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Introduction Immunosenescence, a decline in immune system function, has been linked to several age-related diseases and geriatric syndromes, including cardiovascular diseases and frailty. Very old adults (aged ≥85 years) live with multiple long-term conditions (MLTC) or multimorbidity—a complex phenomenon of poor health defined by either counts (≥2 diseases), indices, or patterns. However, little is known about the relationship between immunosenescence and MLTC in this age group. We utilised baseline data from the Newcastle 85+ Study to investigate the association between previously defined immunosenescence profilesa and MLTC. Method We used data from 703 participants who had multimorbidity and complete data for 16 chronic diseases and geriatric syndromes (i.e. analytic sample). MLTC counts were derived from the number of conditions and categorised into

A reduction in nicotinic receptor (nAChR) binding has previously been observed in putamen in Parkinson''s disease (PD) and dementia with Lewy bodies (DLB). The present study demonstrates no concommitant reduction in the expression of α2-α7, β2 and β3 nAChR subunit proteins. Alphasynuclein, which can interfere with membrane protein function and is a key constituent of PD and DLB pathology, was increased (insoluble fraction) in both disorders, although nAChR binding loss did not correlate with α-synuclein expression within patient groups. The results point to a possible abnormality of striatal nicotinic receptor assembly in PD and DLB. [Copyright &y& Elsevier]

Objectives - Comparisons were made of nicotinic receptors in 3 major forms of dementia in old age. Although it is well established the involvement of nicotinic receptors in Alzheimer's disease (AD), their status in the other two main causes of dementia in old age – dementia with Lewy bodies (DLB) and vascular dementia (VaD) is not widely reported. Methods – Temporal cortex was examined for epibatidine and α-bungarotoxin binding, and immunoreactivity of α4 and α7 nAChR subunits. Results – There were selective abnormalities in nicotinic receptor subtypes in the disorders examined. In AD there is a loss of high affinity receptor binding, reflecting a selective loss of α4 subunit, but no change in α7 subunits. Similar abnormalities in ligand binding are also apparent in DLB. In the VaD series, there was no overall loss of epibatidine binding or immunoreactivity for α4 or α7 subunits. Conclusions – Loss of cortical receptor α4 subunit appears to be a characteristic feature of neurodegenerative dementia but not dementia of vascular origin. Since nicotinic receptors control cerebral vasodilation, the relative integrity of the receptors in VaD may auger well for nicotinic therapy in this disorder in which there is a cholinergic abnormality, to judge by the loss of the presynaptic enzyme. [ABSTRACT FROM AUTHOR]

: The chromosome instability observed in peripheral blood lymphocytes in ulcerative colitis could be a biomarker of cancer susceptibility.: To determine whether accelerated telomere shortening could explain chromosome instability and assess the effect of drugs and smoking on telomere dynamics in these cells.: Peripheral blood lymphocytes were isolated from ulcerative colitis, Crohn's disease and non-inflammatory bowel disease control patients. Telomere lengths were measured by quantitative real-time polymerase chain reaction. After activation and cell separation, telomerase activity and human telomerase reverse transcriptase messenger ribonucleic acid were measured by telomerase repeat amplification protocol enzyme-linked immunosorbent serological assay and quantitative real-time polymerase chain reaction, respectively.: Age-related telomere loss in peripheral blood lymphocytes was similar in ulcerative colitis, Crohn's disease and control patients. Telomerase activity decreased with age in all groups and correlated positively with telomere length (r = 0.489,P =0.006). Among Crohn's disease patients, azathioprine was associated with decreased telomerase activity (0.66 vs. 1.54,P = 0.026,P < 0.05) and smoking was associated with decreased human telomerase reverse transcriptase mRNA expression (10.5 vs. 33.3,P =0.036,P < 0.05).: Telomere shortening is not accelerated and therefore cannot be the cause of the chromosome instability observed in ulcerative colitis peripheral blood lymphocytes. Azathioprine and cigarette smoking modify telomerase expression in these cells. [ABSTRACT FROM AUTHOR]

