This study aimed to investigate the effects of dietary supplementation of rhamnolipids (RLS) on growth performance, gut morphology, antioxidant function, lipid metabolism, immune responses, and gut microbiota in Linnan yellow-feathered broilers. A total of 390 one-day-old broilers were randomly assigned to three groups: Control (CON), 250 mg/kg RLS (RLS250), or 500 mg/kg RLS (RLS500). The broilers were fed with basal diet, or basal diet supplemented with 250 or 500 mg/kg RLS for 56 days. Each treatment contained 10 replicates with 13 chickens per replicate. Results showed that diet supplemented with RLS250 and RLS500 markedly improved final BW and ADG on day 56. RLS reduced the CD and increased the VH/CD of jejunum and ileum. RLS significantly increased the levels of total T-AOC and GSH-Px on day 28, while the levels of T-AOC and SOD were higher than CON groups on day 56. RLS treatment also regulated the lipid metabolism in the broilers by increasing the concentration of serum HDL-C and decreased LDL-C. The levels of serum immunoglobulins including IgA, IgM and IgY in RLS250 and RLS500 groups were notably higher than those of CON groups on day 56. Meanwhile, ileum IgA and IgM in RLS500 groups were evidently higher than other two groups. RLS significantly increased the level of IL-10. RLS showed no significant effects on VFA in cecum of broilers. Results of 16S rRNA sequencing showed that RLS optimized the microbiota by lowering the relative abundance of Anaerofilum and DUT089, and regulating g__norank_f__ Ruminococcaceae. This study found that supplemented with RLS in diet improved the growth performance, antioxidant function, and immune function, and regulated intestinal microbiota of broilers, revealing that RLS is potential feed additive for use in animal husbandry.

Introduction: Chronic kidney disease (CKD) is characterized by a decline in renal function, increased mortality, and significant impairments in the immune system and function of immune cells. These alterations are often derived by uremic toxins, which, in turn, modify the immune system's response to infections. Our research investigates the progression of Porphyromonas gingivalis (P. gingivalis) infection during CKD and its subsequent impact on kidney failure. Methods: We utilized two infectious models, a chamber model representing short-term local inflammation and alveolar bone loss that mimic chronic infection of periodontium, both in conjunction with a CKD model. Additionally, our in vitro studies employed primary macrophages, osteoclasts, and lymphocytes to characterize the immune responses to P. gingivalis and pathogen-associated molecular patterns (PAMPs) in the presence of uremic toxins. Results and Conclusion: Our findings demonstrate that uremic toxins, such as indoxyl sulfate (IS), alter responses of macrophages and lymphocytes to P. gingivalis. In vivo, CKD significantly enhanced P. gingivalis survival and infection-induced alveolar bone loss. The increased distribution of pathogen within peripheral tissues was associated with altered inflammatory responses, indicating that CKD promotes infection. Moreover, P. gingivalis-infected mice exhibited a marked increase in renal inflammation, suggesting that the relationship between uremia and infection is bidirectional, with infection exacerbating kidney dysfunction. Furthermore, we observed that infected CKD mice exhibit decreased serum immunoglobulin G (IgG) levels compared to infected mice without CKD, implying that uremia is associated with immune dysfunction characterized by immunodepression and impaired B lymphocyte function.

Aging is the result of various compounding stresses that gradually overcome the homeostatic regulation of the cell, resulting in irreversible damage. This manifests as many acute and chronic conditions, the most common of which are neurodegeneration and dementia. Epidemiological studies have shown significant, strong correlations between viral infection and neurodegenerative diseases. This review overlays the characteristics of viral pathogenesis with the hallmarks of aging to discuss how active and latent viruses contribute to aging. Through our contextualization of myriad basic science papers, we offer explanations for premature aging via viral induction of common stress response pathways. Viruses induce many stresses: dysregulated homeostasis by exogenous viral proteins and overwhelmed protein quality control mechanisms, DNA damage through direct integration and epigenetic manipulation, immune-mediated oxidative stress and immune exhaustion, and general energy theft that is amplified in an aging system. Overall, this highlights the long-term importance of vaccines and antivirals in addition to their acute benefits.

Skin aging is a complex, multifactorial process involving cellular damage, inflammation, and increased susceptibility to diseases. Despite its importance, the role of SPRY1 in skin aging remains poorly understood. This study aims to investigate the function of SPRY1 in skin aging, particularly its impact on macrophage M1 polarization, and explore its potential as a therapeutic target for mitigating skin aging and melanoma.

Bioinformatics analyses were performed using datasets from the GTEx and GEO databases, alongside in vitro cellular experiments. These included Weighted Gene Co-expression Network Analysis (WGCNA), single-cell sequencing, and various cellular assays in RAW264.7 murine monocyte/macrophage leukemia cells and NIH/3T3 mouse skin fibroblasts. The assays comprised gene transfection, Cell Counting Kit-8 (CCK-8) assays, quantitative real-time PCR (qRT-PCR), and measurements of reactive oxygen species (ROS) and superoxide dismutase (SOD) activity.

SPRY1 was identified as a key gene within modules linked to skin aging. Single-cell sequencing revealed its enrichment in macrophages and keratinocytes. Knockdown of SPRY1 in RAW264.7 cells resulted in a shift from M1 to M2 macrophage polarization, reduced oxidative stress, and decreased expression of inflammatory markers. In NIH/3T3 cells, SPRY1 knockdown reduced cell viability and lowered the expression of inflammatory genes. Additionally, SPRY1 expression was downregulated in melanoma, and its reduced levels were associated with poorer survival outcomes.

SPRY1 accelerates skin aging by promoting macrophage M1 polarization and may serve as a promising therapeutic target. Future research should focus on in vivo validation and further exploration of its regulatory networks to develop novel treatments.

Old age raises the susceptibility of age-related disease in domestic dogs. Discovering effective anti-aging interventions is key for mitigating age-related disease and conserving "healthspan" in pet dogs. In this study, 2 bacterial strains were isolated from canine feces. After screening and identifying the strains, Weissella confusa ZJUIDS-D034 and Enterococcus faecalis ZJUIDS-D016 were chosen to intervene during d-galactose-induced senescence in mice. We found that administering Weissella confusa ZJUIDS-D034 and Enterococcus faecalis ZJUIDS-D016 improved the aging phenotype of mice, including an increase in antioxidant activity, a decrease in pro-inflammatory cytokines, and the restoration of intestinal and liver tissue damage. In addition, Weissella confusa ZJUIDS-D034 and Enterococcus faecalis ZJUIDS-D016 lead to changes in the structure of intestinal microbiota in aging mice. Specifically, there was a decrease in the abundance of the Cyanobacteria and an increase in the abundance of Akkermansia and Lactobacillus. More importantly, there was a significant increase in acetic acid, a short-chain fatty acid, due to intervention with the 2 strains. This increase might be attributed to higher Akkermansia. We show that the modulation of gut microbiota and metabolism in aging mice may be a promising strategy through which Weissella confusa ZJUIDS-D034 and Enterococcus faecalis ZJUIDS-D016 might exert their anti-aging effects.

