaired DNA damage has been implicated as a causal factor in cancer and aging. XpdTTD mice, harboring defects in nucleotide excision repair and transcription due to a mutation in the Xpd gene (R722W), display severe symptoms of premature aging but have a reduced incidence of cancer. To gain further insight into the molecular basis of the mutant-specific manifestation of age-related phenotypes, we used comparative microarray analysis of young and old female livers to discover gene expression signatures distinguishing XpdTTD mice from their age-matched wild type controls. We found a transcription signature of increased apoptosis in the XpdTTD mice, which was confirmed by in situ immunohistochemical analysis and found to be accompanied by increased proliferation. However, apoptosis rate exceeded the rate of proliferation, resulting in homeostatic imbalance. Interestingly, a metabolic response signature was observed involving decreased energy metabolism and reduced IGF-1 signaling, a major modulator of life span. We conclude that while the increased apoptotic response to endogenous DNA damage contributes to the accelerated aging phenotypes and the reduced cancer incidence observed in the XpdTTD mice, the signature of reduced energy metabolism is likely to reflect a compensatory adjustment to limit the increased genotoxic stress in these mutants. These results support a general model for premature aging in DNA repair deficient mice based on cellular responses to DNA damage that impair normal tissue homeostasis

Checklists for Applicants submitting dossiers on Cosmetic Ingredients to be evaluated by the SCCS

Checklists for Applicants submitting dossiers on Cosmetic Ingredients to be evaluated by the SCCSThe SCCS adopted these Checklists on 07 March 2017Checklists for Applicants submitting dossiers on Cosmetic Ingredients to be evaluated by the SCCSThe SCCS adopted these Checklists on 07 March 201

Cross-sectional analysis of baseline differences of candidates for rotator cuff surgery: a sex and gender perspective

<p>Abstract</p> <p>Background</p> <p>The word "sex" refers to biological differences between men and women. Gender refers to roles, behaviors, activities, and attributes that a given society considers appropriate for men and women. Traditionally, treatment decisions have been based on patient's sex without including the gender. Assessment of disability secondary to musculoskeletal problems would not be complete or accurate unless potentially relevant biological and non-biological aspects of being a man or woman are taken into consideration. The purposes of this study were to: 1) investigate the difference in pre-operative characteristics between men and women who were candidates for rotator cuff surgery; and, 2) assess the relationship between level of disability and factors that represent sex and factors that signify gender.</p> <p>Method</p> <p>This was a cross-sectional study. The primary outcome measure of disability was a disease-specific outcome measure, the Western Ontario Rotator Cuff (WORC) index, and independent variables were sex, age, hand dominance, shoulder side involvement, BMI, co-morbidity, medication use, work status, smoking habits, strength, range of motion, level of pathology, concurrent osteoarthritis, expectations for recovery, and participation restriction. Parametric, non-parametric, univariable, subgroup, and multivariable analyses were conducted.</p> <p>Results</p> <p>One hundred and seventy patients were included in the study. The mean age was 57 ± 11, 85 were females. Women reported higher levels of disability despite similar or lower levels of pathology. Scores of the WORC were strongly influenced by factors that represented "gender" such as participation restriction (F = 28.91, p < 0.0001) and expectations for improved activities of daily living (F = 5.80, p = 0.004). Painfree combined range of motion, which represented an interaction between "sex" and "gender" was also associated with disability after being adjusted for all other relevant baseline factors (F = 25.82, p < 0.0001).</p> <p>Conclusion</p> <p>Gender-related factors such as expectations and participation limitations have an independent impact on disability in men and women undergoing rotator cuff related surgery.</p

The sex difference in gait speed among older adults: how do sociodemographic, lifestyle, social and health determinants contribute?