Summary: Data on vitamin D status in very old adults are lacking. The aim of this study was to assess 25-hydroxyvitamin D [25(OH)D] concentrations and its predictors in 775 adults aged 85 years old living in North-East England. Low 25(OH)D was alarmingly high during winter/spring months, but its biological significance is unknown. Introduction: Despite recent concerns about the high prevalence of vitamin D deficiency in much of the British adult and paediatric population, there is a dearth of data on vitamin D status and its predictors in very old adults. The objective of the present study was to describe vitamin D status and its associated factors in a broadly representative sample of very old men and women aged 85 years living in the North East of England (55° N). Methods: Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were analysed in 775 participants in the baseline phase of the Newcastle 85+ cohort study. Season of blood sampling, dietary, health, lifestyle and anthropometric data were collected and included as potential predictors of vitamin D status in ordinal regression models. Results: Median serum 25(OH)D concentrations were 27, 45, 43 and 33 nmol/L during spring, summer, autumn and winter, respectively. The prevalence of vitamin D deficiency according to North American Institute of Medicine guidelines [serum 25(OH)D <30 nmol/L] varied significantly with season with the highest prevalence observed in spring (51 %) and the lowest prevalence observed in autumn (23 %; P < 0.001). Reported median (inter-quartile range) dietary intakes of vitamin D were very low at 2.9 (1.2-3.3) μg/day. In multivariate ordinal regression models, non-users of either prescribed or non-prescribed vitamin D preparations and winter and spring blood sampling were associated with lower 25(OH)D concentrations. Dietary vitamin D intake, disability score and disease count were not independently associated with vitamin D status in the cohort. Conclusion: There is an alarming high prevalence of vitamin D deficiency (<30 nmol/L) in 85-year-olds living in North East England at all times of the year but particularly during winter and spring. Use of vitamin D containing preparations (both supplements and medications) appeared to be the strongest predictor of 25(OH)D concentrations in these very old adults. [ABSTRACT FROM AUTHOR]

Objective To investigate the associations between low and high concentrations of baseline serum 25-hydroxyvitamin D [25( OH)D] and all-cause mortality in very old (≥85 years) men and women over 6 years. Design, setting and subjects Prospective mortality data from 775 participants in the Newcastle 85+ Study were analysed for survival in relation to 25( OH)D (season-specific quartiles and predefined cut-off values) and sex using Cox proportional hazards models. The models were fitted to the entire and restricted (nonusers of vitamin D-containing supplements and medication) cohorts. Results For the entire cohort, mortality was higher in both the lowest and highest 25( OH)D season-specific quartiles [ SQ1: hazard ratio ( HR) 1.31, 95% confidence interval ( CI) 1.01-1.69, P = 0.04; SQ4: HR 1.44, 95% CI 1.12-1.85, P = 0.004] compared with the combined middle quartiles ( SQ2 + SQ3), after adjustment for sociodemographic factors. The increased risk for the highest quartile remained significant after further adjustment for lifestyle variables ( SQ4: HR 1.37, 95% CI 1.06-1.77, P = 0.02) and was seen only in women in sex-specific analyses. Similarly, in sensitivity analyses with predefined 25( OH)D cut-off values, the highest 25( OH)D concentration (≥75 nmol L−1) was associated with a 2.4-fold increased risk of mortality in women (restricted cohort) after adjusting for all covariates. Conclusion Low and high season-specific 25( OH)D quartiles were associated with increased risks of mortality over 6 years in the very old; this effect was particularly noticeable in women, including those who reported taking vitamin D-containing supplements/medication. [ABSTRACT FROM AUTHOR]