This study examined the unique associations of different dimensions of the resilience factor, benefit finding, on concurrent and prospective psychological and biological adjustment outcomes over the first year after a colorectal cancer diagnosis.

Individuals newly diagnosed with colorectal cancer (n = 133, mean age = 56 years old, 59% female, 46% Hispanic) completed questionnaires assessing the multidimensional aspects of benefit finding around 4 months post-diagnosis (T1). Psychological (depressive symptoms and life satisfaction) and biological [C-reactive protein (CRP) and interleukin-10 (IL-10)] adjustments were assessed at T1 and one-year post-diagnosis (T2).

Structural equation modeling revealed that at T1, greater reprioritization was concurrently related to higher depressive symptoms (p=.020). Lower acceptance, lower empathy, and greater positive self-view predicted higher life satisfaction at T2 (ps<.010). Additionally, lower empathy and greater family valuation predicted higher CRP at T2 (ps<.004), whereas greater positive self-view predicted higher IL-10 at T2 (p=.039). Greater overall benefit finding was associated with lower IL-10 at T1 (p=.013).

Various aspects of benefit finding differentially relate to psychological and inflammatory markers during the first year after diagnosis in persons with colorectal cancer. Interventions designed to specifically enhance positive self-view may promote both the psychological and biological health of individuals with cancer.

Since the first description of a set of characteristics of aging as so-called hallmarks or pillars in 2013/2014, these characteristics have served as guideposts for the research in aging biology. They have been examined in a range of contexts, across tissues, in response to disease conditions or environmental factors, and served as a benchmark for various anti-aging interventions. While the hallmarks of aging were intended to capture generalizable characteristics of aging, they are derived mostly from studies of rodents and humans. Comparative studies of aging including species from across the animal tree of life have great promise to reveal new insights into the mechanistic foundations of aging, as there is a great diversity in lifespan and age-associated physiological changes. However, it is unclear how well the defined hallmarks of aging apply across diverse species. Here, we review each of the twelve hallmarks of aging defined by Lopez-Otin in 2023 with respect to the availability of data from diverse species. We evaluate the current methods used to assess these hallmarks for their potential to be adapted for comparative studies. Not unexpectedly, we find that the data supporting the described hallmarks of aging are restricted mostly to humans and a few model systems and that no data are available for many animal clades. Similarly, not all hallmarks can be easily assessed in diverse species. However, for at least half of the hallmarks, there are methods available today that can be employed to fill this gap in knowledge, suggesting that these studies can be prioritized while methods are developed for comparative study of the remaining hallmarks.

The escalating threat of global infectious disease outbreaks has underscored the imperative for robust infection prevention and control (IPC) measures, particularly within the high-risk context of residential care facilities. This research aimed to investigate the experiences and roles of IPC professionals (IPCPs) in such settings during global outbreaks.

Utilising an integrative review methodology, four electronic databases - Medline, CINAHL, Embase, and Scopus - were searched from 2003 onwards for relevant papers. A two-tiered independent screening approach was employed to select eligible articles, followed by a consensus-based appraisal and thematic analysis of included studies.

The final review encompassed eight articles. IPCPs faced systemic organisational and ground-level operational hurdles, including inequitable access to resources, and lack of training and outbreak preparedness. External and internal variables impacted the effectiveness of outbreak responses, affecting resident and occupational health, and perceptions of IPC over time.

The review identified systemic challenges IPCPs face in residential care during outbreaks, including resource inequity and lack of standardised training. Centralised resources and standardised educational benchmarks may help to mitigate these issues. Policy changes are required to enhance healthcare readiness, quality, and research in residential care settings.

From embryogenesis to aging, billions of cells perish daily in mammals. The multistep process by which phagocytes engulf these deceased cells without eliciting an inflammatory response is called efferocytosis. Despite significant insights into the fundamental mechanisms of efferocytosis, its implications in disorders such as aging and cancer remain elusive. Upon summarizing and analyzing existing studies on efferocytosis, it becomes evident that efferocytosis is our friend in resolving inflammation, yet it transforms into our foe by facilitating tumor development and metastasis. This review illuminates recent discoveries regarding the emerging mechanisms of efferocytosis in clearing apoptotic cells, explores its connections with aging, examines its influence on tumor development and metastasis, and identifies the regulatory factors of efferocytosis within the tumor microenvironment. A comprehensive understanding of these efferocytosis facets offers insights into crucial physiological and pathophysiological processes, paving the way for innovative therapeutic approaches to combat aging and cancer.

Conventional sunscreens shield the skin from ultraviolet (UV) rays up to 370 nm leaving wavelengths between 370 and 400 nm unfiltered despite their potentially harmful biological and clinical effects.

The beneficial effects of methoxypropylamino cyclohexenylidene ethoxyethylcyanoacetate (MCE) UVA1 filter were explored at 1% in a SPF50 sunscreen under outdoors summer conditions against pigmentation and aging signs compared against a reference SPF50 without the MCE filter.

A prospective randomized comparative intra-individual study was conducted in 52 Brazilian women (phototype I-III). A hemiface application was performed for the SPF50 sunscreen with 1% MCE and SPF50 reference without MCE before 1-h outdoor sunlight exposure, twice daily for 4 weeks. Study endpoint included expert panel grading of pigmentation (3), vascular (1) signs as well as facial skin ageing and assessment of facial skin radiance and skin homogeneity by a naïve panel.

Significant differences were reported for all facial signs comparing areas protected with SPF50/MCE and SPF50, respectively: upper lip wrinkles, crow's feet wrinkles, upper lip texture, upper lip pigmentation, vascular abnormalities (all p < 0.0001), texture of the mouth contour (p = 0.001), ptosis of lower face (p = 0.003), lateral facial pigmentation (p = 0.005), and whole face pigmentation (p = 0.01). The evaluations performed by naïve panel showed a significant superiority of the SPF50/MCE product for skin homogeneity (p = 0.043).