Background: This study explores whether a sex difference in sensitivity to (strength of the association) and/or in exposure to (prevalence) determinants of gait speed contributes to the observed lower gait speed among older women compared to men. Methods: Data from the Longitudinal Aging Study Amsterdam (LASA) were used. In total 2407 men and women aged 55–81 years were included, with baseline measurements in 1992/2002 and follow-up measurements every 3–4 years for 15/25 years. Multivariable mixed model analysis was used to investigate sex differences in sensitivity (interaction term with sex) and in exposure to (change of the sex difference when adjusted) socio-demographic, lifestyle, social and health determinants of gait speed. Results: Women had a 0.054 m/s (95 % CI: 0.076 − 0.033, adjusted for height and age) lower mean gait speed compared to men. In general, men and women had similar determinants of gait speed. However, higher BMI and lower physical activity were more strongly associated with lower gait speed in women compared to men (i.e. higher sensitivity). More often having a lower educational level, living alone and having more chronic diseases, pain and depressive symptoms among women compared to men also contributed to observed lower gait speed in women (i.e. higher exposure). In contrast, men more often being a smoker, having a lower physical activity and a smaller personal network size compared to women contributed to a lower gait speed among men (i.e. higher exposure). Conclusions: Both a higher sensitivity and higher exposure to determinants of gait speed among women compared to men contributes to the observed lower gait speed among older women. The identified (modifiable) contributing factors should be taken into account when developing prevention and/or treatment strategies aimed to enhance healthy physical aging. This might require a sex-specific approach in both research and clinical practice, which is currently often lacking

Impaired Genome Maintenance Suppresses the Growth Hormone–Insulin-Like Growth Factor 1 Axis in Mice with Cockayne Syndrome

Cockayne syndrome (CS) is a photosensitive, DNA repair disorder associated with progeria that is caused by a defect in the transcription-coupled repair subpathway of nucleotide excision repair (NER). Here, complete inactivation of NER in Csb(m/m)/Xpa(−/−) mutants causes a phenotype that reliably mimics the human progeroid CS syndrome. Newborn Csb(m/m)/Xpa(−/−) mice display attenuated growth, progressive neurological dysfunction, retinal degeneration, cachexia, kyphosis, and die before weaning. Mouse liver transcriptome analysis and several physiological endpoints revealed systemic suppression of the growth hormone/insulin-like growth factor 1 (GH/IGF1) somatotroph axis and oxidative metabolism, increased antioxidant responses, and hypoglycemia together with hepatic glycogen and fat accumulation. Broad genome-wide parallels between Csb(m/m)/Xpa(−/−) and naturally aged mouse liver transcriptomes suggested that these changes are intrinsic to natural ageing and the DNA repair–deficient mice. Importantly, wild-type mice exposed to a low dose of chronic genotoxic stress recapitulated this response, thereby pointing to a novel link between genome instability and the age-related decline of the somatotroph axis

Tissue specific mutagenic and carcinogenic responses in NER defective mouse models.

Several mouse models with defects in genes encoding components of the nucleotide excision repair (NER) pathway have been developed. In NER two different sub-pathways are known, i.e. transcription-coupled repair (TC-NER) and global-genome repair (GG-NER). A defect in one particular NER protein can lead to a (partial) defect in GG-NER, TC-NER or both. GG-NER defects in mice predispose to cancer, both spontaneous as well as UV-induced. As such these models (Xpa, Xpc and Xpe) recapitulate the human xeroderma pigmentosum (XP) syndrome. Defects in TC-NER in humans are associated with Cockayne syndrome (CS), a disease not linked to tumor development. Mice with TC-NER defects (Csa and Csb) are - except for the skin - not susceptible to develop (carcinogen-induced) tumors. Some NER factors, i.e. XPB, XPD, XPF, XPG and ERCC1 have functions outside NER, like transcription initiation and inter-strand crosslink repair. Deficiencies in these processes in mice lead to very severe phenotypes, like trichothiodystrophy (TTD) or a combination of XP and CS. In most cases these animals have a (very) short life span, display segmental progeria, but do not develop tumors. Here we will overview the available NER-related mouse models and will discuss their phenotypes in terms of (chemical-induced) tissue-specific tumor development, mutagenesis and premature aging features

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies