The researchers isolated peripheral blood mononuclear cells and examined CD4+ and CD8+ T cells from the three participant groups. To mimic the short increase in adrenaline associated with acute exercise, they exposed cells to the β-adrenergic agonist isoproterenol for 30 minutes. Selected cultures also received ICI-118,551, a selective β2-adrenergic receptor blocker, allowing the investigators to distinguish effects that depended on β2 signaling from effects that remained when that pathway was inhibited. After a one-hour rest, cells were stimulated for four hours with phorbol 12-myristate 13-acetate, or PMA, and ionomycin. These compounds induce rapid T-cell activation through protein kinase C activation and intracellular calcium flux, bypassing recognition of antigen by the T-cell receptor. This approach was chosen because its rapid kinetics helped separate short-term responses to isoproterenol from longer-term adaptations that could desensitize adrenergic signaling.

Age-related differences were clearest in CD8+ T cells. Following PMA and ionomycin stimulation, the early activation marker CD69 increased significantly only in the young group. Young participants consequently displayed greater CD8+ activation than both older groups, including the highly active older adults, with reported comparisons of p < 0.001 against the highly active group and p = 0.003 against the moderately active group. Blocking β2-adrenergic receptors during adrenergic stimulation also reduced CD8+ activation, and this condition effect was significant at p = 0.011. CD4+ cells behaved differently: PMA and ionomycin increased CD69 expression, but there was no significant group-by-condition interaction showing that age or habitual activity altered that response. In the activated CD8+ population, adrenergic stimulation itself did not improve CD69 expression, while adding the β2 blocker reduced activation relative to adrenergic stimulation alone. The findings therefore identify a selective age-related vulnerability in the CD8+ subset that was not visibly restored by higher habitual activity under the tested conditions.

Metabolic measurements suggested that habitual activity was associated more clearly with glucose-transporter regulation than with recovery of CD8+ activation. Surface expression of glucose transporter 1, or Glut1, increased after PMA and ionomycin in both CD4+ and CD8+ T cells, with condition effects of p = 0.002 and p < 0.001, respectively. In unstimulated CD8+ cells, combining β2-receptor blockade with isoproterenol increased Glut1 expression in every group relative to adrenergic stimulation alone, with p < 0.001 in each comparison. The increase was significantly greater in highly active older adults than in moderately active older adults at p = 0.043. The difference between the highly active older and young groups showed a nonsignificant trend at p = 0.073. Among activated CD8+ cells, β2 blockade also produced a larger Glut1 increase than stimulation alone. Because blocking β2 did not eliminate the metabolic response, the measured metabolic effect of isoproterenol could not be attributed solely to β2-adrenergic receptors.

That result complicates a simple model in which β2 signaling uniformly improves T-cell metabolism. The authors proposed that residual or opposing adrenergic effects might involve β1-adrenergic receptors, although the study did not directly test that mechanism. This possibility is compatible with the observation that β2 blockade reduced rather than enhanced CD8+ activation in some conditions. It indicates that the balance among receptor subtypes may depend on whether cells are resting or activated and on the duration and context of stimulation. The investigators specifically called for future experiments that distinguish β1 from β2 effects. Their hypothesis is also consistent with earlier mouse work cited by the authors, in which β-adrenergic blockade improved aspects of exhausted CD8+ T-cell function, but that animal research does not establish what occurred in the present human participants.

Neither age nor habitual activity altered the measured abundance of ADRB2 messenger RNA in CD4+ or CD8+ T cells. The researchers also found no group differences in intracellular cyclic AMP, or cAMP, after a two-minute exposure to 10 micromolar isoproterenol. Isoproterenol did significantly raise cAMP overall, at p = 0.0027, showing that the treatment engaged a functional intracellular signaling response. Nevertheless, the similar cAMP responses across groups argue against gross differences in β2-receptor transcription or canonical cAMP responsiveness as the explanation for the activation and Glut1 patterns. They do not rule out subtler changes in receptor protein abundance, cell-surface density, receptor sensitivity, downstream signaling or post-transcriptional regulation. Quantitative reverse-transcription polymerase chain reaction provided only an indirect indication of receptor expression rather than a direct measurement of receptor protein abundance or surface density.

Direct measurements of fuel use and lipid storage were less decisive than the Glut1 results. A fluorescent glucose analogue, 2-NBDG, showed a nonsignificant trend toward increased uptake after activation in CD4+ cells from the moderately active older group, at p = 0.088, but there was no corresponding effect in CD8+ cells and no significant group difference. Lipid accumulation measured with BODIPY did not increase with activation in CD4+ cells, while PMA and ionomycin reduced lipid accumulation in CD8+ cells as a condition effect at p = 0.010. The authors cautioned that 2-NBDG is an imperfect surrogate for glucose metabolism in T cells and that elevated surface Glut1 does not necessarily demonstrate increased glycolytic flux. Actual glucose use also depends on transporter localization, co-stimulatory signaling, nutrient availability and downstream metabolic pathways. A four-hour activation window may also have been too short to produce substantial changes in glucose utilization or lipid accumulation, while the study lacked a true positive control for those two assays.

The study design limits how broadly its associations can be interpreted. Habitual activity among the older participants was measured objectively for seven days with accelerometry. Highly active older adults accumulated a mean 149.5 ± 22.9 minutes per day of moderate-to-vigorous physical activity, compared with 71.5 ± 29.1 minutes per day among moderately active older adults; both groups met physical-activity recommendations. Young participants’ activity was instead estimated through a general-health questionnaire that was not validated, so the comparison across the age boundary was less rigorous. The sample included only six participants per group and no physically inactive older adults. It also lacked sex balance, omitted direct analysis of naïve, memory and senescent T-cell proportions, and could not fully account for hormones, inflammatory signals, blood-flow changes and other physiological conditions present during real exercise. Only one blocker concentration was tested, limiting validation of its selectivity in T cells, while α-adrenergic receptors and other simultaneous exercise signals were not included in the model.

The results should therefore be treated as hypothesis-generating rather than evidence of a causal effect of exercise. Although highly active older adults retained the age-related deficit in CD8+ activation, their CD8+ cells showed a different pattern of Glut1 regulation during adrenergic stimulation, including a stronger response to β2 blockade than was seen in moderately active older adults. The experiment also followed one brief isoproterenol exposure, whereas repeated or sustained adrenergic signaling may produce different immune effects. PMA and ionomycin provide controlled pharmacological activation but do not reproduce antigen presentation, physiological stress or the full neuroendocrine environment of exercise. No result in this study demonstrated that more active older adults had stronger vaccine responses, controlled tumors more effectively or experienced fewer infections. What the data show is narrower: in an in vitro model of acute adrenergic stimulation, habitual activity level was associated with how CD8+ T cells integrated signals affecting glucose-transporter expression, while the age-related impairment of CD8+ activation remained. Larger studies incorporating more physiological stimulation, direct metabolic measurements and separate tests of β1 and β2 receptors will be needed to determine the biological meaning of these associations.

Subject of Research: Associations among habitual physical activity, aging, adrenergic signaling and human T-cell activation and metabolism

Article Title: Impact of habitual physical activity and age on T cell metabolism and activation via β2-adrenergic receptor modulation

Article References: Sardeli, A. V., Ramkrapes, A., Boyes-Jensen, J., Hazeldine, J., Batatinha, H., Duggal, N. A., Calebiro, D., & Turner, J. E. (2026). Impact of habitual physical activity and age on T cell metabolism and activation via β2-adrenergic receptor modulation. Frontiers in Aging, 7, Article 1869552. https://doi.org/10.3389/fragi.2026.1869552

Image Credits: AI Generated

DOI: 10.3389/fragi.2026.1869552

Keywords: habitual physical activity, immune aging, CD8+ T cells, adrenergic signaling, β2-adrenergic receptor, T-cell activation, cellular metabolism, Glut1, immunosenescence, exploratory human study, Impact, habitual

The study drew on 4,209 volunteers recruited between January 2022 and December 2023 through the First Affiliated Hospital of Guangzhou Medical University (Loudi Hospital), including 2,898 women and 1,311 men. All participants were healthy controls screened to exclude active immune disorders, malignancies, recent infections, and immunosuppressive therapy. Researchers measured ten immune parameters in peripheral blood using flow cytometry, covering total T cells, CD4+ and CD8+ T cell subsets, the CD4/CD8 ratio, B cells, natural killer cells, NKT cells, and expression of the checkpoint molecule PD-1 on several cell types.

