Pathophysiology of Aging and Age-related Diseases

Background and objectives: The combination of depression and sarcopenia, a condition prevalent worldwide, may cause dis-tinct problems that should not be underestimated. However, to the best of our knowledge, no reports have investigated the combined effects of depression and sarcopenia. In this study, we compared physical function, nutritional status, and daily functioning among older adults with only depression (OD), those with only sarcopenia (OS), and those with sarcopenia with depression (SD) to examine the effects of the combination of depression and sarcopenia. Materials and Methods: The participants were 186 communi-ty-dwelling older individuals who required support or care. The participants were classified into four groups based on the presence or absence of sarcopenia and depression: Control, OD, OS, and SD. The following parameters were evaluated in the four groups: grip strength, walking speed, skeletal muscle mass index (SMI), Mini Nutritional Assessment Short-Form (MNA-sf), and long-term care certification level. In addition, univariate and multivariate analyses of the survey results were performed to identify risk factors leading from OS to SD. Results: We found that 31.2% of older participants who needed support or nursing care had SD, which had more pronounced adverse effects on grip strength, walking speed, SMI, MNA-sf, and level of nursing care than OD or OS. Furthermore, multivariate analysis of SD vs. OS showed that decreased grip strength and worsening MNA-sf were independent risk factors. Conclusions: SD is common among older individuals living in the community. Patients with SD require support and care, and the condition has a greater impact on physical function, nutritional status, and decline in life function compared to OD and OS. Therefore, it is desirable to elucidate the process leading to SD and investigate the risk factors and prognosis. It is expected that sarcopenia with depression will be investigated worldwide in the future. Full article

Background and Objectives: The purpose of this study is to enhance the quality of life in elderly patients with lung cancer by understanding relations of uncertainty, appraisal of uncertainty, self-efficacy, and quality of life targeting elderly patients with lung cancer receiving anticancer therapy, and also analyzing the factors affecting the quality of life based on Mishel’s theory. Materials and Methods: The subjects were a total of 112 lung cancer patients aged 65 or older receiving anticancer therapy. The data was collected by using self-report questionnaires targeting patients in hemato-oncology at Chungbuk National University Hospital. The data were analyzed using descriptive statistics, a t-test, an analysis of variance, Pearson’s correlational coefficients, and hierarchical regression analysis. Results: In stage 1, anticancer therapy (chemotherapy) (β = −0.34, p < 0.001), economic condition (low) (β = −0.30, p < 0.001), the number of anticancer therapies (three times or more) (β = −0.29, p < 0.001), and education (graduation from high school or higher) (β = 0.18, p = 0.033) were influencing factors (F = 0.52, p < 0.001). In stage 2, self-efficacy (β = 0.41, p < 0.001), appraisal of uncertainty: danger (β = −0.29, p < 0.001), appraisal of uncertainty: opportunity (β = 0.18, p = 0.018), the number of anticancer therapies (three times or more) (β = −0.17, p = 0.006), and anticancer therapy (chemotherapy) (β = −0.14, p = 0.031) were influencing factors, which showed 74.2% explanatory power (F = 26.17, p < 0.001). Conclusions: In order to improve the quality of life of subjects, it would be necessary to develop interventions for raising their self-efficacy by considering their degree of education, economic condition, the types and numbers of anticancer therapies, and understanding of the appraisal of uncertainty about the disease is assessed as an opportunity factor or a danger factor. Full article

Total bilirubin consists of an unconjugated form, solubilized by its binding to albumin, and a conjugated form representing a minor part of the circulating bilirubin. As total bilirubin in physiological concentrations is a powerful antioxidant, its concentration gradient may reflect the health status of an individual, and serve as a prognostic indicator of outcome in primary and secondary cardiovascular disease prevention. The aim of this study was to assess the association between total bilirubin and incident cardiovascular events following a myocardial infarction. Total bilirubin in serum was measured at baseline 2–8 weeks after hospitalization for an MI in 881 patients, aged 70 to 82 years, included in the OMEMI (Omega-3 Fatty acids in Elderly with Myocardial Infarction) study, where patients were followed-up for up to 2 years. The first major adverse clinical event (MACE) was the primary endpoint and consisted of nonfatal MI, unscheduled coronary revascularization, stroke, hospitalization for heart failure or all-cause death. As total bilirubin was non-normally distributed, log-transformed values and quartiles of bilirubin were analyzed using Cox regression models. The median (Q1, and Q3) baseline concentration of bilirubin was 11 (9, and 14) µmol/L, and higher log-transformed concentrations were associated with male sex, lower New York Heart Association (NYHA) class and non-smoking. MACE occurred in 177 (20.1%) patients during the follow-up. Higher concentrations of bilirubin were associated with a lower risk of MACE: HR 0.67 (95%CI 0.47–0.97) per log-unit increase, p = 0.032. Patients in the lowest quartile of bilirubin (<9 µmol/L) had the highest risk with HR 1.61 (95%CI 1.19–2.18), p = 0.002, compared to quartiles 2–4. This association remained significant even after adjusting for age, sex, body mass index (BMI), smoking status, NYHA class and treatment allocation: HR 1.52 (1.21–2.09), p = 0.009. Low concentrations of bilirubin (<9 µmol/L) are associated with increased nonfatal cardiovascular events or death in elderly patients with a recent myocardial infarction. Full article

