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Immunity & Ageing : I & A Jun 2024Sepsis is a dysregulated host response to severe infections, and immune dysfunction plays a crucial role in its pathogenesis. Elderly patients, a special population...
Sepsis is a dysregulated host response to severe infections, and immune dysfunction plays a crucial role in its pathogenesis. Elderly patients, a special population influenced by immunosenescence, are more susceptible to sepsis and have a worse prognosis. However, the immunopathogenic mechanisms underlying sepsis in elderly patients remain unclear. Here, we performed single-cell RNA sequencing of peripheral blood samples from young and old subjects and patients with sepsis. By exploring the transcriptional profiles of immune cells, we analyzed immune cell compositions, phenotype shifts, expression heterogeneities, and intercellular communication. In elderly patients with sepsis, innate immune cells (e.g., monocytes and DCs) exhibit decreased antigen presentation, presenting an overactive inflammatory and senescent phenotype. However, the immunophenotype of T cells shifted to characterize effector, memory, and exhaustion. Moreover, we identified strong interferon-γ responses of T cells in both aging and sepsis groups and a deranged inflammaging status in elderly sepsis patients. Tregs in elderly patients with sepsis showed increased abundance and enhanced immunosuppressive effects. In addition, metabolism-associated pathways were upregulated in T cells in elderly patients with sepsis, and the lysine metabolism pathway was enriched in Tregs. Cell-cell interaction analysis showed that the expression profile of ligand-receptor pairs was probably associated with aggravated immune dysfunction in elderly patients with sepsis. A novel HLA-KIR interaction was observed between Tregs and CD8 + T cells. These findings illustrate the immunological hallmarks of sepsis in elderly patients, and highlight that immunosuppressive and metabolic regulatory pathways may undergo important alterations in elderly patients with sepsis.
PubMed: 38909272
DOI: 10.1186/s12979-024-00446-z -
Alzheimer's Research & Therapy Jun 2024Aim of this study was to detect predictors of better adherence to the AgeWell.de-intervention, a two-year randomized multi-domain lifestyle intervention against... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Aim of this study was to detect predictors of better adherence to the AgeWell.de-intervention, a two-year randomized multi-domain lifestyle intervention against cognitive decline.
METHODS
Data of 317 intervention group-participants comprising a risk group for dementia (Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) score of ≥ 9; mean age 68.9 years, 49.5% women) from the AgeWell.de intervention study were analysed. Regression models with four blocks of predictors (sociodemographic, cognitive and psychosocial, lifestyle factors and chronic conditions) were run on adherence to the components of nutrition, enhancement of social and physical activity and cognitive training. Adherence to each component was operationalised by assessing the degree of goal achievement per component at up to seven time points during the intervention period, measured using a 5-point Likert scale (mean score of goal achievement).
RESULTS
Increasing age was negatively associated with adherence, while higher education positively predicted adherence. Participants with better mental state (Montreal Cognitive Assessment (MoCA)-score > 25) at baseline and higher self-efficacy adhered better. Diabetes and cardiovascular conditions were not associated with adherence, whereas smoking negatively affected adherence. Highest education and quitting smoking in the past were the only predictors associated with all four intervention components.
CONCLUSION
Results identified predictors for better and worse adherence. Particularly self-efficacy seems to be of considerable influence on adherence. This should be considered when designing future intervention trials.
TRIAL REGISTRATION
German Clinical Trials Register (ref. number: DRKS00013555).
Topics: Humans; Female; Male; Aged; Cognitive Dysfunction; Self Efficacy; Life Style; Patient Compliance; Middle Aged; Exercise; Dementia; Aged, 80 and over
PubMed: 38909256
DOI: 10.1186/s13195-024-01499-4 -
Alzheimer's Research & Therapy Jun 2024Aging and sex are major risk factors for developing late-onset Alzheimer's disease. Compared to men, women experience worse neuropathological burden and cognitive...
Age, sex and Alzheimer's disease: a longitudinal study of 3xTg-AD mice reveals sex-specific disease trajectories and inflammatory responses mirrored in postmortem brains from Alzheimer's patients.
BACKGROUND
Aging and sex are major risk factors for developing late-onset Alzheimer's disease. Compared to men, women experience worse neuropathological burden and cognitive decline despite living longer with the disease. Similarly, male 3xTg-AD mice, developed to model Alzheimer's disease, no longer consistently exhibit standard Alzheimer's neuropathology yet experience higher rates of mortality - providing a unique opportunity to further elucidate this dichotomy. We hypothesized that sex differences in the biological aging process yield distinct pathological and molecular Alzheimer's disease signatures in males and females, which could be harnessed for therapeutic and biomarker development.