Overall, this study demonstrates a significant gain of protection with the SPF50 containing 1% MCE in reducing hyperpigmentation, redness and aging signs compared to the same SPF50 sunscreen without MCE, thus supporting the need for an enlarged UVA1 photoprotection.

While the impact of chronic, low-grade inflammation on cognitive functioning is documented in the context of neurodegenerative disease, less is known about the association between acute increases in inflammation and cognitive functioning in daily life. This study investigated how changes in interleukin-6 (IL-6) levels were associated with performance on an inhibitory control task, the go/no-go task. We further examined whether the opportunity to earn different incentive types (social or monetary) and magnitudes (high or low) was associated with differential performance on the task, depending on IL-6 levels. Using a within-participant design, individuals completed an incentivized go/no-go task before and after receiving the annual influenza vaccine. Multilevel logistic regressions were performed on the trial-level data (Nobs = 30,528). For no-go trials, we did not find significant associations in IL-6 reactivity and changes in trial accuracy between sessions. For go trials, we found significant differences in the associations between IL-6 reactivity and changes in accuracy as a function of the incentive condition. Notably, greater IL-6 reactivity was consistently associated with fewer omission errors (i.e., greater accuracy on go trials) on high-magnitude social incentives (i.e., viewing a picture of a close-other) when compared to both low-magnitude social and high-magnitude monetary incentives. Together, these results suggest that mild fluctuations in inflammation might alter the valuation of an incentive, and possibly a shift toward devoting greater attentional resources when a large social incentive is on the line. Overall, this study sheds light on how everyday, low-grade fluctuations in inflammation may influence cognitive abilities essential for daily life and effective inhibitory control.

Patients with metabolic disorders benefit from using anthocyanins. Nevertheless, the findings drawn from extant trials remain contentious. Thus, this meta-analysis evaluated anthocyanin's effect on inflammatory biomarkers in patients with metabolic disorders.

We comprehensively searched electronic databases, including PubMed, Scopus, Web of Science, and CENTRAL, from their inception to June 14, 2024.

A total of 11 randomized controlled clinical trials with 14 arms were analyzed. There was no significant effect of anthocyanin supplementation on interleukin (IL)-1β levels (standardized mean difference [SMD] = -0.01, 95% CI: -0.33, 0.31; P = 0.941, I 2 = 62.4%, P = 0.031), tumor necrosis factor-α (TNF-α) (SMD = -0.49, 95% CI: -1.07, 0.09; P = 0.098, I 2 = 94.0%, P < 0.001) and IL-6 (SMD = -0.69, 95% CI: -1.45, 0.06; P = 0.073, I 2 = 95.2%, P < 0.001), respectively. A significant between-study heterogeneity was identified, which was reduced when subgrouping by sample size, dosage, and study population. However, subgroup analysis showed that it might decrease TNF-α and IL-6 in patients with hypertension, and if the intervention lasted less than 12 weeks.

There was no significant impact of anthocyanin supplementation on IL-1β, TNF-α, and IL-6; however, it should be noted that the intervention has a decreasing impact on individuals with hypertension. Our observed effect sizes on IL-1β, TNF-α, and IL-6 are not clinically important.

Telomeres are crucial for cancer progression. Immune signalling in the tumour microenvironment has been shown to be very important in cancer prognosis. However, the mechanisms by which telomeres might affect tumour immune response remain poorly understood. Here, we observed that interleukin-1 signalling is telomere-length dependent in cancer cells. Mechanistically, non-telomeric TRF2 (telomeric repeat binding factor 2) binding at the IL-1-receptor type-1 (IL1R1) promoter was found to be affected by telomere length. Enhanced TRF2 binding at the IL1R1 promoter in cells with short telomeres directly recruited the histone-acetyl-transferase (HAT) p300, and consequent H3K27 acetylation activated IL1R1. This altered NF-kappa B signalling and affected downstream cytokines like IL6, IL8, and TNF. Further, IL1R1 expression was telomere-sensitive in triple-negative breast cancer (TNBC) clinical samples. Infiltration of tumour-associated macrophages (TAM) was also sensitive to the length of tumour cell telomeres and highly correlated with IL1R1 expression. The use of both IL1 Receptor antagonist (IL1RA) and IL1R1 targeting ligands could abrogate M2 macrophage infiltration in TNBC tumour organoids. In summary, using TNBC cancer tissue (>90 patients), tumour-derived organoids, cancer cells, and xenograft tumours with either long or short telomeres, we uncovered a heretofore undeciphered function of telomeres in modulating IL1 signalling and tumour immunity.

Musculoskeletal disorders pose major public health challenges, and accelerated biological aging may increase their risk. This study investigates the association between biological aging and musculoskeletal disorders, with a focus on sex-related differences.

We analyzed data from 172,332 UK Biobank participants (mean age of 56.03 ± 8.10 years). Biological age was calculated using the KDM-BA and PhenoAge algorithms based on blood biomarkers. Musculoskeletal disorders were diagnosed using the ICD-10 criteria, with sample sizes ranging from 1,182 to 23,668. Logistic regression assessed cross-sectional associations between age acceleration (AA) metrics and musculoskeletal disorders. Accelerated Failure Time (AFT) model was used for survival analysis to evaluate the relationships between AAs and musculoskeletal disorders onset. Models were adjusted for demographic, lifestyle, and socio-economic covariates. The threshold of P-values were set by the Holm-Bonferroni correction.

Cross-sectional analyses reveal significant associations between AAs and fourteen musculoskeletal disorders. Survival analyses indicate that AAs significantly accelerate the onset of nine musculoskeletal disorders, including inflammatory polyarthropathies (RTKDM-BA = 0.993; RTPhenoAge = 0.983), systemic connective tissue disorders (RTKDM-BA = 0.987; RTPhenoAge = 0.980), spondylopathies (RTPhenoAge= 0.994), disorders of bone density and structure (RTPhenoAge= 0.991), gout (RTPhenoAge= 0.968), arthritis (RTPhenoAge= 0.991), pain in joint (RTPhenoAge= 0.989), low back pain (RTPhenoAge= 0.986), and osteoporosis (RTPhenoAge= 0.994). Sensitivity analyses are consistent with the primary findings. Sex-specific variations are observed, with AAs accelerating spondylopathies, arthritis, and low back pain in females, while osteoporosis is accelerated in males.

Accelerated biological aging is significantly associated with the incidence of several musculoskeletal disorders. These insights highlight the importance of biological age assessments in gauging musculoskeletal disorder risk, aiding early detection, prevention, and management.