Because raw immune measurements rarely follow a normal distribution, the team applied Box-Cox transformations and Tukey’s method to remove outliers before analysis, leaving between 4,123 and 4,204 reference individuals per parameter. Age-related trends were then examined with sex-stratified smooth curves and non-parametric tests, and a 1:1 propensity score matching procedure was used to build age-balanced male and female cohorts for direct comparison.

The headline finding is a sharp sexual dimorphism in B cell dynamics. In women, the proportion of CD19+ B cells rose with age, while in men it fell, producing opposite trajectories that the authors link tentatively to hormonal regulation and X-chromosome-encoded immune genes. After age matching, women had significantly higher B cell percentages than men, but a stratified analysis showed this gap was not significant before age 50 and only emerged after menopause, pointing to the postmenopausal window as the critical period.

T cell subsets told an equally striking story. In women, CD4+ helper T cells and the CD4/CD8 ratio climbed to a peak in the 55-to-59-year age group, while CD8+ cytotoxic T cells declined steadily across the lifespan. The authors describe this as a “scissor-like” pattern that closely parallels the abrupt drop in estrogen levels around menopause. Because hormone levels were not directly measured, they caution that this mechanistic interpretation remains speculative, but the timing of the immune shift aligns closely with the typical age of menopause as defined by the STRAW+10 staging framework.

PD-1, an immune checkpoint molecule best known as the target of modern cancer immunotherapies, showed a complex, cell-type-specific pattern. Women had lower PD-1 expression on CD4+ T cells and NK cells but higher PD-1 on CD8+ T cells, and the proportion of CD8+ PD-1+ cells showed a transient peak in the 60-to-64-year group. The authors suggest this may mark a window of heightened functional dysregulation in cytotoxic immunity, with potential relevance for how immune checkpoint status should be interpreted across demographic groups.

Innate immunity shifted as well. Natural killer cell percentages increased with age in both sexes, but the rise was markedly steeper in men, and the fraction of NK cells expressing PD-1 declined significantly with age in women. NKT cells, by contrast, showed no significant age-related trend. After age matching, women had higher NK cell and NKT cell proportions than men, alongside their higher CD4/CD8 ratios, reinforcing the picture of two distinct immune aging trajectories.

The findings carry practical implications. Because women generally mount stronger vaccine responses but suffer more autoimmune disease, and because PD-1 expression shapes anti-tumor immunity and postoperative infection risk, the authors argue that both sex and reproductive stage should be factored into studies of immune aging and into interventions such as vaccination strategies for middle-aged women. The observed B cell persistence in older women may represent a distinctive adaptive feature of female immunosenescence, though its consequences for humoral immunity remain to be tested.

The study has clear limitations. It is cross-sectional, so it captures age-related differences between individuals rather than tracking immune changes within the same person over time. Without menstrual records or hormone measurements, the researchers could not formally stage participants under STRAW+10 and instead used age groups as an approximation, meaning the 50-to-54-year group inevitably mixes perimenopausal and early postmenopausal women. The authors call for longitudinal studies that pair hormone monitoring with systematic reproductive staging to confirm whether the menopausal transition itself drives the immune shifts observed here.

Even with those caveats, the scale of the cohort and the consistency of the sex differences make a strong case that immunosenescence is not a single process but two, diverging sharply at midlife. For a field in which clinical trial populations and reference ranges have historically skewed male, the message is that middle-aged women may need their own immunological yardsticks, and that menopause deserves a place alongside chronological age as a variable in immune research.

Subject of Research: Sex differences in lymphocyte subset changes during the menopausal transition and immunosenescence

Article Title: Dynamic Shifts in Lymphocyte Subsets During the Menopausal Transition and Sexual Dimorphism in Immunosenescence

Article References: Xuan, C., He, L., Bohan, Z., Junming, X., Qingchao, L., & Junting, H. (2026). Dynamic Shifts in Lymphocyte Subsets During the Menopausal Transition and Sexual Dimorphism in Immunosenescence. Immunity, Inflammation and Disease, 14(10), Article e70558. https://doi.org/10.1002/iid3.70558

Image Credits: AI Generated

DOI: 10.1002/iid3.70558

Keywords: immunosenescence, menopause, lymphocyte subsets, PD-1, T cells, B cells, natural killer cells, sexual dimorphism, flow cytometry, estrogen, immune aging, propensity score matching

The research team, led by pulmonologist Homer L. Twigg III, took advantage of a unique resource: a CLIA-approved clinical bronchoalveolar lavage laboratory that serves clinicians across central Indiana. Bronchoalveolar lavage, or BAL, involves threading a bronchoscope into the airways and instilling saline to wash out cells and soluble proteins from the alveolar spaces, the site where gas exchange occurs. Since October 2020, the laboratory had been receiving BAL fluid from patients undergoing bronchoscopy as part of their clinical work-up for persistent pulmonary symptoms after COVID-19. The only requirement for inclusion in the study cohort was a documented positive SARS-CoV-2 PCR test at some point before the lavage was performed.

By May 2022, the investigators had collected 37 BAL samples from 37 different patients. Five of these were obtained less than 28 days after a positive test and were classified as acute infections, while the remaining 32 were collected between 28 and 730 days after diagnosis, with a median of 178 days. The samples were processed by cytocentrifugation to generate cell differentials, and specimens contaminated with more than 15 percent buccal mucosal or airway epithelial cells were excluded. Two control groups were used for comparison: five healthy volunteers undergoing research bronchoscopy, and seven patients whose clinical BAL samples predated the pandemic entirely.

The cellular analysis revealed that suspected post-COVID-19 lung disease splits into three distinct inflammatory phenotypes. The first was essentially a normal BAL cell differential, with no increase in lymphocytes and minimal neutrophil accumulation. The second was a neutrophilic predominant pattern, defined by neutrophils making up at least 10 percent of the total nucleated cell population and exceeding the lymphocyte fraction. The third was a lymphocytic predominant pattern, in which lymphocytes accounted for at least 15 percent of cells and outnumbered neutrophils. Among the 12 patients with elevated lymphocytes, 8 had markedly inverted CD4-to-CD8 ratios, a finding classically associated with hypersensitivity pneumonitis, nonspecific interstitial pneumonia, chronic viral infections, and cryptogenic organizing pneumonia. The two patients with elevated rather than inverted ratios had underlying conditions, sarcoidosis in one case and mycobacterial antigen-associated hypersensitivity pneumonitis in the other, both known to drive CD4-predominant alveolitis.

Perhaps the most striking result came from the search for viral remnants. Using a commercial ELISA with a sensitivity of 0.256 picograms per milliliter, the team measured SARS-CoV-2 spike protein in acellular BAL fluid. Spike protein was readily detected in unconcentrated lavage fluid from the post-COVID patients compared with controls, and the difference remained significant even after correcting for dilution by expressing concentrations as picograms per milliliter of epithelial lining fluid, calculated using the urea method developed by Rennard and colleagues. Remarkably, spike protein was detected up to 627 days after the initial diagnostic test, supporting the hypothesis that residual viral proteins persist in the lung long after acute infection has cleared. The authors note that expanded data on persistent spike and nucleocapsid proteins, as well as viral nucleic acids, in this same cohort are described in a separate submitted manuscript.

