Immunity & Ageing最新文献

Immunosenescence is the gradual deterioration in the functionality of the immune system that has various clinical manifestations, such as a weakened response to vaccination, higher susceptibility to viral/bacterial/fungal infection, and higher incidence rates regarding the ageing-based disorders. Conventionally used models, like animal or 2D models for unraveling the interactions between ageing and immunity are unable to depict the complexity of bodily environments. However, this major limitation can be addressed via using the organoid technology. For clarification, organoids are tissue-resembling 3D structures that are generated from stem cells; they have the major superiority of preserving the human physiology, multicellular intricateness, and the capability of dynamic interactions between the existing elements. Organoid-based technology has been applied for the study of different organ-specific immunosenescence, such as in the intestine, brain, liver, and skin. Besides, organoids offer the bright innovative future of senolytic CAR T lymphocytes and other regenerative-based therapies. This review narrates the cutting-edge application of organoids and the mechanisms involved in the detailed molecular processes of organ-specific immunosenescence.

Background: Amidst the ongoing COVID-19 pandemic, understanding factors that influence vaccine efficacy is crucial, particularly in older adults. Regular physical exercise and/or structured physical activity (SPA) has emerged as a potential modulator of immune responses, enhancing vaccine effectiveness. This systematic review aims to consolidate current evidence on the impact of SPA/exercise on both immune and inflammatory responses to COVID-19 vaccination in adults and older individuals.

Methods: Most relevant studies were extracted from indexed databases using health subject terms in English, Portuguese, and Spanish. Studies that examined the impact of regular exercise or SPA on inflammatory and/or immunological responses in relation to COVID-19 immunization were selected. In particular, all chosen studies included individuals who received vaccinations either prior to or following the exercise regimen or SPA, and the main goal was to evaluate these effects on immunological and/or inflammatory reactions induced by vaccination.

Results: Among the 7 studies included (n = 1149), the effects of regular exercise or PA on vaccine-induced immune responses while concurrently assessing inflammatory markers were examined. The findings suggest that moderate to high-intensity structured physical activity (50-70% of maximum heart rate for aerobic exercise and 60-80% of 1RM for resistance training), performed 3-5 times per week, was able to enhance immune responses to COVID-19 vaccination, particularly by mitigating chronic low-grade inflammation. Acute exercise can transiently boost immunity, whilst engagement in moderate SPA over a period of six months may contribute to sustained improvements in immune function, especially in older adults. However, these findings should be interpreted with caution due to variability in study design, sample characteristics, and potential confounding factors.

Conclusion: Regular exercise and SPA play a significant role in improving immune/inflammatory responses to COVID-19 vaccination. Older adults, in particular, may benefit from regular SPA and exercise as a strategy to counteract immunosenescence and optimize vaccine efficacy. However, further research is needed to better refine exercise protocols and determine long-term benefits in different populations.

Sarcopenia and atherosclerosis are prevalent age-related conditions increasingly recognized as interconnected through shared immune-mediated pathways. This review elucidates how "inflammaging" driven by dysregulated immune responses. Key age-related mechanisms include macrophage polarization imbalance, T/B cell dysregulation, and activation of pro-inflammatory signaling pathways. These processes promote oxidative stress, insulin resistance, creating a vicious cycle that exacerbates muscle and vascular decline. Emerging therapeutic strategies offering potential for dual-benefit interventions. Understanding these immune interactions provides a foundation for integrated approaches to mitigate sarcopenia and atherosclerosis in aging.

Ageing is a well-recognised factor influencing immune competence; however, elderly individuals remain underrepresented in clinical trials, resulting in gaps in our understanding of their immune responses to disease. To address this gap, we investigated circulating soluble immune checkpoints (sICs) and cytokines in the elderly and middle-aged individuals, both healthy and patients with colorectal cancer (CRC). Our findings revealed a decline in sICs and cytokine levels in healthy elderly individuals compared to their middle-aged counterparts. Key analytes -Galectin-9, sLAG-3, sPD-L1 and sTIM-3- effectively distinguished age groups in healthy volunteers (HVs). However, these differences were not observed when applying this signature in CRC patients, where the combined analysis of plasma Galectin-9, IL-10 and CXCL10 did reliably discriminate between elderly CRC patients and age-matched HVs. This result highlights the potential of these immunological factors as non-invasive biomarkers for cancer detection in this population. In contrast, a much larger number of soluble markers was needed to distinguish CRC patients from HVs among the middle-aged. Collectively, these findings underscore the relevance of observing age stratification for biomarker discovery and lay the groundwork for further exploration of soluble immune mediators in ageing related to tumour pathophysiology.

Objective: To investigate the distribution characteristics of peripheral blood lymphocyte subsets in elderly psoriasis patients and analyze the interactions between immunosenescence and psoriasis and their impact on immune cell subpopulations.

Methods: This cross-sectional study enrolled 318 psoriasis patients and 167 healthy controls, stratified by age into elderly (≥ 65 years) and non-elderly (18-64 years) groups. Peripheral blood lymphocyte subsets, including CD3⁺ T cells, CD4⁺ T cells, CD8⁺ T cells, B cells, and NK cells, were analyzed using four-color flow cytometry. Generalized linear models were employed to analyze associations between PASI scores and lymphocyte subsets, and correlation network analysis was constructed to evaluate interaction patterns among immune cell populations.

Results: The elderly psoriasis group demonstrated significantly reduced CD8⁺ T cell percentage compared to controls (24.52% vs. 28.62%, P < 0.001), accompanied by an elevated Th/Ts ratio (1.57 vs. 1.27, P < 0.001) and significantly increased NK cell percentage and absolute count. Generalized linear modeling revealed a significant negative interaction effect between psoriasis and age on CD8⁺ T cell percentage (β = -3.979, P = 0.019), while the Th/Ts ratio exhibited a significant positive interaction effect (β = 0.230, P = 0.010). B cell absolute count showed a positive correlation with PASI score (r = 0.180, P = 0.001), with this correlation being more pronounced in elderly patients (r = 0.308, P = 0.014). Network analysis demonstrated reduced connectivity density among immune cell subpopulations in elderly patients.

Conclusions: Elderly psoriasis patients exhibit age-related alterations in peripheral blood lymphocyte subset distribution, characterized by decreased CD8⁺ T cells, elevated Th/Ts ratio, and increased NK cells. B cells may serve as potential biomarkers for assessing disease severity in elderly psoriasis patients.

Influenza viruses remain a significant threat to both animals and public health. Each season influenza virus infection causes significant morbidity and mortality, especially in the elderly population. Annual vaccination boosts antibody titers against circulating influenza strains in elderly individuals, albeit the antibody responses are not as robust as those in younger adults. In addition, the elderly have a rapid decline in antibody titers over a 6-month period following an influenza virus immunization with antibody titers often returning to baseline at the beginning of each influenza season. Thus, there is a need for next-generation influenza vaccines that induce broadly and long-lasting protective immunity against influenza viruses in high-risk, elderly populations. In this study, Computationally Optimized Broadly Reactive Antigen (COBRA)-based H1 and H3 hemagglutinin (HA) vaccines were tested in combination with toll-like receptor (TLR) agonists as adjuvants in elderly ferrets with immune memory to historical influenza viruses to assess the breadth of protective antibody responses. These COBRA vaccines were mixed with either TRAC478, which is a combination of two TLR agonists, INI-2002 (a synthetic TLR4 agonist) and INI-4001 (a synthetic TLR7/8 agonist), or SAS, which is a mixture of INI-2002 and a semi-synthetic saponin. Elderly ferrets vaccinated with H1/H3 COBRA HA proteins plus TRAC478, or SAS had antibodies with hemagglutination-inhibition (HAI) activity against a panel of H1N1 and H3N2 influenza viruses that were significantly higher than animals vaccinated with unadjuvanted HA vaccine only. These elderly ferrets were protected following challenge with influenza virus with little to no detectable signs of disease or weight loss. In addition, there were reduced viral titers detected in nasal washes compared to elderly ferrets vaccinated with unadjuvanted HA proteins. Overall, both TRAC478 and SAS were effective adjuvants to enhance protective antibodies in elderly ferrets compared to animals that were vaccinated with only COBRA HA protein.

Cellular senescence is a fundamental biological process characterized by stable cell cycle arrest, genomic instability, and the acquisition of a proinflammatory secretory phenotype. While senescence is traditionally associated with aging, growing evidence reveals that chronic infections such as viral, bacterial, and protozoan parasites can serve as powerful inducers of senescence, contributing to premature aging and long-term tissue damage. This review explores the diverse mechanisms by which persistent pathogens trigger or sustain senescence in host cells. We highlight how these chronic infections manipulate host DNA repair, mitochondrial dynamics, telomere maintenance, oxidative stress, and immune function to promote senescence and immunosenescence. Emerging findings also reveal how pathogens hijack the host cellular machinery to induce senescence across various tissue types. In many cases, senescence not only enables pathogen persistence but also drives pathological outcomes such as fibrosis, neurodegeneration, cardiomyopathy, and immune exhaustion. Collectively, this emerging evidence highlights a unifying strategy among diverse pathogens: the exploitation of cellular senescence to support chronic infection and promote disease. Understanding how infectious agents drive senescence offers new insights into age-related pathologies and highlights potential therapeutic targets, such as senolytic and senomorphic agents, to mitigate the long-term impacts of chronic infections.

We have previously demonstrated that proinflammatory T cells in adipose tissue and the liver play a mechanistic role in glucose intolerance in old mice. Further, we and others have demonstrated that early life thymectomy results in a T cell phenotype that shares many features of classical T cell aging in an otherwise young healthy mouse. In this investigation, we sought to test the hypothesis that inducing premature T cell aging via early life thymectomy results in T cell mediated inflammation of the liver and visceral adipose tissue, as well as glucose intolerance in otherwise young mice. Mice were thymectomized at three weeks of age. At 9 months of age, thymectomized mice exhibited glucose intolerance that was independent of body mass along with greater frailty. Thymectomized mice exhibited blunted proportions of naïve and greater proportions of memory cells in the spleen, liver and perigonadal adipose tissue (pgWAT). Bulk RNAseq of the pgWAT revealed that thymectomized mice exhibited an upregulation of genes responsible for immune activation, chemokine signaling, and inflammation along with a downregulation of genes responsible for metabolic function. We also found that T cells in the pgWAT of thymectomized mice exhibited greater chemokine receptor expression as well as increased markers of histopathological inflammation that were independent of greater adipose tissue expansion. These results suggest that early life thymectomy results in T cell mediated pgWAT inflammation, systemic glucose intolerance and frailty in adult mice.