The brain is a privileged organ with regard to its trace element composition and maintains a robust barrier system to sequester this specialized environment from the rest of the body and the vascular system. Stroke is caused by loss of adequate blood flow to a region of the brain. Without adequate blood flow ischaemic changes begin almost immediately, triggering an ischaemic cascade, characterized by ion dysregulation, loss of function, oxidative damage, cellular degradation, and breakdown of the barrier that helps maintain this environment. Ion dysregulation is a hallmark of stroke pathophysiology and we observe that most elements in the brain are dysregulated after stroke. X-ray fluorescence-based detection of physiological changes in the neurometallome after stroke reveals profound ion dysregulation within the lesion and surrounding tissue. Not only are most elements significantly dysregulated after stroke, but the level of dysregulation cannot be predicted from a cell-level description of dysregulation. X-ray fluorescence imaging reveals that the stroke lesion retains <25% of essential K+ after stroke, but this element is not concomitantly elevated elsewhere in the organ. Moreover, elements like Na+, Ca2+, and Cl- are vastly elevated above levels available in normal brain tissue (>400%, >200%, and >150%, respectively). We hypothesize that weakening of the blood-brain barrier after stroke allows elements to freely diffuse down their concentration gradient so that the stroke lesion is in equilibrium with blood (and the compartments containing brain interstitial fluid and cerebrospinal fluid). The change observed for the neurometallome likely has consequences for the potential to rescue infarcted tissue, but also presents specific targets for treatment.

There is an increasing awareness that aging of the immune system, or immunosenescence, is a key biological process underlying many of the hallmark diseases of aging and age-related decline broadly. While immunosenescence can be in part due to normal age-related changes in the immune system, emerging evidence posits that viral infections may be biological stressors of the immune system that accelerate the pace of immunosenescence.

We used a convenience sample of 42 individuals aged 65 years and older to examine correlations between antiviral immunoglobulin G (IgG) levels for 4 human herpesviruses (cytomegalovirus [CMV], herpes simplex virus [types 1 and 2], and Epstein-Barr virus) and multiple indicators of T-cell immunosenescence.

We found that most of the sample (n = 33) was antiviral IgG positive for 2 or more of the 4 herpesvirus infections. We also examined correlations between both the total number of viruses for which an individual had antiviral IgG and each individual virus and multiple indicators of T-cell immunosenescence, particularly p16 expression. The strongest correlations were observed between the total number of viruses for which an individual had detectable antiviral IgG and p16 mean fluorescent intensity (MFI) among CD27-CD28-CD57+ CD4+ cells (r = 0.60; P < .001) and between anti-CMV IgG and p16 MFI of CD27-CD57+ CD4+ cells (r = 0.59; P < .001).

Broadly, our findings offer compelling preliminary evidence for future investigations to incorporate multiple indicators of persistent viral infections and a more comprehensive set of markers of T-cell immunosenescence in population-based studies of aging.

Experiencing more stressful life events has been linked to higher levels of inflammation, but this association may depend on when in the lifespan the stressors occur. To address this knowledge gap, we tested two lifespan theories, the accumulation of risks and sensitive period models, by assessing the association between the total number of stressful events and their life stage occurrence on later-life C-reactive protein (CRP). We harmonized data across two cohort studies, maximizing variation in stressors reported across the lifespan. Participants (Ntotal = 7,952, 57.7% female, Mage = 69) from the Health and Retirement Study (HRS: n = 5,136, Mage = 70.6) and the English Longitudinal Study of Aging (ELSA: n = 2,816, Mage = 66.1) completed retrospective surveys of stressful life events and indicated what year(s) each event occurred and had blood drawn ∼4.5 years later. Stressful events were summed across the participants' lifespans (age 0 to current age) and within childhood (0-17 years), young adulthood (18-39), midlife (40-59), and late adulthood (60+). In main effects models, more cumulative stressors (γ = .05, SE = .02, p = .012) and stressors in young adulthood (γ = .06, SE = .03, p = .037) were associated with higher levels of CRP. In models with all life stages together among adults age 65+ (n = 4,972), experiencing more stressors in midlife significantly predicted higher levels of CRP (γ = .08, SE = .04, p = .038). Our findings replicate prior evidence of an association between cumulative stressors and inflammation and extend this work by identifying stressors in young adulthood and midlife as potentially unique sensitive periods that predict higher levels of later-life inflammation.

As a consequence of increased lifespan and rising number of elderly individuals developing end-stage organ disease, the higher demand for organs along with a growing availability for organs from older donors pose new challenges for transplantation. During aging, dynamic adaptations in the functionality and structure of the biological systems occur. Consistently, immunosenescence (IS) accounts for polydysfunctions within the lymphocyte subsets, and the onset of a basal but persistent systemic inflammation characterized by elevated levels of pro-inflammatory mediators. There is an emerging consensus about a causative link between such hallmarks and increased susceptibility to morbidities and mortality, however the role of IS in solid organ transplantation (SOT) remains loosely addressed. Dissecting the immune-architecture of immunologically-privileged sites may prompt novel insights to extend allograft survival. A deeper comprehension of IS in SOT might unveil key standpoints for the clinical management of transplanted patients.

Age-related macular degeneration (AMD) is both a poorly understood and devastating disease. Here, we analyze the physico-chemical forces at stake, including osmolarity, redox shift, and pressure due to inflammation. Hyperosmolarity plays a key role in diseases of the anterior segment of the eye such as glaucoma, cataracts or dry eyes, and corneal ulceration. However, its role in macular degeneration has been largely overlooked. Hyperosmolarity is responsible for metabolic shifts such as aerobic glycolysis which increases lactate secretion by Muller cells. Increased osmolarity will also cause neoangiogenesis and cell death. Because of its unique energetic demands, the macula is very sensitive to metabolic shifts. As a proof of concept, subretinal injection of drugs increasing hyperosmolarity such as polyethylene glycol causes neoangiogenesis and drusen-like structures in rodents. The link between AMD and hyperosmolarity is reinforced by the fact that treatments aiming to restore mitochondrial activity, such as lipoic acid and/or methylene blue, have been experimentally shown to be effective. We suggest that metabolic shift, inflammation, and hyperosmolarity are hallmarks in the pathogenesis and treatment of AMD.