The effect of natural aging on physiologic mechanisms that regulate attentional set-shifting represents an area of high interest in the study of cognitive function. In visual discrimination learning, reward contingency changes in categorization tasks impact individual performance, which is constrained by attention-shifting costs. Perseveration (PE) and learned irrelevance (LI) are viewed as two different mechanisms that shape responses to stimuli, which are predicated on the shift in stimulus form. To date, only studies examining patients with Parkinson’s disease have provided some insight into the relationship between individual age and performance in PE and LI tasks. We enrolled 60 healthy individuals (mean [SD] age, 63.0 [12.6]) without a history of dementia, a cerebrovascular incident, or a neurodegenerative disease. No association was observed between crystallized intelligence or verbal fluency scores and reaction time in both PE (r = 0.074, p = 0.603; r = −0.124, p = 0.346) and LI (r = −0.076, p = 0.562; r = −0.081, p = 0.536) task conditions, respectively. In contrast, a statistically significant linear relationship was observed between age and reaction time (RT) for PE (r = 0.259, p = 0.046) but not for LI (r = 0.226, p = 0.083). No significant linear relationship was observed for changing RTs in PE and LI (r = 0.209, p = 0.110). The present study is the first report that provides a descriptive overview of age-related differences in PE and LI in a sample of cognitively unimpaired middle- to older-aged adults. Full article

Background and Objectives: To examine the relationship between the presence of earlobe crease (EC) and overactive bladder (OAB). Materials and Methods: The earlobes of the participants were examined macroscopically. ECs were further divided into four groups (grades 0–3) according to severity. Subjective symptoms were assessed using the OAB symptom score (OABSS), and objective findings were assessed using uroflowmetry. The relationship between these findings and the presence or absence and severity of EC was also examined. A score of ≥2 points on OABSS question 3 (urinary urgency), with a total score of ≥3 points, indicated OAB. Results: We analyzed 246 participants, including 120 (48.8%) in the EC group and 126 (51.2%) in the non-EC (N-EC) group. On the OABSS, the EC group scored higher than the N-EC group for all questions and for the total score. The total OABSS of EC grade 3 was the highest of all groups. A total of 115 (95.8%) patients in the EC group (100% in grade 3) and 69 (54.8%) in the N-EC group met the OAB criteria (p < 0.001). The voided volume and maximum flow rate of the EC group were significantly lower than those of the N-EC group (both p < 0.001). The post-void residual urine volume in the EC group was significantly higher than that in the N-EC group (p = 0.029). Multivariate analysis revealed that EC was an independent risk factor for OAB (odds ratio, 8.15; 95% confidence interval, 2.84–24.75; p < 0.001). Conclusions: The presence of an earlobe crease may be a predictive marker for OAB. Full article

Postmenopausal aging has become relevant for understanding health during the transition life stages—the aging process being involved in several disturbances of the human condition. The present study aimed to investigate the relationship between postmenopausal aging and sociodemographic, anthropometric, body composition, nutritional, and biochemical (i.e., protein and lipid profiles, phosphorous-calcium metabolism, and antioxidant status) factors in postmenopausal women. This cross-sectional study enrolled 78 healthy postmenopausal women (44–76 years). The anthropometrical data showed no differences by age. Biochemical parameters, especially those involved in the protein and phosphorous-calcium metabolism, were influenced by age in our cohort of postmenopausal women. In contrast, no associations were found when considering lipid and antioxidant parameters. Height, fiber intake, blood glucose, protein profile and phosphorous-calcium metabolism markers seem to be the most affected nutritional-related factors by age in our cohort of healthy postmenopausal women. Primary prevention strategies focused on parameters at risk of disruption with postmenopausal aging are necessary to ensure the quality of life in older ages. Full article