To probe the pulmonary antibody response, the investigators turned to the PepSeq platform, a highly multiplexed serological technique that uses libraries of thousands of DNA-barcoded peptides with next-generation sequencing readout. For these experiments, a human virome-wide assay comprising 15,000 peptides was employed, with samples sequenced to a depth of more than 50 reads per peptide and replicate samples showing a median Z-score concordance of 0.94. Of the first 23 post-COVID subjects tested, 14, or 61 percent, had anti-SARS-CoV-2 antibodies in their BAL fluid, including many with polyclonal responses targeting epitopes on both spike and nucleocapsid proteins. Because the unstructured 30-mer peptides used in PepSeq cannot generally detect antibodies against conformational epitopes, the team also measured neutralizing activity with the cPass assay, which tests the ability of a sample to block binding between spike protein and the ACE2 receptor. Eleven of the 37 BAL samples, or 30 percent, exceeded the assay’s 30 percent inhibition cutoff, while no control sample exceeded 18 percent, and there was complete concordance between neutralizing antibody detection and PepSeq positivity.

The clinical correlations, however, proved more elusive. All subjects underwent chest CT scanning before bronchoscopy, and the scans were reviewed blindly by a NIOSH B Reader radiologist and grouped into predominantly ground glass opacities, predominantly fibrotic or interstitial changes, an equal mixture of both, or other patterns. No clear association emerged between radiographic appearance and the type of inflammatory milieu found in the lung. Long-term outcomes, tracked through chart review as of January 1, 2026, included vital status, need for lung transplant, and need for supplemental oxygen. The BAL inflammatory pattern was unable to predict long-term outcome in this underpowered analysis, although an intriguing signal appeared: no early adverse outcomes were observed among subjects with a normal BAL differential. In unadjusted logistic regression, the odds of a good outcome relative to the neutrophilic pattern were 2.13 for the normal group and 2.24 for the lymphocytic group, with confidence intervals that crossed one.

The findings carry significant implications for how post-COVID-19 lung disease is studied and treated. Because the NASEM definition of long COVID adopted by the NIH RECOVER initiative is purely clinical, relying on symptoms and radiographic findings after documented infection, patients grouped together under that umbrella may in fact harbor fundamentally different processes. The authors suggest that patients with a CD8-predominant lymphocytic pattern may have cryptogenic organizing pneumonia and could respond to corticosteroids, while those with neutrophilic inflammation may have the usual interstitial pneumonia pattern described in surgical lung biopsies of post-COVID patients. Patients with normal lavage fluid, who underwent bronchoscopy because of persistent CT abnormalities, likely have stable scar tissue from their acute infection, which could explain why some post-COVID fibrotic changes fail to progress and may even resolve, echoing the experience after SARS-CoV-1.

The persistence of spike protein also fits into a broader picture of chronic viral antigen stimulation. Prior work has documented residual viral proteins long after other infections, including HIV Nef protein in the lungs of aviremic patients and residual antigen presentation following influenza. Autopsy studies performed a median of 39 days after infection found persistent viral genomic RNA in nearly all patients, and a systematic review detected SARS-CoV-2 RNA in various tissues in 5 to 59 percent of subjects up to six months after acute infection. Persistent antigen can sustain chronic inflammation through multiple mechanisms, including ongoing B and T cell responses, T cell exhaustion and immunosenescence, direct stimulation of macrophages through TLR2, and activation of the complement system, which could plausibly drive the neutrophilic inflammation seen in a third of the patients. Notably, some form of immunosuppression was prevalent in the cohort, affecting 28 of 37 subjects, which the authors suggest may contribute to failure to clear the virus.

The investigators are careful to acknowledge the limitations of their work. The cohort is small and underpowered for linking inflammatory patterns to outcomes, the samples were collected relatively early in the pandemic before widespread vaccination and when more virulent strains circulated, and the cPass 30 percent cutoff was developed for plasma rather than BAL fluid, making the neutralization findings exploratory. There is also no comparison cohort of previously infected patients without chronic lung disease. Still, the study demonstrates that post-COVID-19 lung disease exists in several immunologically distinct forms, that viral proteins can linger in the lung for up to two years, and that clinical presentation alone may be an unreliable guide to the biology underneath. Whether residual SARS-CoV-2 components drive these phenotypes, and whether SARS-CoV-2-specific immune responses can ameliorate the disease, is currently under study.

Subject of Research: Inflammatory and immunologic profiling of bronchoalveolar lavage fluid in patients with post-COVID-19 lung disease

Article Title: Inflammatory and immunologic analysis of bronchoalveolar lavage from patients with post-COVID-19 lung disease

Article References: Twigg, H. L., III, Wilson, R., Yu, A. Q., Li, W., Altin, J. A., Tarver, R. D., Knight, I., Smith, P. A., Fraser, M. E., Castelluccio, P., & Rie, J. (2026). Inflammatory and immunologic analysis of bronchoalveolar lavage from patients with post-COVID-19 lung disease. Frontiers in Microbiology, 17, Article 1923299. https://doi.org/10.3389/fmicb.2026.1923299

Image Credits: AI Generated

DOI: 10.3389/fmicb.2026.1923299

Keywords: long COVID, post-COVID-19 lung disease, bronchoalveolar lavage, SARS-CoV-2, spike protein, viral persistence, neutralizing antibodies, PepSeq, pulmonary inflammation, interstitial lung disease, alveolar macrophages, immunosenescence

The research, conducted within the framework of the COVAC-3 project, followed 388 residents aged 65 and older across 13 long-term care facilities in five Italian regions: Calabria, Friuli-Venezia Giulia, Lazio, Puglia, and Veneto. Participants were enrolled between November 2023 and February 2024 and tracked for 12 months, with blood drawn at four time points: baseline, three months, six months, and twelve months. At each visit, the researchers measured quantitative IgG antibodies against the SARS-CoV-2 Spike protein, the principal target of vaccine-induced immunity, alongside semi-quantitative antibodies against the Nucleocapsid protein, which serve as a serological fingerprint of prior natural infection.

The study population was typical of institutionalized elderly cohorts in its fragility. The mean age was 84.2 years, roughly 71 percent were women, and residents carried an average of four chronic conditions each, ranging from hypertension and cognitive decline to diabetes and heart failure. About half had received a booster dose during the 2023/2024 campaign, while 67 percent showed serological evidence of a previous SARS-CoV-2 infection. This overlapping mixture of repeated vaccination and natural exposure is precisely what makes immune responses in this population so difficult to disentangle using traditional statistical approaches that examine one variable at a time.

To cut through that complexity, the team turned to unsupervised machine learning. First, they used Principal Component Analysis to compress a large matrix of longitudinal antibody measurements, demographics, and vaccination history into a handful of dimensions capturing the main sources of variability. The first principal component was dominated by anti-Spike titers across all time points, essentially reflecting the magnitude and persistence of the vaccine-induced humoral response. The second was driven by anti-Nucleocapsid levels, a proxy for natural infection, and the third distinguished residents vaccinated within a month of baseline from those boosted earlier or not at all. Together, the first three components explained 66.4 percent of the total variance.

K-means clustering was then applied to those component scores, and the number of groups was chosen using a battery of internal validation metrics, including the Silhouette, Calinski-Harabasz, and Davies-Bouldin indices, combined with bootstrap resampling to test reproducibility. Three clusters emerged, and they proved remarkably stable: the mean Adjusted Rand Index across 100 bootstrap iterations was 0.74, indicating strong partition consistency. The three groups were also nearly equal in size, with 130, 125, and 133 residents respectively, and baseline characteristics differed significantly among them.