Systemic Immune-Inflammation Index (SII), calculated by (neutrophils count × platelet count)/lymphocytes count, is a novel index of the local immune response and systemic inflammation response. The SII has been shown to play an important role in the prognosis of many diseases, including cardiovascular diseases, cancer and COPD. However, its role in the prognosis of bronchiectasis remains unclear and requires further investigation. This study aimed to investigate the association between SII and readmissions in patients with acute exacerbations of bronchiectasis.

We conducted a retrospective cohort study of all bronchiectasis patients admitted to the respiratory ward in Beijing Chaoyang Hospital from January 2020 to January 2022. Patients were classified into four groups according to the quartiles of log2(SII) at admission. The primary endpoint was readmission at 1-year follow up. Univariate and multivariate cox regression models were applied to investigate the relationship between SII and readmissions at 1-year follow up in patients with bronchiectasis.

A total of 521 patients were included in our study. The median (IQR) SII at admission were 506.10 (564.84). Patients with higher SII tended to be older, male, past and current smokers, have lower BMI, and more dyspnea symptoms. They also had higher inflammatory markers and received a greater spectrum of antibiotics and more intravenous glucocorticoids. Higher SII at admission were independently associated with readmission in patients with acute exacerbations for bronchiectasis following confounder adjustment (OR =1.007; 95% CI, 1.003-1.011; p <0.001).

Patients with elevated SII levels were typically older males, often smokers, with lower BMI and increased dyspnea. They received more antibiotics and intravenous glucocorticoids. Higher SII at admission are associated with readmission in patients with acute exacerbations of bronchiectasis. SII has potential clinical value as a predictive biomarker for clinical outcomes in bronchiectasis, offering a valuable tool for management strategies.

Extracts of Salvia officinalis (S. officinalis) have been described to have many therapeutic properties. However, the effect of S. officinalis on copper sulfate toxicity has not been previously reported. The aim of this study was to investigate the toxicity of copper sulfate and the potential beneficial effects of S. officinalis aqueous infusion on proinflammatory response and antioxidant status. 56 male mice were used and equally divided into 6 groups: control group, copper sulfate treated group (40 mg/kg), S. officinalis aqueous infusion treated groups (200 mg/kg and 400 mg/kg) separately or in combination with copper. IL-6 (interleukine-6) and TNF-α (Tumor necrosis factor alpha) were assessed by Elisa. Catalase (CAT), superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities, malondialdehyde (MDA) and oxygen peroxide levels were determined. Serum biochemical parameters were analyzed. Copper enhanced aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Lactate dehydrogenase (LDH) (p < 0.05). Copper enhances significantly IL-6, TNF-α and MDA levels in liver and kidney and reduced CAT, SOD and AChE activities (p < 0.05). Aqueous infusion of S. officinalis at 400 mg/kg abolished copper-induced changes in AST and ALT activity. S. officinalis aqueous infusion at 200 mg/kg reversed copper-induced IL-6 in kidney and TNF-α in liver at both doses. S. officinalis aqueous infusion at 400 mg/kg restored SOD in kidney and CAT and AChE activities in both liver and kidney. S. officinalis aqueous infusion may be useful in partially ameliorating tissue disorders induced by copper exposure such as inflammatory response, oxidative stress imbalance and organ dysfunction through its phenolic compounds and higher antioxidant capacity.

To explore the causal relationships between 91 circulating inflammatory cytokines and sarcopenia-related traits (low hand grip strength, appendicular lean mass, and usual walking pace) by Mendelian randomized analysis.

Independent genetic variations of inflammatory cytokines and sarcopenia-related traits were selected as instrumental variables from publicly available genome-wide association studies (GWAS). The MR analysis was primarily conducted using the inverse variance-weighted (IVW) method. Sensitivity analyses included Steiger filtering and MR PRESSO, with additional assessments for heterogeneity and pleiotropy.

The IVW method indicated a causal relationship between Vascular Endothelial Growth Factor A (VEGF-A) and low hand grip strength (OR = 1.05654, 95% CI: 1.02453 to 1.08956, P = 0.00046). Additionally, Tumor Necrosis Factor-beta (TNF-β) was found to have a causal relationship with appendicular lean mass (ALM) (β = 0.04255, 95% CI: 0.02838 to 0.05672, P = 3.96E-09). There was no evidence suggesting a significant causal relationship between inflammatory cytokines and usual walking pace.

Our research substantiated the causal association between inflammatory cytokines, such as VEGF-A and TNF-β, and sarcopenia. This finding may provide new avenues for future clinical treatments.

Aging induces a progressive decline in the vasculature's structure and function. Vascular aging is a determinant factor for vascular ailments in the elderly. FAM19A5, a recently identified adipokine, has demonstrated involvement in multiple vascular aging-related pathologies, including atherosclerosis, cardio-cerebral vascular diseases and cognitive deficits. This review summarizes the current understanding of FAM19A5' role and explores its putative regulatory mechanisms in various aging-related disorders, including cardiovascular diseases (CVDs), metabolic diseases, neurodegenerative diseases and malignancies. Importantly, we provide novel insights into the underlying therapeutic value of FAM19A5 in osteoporosis. Finally, we outline future perspectives on the diagnostic and therapeutic potential of FAM19A5 in vascular aging-related diseases.

An immune reaction known as inflammation serves as a shield from external danger signals, but an overactive immune system may additionally lead to tissue damage and even a variety of inflammatory disorders. By inheriting biological functionalities and serving as both a therapeutic medication and a drug carrier, cell membrane-based nanotherapeutics offer the potential to treat inflammatory disorders. To further strengthen the anti-inflammatory benefits of natural cell membranes, researchers alter and optimize the membranes using engineering methods. This review focuses on engineered cell membrane-based nanotherapeutics (ECMNs) and their application in treating inflammation-related diseases. Specifically, this article discusses the methods of engineering cell membranes for inflammatory diseases and examines the progress of ECMNs in inflammation-targeted therapy, inflammation-neutralizing therapy, and inflammation-immunomodulatory therapy. Additionally, the article looks into the perspectives and challenges of ECMNs in inflammatory treatment and offers suggestions as well as guidance to encourage further investigations and implementations in this area.

