Effect of Exercise on Acute Senescent Lymphocyte Counts: A Systematic Review and Meta-Analysis

<b><i>Background:</i></b> Highly differentiated, senescent lymphocytes are pro-inflammatory and contribute to age-related systemic inflammation, called inflammageing. There are several reports of acute changes in senescent lymphocyte counts post exercise, which potentially have consequences for systemic inflammation. However, there is little consensus since the studies differ with respect to participants, exercise protocols, cellular markers assessed, and the time point of assessment post exercise. <b><i>Objective:</i></b> We performed a systematic review and meta-analysis to assess the impact of exercise on senescent lymphocyte counts in blood immediately, 1 h and 2 h post exercise. <b><i>Methods:</i></b> The search was performed in PubMed (MEDLINE), Web of Science, Embase, Scopus, and Cochrane, on January 11, 2021. The 13 studies selected tested aerobic exercise effects, mainly in young men. They assessed the counts of lymphocytes (CD4 T cells, CD8 T cells, and NK cells), with the following immune cell marker combinations: KLRG1+, CD57+ (only NK cells), EMRA T cells (CD45RA+CCR7−CD28−CD27−), CD28−CD27−, KLRG1+CD28−, and CD28−. Independent extraction of articles was done by 2 researchers. <b><i>Results:</i></b> Standardized mean difference (SMD) and 95% confidence interval between baseline and post exercise showed significant increase (SMD &#x3e;0.9, <i>p</i> &#x3c; 0.003) in all types of senescent lymphocytes counts immediately post exercise. At 1 h post exercise, senescent CD4 T cells returned to baseline values (<i>p</i> = 0.74), CD8 T cells were reduced (−0.26 [−0.41; −0.11], <i>p</i> = 0.001), and senescent NK cells were raised (0.62 [0.14; 1.10], <i>p</i> = 0.01) above baseline. By 2 h post exercise, senescent CD4 T cells were reduced (−0.94 [−1.40; −0.48], <i>p</i> &#x3c; 0.001), CD8 T cells remained below baseline (−0.53 [−1.04; −0.009], <i>p</i> = 0.04), and NK cells had returned to baseline values (−0.29 [−0.64; 0.07], <i>p</i> = 0.11). The main determinants of heterogeneity between studies were cytomegalovirus (CMV) serostatus and the characteristics of exercise protocols. CMV+ individuals had a higher immediate lymphocytosis and 1 h post lymphopenia than CMV− individuals. Exercise performed at higher intensities and shorter durations led to higher magnitude of change in senescent lymphocyte counts at all time-points. <b><i>Conclusion:</i></b> The differing effects of exercise on senescent NK cells and CD4 and CD8 T cells suggest differing susceptibility to factors modulating lymphocyte extravasation such as adrenaline and exercise intensity.

Correlates of Older Adults’ E-Health Information-Seeking Behaviors

<b><i>Introduction:</i></b> The Internet is an important source for health information and a medium for older adults’ empowerment in health decision-making and self-caring. Therefore, we aimed to identify the potential motivators and probable barriers of e-health information-seeking behaviors (e-HISB) among older Iranian adults. <b><i>Methods:</i></b> A cross-sectional study assessed the usefulness of self-efficacy, perceived encouragement, positive attitude toward e-HISB, perceived usefulness, challenges of being visited by physicians, and perceived barriers in predicting e-HISB in a sample of 320 older adults in Tabriz, Iran. <b><i>Results:</i></b> The self-efficacy for online information seeking, positive attitude toward e-HISB, and perceived usefulness increased the odds of e-HISB by 12.00%, 24.00%, and 15.00%, respectively. In addition, e-health literacy, conflicting information, distrust of online information, and web designs that were not senior-friendly were the major barriers to e-HISB. <b><i>Discussion/Conclusion:</i></b> The theoretical and practical implications of the motivators and barriers of e-HISB can be instrumental in designing and executing programs aimed at improving e-health literacy among older adults especially during the COVID-19 pandemic.

