Immunity & Ageing最新文献

Background: Obesity induces chronic inflammation and cellular senescence, contributing to metabolic and immune dysfunction. This study investigates the effects of plasma obtained from obese and non-obese C57BL/6 donor mice on senescence and inflammation markers in recipient mice.

Methods: Recipient C57BL/6 mice received intraperitoneal injections of 150 μl of pooled plasma from either obese (PO group) or non-obese (PNO group) donors once weekly for four weeks. Body weight, epididymal adiposity index, and thymus index were recorded. Senescence-associated β-galactosidase (SA-β-gal) activity was assessed in epididymal white adipose tissue (eWAT) and peripheral blood mononuclear cells (PBMCs). Gene expression of p16, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Plasma concentrations of IL-6 and TNF-α were measured using enzyme-linked immunosorbent assay (ELISA).

Results: Mice in the PO group showed significantly increased SA-β-gal activity in eWAT (P < 0.05) and PBMCs (P < 0.001) compared to the PNO group. In eWAT, p16 expression was significantly elevated (P = 0.019; log₁₀-fold change: 1.48). In PBMCs, IL-6 (P < 0.001; log₁₀-fold change: 0.90), p16 (P < 0.001; log₁₀-fold change: 1.41), and TNF-α (P < 0.001; log₁₀-fold change: 2.83) expressions were significantly upregulated in the PO group. No significant differences were observed in plasma cytokines, body weight, epididymal adiposity, or thymus index.

Conclusions: These results indicate that the pro-inflammatory and pro-senescence effects of obese plasma are not limited to the original donor but can actively transfer aging-related changes and immune dysfunctions to healthy recipient tissues, highlighting the need for further therapeutic exploration.

Background: Accelerated immune aging has been implicated in patients with end-stage kidney disease, but a detailed examination of immune profiles correlated with long-term outcomes for these individuals has never been performed. Therefore, we conducted a prospective observational study ("Immunity in end-stage renal disease", iESRD) to investigate the effects of immune aging on mortality among these patients. An exploratory panel of immune cell subsets was analyzed by flow cytometry at baseline (neutrophils, CD3-negative lymphocytes, CD4 and CD8 T cell differentiation stages, and three subsets of monocytes). Immune cell distribution patterns were identified through data-driven principal component analysis (PCA).

Results: A total of 409 hemodialysis patients (mean age 61.7 years, range 29.5-89.1) were enrolled and followed for three years, during which 75 deaths occurred. Compared with survivors, deceased patients displayed features of more advanced immune aging, which was also correlated with older chronological ages. For individual subset, a higher level of CD8 naïve cells and a lower level of CD4 effector memory cells at baseline were associated with lower mortality. For comprehensive immune signature, principal component analysis identified three major patterns, with PC3-characterized by loss of naïve T cells and enrichment of effector memory T cells and non-classical monocytes-strongly associated with age and independently corelated to all-cause (hazard ratio [HR] 1.31, P = 0.02) and cardiovascular mortality (HR 1.49, P = 0.04). A trend toward mortality risk in higher CMV IgG titer individuals was also observed. Importantly, PC3 retained prognostic value independent of chronological age, suggesting that immune dysfunction may contribute to excess mortality in dialysis patients.

Conclusions: Our results confirmed that an age-associated immune signature was associated with all-cause and cardiovascular mortality in hemodialysis patients. This immune monitoring may be extended to other chronic disease populations associated with aging.

Background: The neutrophil-to-lymphocyte ratio (NLR) is a low-cost inflammatory biomarker increasingly investigated in older populations as a cross-cutting indicator of immunosenescence and inflammaging. While elevated NLR has been shown to predict poor short-term outcomes in patients with COVID-19, its long-term prognostic role-particularly in older adults and in a sex-specific perspective-remains unclear. The aim of this study was to examine the association between admission NLR and 3.5-year all-cause mortality in older adults hospitalised with COVID-19, with a focus on sex-specific patterns.

Methods: Prospective observational cohort study with 3.5-year follow-up. A total of 440 patients aged ≥ 65 years hospitalized with confirmed SARS-CoV-2 infection were enrolled. NLR was calculated at admission and dichotomized using the optimal cut-off value (12.63) identified via maximally selected rank statistics. Associations between NLR and mortality were assessed using Cox proportional hazards models, adjusted for age, sex, and vaccination status. Effect modification by sex was explored through interaction terms and sex-stratified analyses.

Results: High NLR at hospital admission was independently associated with an increased risk of long-term all-cause mortality (adjusted HR 1.71; 95% CI: 1.21-2.43; p < 0.001). In sex-stratified analyses, this association remained significant only in females (HR 2.50; 95% CI: 1.49-4.22; p < 0.001). Sensitivity analyses revealed a significant association for mortality within 90 days of admission (HR 1.80; 95% CI: 1.15-2.81; p = 0.010), whereas no association was found for deaths occurring beyond 90 days (HR 0.83; 95% CI: 0.43-1.61; p = 0.58).

Conclusions: NLR identifies a time-limited window of high vulnerability in older adults, particularly among women, reflecting the interplay between acute inflammation, immunosenescence, and processes typically associated with frailty. These findings highlight NLR as a pragmatic marker of inflammaging that could support sex-sensitive risk stratification and post-discharge interventions in geriatric care.

Trial registration: Not applicable.

Background: Aging is characterized by progressive immunosenescence and inflammaging, in which impaired gut barrier and dysregulated mucosal immunity exacerbate systemic senescence. While probiotics modulate gut health, their role in mitigating age-related immune dysfunction via specific microbial metabolites remains unclear. This study aims to investigate the effects of Bacillus velezensis DS2, a novel probiotic, in alleviating inflammaging, with a focus on tryptophan-metabolic signaling and immune regulation.

Results: In senescent endothelial cells, DS2-sourced indole-3-lactic acid (ILA) activated aryl hydrocarbon receptor (AhR) signaling. This activation reduced the expression of senescence markers (p16, γ-H2A.X) and decreased the levels of pro-inflammatory molecules (ICAM-1, VCAM-1). In aged mice, DS2 supplementation increased the abundance of beneficial bacteria, including Lactobacillus and Ligilactobacillus. DS2 administration also elevated plasma ILA and IL-22 levels, and reduced intestinal permeability. This was evidenced by the expansion of IL-22-producing type 3 innate lymphoid cells (ILC3s) and activation of the AhR-IL-22 axis. Consequently, DS2 enhanced intestinal barrier integrity and mitigated systemic inflammation (TNF-α, IL-6). Exogenous ILA was sufficient to recapitulate these benefits by potentiating gut mucosal immunity and attenuating inflammaging, as all these effects were abolished by the AhR antagonist CH223191.

Conclusions: We demonstrate that DS2 mitigates inflammaging by producing ILA, which acts as a key metabolite to activate the AhR-IL-22-ILC3 axis. Our findings highlight the potential of targeting the gut-immune axis with specific probiotics as a novel strategy against age-related immune decline.