Kombucha is a fermented, acidic beverage that dates back thousands of years as a remedy for various health problems in East Asia. Due to its health benefits, kombucha has gained popularity and attracted the attention of both consumers and researchers. The health benefits of kombucha are predominantly attributed to its bioactive compounds that have antioxidant, antimicrobial, probiotic, and other positive effects owing to fermentation. Many factors such as the type of the substrate used, the symbiotic culture of the bacterial yeast composition, and fermentation conditions influence the extent of these properties. This review focuses on recent developments regarding the bioactive constituents of kombucha and its potential health benefits (antimicrobial, antioxidant, antidiabetic, hepatoprotective effects) as well as its impact on multiple sclerosis, nephrotoxicity, gastric ulceration and gut microbiota. Additionally, the composition of kombucha, alternative uses of its biofilm, and potential toxicity are also discussed. Kombucha is a healthy and safe beverage with multiple health benefits that are primarily related to the presence of bacteria, yeasts, and other bioactive constituents. Moreover, kombucha has been suggested as a potential source of probiotics and eco-friendly materials (kombucha-derived bacterial cellulose) for several industries including food and textile.

Aging is a gradual and irreversible process that is accompanied by an overall decline in cellular function and a significant increase in the risk of age-associated disorders. Generally, delaying aging is a more effective method than treating diseases associated with aging. Currently, researchers are focused on natural compounds and their therapeutic and health benefits. Curcumin is the main active substance that is present in turmeric, a spice that is made up of the roots and rhizomes of the Curcuma longa plant. Curcumin demonstrated a positive impact on slowing down the aging process by postponing age-related changes. This compound may have anti-aging properties by changing levels of proteins involved in the aging process, such as sirtuins and AMPK, and inhibiting pro-aging proteins, such as NF-κB and mTOR. In clinical research, this herbal compound has been extensively examined in terms of safety, efficacy, and pharmacokinetics. There are numerous effects of curcumin on mechanisms related to aging and human diseases, so we discuss many of them in detail in this review.

The global burden of chronic diseases has been increasing, with evidence suggesting that diet and exposure to environmental pollutants, such as per- and polyfluoroalkyl substances (PFAS) and heavy metals, may contribute to their development. The Dietary Inflammatory Index (DII) assesses the inflammatory potential of an individual's diet. However, the complex interplay between PFAS, heavy metals, and DII remains largely unexplored.

The goal of this cross-sectional study was to investigate the associations between diet operationalized as the DII with individual and combined lead, cadmium, mercury, perfluorooctanoic acid (PFOA), and perfluorooctanesulfonic acid (PFOS) exposures using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018.

Descriptive statistics, a correlational analysis, and linear regression were initially used to assess the relationship between the variables of interest. We subsequently employed Bayesian kernel Machine regression (BKMR) to analyze the data to assess the non-linear, non-additive, exposure-response relationships and interactions between PFAS and metals with the DII.

The multi-variable linear regression revealed significant associations between the DII and cadmium and mercury. Our BKMR analysis revealed a complex relationship between PFAS, metal exposures, and the DII. In our univariate exposure-response function plot, cadmium and mercury exhibited a positive and negative linear relationship, respectively, which indicated a positive and negative relationship across the spectrum of exposures with the DII. In addition, the bivariate exposure-response function between two exposures in a mixture revealed that cadmium had a robust positive relationship with the DII for different quantiles of lead, mercury, PFOA, and PFOS, indicating that increasing levels of cadmium are associated with the DII. Mercury's bivariate plot demonstrated a negative relationship across all quantiles for all pollutants. Furthermore, the posterior inclusion probability (PIP) results highlighted the consistent importance of cadmium and mercury with the inflammatory potential of an individual's diet, operationalized as the DII in our study, with both showing a PIP of 1.000. This was followed by PFOS with a PIP of 0.8524, PFOA at 0.5924, and lead, which had the lowest impact among the five environmental pollutants, with a PIP of 0.5596.

Our study suggests that exposures to environmental metals and PFAS, particularly mercury and cadmium, are associated with DII. These findings also provide evidence of the intricate relationships between PFAS, heavy metals, and the DII. The findings underscore the importance of considering the cumulative effects of multi-pollutant exposures. Future research should focus on elucidating the mechanistic pathways and dose-response relationships underlying these associations in a study that examines causality, which will enable a deeper understanding of the dietary risks associated with environmental pollutants.

Many of those infected with COVID-19 experience long-term disability due to persistent symptoms known as Long-COVID, which include ongoing respiratory issues, loss of taste and smell, and impaired daily functioning.

This study aims to better understand the chronology of long-COVID symptoms.

We prospectively enrolled 403 adults from the University of Iowa long-COVID clinic (June 2020 to February 2022). Participants provided symptom data during acute illness, symptom progression, and other clinical characteristics. Patients in this registry received a survey containing questions including current symptoms and status since long-COVID diagnosis (sliding status scale, PHQ2, GAD2, MMRC). Those >12 months since acute-COVID diagnosis had chart review done to track their symptomology.

Of 403 participants contacted, 129 (32%) responded. The mean age (in years) was 50.17 +/-14.28, with 31.8% male and 68.2% female. Severity of acute covid treatment was stratified by treatment in the outpatient (70.5%), inpatient (16.3%), or ICU (13.2%) settings. 51.2% reported subjective improvement (sliding scale scores of 67-100) since long-COVID onset. Ages 18-29 reported significantly higher subjective status scores. Subjective status scores were unaffected by severity. 102 respondents were >12 months from their initial COVID-19 diagnosis and were tracked for longitudinal symptom persistence. All symptoms tracked had variance (mean fraction 0.58, range 0.34-0.75) in the reported symptoms at the time of long-COVID presentation when compared with patient survey report. 48 reported persistent dyspnea, 23 (48%) had resolved it at time of survey. For fatigue, 44 had persistence, 12 (27%) resolved.

Overall, 51.2% respondents improved since their long-COVID began. Pulmonary symptoms were more persistent than neuromuscular symptoms (anosmia, dysgeusia, myalgias). Gender, time since acute COVID infection, and its severity didn't affect subjective status or symptoms. This study highlights recall bias that may be prevalent in other long-COVID research reliant on participant memory.

Emerging evidence suggests that psychosocial stress ages the immune system. Accordingly, immune aging may be an important potential mechanism linking psychosocial stress to aging-related decline and disease. Incarceration and housing insecurity represent severe and complex experiences of a multitude of psychosocial stressors, including discrimination, violence, and poverty. In this study, we investigated the association between incarceration and/or housing insecurity and advanced immune age in adults aged 55 and older. Our sample was derived from the Health and Retirement Survey (HRS), with n = 7003 individuals with valid housing insecurity data and n = 7523 with valid incarceration data. From 2016 Venous Blood Study data, we assessed immune aging using a comprehensive set of immune markers including inflammatory markers (IL-6, CRP, s-TNFR1), markers of viral control (CMV IgG antibodies), and ratios of T cell phenotypes (CD8+:CD4+, CD+ Memory: Naïve, CD4+ Memory: Naïve, CD8+ Memory: Naïve ratios). We found that both incarceration and housing insecurity were strongly associated with more advanced immune aging as indicated by increased inflammation, reduced viral control, and reduction in naïve T cells relative to memory T cells. Given that those who experienced incarceration, housing insecurity, and/or are racialized minorities were less likely to be included in this study, our results likely underestimated these associations. Despite these limitations, our study provided strong evidence that experiencing incarceration and/or housing insecurity may accelerate the aging of the immune system.