METHODS
We aged male and female, 3xTg-AD and B6129 control mice across their respective lifespans (n = 3-8 mice per sex, strain, and age group) and longitudinally assessed neuropathological hallmarks of Alzheimer's disease, markers of hepatic inflammation, splenic mass and morphology, as well as plasma cytokine levels. We conducted RNA sequencing analysis on bulk brain tissue and examined differentially expressed genes (DEGs) between 3xTg-AD and B6129 samples and across ages in each sex. We also examined DEGs between clinical Alzheimer's and control parahippocampal gyrus brain tissue samples from the Mount Sinai Brain Bank study in each sex.
RESULTS
3xTg-AD females significantly outlived 3xTg-AD males and exhibited progressive Alzheimer's neuropathology, while 3xTg-AD males demonstrated progressive hepatic inflammation, splenomegaly, circulating inflammatory proteins, and minimal Alzheimer's neuropathological hallmarks. Instead, 3xTg-AD males experienced an accelerated upregulation of immune-related gene expression in the brain relative to females. Our clinical investigations revealed that individuals with Alzheimer's disease develop similar sex-specific alterations in neuronal and immune function. In diseased males of both species, we observed greater upregulation of complement-related gene expression, and lipopolysaccharide was predicted as the top upstream regulator of DEGs.
CONCLUSIONS
Our data demonstrate that chronic inflammation and complement activation are associated with increased mortality, indicating that age-related changes in immune response contribute to sex differences in Alzheimer's disease trajectories. We provide evidence that aging and transgene-driven disease progression trigger a widespread inflammatory response in 3xTg-AD males, which mimics the impact of lipopolysaccharide stimulation despite the absence of infection.
Topics: Alzheimer Disease; Animals; Female; Male; Mice, Transgenic; Mice; Brain; Humans; Longitudinal Studies; Aging; Disease Models, Animal; Sex Characteristics; Inflammation; Sex Factors; Age Factors; Cytokines
PubMed: 38909241
DOI: 10.1186/s13195-024-01492-x -
Immunity & Ageing : I & A Jun 2024The magnitude and durability of cell-mediated immunity in older and severely frail individuals following coronavirus disease 2019 (COVID-19) vaccination remain unclear....
Kinetics of pro- and anti-inflammatory spike-specific cellular immune responses in long-term care facility residents after COVID-19 mRNA primary and booster vaccination: a prospective longitudinal study in Japan.
BACKGROUND
The magnitude and durability of cell-mediated immunity in older and severely frail individuals following coronavirus disease 2019 (COVID-19) vaccination remain unclear. A controlled immune response could be the key to preventing severe COVID-19; however, it is uncertain whether vaccination induces an anti-inflammatory cellular immune response. To address these issues, a 48-week-long prospective longitudinal study was conducted. A total of 106 infection-naive participants (57 long-term care facility [LTCF] residents [median age; 89.0 years], 28 outpatients [median age; 72.0 years], and 21 healthcare workers [median age; 51.0 years]) provided peripheral blood mononuclear cell (PBMC) samples for the assessment of spike-specific PBMC responses before primary vaccination, 24 weeks after primary vaccination, and three months after booster vaccination. Cellular immune responses to severe acute respiratory syndrome coronavirus 2 spike protein were examined by measuring interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-2, IL-4, IL-6, and IL-10 levels secreted from the spike protein peptide-stimulated PBMCs of participants.
RESULTS
LTCF residents exhibited significantly lower IFN-γ, TNF, IL-2, and IL-6 levels than healthcare workers after the primary vaccination. Booster vaccination increased IL-2 and IL-6 levels in LTCF residents comparable to those in healthcare workers, whereas IFN-γ and TNF levels in LTCF residents remained significantly lower than those in healthcare workers. IL-10 levels were not significantly different from the initial values after primary vaccination but increased significantly after booster vaccination in all subgroups. Multivariate analysis showed that age was negatively associated with IFN-γ, TNF, IL-2, and IL-6 levels but not with IL-10 levels. The levels of pro-inflammatory cytokines, including IFN-γ, TNF, IL-2, and IL-6, were positively correlated with humoral immune responses, whereas IL-10 levels were not.