The first profile, labeled the Vaccine-Driven group, consisted of residents with moderate anti-Spike titers, little serological evidence of past infection, and a gradual, progressive antibody decline over the year. The second, the Hybrid Immunity group, comprised individuals with clear markers of prior infection but minimal uptake of the recent booster. Despite lower starting antibody concentrations, this group displayed the flattest trajectory of all, with antibody levels remaining essentially stable throughout the 12 months of follow-up. The third and most striking profile, the High-Peak Hybrid Responder group, combined recent boosting with prior infection and showed the highest baseline anti-Spike titers of the entire cohort, with a median of 10,700 BAU/mL, followed by the steepest rate of waning.

Linear mixed-effects models quantified these differences rigorously. The Vaccine-Driven reference cluster declined modestly but significantly over time, while the High-Peak Hybrid Responder group showed a significantly steeper slope, with an average marginal effect of minus 0.088 on log-transformed antibody levels per follow-up unit, compared with minus 0.031 in the reference group. The Hybrid Immunity group, by contrast, showed no statistically significant change at all. The pattern suggests that a high initial peak, driven by recent antigenic stimulation, is followed by a proportionally larger absolute drop, a phenomenon consistent with the natural decay kinetics observed after booster vaccination in older adults in previous studies.

Clinically, the picture was reassuring. Only 12 of the 388 residents, or 3.1 percent, developed documented symptomatic SARS-CoV-2 infection during the follow-up year, and there were no COVID-19-related deaths in the cohort. The few incident cases were spread across all three clusters, with no statistically significant association between cluster membership and infection risk, although the authors caution that the very low number of events limits the statistical power of that comparison. Notably, cognitive decline and dementia were more frequent in the High-Peak Hybrid Responder group, at nearly 70 percent, than in the other two profiles, hinting at possible links between immune trajectory patterns and clinical frailty dimensions that merit further investigation.

The researchers are careful to draw a clear line between description and prediction. Because the clustering itself incorporated longitudinal antibody measurements, the subsequent trajectory modeling serves as a descriptive characterization of the data-derived groups rather than an independent validation of clinical protection. Antibody titers, they note, represent only one dimension of immunity; they do not capture neutralization capacity or the T-cell responses that are particularly relevant in older adults. The observational design also meant booster timing could not be standardized, and a small number of post-baseline vaccinations and infections could not be fully accounted for in the primary model.

Even with those caveats, the study carries a meaningful message for public health. Rather than stratifying elderly populations by chronological age or comorbidity counts alone, multidimensional, data-driven profiling could help identify subgroups with genuinely different antibody dynamics, potentially informing more tailored booster schedules for long-term care residents. The work also demonstrates that unsupervised machine learning, applied thoughtfully to longitudinal serological data, can reveal structure in highly heterogeneous immune responses without imposing predefined biological assumptions. As booster campaigns continue and hybrid immunity becomes the norm rather than the exception, approaches like this one may become essential tools for understanding who retains protection, who wanes fastest, and when the next dose will do the most good.

Subject of Research: Longitudinal SARS-CoV-2 antibody response profiles in long-term care facility residents identified through unsupervised machine learning

Article Title: Longitudinal immune trajectories following SARS-CoV-2 vaccination in long-term care facility residents: an unsupervised analysis approach

Article References: Palmieri, A., Damiano, C., Leone, P., Trevisan, C., Malara, A., Zucchelli, A., Incalzi, R. A., Prato, R., Fortunato, F., Baldovin, T., Coin, A., Minchella, P., Giordano, S., Palamara, A. T., Onder, G., & Fedele, G. (2026). Longitudinal immune trajectories following SARS-CoV-2 vaccination in long-term care facility residents: an unsupervised analysis approach. Frontiers in Aging, 7, Article 1963384. https://doi.org/10.3389/fragi.2026.1963384

Image Credits: AI Generated

DOI: 10.3389/fragi.2026.1963384

Keywords: SARS-CoV-2, vaccination, long-term care facilities, machine learning, K-means clustering, principal component analysis, hybrid immunity, antibody waning, immunosenescence, older adults, humoral immunity, booster doses

Respiratory viral infections remain a leading global cause of illness and death, with influenza virus alone responsible for an estimated 3 to 5 million severe cases and up to 650,000 deaths each year. Older adults bear a disproportionate share of this burden, experiencing substantially higher mortality than younger populations. Vaccination remains the main strategy to reduce influenza disease, but its effectiveness in people aged 60 and older is markedly lower than in younger adults, with most studies reporting protection of roughly 20 to 50 percent in older individuals compared with 60 to 90 percent in younger groups. This gap has created an urgent need for approaches that safeguard aging populations against influenza and other respiratory infections, and the upper respiratory tract microbiota has emerged as a promising target.

The human respiratory tract is divided into upper and lower compartments. The upper tract includes the anterior nares, nasal passages, paranasal sinuses, nasopharynx, and oropharynx, while the lower tract comprises the larynx, trachea, bronchi, and alveoli. Because the upper tract is the primary entry point for inhaled air and hosts the highest microbial density, it acts as a gatekeeper to the lower airways. Within it, the nasopharynx and oropharynx provide distinct environments shaped by immune activity, mucus flow, temperature, tissue architecture, and cell composition. Bacterial biomass varies dramatically by site, with around 1,000 bacteria in the nasopharynx and up to 1 million in the oropharynx. Disruption of these ecosystems by viral infection can reduce colonization resistance, worsen local inflammatory responses, and facilitate the spread of pathogens into the lower respiratory tract, leading to more severe disease.

Although the role of the upper-airway microbiome in respiratory health is increasingly recognized, evidence on how aging shapes these communities remains limited. Studies in older adults have shown reduced oropharyngeal diversity, changes in community composition, and a loss of niche distinctness compared with younger individuals. These age-related shifts are discussed in relation to immunosenescence and chronic low-grade inflammation and may contribute to the higher burden of respiratory infections in older adults. However, little has been known about upper-airway microbiota dynamics during acute respiratory illness in this population and its interaction with the host, leaving an important gap in understanding infection risk and resilience.

To address this gap, Kool and colleagues analyzed nasopharyngeal and oropharyngeal swabs from 221 participants aged 60 to 88, including 136 who experienced influenza-like illness during the 2014-2015 season and 85 who reported no symptoms and had no detectable respiratory pathogens at the time of sampling. The researchers characterized microbial composition, bacterial load, and cytokine patterns in a healthy state and determined the impact of acute infection. Influenza-like illness was defined according to the Dutch Pel criteria, which categorize individuals as having the condition based on the presence of fever of at least 37.8 degrees Celsius and at least one additional symptom such as headache, myalgia, sore throat, coughing, rhinitis, or chest pain. Swabs were collected within 72 hours of reported symptoms, and the causative viruses and bacteria were identified using multiplex ligation-dependent probe amplification and conventional bacterial culture.

Cluster analyses of the nasopharyngeal samples revealed three distinct community state types based on their dominant genera. The first was dominated by Moraxella, the second was characterized by Haemophilus, Staphylococcus, and Streptococcus, and the third was dominated by Corynebacterium and Dolosigranulum. The Moraxella-dominated cluster had the lowest diversity and evenness, while the other two were the most diverse. Beta-diversity analysis based on Bray-Curtis dissimilarity demonstrated clear separation between the three clusters, confirmed by permutational analysis of variance with an R-squared of 0.41 and a p value of 0.001. In contrast, no meaningful clustering structure was identified in the oropharyngeal samples, suggesting that the two niches have fundamentally different microbial ecosystems.

When the researchers compared healthy and infected individuals, they found that nasopharyngeal microbiome composition differed significantly between the two groups, with a PERMANOVA R-squared of 0.025 and a p value of 0.002, while no differences were observed in the oropharyngeal microbiome. Infected individuals were significantly more frequently found in the Moraxella-dominated and mixed clusters, with 73 percent and 69 percent infected samples respectively, whereas the Corynebacterium and Dolosigranulum-dominated cluster contained an equal mix of healthy and infected individuals. Genus-level differential-abundance analysis revealed that Corynebacterium and Dolosigranulum were more abundant in healthy individuals, while Streptococcus and Haemophilus were more abundant in infected individuals. Together, these findings suggest that the nasopharynx, rather than the oropharynx, is the most reflective niche for compositional change during acute infection.