Background: Many neurological manifestations are part of COVID-19 infections, including movement disorders, but a clinical picture closely resembling stiff-person syndrome has not yet been described. Case presentation: We report a case of a stiff-person-like syndrome in the context of COVID-19 infection. A 79-year-old woman, with no prior history of diseases, presented global reversible stiffness associated with SARS-CoV-2 infection. We aim to shed light on several particularities regarding this clinical picture and its evolution in close relationship with the infectious disease progression, with full regression of symptoms and signs once the infectious process ceased. The impairment of speech and motility caused the wrong diagnosis of stroke in the Emergency Room. In addition, we would also like to emphasize the concomitant rhabdomyolysis, closely linked to the grade of muscle rigidity. Conclusions: We would like to raise awareness regarding this clinical setting and its association with SARS-COV-2 infection, to aid in its future recognition and management. To our knowledge, this is the first case of a stiff-person-like syndrome to be described in association with COVID-19 infection. Full article

Atherosclerosis is associated with low-grade inflammation involving circulating monocytes. It has been shown that the levels of intermediate pro-inflammatory monocytes are associated with cardiovascular mortality and risk of ischemic stroke. It also has been shown that physical activity (PA) decreases inflammation markers, incidence of strokes, and mortality. In this cross-sectional study, we tested the effect of PA on circulating monocytes phenotype rate. A total of 29 patients with a carotid stenosis > 50% were recruited. Levels of physical activity (MET.min/week) were measured by the GPAQ questionnaire, arterial samples of blood were collected to analyze monocyte phenotype (classical, intermediate and non-classical) assessed by flow cytometry, and venous blood samples were used to dose antioxidant activity and oxidative damage. Antioxidant capacity was reduced and oxidative damage increased in patients. There was a significant decrease in the percentage of classical and intermediate monocytes in moderately active patients as compared with non-active and highly active patients. Inversely, the rate of non-classical monocytes increased in moderately active patients. Intense PA appears to blunt the beneficial effects of moderate PA. Our study also suggests that PA could be beneficial in such patients by reducing the rate of intermediate monocytes known to predict the risk of ischemic stroke and by increasing the non-classical monocytes involved in lesions’ healing. Nevertheless, a longitudinal study would be necessary to confirm this hypothesis. Full article

The present study aimed to investigate the association between the functional connectivity (FC) of the olfactory cortex and olfactory performance in Parkinson’s disease (PD). Eighty-two early PD patients and twenty-one healthy controls underwent structural and resting-state functional MRI scans, as well as neuropsychological assessments from the Parkinson’s Progression Markers Initiative database. A whole brain voxel-wise regression analysis was conducted to evaluate the relationship between the FC of the entorhinal cortex (EC-FC) and olfactory performance. Then, a one-way ANCOVA, based on the regions of interest, was performed with SPSS to investigate the group differences and correlation analysis that were used to analyze the relationships between the FC and neuropsychological assessments. In addition, regression models were used to evaluate the risk factors for the decreased olfactory function. A significantly negative correlation was observed between the olfactory performance and the left EC-FC in the right dorsal cingulate gyrus (dCC) in patients. The PD patients with anosmia exhibited significantly higher FC values than the PD patients with normal olfaction or the PD patients with mild to moderate microsomia. Except for the olfactory performance, no significant correlation was detected between the neuropsychological assessments and the FC values. A linear regression analysis revealed that the increased FC and Geriatric Depression Scale are independently associated with lower the University of Pennsylvania Smell Identification Test scores. The current findings enhanced the understanding of olfactory dysfunction-related pathophysiological mechanisms in early PD and suggested that the left EC-FC in the right dCC may be a potential neuroimaging biomarker for olfactory performance. Full article

The mechanisms underlying the occurrence of postoperative delirium development are unclear and measurement of plasma metabolites may improve understanding of its causes. Participants (n = 54) matched for age and gender were sampled from an observational cohort study investigating postoperative delirium. Participants were ≥65 years without a diagnosis of dementia and presented for primary elective hip or knee arthroplasty. Plasma samples collected pre- and postoperatively were grouped as either control (n = 26, aged: 75.8 ± 5.2) or delirium (n = 28, aged: 76.2 ± 5.7). Widespread changes in plasma metabolite levels occurred following surgery. The only metabolites significantly differing between corresponding control and delirium samples were ornithine and spermine. In delirium cases, ornithine was 17.6% higher preoperatively, and spermine was 12.0% higher postoperatively. Changes were not associated with various perioperative factors. In binary logistic regression modeling, these two metabolites did not confer a significantly increased risk of delirium. These findings support the hypothesis that disturbed polyamine metabolism is an underlying factor in delirium that warrants further investigation. Full article