CONCLUSIONS
Older and severely frail individuals may exhibit diminished spike-specific PBMC responses following COVID-19 vaccination compared to the general population. A single booster vaccination may not adequately enhance cell-mediated immunity in older and severely frail individuals to a level comparable to that in the general population. Furthermore, booster vaccination may induce not only a pro-inflammatory cellular immune response but also an anti-inflammatory cellular immune response, potentially mitigating detrimental hyperinflammation.
PubMed: 38909235
DOI: 10.1186/s12979-024-00444-1 -
Alzheimer's Research & Therapy Jun 2024Studies suggest that cerebrospinal fluid (CSF) levels of amyloid-β (Aβ)42 and Aβ40 present a circadian rhythm. However sustained sampling of large volumes of CSF with...
BACKGROUND
Studies suggest that cerebrospinal fluid (CSF) levels of amyloid-β (Aβ)42 and Aβ40 present a circadian rhythm. However sustained sampling of large volumes of CSF with indwelling intrathecal catheters used in most of these studies might have affected CSF dynamics and thereby confounded the observed fluctuations in the biomarker levels.
METHODS
We included 38 individuals with either normal (N = 20) or abnormal (N = 18) CSF Aβ42/Aβ40 levels at baseline. CSF and plasma were collected at two visits separated by an average of 53 days with lumbar punctures and venipunctures performed either in the morning or evening. At the first visit, sample collection was performed in the morning for 17 participants and the order was reversed for the remaining 21 participants. CSF and plasma samples were analyzed for Alzheimer' disease (AD) biomarkers, including Aβ42, Aβ40, GFAP, NfL p-tau181, p-tau217, p-tau231 and t-tau. CSF samples were also tested using mass spectrometry for 22 synaptic and endo-lysosomal proteins.
RESULTS
CSF Aβ42 (mean difference [MD], 0.21 ng/mL; p = 0.038), CSF Aβ40 (MD, 1.85 ng/mL; p < 0.001), plasma Aβ42 (MD, 1.65 pg/mL; p = 0.002) and plasma Aβ40 (MD, 0.01 ng/mL, p = 0.002) were increased by 4.2-17.0% in evening compared with morning samples. Further, CSF levels of 14 synaptic and endo-lysosomal proteins, including neurogranin and neuronal pentraxin-1, were increased by 4.5-13.3% in the evening samples (MD, 0.02-0.56 fmol/µl; p < 0.042). However, no significant differences were found between morning and evening levels for the Aβ42/Aβ40 ratio, different p-tau variants, GFAP and NfL. There were no significant interaction between sampling time and Aβ status for any of the biomarkers, except that CSF t-tau was increased (by 5.74%) in the evening samples compared to the morning samples in Aβ-positive (MD, 16.46 ng/ml; p = 0.009) but not Aβ-negative participants (MD, 1.89 ng/ml; p = 0.47). There were no significant interactions between sampling time and order in which samples were obtained.
DISCUSSION
Our findings provide evidence for diurnal fluctuations in Aβ peptide levels, both in CSF and plasma, while CSF and plasma p-tau, GFAP and NfL were unaffected. Importantly, Aβ42/Aβ40 ratio remained unaltered, suggesting that it is more suitable for implementation in clinical workup than individual Aβ peptides. Additionally, we show that CSF levels of many synaptic and endo-lysosomal proteins presented a diurnal rhythm, implying a build-up of neuronal activity markers during the day. These results will guide the development of unified sample collection procedures to avoid effects of diurnal variation for future implementation of AD biomarkers in clinical practice and drug trials.
Topics: Humans; Amyloid beta-Peptides; Alzheimer Disease; Female; Biomarkers; Male; Aged; Peptide Fragments; tau Proteins; Middle Aged; Circadian Rhythm; Neurofilament Proteins; Aged, 80 and over; Glial Fibrillary Acidic Protein
PubMed: 38909218
DOI: 10.1186/s13195-024-01503-x -
BMC Cardiovascular Disorders Jun 2024Fibrosing mediastinitis (FM) is a rare disease characterized by excessive proliferation of fibrous tissue in the mediastinum and can cause bronchial stenosis, superior...
INTRODUCTION
Fibrosing mediastinitis (FM) is a rare disease characterized by excessive proliferation of fibrous tissue in the mediastinum and can cause bronchial stenosis, superior vena cava obstruction, pulmonary artery and vein stenosis, etc. CASE PRESENTATION: An aging patient with intermittent chest tightness and shortness of breath was diagnosed with FM associated pulmonary hypertension (FM-PH) by echocardiography and enhanced CT of the chest, and CT pulmonary artery (PA)/ pulmonary vein (PV) imaging revealed PA and PV stenosis. Selective angiography revealed complete occlusion of the right upper PV, and we performed endovascular intervention of the total occluded PV. After failure of the antegrade approach, the angiogram revealed well-developed collaterals of the occluded RSPV-V2b, so we chose to proceed via the retrograde approach. We successfully opened the occluded right upper PV and implanted a stent.