Primary giant cell tumors of soft tissues (GCT-ST) are rare neoplasms that share histopathological and immunohistochemical characteristics with osseous giant cell tumors. While GCT-ST generally exhibits a benign progression and can affect individuals of various ages, older patients may face a higher risk of recurrence and aggressive disease progression. In this case report, we present the case of a 63-year-old woman who experienced recurrent GCT-ST nine months after the complete excision of an initially localized tumor. Despite the mainstay treatment of GCT-ST being tumor-free margin surgical excision, this case demonstrates the occurrence of recurrences. The etiology of recurrence in GCT-ST remains unclear, highlighting the need for further studies and careful patient follow-up to prevent potential complications such as lung metastasis or widespread metastasis. Thus, this report aims to raise awareness of these tumors and emphasize the importance of diligent patient follow-up to facilitate early identification and management, thereby preventing potential complications such as lung or widespread metastasis.

Biomarkers in population health research serve as indicators of incremental physiological deterioration and contribute to our understanding of mechanisms through which social disparities in health unfold over time. Yet, few population-based studies incorporate biomarkers of aging in early midlife, when disease risks may emerge and progress across the life course. We describe the distributions of several biomarkers of inflammation and neurodegeneration and their variation by sociodemographic characteristics using blood samples collected during Wave V of the National Longitudinal Study of Adolescent to Adult Health (ages 33-44 years). Higher mean levels of inflammatory and neurodegenerative biomarkers were associated with greater socioeconomic disadvantage. For example, the neurodegenerative markers, Neurofilament Light Chain and total Tau proteins were higher among lower income groups, though the relationship was not statistically significant. Similarly, proinflammatory marker Tumor Necrosis Factor-α (TNF-α) levels were higher among those with lower education. Significant differences in the mean levels of other proinflammatory markers were observed by race/ethnicity, sex, census region, BMI, and smoking status. These descriptive findings indicate that disparities in biomarkers associated with aging are already evident among young adults in their 30s and attention should focus on age-related disease risk earlier in the life course.

We conducted research on CDK4/6 inhibitors (CDK4/6i) simultaneously in the preclinical and clinical spaces to gain a deeper understanding of how senescence influences tumor growth in humans.

We coordinated a first-in-kind phase II clinical trial of the CDK4/6i abemaciclib for patients with progressive dedifferentiated liposarcoma (DDLS) with cellular studies interrogating the molecular basis of geroconversion.

Thirty patients with progressing DDLS enrolled and were treated with 200 mg of abemaciclib twice daily. The median progression-free survival was 33 weeks at the time of the data lock, with 23 of 30 progression-free at 12 weeks (76.7%, two-sided 95% CI, 57.7%-90.1%). No new safety signals were identified. Concurrent preclinical work in liposarcoma cell lines identified ANGPTL4 as a necessary late regulator of geroconversion, the pathway from reversible cell-cycle exit to a stably arrested inflammation-provoking senescent cell. Using this insight, we were able to identify patients in which abemaciclib induced tumor cell senescence. Senescence correlated with increased leukocyte infiltration, primarily CD4-positive cells, within a month of therapy. However, those individuals with both senescence and increased TILs were also more likely to acquire resistance later in therapy. These suggest that combining senolytics with abemaciclib in a subset of patients may improve the duration of response.

Abemaciclib was well tolerated and showed promising activity in DDLS. The discovery of ANGPTL4 as a late regulator of geroconversion helped to define how CDK4/6i-induced cellular senescence modulates the immune tumor microenvironment and contributes to both positive and negative clinical outcomes. See related commentary by Weiss et al., p. 649.

Bergaptol (5-hydroxypsoralen or 5-hydroxyfuranocoumarin) is a naturally occurring furanocoumarin widely found in citrus fruits, which has multiple health benefits. Nonetheless, no specific review articles on bergaptol have been published. Compiling updated information on bergaptol is crucial in guiding future research direction and application. The present review focuses on the research evidence related to the pharmacological properties and toxicity of bergaptol. Bergaptol has anti-inflammatory, antioxidant, anti-cancer, anti-osteoporosis, anti-microbial, and anti-lipidemic effects. It can inhibit the activities of cytochrome P450s (CYP), especially CYP2C9 and CYP3A4, thereby affecting the metabolism and concentrations of some drugs and toxins. Compared with other coumarins, bergaptol has the least potency to inhibit CYP3A4 in cancer cells. Instead, it can suppress drug efflux transporters, such as P-glycoprotein, thereby overcoming chemotherapeutic drug resistance. Furthermore, bergaptol has antimicrobial effects with a high potential for inhibition of quorum sensing. In vivo, bergaptol can be retained in plasma for longer than other coumarins. Nevertheless, its toxicity has not been clearly reported. In vitro study suggests that, unlike most furocoumarins, bergaptol is not phototoxic or photomutagenic. Existing research on bergaptol has mostly been conducted in vitro. Further in vivo and clinical studies are warranted to identify the safe and effective doses of bergaptol for its multimodal application.

Fatigue, low muscle endurance, muscle weakness and low-grade inflammation are strongly related to frailty at higher age. When signs of self-perceived fatigue and low muscle endurance are interrelated with low-grade inflammation at midlife, they might be used as early markers for frailty. This study investigated whether the interrelationships among self-perceived fatigue, muscle endurance and inflammation can be observed at midlife.

A total of 965 participants of the Copenhagen Aging and Midlife Biobank (aged 52 ± 4 years, 536 males, 426 females) were assessed for self-perceived fatigue (20-item multidimensional fatigue inventory), muscle endurance (grip work), circulating markers of inflammation (hsCRP, IL-6, IL-10, TNF-alpha and IFN-γ), daily physical activity (PAS-2), body composition (%body fat assessed by bio-impedance) and self-reported health status. Participants were categorised (correcting for age and gender) according to high fatigue and/or low muscle endurance, differences in inflammatory profile between fatigue categories were assessed by ANCOVA (corrected for PAS-2, %body fat and presence of inflammatory conditions).