Standing, Transition, and Walking Ability in Older Adults: The Case for Independently Evaluating Different Domains of Mobility Function

<b><i>Background:</i></b> Independent mobility is a complex behavior that relies on the ability to walk, maintain stability, and transition between postures. However, guidelines for assessment that details <i>what</i> elements of mobility to evaluate and <i>how</i> they should be measured remain unclear. <b><i>Methods:</i></b> Performance on tests of standing, sit-to-stand, and walking were evaluated in a cohort of 135 complex, comorbid, and older adults (mean age 87 ± 5.5 years). Correlational analysis was conducted to examine the degree of association for measures within and between mobility domains on a subset of participants (<i>n</i> = 83) able to complete all tasks unaided. Participants were also grouped by the presence of risk markers for frailty (gait speed and grip strength) to determine if the level of overall impairment impacted performance scores and if among those with risk markers, the degree of association was greater. <b><i>Results:</i></b> Within-domain relationships for sit-to-stand and walking were modest (rho = 0.01–0.60). Associations either did not exist or relationships were weak for measures reflecting different domains (rho = −0.35 to 0.25, <i>p</i> &#x3e; 0.05). As expected, gait speed differed between those with and without frailty risk markers (<i>p</i> &#x3c; 0.001); however, balance and sit-to-stand measures did not (<i>p</i> ≥ 0.05). <b><i>Conclusions:</i></b> This study highlights the need to independently evaluate different mobility domains within an individual as a standard assessment approach. Modest within-domain relationships emphasize the need to account for multiple, unique control challenges within more complex domains. These findings have important implications for standardized mobility assessment and targeted rehabilitation strategies for older adults.

Polypharmacy and Hyperpolypharmacy in Older Individuals with Parkinson’s Disease: A Systematic Review and Meta-Analysis

<b><i>Background and Aim:</i></b> Polypharmacy (concomitant use of 5–9 medicines) and hyperpolypharmacy (concomitant use of over 10 medicines) were observed to be more frequent in older adults (≥65 years) and associated with adverse outcomes. Their prevalence and risk in older patients with Parkinson’s disease (PD) remain unknown. We aimed to synthesize the extant evidence on the prevalence and risk of polypharmacy and hyperpolypharmacy in older adults with PD. <b><i>Methods:</i></b> A systematic literature search was performed in PubMed/MEDLINE, Scopus, and Embase databases to identify pertinent studies published from 2000 to July 2021. Observational studies reporting the prevalence and association with disease of polypharmacy/hyperpolypharmacy in older adults with PD were meta-analyzed. Pooled prevalence and odds ratio (OR) with 95% confidence intervals (CIs) were calculated. <b><i>Results:</i></b> Out of the total 499 studies identified, 6 fulfilled the inclusion criteria and comprised 7,171 participants. The overall prevalence of polypharmacy and hyperpolypharmacy was 40% (95% CI: 37–44) and 18% (95% CI: 13–23), respectively. A meta-analysis of 4 studies indicated a significant association between polypharmacy (OR: 1.94, 95% CI: 1.26–2.62; <i>p</i> &#x3c; 0.001) and PD. Hyperpolypharmacy was also strongly associated with PD (OR: 3.11, 95% CI: 2.08–4.14; <i>p</i> &#x3c; 0.001). <b><i>Conclusion:</i></b> Polypharmacy (40%) and hyperpolypharmacy (18%) are highly prevalent and eventually increase the risk of drug-related problems in older adults with PD. Therefore, interventions that ensure rational geriatric pharmacotherapy are of critical importance for the older population with neurogenerative disorders.

Transitions in Social Network Types over Time among Older Adults

<b><i>Objective:</i></b> Network typology studies have identified heterogeneous types of older adults’ social networks. However, little is known about stability and change in social network types over time. We investigate transitions in social network types among older adults, aged 60 years and older, and factors associated with such transitions. <b><i>Methods:</i></b> We used data on 1,305 older adults, participating in 2 waves of a national, longitudinal survey, conducted in 2016–2017 and 2019, in Singapore. Latent transition analysis identified the distinct types of social networks and their transition patterns between the waves. Multinomial logistic regression examined the association of baseline and change in physical, functional, and mental health and baseline sociodemographic characteristics with network transitions into more diverse or less diverse types. <b><i>Results:</i></b> We found 5 social network types at both waves, representing the most to the least diverse types – diverse, unmarried and diverse, extended family, immediate family, and restricted. Between waves, about 57% of respondents retained their social network type, whereas 24% transitioned into more diverse types and 19% into less diverse types. Those who were older and less educated and those with worsening functional and mental health were more likely to transition into less diverse types versus remaining in the same type. <b><i>Discussion:</i></b> The findings capture the dynamics in social network composition among older adults in the contemporary aging society. We highlight sociodemographic and health disparities contributing to later life social network diversity.