The immune response mirrored this site specificity. In nasopharyngeal samples, infection was associated with a broad local response, with pro-inflammatory and innate immune markers such as IL-6, CXCL8, CCL2, and CXCL5, antiviral and interferon-associated markers including CXCL9, CXCL10, IFN-lambda1, and granzyme A, the tissue remodeling marker CRP, and the B cell survival factor APRIL all higher in infected individuals. In contrast, the oropharyngeal niche showed only limited changes, with only B-cell activating factor and CRP increased in infected individuals. Systemically, infected individuals had higher levels of pro-inflammatory markers, antiviral and interferon-associated chemokines, and the regulatory cytokine IL-10, while eotaxin, a chemokine associated with eosinophil recruitment and allergic inflammation, was higher in healthy individuals.

To probe the host-microbe interaction, the researchers constructed a network of cytokines identified as increased in infected individuals and the bacterial genera significantly associated with them. Among the genera enriched in infected participants, Haemophilus was positively associated with IL-6 and CXCL10, Streptococcus was positively linked to CXCL9, IL-6, and CXCL10, and Moraxella showed a positive link with CXCL10. In contrast, genera enriched in healthy participants showed only negative associations. Corynebacterium was negatively associated with IL-6, CXCL9, and CXCL10, while Staphylococcus was negatively linked to granzyme A, CXCL9, and CXCL10. This negative association suggests that Corynebacterium is linked to lower local inflammation, consistent with its association with the healthy, Corynebacterium and Dolosigranulum-dominated microbiome.

The nasopharyngeal community composition was also associated with clinical features and symptom burden. The Corynebacterium and Dolosigranulum-dominated cluster was associated with significantly lower odds of several respiratory symptoms, including influenza-like illness symptoms and fever, cough, sore throat, and nasal symptoms. In contrast, the Moraxella-dominated cluster was associated with significantly higher odds of nasal symptoms only, and the mixed cluster showed no significant associations with any symptom. These findings suggest that community membership is more consistently related to local, nasal symptoms than to systemic symptoms. At the genus level, a higher number of cumulative bacterial pathogens detected was positively associated with Haemophilus, while a higher number of total and viral pathogens detected was negatively associated with Corynebacterium. Smoking was positively associated with Porphyromonas and negatively associated with Corynebacterium, aligning with previous reports that Corynebacterium is underrepresented in the nasopharyngeal microbiota of smokers.

Perhaps most strikingly, the researchers found that nasopharyngeal immune responses remained elevated 7 to 9 weeks after infection. Several markers, including IL-6, CRP, IP-10, IL-1Ra, IFN-gamma, and IL-10, remained elevated when compared with healthy controls, indicating ongoing immune activation. Although effect sizes were smaller than in the acute phase and fewer markers reached statistical significance after adjustment, immune levels had not returned to those observed in healthy individuals. A distance-to-healthy centroid analysis showed that most participants moved closer to healthy immune profiles between the acute and recovery visits, but recovery samples remained distinct from healthy controls, indicating that immune normalization was partial rather than complete. This suggests that local immune recovery in the nasopharynx is slower than symptom resolution after acute infection.

The study’s authors note that persistent immune activation at mucosal sites may reflect several biological processes. Epithelial repair and restoration of barrier integrity can require sustained chemokine signaling, residual viral RNA or antigen may continue to stimulate low-level innate responses even after symptoms decline, and immune cell populations recruited during acute infection may remain locally active during resolution. Prolonged but declining interferon and chemokine signaling in the upper airway has been described in both experimental and natural human influenza infection. Such prolonged, microbiome-associated immune activation may delay full recovery of mucosal balance and thereby increase the risk of secondary bacterial infections, particularly in older adults and other vulnerable groups.

These findings show that influenza-like illness in older adults is associated with site-specific immune and microbiome responses in the upper respiratory tract. The nasopharynx emerged as the primary site of biological change, characterized by strong local innate immune activation and associations between specific genera and inflammatory mediators. Communities enriched in infected individuals, including those characterized by Moraxella, Haemophilus, and Streptococcus, were linked to higher levels of pro-inflammatory and interferon-related cytokines, while Corynebacterium and Dolosigranulum-associated communities were linked to lower inflammatory signatures and reduced symptom burden. The oropharyngeal niche showed comparatively limited immune and microbiome changes during infection, suggesting functional specialization between upper airway niches. While the nasopharynx reflected early antiviral immune activation, the oropharynx appeared more stable at both the microbial and immune level, possibly attributed to daily influences such as saliva flow, food intake, and oral hygiene practices that promote resilience and prevent dysbiosis.

More broadly, these results highlight the importance of considering anatomical niche when studying respiratory infections in aging populations, as immune responses and microbial associations differ between the nasopharynx and oropharynx. The results also emphasize the need to monitor mucosal immune responses beyond the acute phase, as prolonged immune activation may delay the restoration of immune and microbial homeostasis and increase susceptibility to secondary infections, particularly in older individuals. Ultimately, identifying microbiome-immune patterns may help enable early risk stratification and more effective preventive strategies in older adults, a population for whom current vaccination approaches leave substantial room for improvement.

Subject of Research: Immunology

Article Title: Linking nasopharyngeal and oropharyngeal microbiota to immune responses during influenza-like illness in an aging population

Article References: Kool, J., Konstanti, P., van Dijken, H., Chu, M. L. J. N., Nanlohy, N. M., Bijvank, E., van Woudenbergh, E., van Beek, J., van Baarle, D., & Fuentes, S. (2026). Linking nasopharyngeal and oropharyngeal microbiota to immune responses during influenza-like illness in an aging population. iScience, 29(11), Article 117929. https://doi.org/10.1016/j.isci.2026.117929

Image Credits: AI Generated

DOI: 10.1016/j.isci.2026.117929

Keywords: microbiome, influenza, aging, nasopharynx, oropharynx, immune response, respiratory infection, immunosenescence, Corynebacterium, Dolosigranulum, Linking, nasopharyngeal

The puzzle the review addresses is a long-standing one. Cellular senescence is a safeguard program: telomere erosion, oxidative damage, oncogene activation, or mitochondrial dysfunction all push cells into a state of permanent growth arrest. Senescent cells adopt a senescence-associated secretory phenotype, or SASP, releasing inflammatory mediators that should flag them for destruction by cytotoxic T cells and natural killer cells. But in aging tissues, these cells persist and multiply. Previous work showed that senescent cells upregulate PD-L1, which engages PD-1 receptors on immune cells and dampens their attack—mirroring the strategy tumors use. What remained unclear was which upstream signals drive PD-L1 upregulation in senescence. Wang and Qin argue that the DNA damage response, a conserved signaling network activated by genotoxic stress, is the key driver.

The DDR can be engaged by multiple senescence-associated stressors. Telomere dysfunction is the most extensively studied: telomeres, the protective caps at chromosome ends, shorten with each round of DNA replication when telomerase is insufficient. When they become critically short, they lose their protective structure and are recognized by the DNA repair machinery as double-strand breaks, initiating a DDR that becomes persistent in replicative senescence rather than transient. Oxidative stress, which accumulates with age, generates reactive oxygen species that damage nuclear DNA and activate the same signaling. Replication stress, arising from conflicts between DNA replication and transcription or from insufficient replication origins, also engages the DDR. In each case, the response persists and shapes cellular behavior well beyond immediate DNA repair—including the regulation of immune checkpoint molecules.

