Vitamin D deficiency associations with metabolic, bone turnover and adverse general health markers in community free living adults

Background Although there is some evidence that vitamin D deficiency is highly prevalent in the Middle East, however its health impact is still not clear. The aim of this study was to assess the prevalence, causes and health implications of vitamin D deficiency in local United Arab Emirates (UAE) citizens. Methods A cross-sectional study was conducted on community free living adults living in the city of Al Ain, UAE. Following informed written consent eligible subject’s blood and urine samples were taken for measurements of vitamin D [25(OH)D], metabolic and bone turnover markers. Clinical assessment that includes general and self-rated health, muscle health, and physical activity were also performed. Results A total of 648 subjects (491 female) were included in this analysis. Their mean (SD) age was 38 (12) years. Mean 25(OH)D was 24 ng/ml (range: 4–67) with 286 (44%) subjects found to have vitamin D deficiency (< 20 ng/ml), 234 (36%) subjects have insufficiency (20-32 ng/ml) and 128 (20%) subjects have optimal concentrations (> 32 ng/ml). 25(OH)D concentrations were significantly higher in local indigenous UAE subjects compared to other Arab expatriates (p = 0.071). Although there were no statistically significant differences in clinical markers between groups, however, utra-sensitive C-reactive protein (us-CRP), parathyroid hormone (PTH), body mass index (BMI) and the bone markers U-PYD and PYD/CR were higher in vitamin D deficient older subjects aged ≥50 years and female subjects younger than 50 years respectively compared to those with insufficiency or optimal concentrations (p value < 0.05. Multiple logistic regression analysis revealed significant and independent association between 25(OH)D status and age and sex (p < 0.05). Conclusion Older subjects with vitamin D deficiency have increased BMI, inflammation and PTH compared with those with insufficiency or optimal concentrations. Co-existence of obesity and vitamin D deficiency may have increased adverse health effects.

The small bowel microbiome changes significantly with age and aspects of the ageing process

Gut microbiome changes have been associated with human ageing and implicated in age-related diseases including Alzheimer’s disease and Parkinson’s disease. However, studies to date have used stool samples, which do not represent the entire gut. Although more challenging to access, the small intestine plays critical roles in host metabolism and immune function. In this paper (Leite et al. (2021), Cell Reports, doi: 10.1016/j.celrep.2021.109765), we demonstrate significant differences in the small intestinal microbiome in older subjects, using duodenal aspirates from 251 subjects aged 18-80 years. Differences included significantly decreased microbial diversity in older subjects, driven by increased relative abundance of phylum Proteobacteria, particularly family Enterobacteriaceae and coliform genera Escherichia and Klebsiella. Moreover, while this decreased diversity was associated with the ‘ageing process’ (comprising chronologic age, number of medications, and number of concomitant diseases), changes in certain taxa were found to be associated with number of medications alone (Klebsiella), number of diseases alone (Clostridium, Bilophila), or chronologic age alone (Escherichia, Lactobacillus, Enterococcus). Lastly, many taxa associated with increasing chronologic age were anaerobes. These changes may contribute to changes in human health that occur during the ageing process.

Immunomodulation by intravenous omega-3 fatty acid treatment in older subjects hospitalized for COVID-19: a single-blind randomized controlled trial

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) with respiratory distress and systemic hyperinflammation. The primary objective of this single-blind randomized controlled proof-of-concept clinical trial was to establish the effects of intravenous (i.v.) omega-3 (n-3) polyunsaturated fatty acid (PUFA) treatment compared to placebo on inflammatory markers in COVID-19, represented by leukocytes as well as inflammatory protein and lipid mediators. Here we also present an exploratory analysis of the mechanisms of action to elucidate the potential to resolve the COVID-19 hyperinflammation through interfering with lipid mediators. Inclusion criteria were COVID-19 diagnosis and clinical status requiring hospitalization. Randomization was 1:1 to a once daily i.v. infusion (2 mL/kg) of either n-3 PUFA emulsion containing 10g of fish oil per 100 mL or placebo (NaCl) for 5 days. Results from 22 older subjects (mean age 81±6.1 years) were analyzed. The neutrophil to lymphocyte ratio was significantly decreased after n-3 PUFA administration. Liquid chromatography–mass spectrometry (LC-MS/MS) -based lipid metabolite analysis established increased proresolving lipid mediator precursor levels and decreased formation of leukotoxin and isoleukotoxin diols by n-3 PUFA treatment. The mechanistic exploration revealed decreased immunothrombosis and preserved interferon-response. Finally, n-3 PUFA treatment may serve to limit cortisone-induced immunosuppression, including preserving leukocyte phagocytic capacity. In conclusion, i.v. n-3 PUFA administration was safe and feasible during hospitalization of multimorbid older subjects for COVID-19. The results identified n-3 PUFA treatment mediated lipid signature of increased proresolving precursor levels and decreased leukotoxin diols in parallel to beneficial immune responses. EudraCT: 2020-002293-28; clinicaltrials.gov: NCT04647604.