Identification of Serum Biomarkers in Patients with Alzheimer’s Disease by 2D-DIGE Proteomics

<b><i>Aim:</i></b> The aim of this study is to identify potential serum biomarkers of Alzheimer’s disease (AD) for early diagnosis and to evaluate these markers on a large cohort. <b><i>Methods:</i></b> We performed two-dimensional difference gel electrophoresis to compare the serum of AD patients and normal controls. Western blot or enzyme-linked immunosorbent assay (ELISA) was used to identify the expression levels of proteins. <b><i>Results:</i></b> In this study, a total of 13 differentially expressed proteins were identified. Among them, 2 proteins (inter-alpha-trypsin inhibitor heavy chain H4 [ITI-H4], Apolipoprotein A-IV) were validated by Western blot and 4 proteins (Cofilin 2, Tetranectin, Zinc-alpha-2-glycoprotein [AZGP1], Alpha-1-microglobulin/bikunin precursor [AMBP]) were validated by ELISA, respectively. Western blot results showed that the full size of the ITI-H4 protein was increased, while a fragment of ITI-H4 was decreased in AD patients. In contrast, 1 fragment of Apo A-IV was mainly found in control group and rare to be detected in AD patients. On the other hand, ELISA results showed that Cofilin 2, Tetranectin, AZGP1, and AMBP were significantly increased in AD patients, and Cofilin 2 is strongly correlated with the Mini-Mental State Examination scores of the AD patients. Serum Cofilin 2 was unchanged in Parkinson disease patients as compared to the control group, indicating a specific correlation of serum Cofilin 2 with AD. Moreover, Cofilin 2 was increased in both the serum and brain tissue in the APP/PS1 transgenic mice. <b><i>Conclusion:</i></b> Our study identified several potential serum biomarkers of AD, including: ITI-H4, ApoA-IV, Cofilin 2, Tetranectin, AZGP1, and AMBP. Cofilin 2 was upregulated in different AD animal models and might play important roles in AD pathology.

Characteristics of Older People from a Poor Residential Environment in Okinawa, Japan: An Emergency Department-Based Cross-Sectional Study

<b><i>Background:</i></b> Evidence for what diseases occur more commonly in older people from a poor residential environment (PRE) is limited. <b><i>Objective:</i></b> We investigated characteristics, especially the underlying reason (disease) for visiting an emergency department (ED), of older people from a PRE in ED settings. <b><i>Methods:</i></b> A cross-sectional study was conducted on people aged ≥65 years who presented to the EDs of 2 hospitals in Okinawa, Japan, between 2015 and 2019. PRE cases were identified by searching relevant words, such as a house overflowing with garbage from hoarding or housing squalor (<i>gomi-yashiki</i> in Japanese), in electric medical records. Controls (2 controls per case) were randomly selected from those without a PRE, with both living at home and matching each PRE case for age and sex. Characteristics of interest between cases and controls were compared using a χ² test. <b><i>Results:</i></b> PRE cases (<i>n</i> = 67), compared with controls (<i>n</i> = 134), were more often transported by ambulance (79.1% vs. 61.9%; <i>p</i> = 0.01). A family member or relative (43.4%) or professional supporter (20.8%) called an ambulance for most PRE cases. PRE cases were more likely to visit the ED due to injury/fracture (16.4% vs. 8.2%), rhabdomyolysis (11.9% vs. 1.5%), undernutrition/dehydration (10.4% vs. 1.5%), and cancer (9.0% vs. 5.2%) than controls (<i>p</i> &#x3c; 0.001). PRE cases had a higher prevalence of being underweight (35.4% vs. 14.9%), dementia (41.8% vs. 16.4%), decubitus ulcer (29.9% vs. 8.2%), living alone (73.1% vs. 23.1%), and receiving public welfare assistance (35.8% vs. 9.0%) than controls (all <i>p</i> ≤ 0.001). <b><i>Conclusion:</i></b> In EDs, older people from a PRE exhibited certain diseases and characteristics.