Background and Objectives: Bones and the skeletal muscle play a key role in human physiology as regulators of metabolism in the whole organism. Bone tissue is identified as a complex and dynamic living unit that could react to physical activity. Hormones, growth factors, signaling factors, and environmental factors control osteogenesis, and it could be regulated at a post-transcriptional level. MicroRNAs (miRNAs) can interfere with mRNAs translation. Increasing data suggest that miRNAs, through different pathways, are involved in the regulation of bone marrow mesenchymal stem cells (BMSCs) differentiation and physical activity-induced bone remodeling. The purpose of this narrative review is to investigate the potential protective role played by physical activity in affecting miRNAs expression in close tissues and elaborate on the complex network of interplay that could drive various metabolic responses of the bone to physical activity. Materials and Methods: A bibliographic search of the scientific literature was carried out in scientific databases to investigate the possible effect of physical activity on age-related features detected in the musculoskeletal system. Results: Several studies suggested that the musculoskeletal system interacting at a biomolecular level could establish crosstalk between bone and muscle in an endocrine or paracrine way through myokines released by muscle at the periosteal interface or in the bloodstream, such as irisin. Mechanical stimuli have a key role in bone formation and resorption, increasing osteogenesis and downregulating adipogenesis of BMSC via regulation of expression of runt-related transcription factor 2 (Runx2) and peroxisome proliferator-activated receptor gamma (PPARγ), respectively. Conclusions: Increasing data suggest that miRNAs, through different pathways, are involved in the regulation of BMSCs differentiation and physical activity-induced bone remodeling. Modulation of miRNAs following physical exercise represents an interesting field of investigation since these non-coding RNAs may be considered defenders against degenerative diseases and as well as useful prognostic markers in skeletal and muscle-skeletal diseases, such as osteoporosis. Full article

Introduction: Dementia is a very common disorder that affects people over 65 years old all over the world. Apart from the cognitive decline, Behavioral and Psychological Symptoms of Dementia (BPSD) are a crucial matter in dementia, because they affect up to 90% of the patients during the course of their illness. Irritability has been found to be a common BPSD and one of the most distressing behaviors for the caregivers. The aim of the current study was to explore the efficacy of a combination of non-pharmacological interventions to treat irritability. Methods: Sixty patients with different types and stages of dementia with irritability were participated in a cross-over RCT. Three non-pharmacological interventions were used; (a) Validation Therapy (VT)/Psycho-educational program, (b) Aromatherapy/massage and (c) Music Therapy (MT). The study assessed the three non-pharmacological interventions in order to find the most effective combination of the interventions. This study did not compare pharmacological and non-pharmacological treatments. The interventions lasted for five days. There was no drop-out rate. All patients were assessed at baseline using Mini Mental State of Examination (MMSE), Addenbrooke’s Cognitive Examination Revised (ACE-R), Geriatric Depression Scale (GDS), Functional Rating Scale for symptoms in dementia (FRSSD), and Neuropsychiatric Inventory (NPI) (sub questions for irritability). Only NPI used for the assessment after each intervention. The analyses used categorical variables, Wilcoxon signed-rank test, Chi-square test and z value score. Results: The most effective combination of non-pharmacological interventions was Aromatherapy/massage (p = 0.003)-VT plus Psycho-educational program (p = 0.014) plus MT (p = 0.018). The same combination was the most effective for the caregivers’ burden, too (p = 0.026). Conclusions: The above combination of non-pharmacological interventions can reduce irritability in patients with dementia and caregivers’ burden. Full article

Inflammation plays an important role in the pathophysiology of depression. This study aims to elucidate the antidepressant effect of baicalein, an anti-inflammatory component of a traditional Chinese herbal medicine (Scutellaria baicalensis), on lipopolysaccharide (LPS)-induced depression-like behavior in mice, and to investigate the underlying mechanisms. In vitro, baicalein exhibited antioxidant activity and protected macrophages from LPS-induced damage. The results of the tail suspension test and forced swimming test (tests for despair potential in mice) showed the antidepressant effect of baicalein on LPS-treated mice. It also substantially decreased the production of pro-inflammatory cytokines, including IL-6, TNF-α, MCP-1, and eotaxin, elicited by LPS in the plasma. Baicalein downregulated NF-κB-p65 and iNOS protein levels in the hippocampus, demonstrated its ability to mitigate neuroinflammation. Additionally, baicalein increased the levels of the mature brain-derived neurotrophic factor (mBDNF) in the hippocampus of LPS-treated mice, and elevated the ratio of mBDNF/proBDNF, which regulates neuronal survival and synaptic plasticity. Baicalein also promoted the expression of CREB, which plays a role in a variety of signaling pathways. In summary, the findings of this study demonstrate that the administration of baicalein can attenuate LPS-induced depression-like behavior by suppressing neuroinflammation and inflammation induced by the peripheral immune response. Full article