Effects of glycine and n-acetylcysteine on glutathione levels and mitochondrial energy metabolism in healthy aging

Glutathione is an intracellular antioxidant that neutralizes reactive oxygen species and prevents tissue damage. Dietary supplementation with the glutathione precursors glycine and n-acetylcysteine supports the maintenance of normal glutathione levels in several age-related diseases, but the optimal doses and their efficacy in healthy elderly are not established. We report results from a randomized controlled clinical trial in 114 healthy volunteers (mean age = 65 years) receiving glycine and n-acetylcysteine (GlyNAC) at three different doses for two weeks (1.2g/1.2, 2.4g/2.4g, 3.6g/.3.6g of each amino acid). Older subjects showed increased oxidative damage and a lower reduced-to-oxidized glutathione ratio (GSH:GSSG) compared to young subjects, but unchanged total glutathione levels. GlyNAC did not increase levels of circulating glutathione compared to placebo treatment, the primary study endpoint. However, stratification analyses suggest that subjects with high oxidative stress and low glutathione status responded with glutathione generation. We find that unrelated to glutathione status, healthy aging was associated with lower levels of fasting glycine that can be increased towards those observed in young subjects with supplementation. Using preclinical models, we find that tissue glycine depletion is a common feature of healthy aging. Supplementation of old mice with glycine efficiently improved age-related decline of mitochondrial respiratory function in skeletal muscle and prevented a gene program associated with protein catabolism observed in control-treated animals. In conclusion, GlyNAC is safe and well-tolerated and may selectively increase glutathione levels in older subjects with oxidative stress and glutathione demand. Our data further suggest that glycine may support mitochondrial function independently of NAC.

Multidimensional Frailty Predicts Mortality Better than Physical Frailty in Community-Dwelling Older People: A Five-Year Longitudinal Cohort Study

Frailty is a common syndrome in older people that carries an increased risk of mortality. Two main models describe frailty, either as a loss of physical functions or as an accumulation of multiple deficits. The aim of our study was to compare the physical frailty index developed in the Cardiovascular Health Study (CHS) with a multidimensional frailty tool, the Multidimensional Prognostic Index (MPI), in predicting death in community-dwelling older subjects. Four hundred and seven community-dwelling older subjects were enrolled. Each subject underwent a comprehensive geriatric assessment (CGA) with calculation of the MPI and CHS index. Mortality was recorded over the following 5 years. In the overall sample (mean age of 77.9 ± 4.5 years; 51.6% female), 53 subjects (13%) died during the 5-year follow-up period. Both the MPI and CHS index were able to predict mortality; however, the MPI was significantly more accurate than the CHS index in predicting mortality (C-index = 0.69 and 0.59, respectively; p < 0.001), with a statistically significant difference of 10%. In conclusion, multidimensional frailty, assessed by the MPI, predicts five-year mortality in community-dwelling older people better than physical frailty, as assessed by the CHS index. These findings suggest the usefulness of assessing frailty by means of CGA-based tools to predict relevant health-negative outcomes in older people.

Is 20 Hz Whole-Body Vibration Training Better for Older Individuals than 40 Hz?

In recent years, whole-body vibration (WBV) training has been used as a training method in health promotion. This study attempted to use WBV at three different frequencies (20, 30, and 40 Hz) with subjects from different age groups to analyze the activation of the rectus femoris muscle. The subjects included 47 females and 51 males with an average age of 45.1 ± 15.2 years. Results indicated significant differences in subjects from different age groups at 20 Hz WBV. Muscle contraction was greater in the subjects who were older (F(4,93) = 82.448, p < 0.001). However, at 30 Hz WBV, the difference was not significant (F(4,93) = 2.373, p = 0.058). At 40 Hz WBV, muscle contraction was less in the older subjects than in the younger subjects (F(4,93) = 18.025, p < 0.001). The spectrum analysis also indicated that at 40 Hz there was less muscle activity during WBV in the older subjects than in the younger ones. Therefore, age was found to have a significant effect on muscle activation during WBV at different frequencies. If the training is offered to elderly subjects, their neuromuscular responses to 20 Hz WBV will be more suitable than to 40 Hz WBV.

Prevalence of symptomatic axial osteoarthritis phenotypes in Spain and associated socio-demographic, anthropometric, and lifestyle variables

Objective Axial osteoarthritis (OA) is a common cause of back and neck pain, however, few studies have examined its prevalence. The aim was to estimate the prevalence and the characteristics of symptomatic axial OA in Spain. Methods EPISER2016 is a cross-sectional multicenter population-based study of people aged 40 years or older. Subjects were randomly selected using multistage stratified cluster sampling. Participants were contacted by telephone to complete rheumatic disease screening questionnaires. Two phenotypes were analyzed, patients with Non-exclusive axial OA (NEA-OA) and Exclusive axial OA (EA-OA). To calculate the prevalence and its 95% confidence interval (CI), the sample design was considered and weighting was calculated according to age, sex and geographic origin. Results Prevalence of NEA-OA by clinical or clinical-radiographic criteria was 19.17% (95% CI: 17.82–20.59). The frequency of NEA-OA increased with age (being 3.6 times more likely in patients aged 80 s or more than in those between 40 and 49 years) and body mass index. It was significantly more frequent in women, as well as in the center of Spain. It was less frequent in those with a higher level of education. Lumbar OA was more frequent than cervical OA. This difference grew with increasing age and was not associated with gender. It was also greater in overweight and obese subjects. Conclusions This is the first study on the prevalence of axial OA phenotypes in Europe describing the associated socio-demographic, anthropometric, and lifestyle variables.

Age-dependent increased sag current in human pyramidal neurons dampens baseline cortical activity

Aging involves various neurobiological changes, although their effect on brain function in humans remains poorly understood. The growing availability of human neuronal and circuit data provides opportunities for uncovering age-dependent changes of brain networks and for constraining models to predict consequences on brain activity. Here we found increased sag current in human layer 5 pyramidal neurons from older subjects, and captured this effect in biophysical models of younger and older pyramidal neurons. We used these models to simulate detailed layer 5 microcircuits and found lower baseline firing in older pyramidal neuron microcircuits, with minimal effect on response. We then validated the predicted reduced baseline firing using extracellular multi-electrode recordings from human brain slices of different ages. Our results thus report changes in human pyramidal neuron input integration properties that can sufficiently account for age-dependent decreases in cortical resting state activity and may underpin a clinical relevance in aging.