Background and purpose Studies investigating the association between 25-hydroxyvitamin D [25( OH) D] and cognition in the very old (85+) are lacking. Methods Cross-sectional (baseline) and prospective data (up to 3 years follow-up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini- Mental State Examination) and attention-specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season-specific 25( OH) D quartiles. Results Those in the lowest and highest season-specific 25( OH) D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06-2.60, P = 0.03; 1.62, 95% confidence interval 1.02-2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25( OH) D quartiles, compared with those in the middle quartiles, had overall slower (log-transformed) attention reaction times for Choice Reaction Time (lowest, β = 0.023, P = 0.01; highest, β = 0.021, P = 0.02), Digit Vigilance Task (lowest, β = 0.009, P = 0.05; highest, β = 0.01, P = 0.02) and Power of Attention (lowest, β = 0.017, P = 0.02; highest, β = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, β = 0.021, P = 0.02; highest, β = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non-users of vitamin D supplements/medication. Conclusion Low and high season-specific 25( OH) D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention-specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment. [ABSTRACT FROM AUTHOR]

Background: To test our hypothesis that eutopic secretory phase endometrium from women with endometriosis is similar to proliferative phase endometrium from fertile women without endometriosis, we explored the expression of regulators of cell fate across the menstrual cycle.Methods: Endometrial biopsies were taken from 73 women, comprising 38 women with surgically diagnosed active peritoneal endometriosis (Group 1) and 35 fertile women without endometriosis (Group 2). Nucleolin, proliferating cell nuclear antigen (PCNA), telomerase and histone gamma-H2AX expression was evaluated by immunohistochemistry and mean telomere length (TL) by quantitative PCR.Results: We have immunolocalized nucleolin and gamma-H2AX in the benign premenopausal endometrium for the first time. All markers were present in the proliferative phase endometrium of all women. In Group 2, during the secretory phase, proliferative markers declined with a paradoxical increase in stromal gamma-H2AX. Women in Group 1, however, showed a persistent immunoreactivity for the proliferative markers, while the staining for gamma-H2AX decreased in secretory endometrium (P < 0.05). This difference between groups was significant in both stroma and glands for nucleolin (P < 0.0001), PCNA (P < 0.01) and gamma-H2AX (P < 0.05) in the secretory phase. We showed a positive correlation between mean TL and nucleolin expression (glandular r = 0.37, P = 0.002; stromal r = 0.4, P = 0.001), telomerase immunoreactivity (glandular r = 0.33, P = 0.009; stromal r = 0.4, P = 0.001) and glandular PCNA (r = 0.35, P = 0.004), whereas a negative correlation was seen between mean TL and gamma-H2AX (r = -0.28, P = 0.04).Conclusions: These findings demonstrate that the state of replication seen in secretory phase endometrium from women with active peritoneal endometriosis is not a simple extension of the proliferative phase. [ABSTRACT FROM AUTHOR]

In order to assess whether markers of cell senescence are related to reproductive failure, the expression of telomerase and telomere length in endometrial biopsies from women with and without reproductive failure were assessed. This pilot study included 45 women of whom 10 had idiopathic recurrent loss of empty gestational sacs. 10 had idiopathic recurrent fetal loss (miscarriage following identification of fetal cardiac activity). 10 had recurrent implantation failure and 15 had two or more normal pregnancies (control group). An endometrial sample was collected during the window of implantation from each woman. The mean endometrial telomere length was determined by quantitative polymerase chain reaction. Telomerase expression was evaluated by immunohistochemistry. The endometria of the control group showed virtually no telomerase immunoreactivity during the window of implantation. However, the immunostaining for telomerase was significantly and differentially increased in various endometrial cellular compartments in women with recurrent reproductive failure (P < 0.05). There were no significant differences in mean telomere length between groups. These data provide a novel insight into the biological correlates of clinical types of recurrent reproductive failure and suggest that specific alterations in the regulation of endometrial cell fate are associated with different types of recurrent reproductive failure. [ABSTRACT FROM AUTHOR]