Overall, muscle endurance, fatigue and inflammatory markers were significantly interrelated. Higher levels of hsCRP (p < 0.001), IL-6 (p < 0.001), IL-10 (p = 0.035) and TNF-alpha (p = 0.028) were observed in participants presenting both low muscle endurance and high fatigue. IFN-γ was highest in those with high fatigue but normal muscle endurance (p = 0.015).

Middle-aged participants with higher fatigue in combination with low muscle endurance show higher levels of inflammation, independently from physical activity, body fat and inflammatory pathology. The underlying mechanisms should be identified and future studies should also investigate whether these individuals show early signs of reduced physiological reserve capacity, which in later life come to full expression by means of frailty.

Chronic systemic inflammation and poverty are both linked to an increased mortality risk. The goal of this study was to determine if there is a synergistic effect of the presence of inflammation and poverty on the 15-year risk of all-cause, heart disease and cancer mortality among US adults.

We analyzed the nationally representative National Health and Nutrition Examination Survey (NHANES) 1999 to 2002 with linked records to the National Death Index through the date December 31, 2019. Among adults aged 40 and older, 15-year mortality risk associated with inflammation, C-reactive protein (CRP), and poverty was assessed in Cox regressions. All-cause, heart disease and cancer mortality were the outcomes.

Individuals with elevated CRP at 1.0 mg/dL and poverty were at greater risk of 15-year adjusted, all-cause mortality (HR = 2.45; 95% CI 1.64, 3.67) than individuals with low CRP and were above poverty. For individuals with just one at risk characteristic, low inflammation/poverty (HR = 1.58; 95% CI 1.30, 1.93), inflammation/above poverty (HR = 1.59; 95% CI 1.31, 1.93) the mortality risk was essentially the same and substantially lower than the risk for adults with both. Individuals with both elevated inflammation and living in poverty experience a 15-year heart disease mortality risk elevated by 127% and 15-year cancer mortality elevated by 196%.

This study extends the past research showing an increased mortality risk for poverty and systemic inflammation to indicate that there is a potential synergistic effect for increased mortality risk when an adult has both increased inflammation and is living in poverty.

Background: A pro-inflammatory metabolic state is key to the chronic disease epidemic. Clinicians' ability to use nutrients to balance inflammation via oxidant homeostasis depends on the quality of antioxidants research. Understanding the intersection of two prominent theories for how antioxidants quell inflammation-nutritional hormesis and oxidant scavenging-will enable therapeutic antioxidant use in clinical practice. Purpose: We sought to survey the literature to answer the question: has the hormetic response of exogenous antioxidants been studied in humans and if so, what is its effect Research Design: This review investigates the less well-established theory, nutritional hormesis. To understand the state of hormetic response research, we conducted a literature review describing the relationship between exogenous antioxidants, hormesis, and chronic disease. We used an adaptive search strategy (PubMed and Scopus), retrieving 343 articles, of which 218 were unique. Most studies reviewed the hormetic response in plant and cell models (73.6%) while only 2.2% were in humans. Results: Given the limited robust evidence, clinicians lack research-based guidance on the appropriate therapeutic dose of exogenous antioxidants or, more concerning, supra-physiological dosing via supplements. A critical hurdle in searching the literature is the lack of standardized nomenclature describing the hormetic effect, challenging the ability of clinicians to make informed decisions. Conclusion: Non-human research shows a biphasic, hormetic relationship with antioxidants but observational studies have yet to translate this into the complexities of human biochemistry and physiology. Therefore, we cannot accurately translate this into clinical care. To remedy this insufficiency, we suggest: (1) Improved data collection quality: controlled diet, standardized antioxidant measurements, bioavailability assessed via biomarkers; (2) Larger, harmonized datasets: research subject transparency, keyword standardization, consensus on a hormesis definition.

Dupuytren's disease is a common fibroproliferative disease that can result in debilitating hand deformities. Partial correction and return of deformity are common with surgical or clinical treatments at present. While current treatments are limited to local procedures for relatively late effects of the disease, the pathophysiology of this connective tissue disorder is associated with both local and systemic processes (e.g., fibrosis, inflammation). Hence, a better understanding of the systemic circulation of Dupuytren related cytokines and growth factors may provide important insights into disease progression. In addition, systemic biomarker analysis could yield new concepts for treatments of Dupuytren that attenuate circulatory factors (e.g., anti-inflammatory agents, neutralizing antibodies). Progress in the development of any disease modifying biologic treatment for Dupuytren has been hampered by the lack of clinically useful biomarkers. The characterization of nonsurgical Dupuytren biomarkers will permit disease staging from diagnostic and prognostic perspectives, as well as allows evaluation of biologic responses to treatment. Identification of such markers may transcend their use in Dupuytren treatment, because fibrotic biological processes fundamental to Dupuytren are relevant to fibrosis in many other connective tissues and organs with collagen-based tissue compartments. There is a wide range of potential Dupuytren biomarker categories that could be informative, including disease determinants linked to genetics, collagen metabolism, as well as immunity and inflammation (e.g., cytokines, chemokines). This narrative review provides a broad overview of previous studies and emphasizes the importance of inflammatory mediators as candidate circulating biomarkers for monitoring Dupuytren's disease.

Glia and neurons face different challenges in aging and may engage different mechanisms to maintain their morphology and functionality. Here, we report that adult-onset downregulation of a Drosophila gene CG32529/GLAD led to shortened lifespan and age-dependent brain degeneration. This regulation exhibited cell type and subtype-specificity, involving mainly surface glia (comprising the BBB) and cortex glia (wrapping neuronal soma) in flies. In accordance, pan-glial knockdown of GLAD disrupted BBB integrity and the glial meshwork. GLAD expression in fly heads decreased with age, and the RNA-seq analysis revealed that the most affected transcriptional changes by RNAi-GLAD were associated with upregulation of immune-related genes. Furthermore, we conducted a series of lifespan rescue experiments and the results indicated that the profound upregulation of immune and related pathways was not the consequence but cause of the degenerative phenotypes of the RNAi-GLAD flies. Finally, we showed that GLAD encoded a heterochromatin-associating protein that bound to the promoters of an array of immune-related genes and kept them silenced during the cell cycle. Together, our findings demonstrate a previously unappreciated role of heterochromatic gene silencing in repressing immunity in fly glia, which is required for maintaining BBB and brain integrity as well as normal lifespan.