CONCLUSIONS
This report may provide new management ideas for the interventional treatment of PV occlusion.
Topics: Humans; Treatment Outcome; Stents; Pulmonary Veins; Chronic Disease; Pulmonary Veno-Occlusive Disease; Stenosis, Pulmonary Vein; Mediastinitis; Male; Phlebography; Angioplasty, Balloon; Aged; Hypertension, Pulmonary; Fibrosis; Collateral Circulation; Pulmonary Circulation; Female
PubMed: 38909188
DOI: 10.1186/s12872-024-03984-y -
BMC Public Health Jun 2024With rapid urbanization, massive migration, and non-family-based eldercare involvement, Chinese concepts of eldercare responsibility and filial piety are shifting. We...
The transition of eldercare responsibility and traditional filial piety concepts and its urban-rural differences in China: an age-period-cohort analysis from 2006 to 2017.
BACKGROUND
With rapid urbanization, massive migration, and non-family-based eldercare involvement, Chinese concepts of eldercare responsibility and filial piety are shifting. We performed age-period-cohort (APC) analyses to assess the transition of old-age pension coverage, eldercare responsibility, and filial piety concepts and its urban-rural differences among Chinese adults using data from the China General Social Survey (2006-2017).
METHODS
Old-age pension coverage (yes/no) and primary eldercare responsibility (government/offspring/self/sharing) were investigated in 2010, 2012, 2013, 2015, and 2017. Filial piety was evaluated using customized questionnaires in 2006 and 2017. The APC effects were estimated using mixed effects and generalized additive models.
RESULTS
Among 66,182 eligible participants (mean age: 48.8 years, females: 51.7%) in the six waves, APC analyses indicated that old-age pension coverage increased with aging and over time. Across cohort groups, it grew as the cohort was younger in urban residents but decreased in rural residents. The concept of offspring-based (> 50%) and government/self/offspring-shared eldercare (> 30%) predominated. APC analyses revealed that the offspring-based concept declined with aging (OR = 0.81, 95% CI: 0.79-0.84), whereas the government-based (OR = 1.37, 95% CI: 1.33-1.41) and self-based (OR = 1.55, 95% CI: 1.47-1.63) concepts increased with aging. People born around the 1940s have a comparatively higher possibility to perceive that the primary eldercare responsibility should be undertaken by the government and elder parents. In contrast, people born in the younger cohort were more likely to perceive that adult children are responsible for their parents' primary eldercare. Filial piety score slightly increased with aging (β = 0.18, SD: 0.05) but decreased as the birth cohort was younger. In addition, rural participants were more likely to perceive offspring-based eldercare and maintain filial piety, and the related urban-rural difference was intensified by aging.
CONCLUSIONS
The traditional concept that eldercare solely relies on offspring has changed to relying on multiple entities, including the government and self-reliance. Diluted filial piety in people born in the young cohort requires reinforcement. Moreover, future healthy aging policies need to focus more on urban-rural disparities to promote equity in social well-being.
Topics: Humans; China; Female; Male; Middle Aged; Rural Population; Aged; Urban Population; Adult; Cohort Studies; Intergenerational Relations; Pensions; Surveys and Questionnaires; Social Responsibility
PubMed: 38909187
DOI: 10.1186/s12889-024-19175-5 -
BMC Public Health Jun 2024Recreational parks can play a significant role in older people's health, with emerging evidence suggesting that changes in the physical environment, such as...
Results from the ENJOY MAP for HEALTH: a quasi experiment evaluating the impact of age-friendly outdoor exercise equipment to increase older people's park visitations and physical activity.
BACKGROUND
Recreational parks can play a significant role in older people's health, with emerging evidence suggesting that changes in the physical environment, such as refurbishments of local parks, can increase park visitations and physical activity engagement. The ENJOY MAP for HEALTH aimed to evaluate the impact of Seniors Exercise Park installations and associated capacity building activities on older people's park visitation, and park-based physical activity.