Comorbidities as Risk Factors for Severe Disease in Hospitalized Elderly COVID-19 Patients by Different Age-Groups in Japan

<b><i>Introduction:</i></b> Old age is an independent risk factor (RF) for severe COVID-19; evidence for clinico-epidemiological characteristics among elderly COVID-19 patients is scarce. We aimed to analyze clinical and epidemiological characteristics and comorbidities associated with COVID-19 inpatients in age-stratified populations of an elderly COVID-19 cohort. <b><i>Methods:</i></b> We conducted a retrospective cohort study, using nationwide registry data of COVID-19 patients hospitalized before October 31, 2020 (major information entered in the registry as of December 28, 2020). Participants were divided by age according to the Japan Geriatrics Society and the Japan Gerontological Society: pre-old (65–74 years), old (75–89 years), and super-old (≥90 years). Multivariable logistic regression (MLR) analyses were conducted to identify stratified risk and relationships with comorbidities associated with worse outcomes in different age-groups of elderly patients. Demographics and supportive care were evaluated by category. <b><i>Results:</i></b> Data of 4,701 patients from 444 hospitals were included. Most patients (79.3%) had at least one comorbidity; the proportion of patients with hypertension was high in all categories. The proportion of patients with dementia, cardiovascular disease, and cerebrovascular disease increased with age. The percentage of patients who underwent invasive mechanical ventilation/extracorporeal membrane oxygenation was lower in the super-old group. In total, 11.5% of patients died (5.3%, pre-old; 15.2%, old; and 22.4%, super-old). MLR showed that the risk of critical illness differed among age-groups. Male sex was a significant RF in all ages. Collagen disease, moderate to severe renal disorder, and dialysis were significant RFs in older patients, while hematological malignancies and metastatic tumors were more important RFs for severe disease in relatively younger patients. Most of the RFs for critical illnesses were associated with death. <b><i>Conclusion:</i></b> Differences in the epidemiological and clinical characteristics among the different age-groups were found.

Circular RNA CCDC66 Regulates Osteoarthritis Progression by Targeting miR-3622b-5p

<b><i>Objective:</i></b> CircCCDC66 is involved in cancer progression, but its role in osteoarthritis (OA) remains unknown. This study was carried out to explore the biological role of circCCDC66 in OA and its underlying mechanism. <b><i>Methods:</i></b> The expression levels of miR-3622b-5p and circCCDC66 in OA cartilage tissues were detected by qRT-PCR. Cell Counting Kit-8 (CCK8) and flow cytometry were used to detect the chondrocyte viability and apoptosis. The expression of chondrocyte inflammatory factors (IL-6 and TNF-α) was measured by ELISA. The target genes of circCCDC66 and miR-3622b-5p were analyzed by bioinformatics analysis and luciferase reporter gene assay. The relationship between circCCDC66 and miR-3622b-5p was analyzed by bioinformatics analysis and luciferase reporter gene assay. <b><i>Results:</i></b> It was found that circCCDC66 expression in OA cartilage tissues was upregulated. CircCCDC66 overexpression inhibited proliferation and promoted apoptosis of chondrocytes and increased IL-6 and TNF-α levels in chondrocytes. miR-3622b-5p was predicted to be a downstream target gene of circCCDC66, and circCCDC66 overexpression inhibited miR-3622b-5p expression in chondrocytes. Moreover, miR-3622b-5p expression was downregulated in OA cartilage tissues. miR-3622b-5p overexpression increased chondrocyte proliferation, inhibited chondrocyte apoptosis, and enhanced the expression of IL-6 and TNF-α in chondrocytes. In addition, circCCDC66 overexpression enhanced SIRT3 expression in chondrocytes, while miR-3622b-5p overexpression inhibited SIRT3 expression in chondrocytes. <b><i>Conclusion:</i></b> CircCCDC66 promoted OA chondrocyte apoptosis by regulating the miR-3622b-5p/SIRT3 axis. CircCCDC66 may be a new therapeutic target of OA.