Immunity & Ageing最新文献

The global demographic shift towards an aging population has amplified the public health challenge posed by immunosenescence, a progressive remodeling of the immune system that compromises host defenses. This age-related decline is characterized by a reduction in adaptive immunity, marked by a diminished pool of naïve T-cells and an increased susceptibility to infections and poor vaccine responses. Simultaneously, it is defined by a paradoxical state of chronic low-grade inflammation, or "inflammaging," which accelerates age-related pathologies. This review posits "immunopause" as a conceptual framework for a state of severe immune decline, a state often viewed as an inevitable consequence of aging. However, the evidence synthesized herein challenges this view by positioning physical exercise as a potent, non-pharmacological intervention capable of countering this process. The report systematically reviews the cellular, molecular, and systemic mechanisms through which exercise exerts its beneficial effects, including the rejuvenation of T-cell repertoires, the regulation of cytokine networks, and the modulation of multi-organ axes involving myokines and the gut microbiome. By improving the efficacy of existing immune cells and shifting the systemic inflammatory milieu, chronic physical activity promotes a more "youthful" and functional immune phenotype. This synthesis not only underscores exercise's potential to enhance vaccine efficacy and serve as an adjuvant therapy for age-related diseases but also argues for a paradigm shift: from viewing immune aging as an immutable process to recognizing it as a modifiable state. The report concludes that exercise provides a scientifically validated strategy to extend healthspan and prevent the pathological state of immunopause.

Background: ​​ Immune function decline (immunosenescence) accelerates systemic aging and adversely impacts cognitive function. Antioxidants may mitigate these effects; however, the role of ascorbic acid (AA), a key antioxidant, in counteracting immunosenescence and enhancing cognition remains inadequately explored.

Results: In this study, AA administration (0.1 mg/g, tail vein, every 2 days for 30 days) significantly improved cognitive function in aged (16-month) C57BL/6 mice, without altering anxiety-like behavior (as assessed in the open field test). This was associated with elevated peripheral blood lymphocytes (T cells, B cells) and CD8⁺ T cells, alongside reduced myeloid cells (CD11b⁺). Single-cell RNA sequencing of PBMCs revealed AA reversed immunosenescent signatures-increasing T/B cell populations and decreasing neutrophils/macrophages-mimicking youthful immune profiles. In vitro, AA skewed hematopoietic stem cell (HSC) differentiation toward CD8⁺ T cells (increasing DN2 stage, suppressing myeloid CD11b⁺ cells) and enhanced splenic CD8⁺ T cell generation. Mechanistically, AA bound MYH9, activating cytoskeletal pathways. MYH9 inhibition (blebbistatin) reduced CD8⁺ T cells and increased CD11b⁺ cells-effects rescued by AA. Crucially, CD8⁺ T cell depletion abolished AA's cognitive benefits, confirming their essential role.

Conclusions: In summary, AA mitigates immunosenescence and improves cognitive function by targeting MYH9 to regulate CD8⁺ T cell differentiation and function. These findings establish a mechanistic basis for AA as a potential therapeutic agent against age-related immune and cognitive decline.

Skin aging is a multifactorial biological process driven by the cumulative effects of oxidative stress, chronic low-grade inflammation, and progressive deterioration of barrier function. Among its pivotal regulatory nodes, the Vitamin D-Vitamin D receptor (VDR) signaling axis acts as an integrative hub that senses and coordinates photic, redox, and metabolic cues to regulate immune homeostasis and structural integrity, thereby shaping the skin's defensive and reparative capacity throughout aging. Disruption of this axis amplifies inflammaging, accelerates dermal and epidermal structural decline, and compromises cutaneous resilience against environmental insults. Phenotypic shifts in keratinocytes, melanocytes, Langerhans cells, and T lymphocytes during aging are tightly linked to VDR-governed transcriptional programs and pathway crosstalk. Mechanistically, Nrf2-mediated antioxidant networks, Wnt/β-catenin and NF-κB signal interplay, stabilization of E-cadherin/β-catenin complexes, lipid metabolic remodeling, and reprogramming of immune tolerance collectively constitute the molecular basis through which Vitamin D mitigates skin aging. This review systematically delineates the critical role of the VDR axis in the onset and progression of skin aging and proposes its repositioning as a programmable molecular node for intervention, aiming to modulate inflammaging and maintain barrier homeostasis to slow the structural and functional decline of aging skin.

People living with HIV-1 (PLWH) are a population at higher risk for communicable disease and therefore a target group for vaccination. Owing to the success of anti-retroviral therapy, PLWH live longer, but face new challenges related to ageing, which add to their underlying immunodeficiencies. We review here the immune dysregulations occurring with chronic HIV-1 infection and ageing in the era of antiretroviral therapy, focusing on cellular mechanisms that can explain the lower immune response to most vaccines in older treated PLWH, and we discuss potential developments to improve vaccination strategies in this specific population.

Ageing is accompanied by a decline in immune function, associated with susceptibility to infections and malignancies, and reduced vaccine efficacy. These immunological changes, affect multiple components of the immune system, particularly T lymphocytes, which exhibit altered subset distributions and accumulate senescent features. CD57, a surface glycoprotein expressed on T cells, has emerged as a potential marker of terminal differentiation and senescence used for immunomonitoring in infection or cancer contexts. However, the use of CD57 as a marker of T cell senescence remains unclear. To investigate this, we analyzed CD57 expression on CD8⁺ and CD4⁺ T cells in healthy donors from two independent cohorts, considering cellular differentiation, age, cytomegalovirus status, and other senescence markers. Our findings reinforce the association between CD57 expression, T cell differentiation, and CMV seropositivity, but not with chronological age. Although CD57 is associated with altered proliferation and survival in all T cell differentiation subsets, it does not fully align with a senescent phenotype. Therefore, we propose that CD57 may be better appreciated as a marker of immunological age. Moreover, the interpretation of CD57 expression must account for CMV serostatus to avoid misleading conclusions, especially in oncology and ageing research.