The review details two routes by which DDR signaling elevates PD-L1. The first is transcriptional, through the cGAS-STING pathway. DNA damage can generate cytosolic DNA, including micronuclei that arise from genomic instability. When a micronuclear envelope ruptures, this DNA is sensed by cGAS, triggering STING activation. STING recruits the kinase TBK1, which phosphorylates IRF3, leading to type I interferon production and subsequent PD-L1 transcription. In senescent cells, the same cascade is engaged by cytoplasmic chromatin fragments—bits of chromatin expelled from the nucleus that the cell mistakes for viral DNA. Beyond cGAS-STING, the central DDR kinases ATM and ATR contribute as well: following DNA damage, the ATM/ATR/Chk1 cascade activates STAT1 and STAT3 signaling and induces IRF1 expression, both of which drive PD-L1 transcription. ATM can also enhance PD-L1 through NF-κB activation. The tumor suppressor p53, another central DDR effector, influences PD-L1 in a context-dependent manner that may vary in senescent cells.

The second route is post-translational and operates independently of transcription. The cell cycle inhibitor p16, a hallmark of senescence, inhibits the kinases CDK4 and CDK6. This inhibition limits ubiquitin-dependent proteasomal degradation of PD-L1, stabilizing the protein on the cell surface even when transcriptional input declines. The two mechanisms cooperate: DDR-driven transcription raises PD-L1 production, while p16-mediated stabilization prevents its breakdown. This dual control may render senescent cells inherently difficult for the immune system to clear, because even if one layer of regulation is disrupted, the other can sustain PD-L1 expression.

At the cell surface, PD-L1 exerts its immunosuppressive effects by binding PD-1 on cytotoxic immune cells. Upon engagement, PD-1 recruits the phosphatases SHP-1 and SHP-2, which dephosphorylate key components of the T cell receptor signaling cascade, dampening T cell activation, proliferation, and cytokine production. The same pathway limits natural killer cell cytotoxic function. In aged lungs, p16-positive alveolar macrophages upregulate PD-L1 through this p16-CDK4/6 mechanism, and these PD-L1-high senescent macrophages create an immunosuppressive microenvironment that favors senescent cell accumulation. Single-cell analyses have revealed a correlation between p16 and PD-L1 expression in both immune and epithelial cells, more pronounced in older mice. Notably, senescent cells that display enhanced MHC class I machinery also express PD-L1, suggesting they can present antigens while simultaneously using PD-L1 to engage PD-1 on T cells—potentially driving T cell exhaustion.

In vivo studies provide functional validation. Activating anti-PD-L1 antibodies that engage Fcγ receptors on effector cells can eliminate PD-L1-positive senescent cells and reduce senescence-associated inflammation, both in naturally aged mice and in models of chronic lung inflammation. These findings indicate that PD-L1 is not merely a passive marker of senescence but a functionally relevant checkpoint that actively protects senescent cells from immune elimination—a senolytic vulnerability that could, in principle, be exploited therapeutically.

Recent work has uncovered a second, entirely different function of PD-L1 that operates not at the surface but in the nucleus. A fraction of PD-L1 translocates to the nucleus through an importin-dependent pathway involving the transport factors KPNA2 and KPNA6. Once inside, it binds directly to the cohesin subunit SA1 (STAG1) via its cytoplasmic tail, an interaction required for SA1 nuclear localization and proper telomere maintenance. Depleting either PD-L1 or SA1 produces comparable genomic instability phenotypes—aneuploidy, telomere cohesion defects, and reduced proliferation—and double knockdown shows no synergistic effect, suggesting they act in the same pathway. The circularity is striking: the same telomere dysfunction that triggers DDR and PD-L1 upregulation is also mitigated by PD-L1’s nuclear function. The response is mounted after the damage has occurred and feeds back to limit further damage—a form of damage control that allows a potentially harmful cell to persist while maintaining genomic integrity.

These observations converge on a self-reinforcing circuit. Telomere attrition and other stressors engage a persistent DDR, which upregulates PD-L1 through transcriptional induction and post-translational stabilization. Elevated PD-L1 allows senescent cells to evade immune clearance and accumulate. These cells secrete SASP factors that promote chronic inflammation, and the inflammatory milieu in turn induces DNA damage and telomere dysfunction in neighboring cells—mediated in part by SASP-driven recruitment of neutrophils, which transfer reactive oxygen species to neighboring cells and inflict telomeric damage. Each round amplifies the burden of senescent cells. The system becomes locked in a pro-inflammatory, immunoevasive state: inflammatory signals that should activate immune responses instead reinforce PD-L1-mediated suppression, accounting for the hallmark aging relationship between chronic inflammation and impaired immune function.

Intervention could, in theory, target any node in this loop—dampening DDR signaling, blocking PD-L1, or reducing inflammation—to restore immune clearance and lower senescent cell burden. But significant challenges remain. The causal relationship between DDR signaling and PD-L1 upregulation in vivo has not been fully defined, and whether DDR precedes PD-L1 upregulation in aging tissues or other senescence-associated signals act independently is unclear. The relative contribution of transcriptional versus post-translational mechanisms likely varies across tissues; p16-mediated stabilization has been demonstrated in alveolar macrophages and epithelial cells, but whether it operates with similar efficiency elsewhere remains unknown. Systemic PD-1/PD-L1 blockade carries a risk of autoimmune toxicity, and because the DDR-induced PD-L1 pathway operates in both senescence and cancer, interventions could yield benefits in both contexts or have unintended consequences depending on the cellular environment. Whether these strategies can be safely translated to humans is not yet clear, but the circuit model offers a clear rationale for testing them—and recasts senescence not as a passive endpoint but as an actively maintained, immunoevasive state that might, with the right molecular leverage, be reversed.

Subject of Research: DNA damage response signaling driving PD-L1-mediated immune evasion in cellular senescence and aging

Article Title: DNA damage response as a driver of PD-L1 expression in cellular senescence: implications for immune evasion and immunosenescence

Article References: Wang, Y., & Qin, L. (2026). DNA damage response as a driver of PD-L1 expression in cellular senescence: implications for immune evasion and immunosenescence. Frontiers in Cell and Developmental Biology, 14, Article 1974523. https://doi.org/10.3389/fcell.2026.1974523

Image Credits: AI Generated

DOI: 10.3389/fcell.2026.1974523

Keywords: cellular senescence, DNA damage response, PD-L1, immune evasion, immunosenescence, telomere dysfunction, cGAS-STING, ATM/ATR, p16, SASP, inflammaging, senolytics

The research team, led by Yuewen Sun and Qigang Lan at Xinqiao Hospital of Army Medical University in Chongqing, began by examining peripheral blood mononuclear cells from patients with end-stage renal disease using single-cell RNA sequencing data. What they found was striking: markers of T cell exhaustion, such as PD-1 and CTLA-4, showed only mild differences between healthy controls and kidney disease patients. But cellular senescence scores were dramatically upregulated, particularly in CD8+ T effector cells. When the researchers validated these findings in clinical samples from 75 non-dialysed patients with chronic kidney disease stages 3 to 5, they confirmed that CD57, a recognized marker of terminally differentiated senescent T cells, was significantly elevated within the CD8+ T cell compartment but not within CD4+ T cells. The proportion of CD28-negative CD57-positive cells, a key hallmark of immunosenescence, was also markedly increased in CD8+ T cells as kidney disease progressed.

Senescence is not merely a passive slowing of cell division. It is an active, irreversible state characterized by persistent DNA damage, cell-cycle arrest, and telomere shortening. The researchers detected elevated levels of γ-H2A.X, a marker of DNA double-strand breaks, and p21, a cyclin-dependent kinase inhibitor that enforces cell-cycle arrest, in CD8+ T cells from chronic kidney disease patients. Senescence-associated β-galactosidase activity was increased, and the cells produced elevated levels of proinflammatory cytokines including tumour necrosis factor and interferon gamma. Telomere length analysis revealed progressive shortening in CD8+ T cells from patients compared with age-matched healthy controls, indicating that the immune cells were aging faster than the patients themselves.