METHOD
The ENJOY MAP for HEALTH was a quasi-experiment study design that involved the installation of specialised Seniors Exercise Park equipment as part of park refurbishment, supported by promotion and community capacity building activities in six municipalities in Victoria, Australia. Direct observations of park users took place prior to park upgrades, one-month post upgrade and 12-months from baseline. The overall number and characteristics of park visitors, and the type and level of physical activity undertaken, were summarised descriptively. Generalised linear models were used to examine the impact of park refurbishment (equipment installation and site activation) on the total number of older people observed in the park, and their engagement in physical activity, accounting for site and seasonal effects.
RESULTS
Overall number of visits increased following park upgrades, with the largest number of visitors observed one-month post upgrade (n = 12,501). The proportion of older people observed at the parks remained relatively low prior to and one-month post upgrade compared to other age groups. However, after adjusting for site and seasonal effects, the number of older people observed in the parks increased significantly post upgrade and site activation compared to prior to the refurbishment (incidence rate ratios (IRR) 3.55; 95% CI 2.68, 4.70). The number of older people observed to be exercising at the Seniors Exercise Park also increased by 100% at 12-months post-installation relative to one-month post upgrade (IRR 2.00; 95% CI 1.26, 3.17).
CONCLUSION
Installation of the Seniors Exercise Parks and the supportive programs and activities following six park upgrades resulted in an increase in older people's park visitation and engagement in physical activity. Community engagement and training of volunteers with the support of local governments are likely to contribute to the increased park usage by older people.
TRIAL REGISTRATION
This trial was registered with the Australian New Zealand Clinical Trials Registry. Trial registration number ACTRN12621000965808. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380745&isReview=true .
Topics: Humans; Parks, Recreational; Exercise; Aged; Victoria; Male; Female; Health Promotion; Environment Design; Aged, 80 and over
PubMed: 38909183
DOI: 10.1186/s12889-024-19042-3 -
Communications Biology Jun 2024Rapid eye movement sleep (REMS) is increasingly suggested as a discriminant sleep state for subtle signs of age-related neurodegeneration. While REMS expression is under...
Rapid eye movement sleep (REMS) is increasingly suggested as a discriminant sleep state for subtle signs of age-related neurodegeneration. While REMS expression is under strong circadian control and circadian dysregulation increases with age, the association between brain aging and circadian REMS regulation has not yet been assessed. Here, we measure the circadian amplitude of REMS through a 40-h in-lab multiple nap protocol in controlled laboratory conditions, and brain microstructural integrity with quantitative multi-parameter mapping (MPM) imaging in 86 older individuals. We show that reduced circadian REMS amplitude is related to lower magnetization transfer saturation (MTsat), longitudinal relaxation rate (R1) and effective transverse relaxation rate (R2*) values in several white matter regions mostly located around the lateral ventricles, and with lower R1 values in grey matter clusters encompassing the hippocampus, parahippocampus, thalamus and hypothalamus. Our results further highlight the importance of considering circadian regulation for understanding the association between sleep and brain structure in older individuals.
Topics: Humans; Aged; Male; Female; Sleep, REM; Circadian Rhythm; Brain; Magnetic Resonance Imaging; Middle Aged; Aging; Aged, 80 and over
PubMed: 38909162
DOI: 10.1038/s42003-024-06415-y -
Communications Biology Jun 2024Human learning varies greatly among individuals and is related to the microstructure of major white matter tracts in several learning domains, yet the impact of the...
Human learning varies greatly among individuals and is related to the microstructure of major white matter tracts in several learning domains, yet the impact of the existing microstructure of white matter tracts on future learning outcomes remains unclear. We employed a machine-learning model selection framework to evaluate whether existing microstructure might predict individual differences in learning a sensorimotor task, and further, if the mapping between tract microstructure and learning was selective for learning outcomes. We used diffusion tractography to measure the mean fractional anisotropy (FA) of white matter tracts in 60 adult participants who then practiced drawing a set of 40 unfamiliar symbols repeatedly using a digital writing tablet. We measured drawing learning as the slope of draw duration over the practice session and measured visual recognition learning for the symbols using an old/new 2-AFC task. Results demonstrated that tract microstructure selectively predicted learning outcomes, with left hemisphere pArc and SLF3 tracts predicting drawing learning and the left hemisphere MDLFspl predicting visual recognition learning. These results were replicated using repeat, held-out data and supported with complementary analyses. Results suggest that individual differences in the microstructure of human white matter tracts may be selectively related to future learning outcomes.
Topics: Humans; White Matter; Male; Female; Adult; Diffusion Tensor Imaging; Young Adult; Learning; Machine Learning; Anisotropy
PubMed: 38909103
DOI: 10.1038/s42003-024-06420-1