Crucially, the senescent phenotype was accompanied by severe mitochondrial dysfunction. The researchers measured oxygen consumption rates using Seahorse extracellular flux analysis and found decreased basal respiration, reduced maximal respiratory capacity, and diminished ATP production in CD8+ T cells from patients. Mitochondrial membrane potential, assessed using tetramethylrhodamine methyl ester staining, was significantly reduced. Reactive oxygen species, measured using dichlorodihydrofluorescein diacetate, were overproduced. These mitochondrial defects are not incidental; they are considered an essential component of the senescent phenotype, and their presence in chronic kidney disease CD8+ T cells suggested that the organelles themselves might be the trigger for premature aging.

To determine whether platelets were responsible, the team established a co-culture system in which platelets from healthy donors or chronic kidney disease patients were incubated with CD8+ T cells from healthy individuals at a ratio of 450 platelets per T cell. After seven days, CD8+ T cells co-cultured with platelets from chronic kidney disease patients showed dramatic acceleration of senescence, with upregulation of γ-H2A.X, p21, senescence-associated β-galactosidase, and CD57. Proinflammatory cytokines were elevated, and telomeres were shortened. Remarkably, mitochondrial membrane potential decreased and impaired respiratory function appeared by day three, preceding the visible senescence markers by two days. Pretreatment with N-acetylcysteine, an antioxidant, effectively prevented both the mitochondrial dysfunction and the cellular senescence, confirming that oxidative stress was the critical mediator.

The researchers then turned their attention to platelet-derived microparticles, submicron vesicles released by activated platelets that are the most abundant microparticles in blood. They confirmed that patients with chronic kidney disease showed enhanced platelet activation, with increased P-selectin and activated GPIIb/IIIa expression, and correspondingly increased microparticle release. Levels of these microparticles in peripheral blood correlated positively with senescence biomarkers and reactive oxygen species in CD8+ T cells, and negatively with mitochondrial membrane potential. When the team labelled microparticles with DiO fluorescent dye, they observed successful internalization by CD8+ T cells both in vitro and after tail-vein injection in mice. Microparticles from chronic kidney disease patients induced mitochondrial dysfunction and senescence in CD8+ T cells, effects that were again relieved by N-acetylcysteine. Notably, the microparticles did not significantly affect proliferation or aggravate senescence in already-senescent CD57-positive cells but mainly promoted the transition of CD57-negative cells toward the senescent phenotype.

Because platelets possess fully functional microRNA machinery, the researchers performed microRNA expression profiling on microparticles from five patients and five healthy controls. They identified 109 upregulated and 57 downregulated microRNAs in chronic kidney disease-derived microparticles. Among the top five upregulated candidates, miR-550a-5p was the most remarkably elevated. When CD8+ T cells were transfected with corresponding microRNA mimics, only miR-550a-5p significantly increased senescence-associated β-galactosidase positivity, γ-H2A.X expression, and p21 expression. The microRNA content in CD8+ T cells was much lower than in microparticles, but levels in patient CD8+ T cells were higher than in healthy controls, suggesting that the microRNA was being transferred from microparticles to T cells. In megakaryocytic MEG-01 cells, only serum from chronic kidney disease patients, not peripheral blood mononuclear cells, elevated miR-550a-5p expression, implying that soluble factors in the uraemic milieu drive its upregulation in platelets.

To identify the molecular target, the team used bioinformatic analysis with TargetScan, miRDB, and MitoCarta 3.0 databases, predicting 19 potential mitochondrial target genes. Gene ontology enrichment showed significant enrichment in mitochondrial protein transport. Among these, PMPCB, the catalytic subunit of mitochondrial processing peptidase, emerged as the leading candidate. This enzyme recognizes and cleaves mitochondrial targeting signals necessary for proper protein import and maturation. The researchers found that PMPCB expression was significantly decreased at both mRNA and protein levels in CD8+ T cells from patients, and that miR-550a-5p mimic transfection selectively reduced PMPCB levels. Dual-luciferase reporter assays confirmed that miR-550a-5p directly binds to the 3-prime untranslated region of human PMPCB, decreasing luciferase activity of the wild-type but not a mutant construct. Knockdown of PMPCB in CD8+ T cells induced decreased mitochondrial membrane potential, impaired respiratory function, increased reactive oxygen species, and upregulated senescence biomarkers, while PMPCB overexpression alleviated miR-550a-5p-induced mitochondrial dysfunction and cellular senescence.

The downstream mechanism involves NDUFS8, a nuclear-encoded core subunit of mitochondrial complex I that is cleaved by mitochondrial processing peptidase. The researchers detected both precursor and mature forms of NDUFS8 in CD8+ T cells from patients, whereas only the mature form existed in healthy controls. Co-culture with patient platelets or miR-550a-5p treatment induced cleavage failure of NDUFS8, and co-immunoprecipitation confirmed a physical interaction between PMPCB and NDUFS8. This cleavage failure impairs electron transfer from NADH to ubiquinone, decreasing the NAD-prime to NADH ratio, a reduction intimately linked to aging. Patients with chronic kidney disease exhibited decreased NAD-prime levels and NAD-prime to NADH ratios in CD8+ T cells. When the team treated cells with nicotinamide mononucleotide, an intermediate in NAD-prime biosynthesis, mitochondrial dysfunction was effectively attenuated and platelet-induced cellular senescence was prevented. Intraperitoneal injection of nicotinamide mononucleotide at 500 milligrams per kilogram in mice treated with miR-550a-5p agomir similarly alleviated mitochondrial dysfunction and senescence in CD8+ T cells.

These findings collectively demonstrate that platelet-derived miR-550a-5p drives CD8+ T cell senescence through the PMPCB-NDUFS8 axis in chronic kidney disease. The study identifies a novel platelet-T cell interaction that contributes to the immunosuppressed state of patients and opens two promising therapeutic avenues: inhibiting miR-550a-5p function or replenishing NAD-prime through nicotinamide mononucleotide supplementation. Because immunosenescence contributes not only to infections but also to cancers, autoimmune diseases, cardiovascular disorders, and neurodegenerative conditions, the implications extend well beyond nephrology. The researchers suggest that antiplatelet agents, which already exhibit anti-aging properties through antioxidant and immunometabolic mechanisms, may serve as an additional strategy for alleviating CD8+ T cell senescence. While direct in vivo evidence that microparticles induce senescence still warrants further investigation, and the specific uraemic toxins responsible for driving miR-550a-5p upregulation remain unknown, this work provides a compelling molecular framework for understanding why patients with chronic kidney disease age their immune systems prematurely and offers tangible targets for intervention.

Subject of Research: Platelet-derived microparticles drive CD8+ T cell senescence in chronic kidney disease by transferring microRNA-550a-5p

Article Title: Platelet-derived microparticles induce CD8+ T cell senescence in chronic kidney disease via the transfer of microRNA-550a-5p

Article References: Sun, Y., Lan, Q., Wang, Y., Xie, M., Wu, X., Lv, L., Xin, Q., Chen, J., Zhong, X., Yao, M., Gong, S., Zhou, S., Wang, J., & Zhao, J. (2026). Platelet-derived microparticles induce CD8+ T cell senescence in chronic kidney disease via the transfer of microRNA-550a-5p. Experimental &amp; Molecular Medicine. https://doi.org/10.1038/s12276-026-01876-z

Image Credits: AI Generated

DOI: 10.1038/s12276-026-01876-z

Keywords: chronic kidney disease, CD8+ T cells, platelet-derived microparticles, microRNA-550a-5p, immunosenescence, mitochondrial dysfunction, PMPCB, NDUFS8, nicotinamide mononucleotide, Experimental & Molecular Medicine, Platelet-derived, microparticles

At birth, both the innate and adaptive arms of immunity are functionally incomplete. Newborns depend heavily on maternal antibodies transferred across the placenta for passive protection, and this shield decays within months: estimated durations of maternal antibody protection are roughly 3.3 months for measles, 2.7 months for mumps, 3.9 months for rubella, and 3.4 months for varicella. Neonates can mount adaptive responses, but their capacity to generate long-lasting immunity is limited by underdeveloped germinal centers, low expression of B-cell co-receptors such as CD21, CD40, CD80, and CD86, impaired Th1 cytokine secretion, and reduced B-cell receptor signaling strength. The review emphasizes that this is not simple deficiency. The neonatal immune system operates in a tolerogenic mode, likely to prevent immunopathological damage as the infant transitions from a semi-allogeneic, sterile uterine environment into a microbe-rich world, even at the cost of vulnerability to uncontrolled pathogen proliferation.

The innate immune system, the first line of defense, is active from birth and responds within minutes to hours, but its cellular players mature on very different schedules. Neutrophils appear in fetal circulation by the end of the first trimester and surge before delivery, yet neonatal neutrophils show weak inflammatory responses, a deficit most pronounced in premature infants. Monocytes and macrophages in newborns exhibit diminished signaling and cytokine responses compared with adults, reaching normal levels within days. Crucially, the review highlights the newborn microbiome as the first teacher of the developing immune system: gut microbes induce interleukin-17 production by group 3 innate lymphoid cells, which drives granulocyte colony-stimulating factor release and neutrophil production through a Toll-like receptor 4 and MyD88-dependent pathway, maintaining systemic immune vigilance against infection.

Dendritic cells, the sentinels that bridge innate and adaptive immunity, tell a similarly staged story. Plasmacytoid dendritic cells, the body’s type I interferon factories against viruses, constitute 53 percent of the dendritic cell pool in infants, the lowest total dendritic cell proportion of any age group. Although preterm infants possess adult-like levels of TLR7 and TLR9 on these cells, they secrete low amounts of interferon-alpha and beta, leaving antiviral innate immunity ineffective relative to adults. A progressive increase in conventional dendritic cell subsets occurs during the transition from infancy to childhood, suggesting major immune remodeling early in life. In older adults, the dominant subset is cDC2 at 49 percent, while cDC1 cells expand preferentially in adulthood, possibly compensating for the age-related decline in CD8-positive T cells. Lower plasmacytoid dendritic cell proportions in healthy older people may partly explain their reduced capacity to fight viral infections.

Natural killer cells and other innate lymphoid populations undergo their own lifelong remodeling. Newborn natural killer cells have reduced cytolytic function, blunted sensitivity to interleukin-2 and interleukin-15, and lower interferon-gamma secretion, yet still provide some antiviral protection. During pregnancy, maternal peripheral natural killer cells migrate to the decidua and differentiate into non-cytotoxic cells with enhanced secretory activity, producing interferon-gamma, vascular endothelial growth factor, and placental growth factor that are critical for immune tolerance, angiogenesis, and fetal development, though their hyperactivation can trigger spontaneous abortion. With age, natural killer cells shift toward a mature CD56dimCD16-positive phenotype but become dysfunctional in cytotoxicity, degranulation, and cytokine secretion, weakening the elimination of senescent and malignant cells. Strikingly, single-cell RNA sequencing of three centenarian cohorts revealed increased peripheral natural killer cell frequencies in these exceptionally long-lived individuals, alongside reduced CD4-positive T and B cell counts.

That centenarian signature has crystallized into one of the review’s central themes: cytotoxic immunity as a marker of healthy aging. A bioinformatic algorithm developed to identify immune populations associated with longevity found that natural killer cells, CD8-positive T cells, and gamma-delta T cells correlate positively with extended lifespan, whereas inflammatory-lineage populations such as CD4-positive T cells, B cells, and dendritic cells show negative associations. Centenarian neutrophils display phagocytic and chemotactic activities comparable to those of young adults, with low superoxide anion levels and preserved glutathione, while frail middle-aged subjects show the worst profiles. Reduced complement C3 and C4 levels in centenarians contrast with the elevated levels seen in older adults at risk of metabolic syndrome and cardiovascular disease, and caloric restriction has been shown to downregulate the C3a/C3 ratio, attenuating age-related inflammation. Maintaining cytotoxic phenotypes and redox balance, the authors suggest, may be exploitable clinically to blunt immunosenescence.

The adaptive arm follows an equally dramatic arc. T lymphocytes mature in the thymus from seven to eight weeks of gestation and populate the periphery by weeks twelve to thirteen, but thymic involution drives a progressive loss of naive T cells that accelerates after age sixty. Newborns carry only about 1 percent antigen-educated T cells; in adults over sixty, that figure reaches 65 percent. The T cell receptor repertoire narrows with age, CD28 expression is lost from more than half of CD8-positive T cells, and transcriptional reprogramming pushes aging T cells toward a Th2 polarization associated with dysregulated B cell responses and reduced antibody neutralizing capacity after influenza vaccination, a failure that contributes to influenza deaths in 70 to 85 percent of elderly cases. B cells, meanwhile, peak in the first year of life at around six months before gradually declining, and in old age naive B cells are replaced by quiescent memory cells with diminished affinity maturation and class switching.

Perhaps the most conceptually provocative section concerns immunological memory itself. Long considered the exclusive property of adaptive immunity, memory-like responses have now been demonstrated in innate cells, a phenomenon termed trained immunity. Monocytes, macrophages, natural killer cells, and even bone marrow progenitors exposed to stimuli such as beta-glucan or the Bacillus Calmette-Guerin vaccine undergo epigenetic and metabolic reprogramming that confers enhanced, non-antigen-specific protection against unrelated pathogens for months. In murine models, BCG vaccination at birth improved survival in neonatal sepsis with profound remodeling of monocyte and neutrophil subsets, though some pattern recognition receptor agonists failed to protect neonatal mice against Leptospira, underscoring the risks of immunostimulation in early life. In adults over fifty in Guinea-Bissau, BCG vaccination elevated interferon-gamma and pro-inflammatory cytokine responses two months later, and some reports suggest it can reduce circulating inflammatory markers of inflammaging, although recent large trials found no boost to influenza vaccine responses and even flagged aggravation of cardiac arrhythmias as a concern.

The demographic stakes are considerable. The World Health Organization estimates that people over sixty numbered 1.2 billion in 2025 and will reach 2 billion by 2050, with 80 percent living in developing countries, while the European Union’s elderly share is projected to grow from 6.0 percent in 2021 to 14.6 percent by 2100. Immunosenescence, driven by thymic involution, naive cell depletion, inverted CD4/CD8 ratios, gut microbiota shifts that increase intestinal permeability, and the accumulation of senescent cells secreting interleukin-6, tumor necrosis factor-alpha, and interleukin-1 beta, raises vulnerability to infections, cancer, autoimmune disease, and neurodegeneration. Yet the aging immune system paradoxically resembles the newborn’s, with weakened antimicrobial activity and compromised adaptive responses at both ends of life. The Bucharest team argues that mapping these stage-specific mechanisms, from the SOX4-positive naive T cells and interferon-gamma that compensate for infant vulnerability to the cytotoxic dominance that defines centenarian immunity, provides the mechanistic foundation for age-adapted vaccines and immunotherapies capable of restoring immune function in the frail and extending healthy lifespan for everyone else.

Subject of Research: Immune system development across the human lifespan, from neonatal immaturity to immunosenescence and centenarian longevity

Article Title: Immune system ontogeny—a subtle evolution to perfection

Article References: Munteanu, A. N., Surcel, M., Dobre, E. G., Constantin, C., & Neagu, M. (2026). Immune system ontogeny—a subtle evolution to perfection. Frontiers in Aging, 7, Article 1872955. https://doi.org/10.3389/fragi.2026.1872955

Image Credits: AI Generated

DOI: 10.3389/fragi.2026.1872955

Keywords: immunosenescence, inflammaging, trained immunity, neonatal immunity, centenarians, natural killer cells, dendritic cells, T cells, B cells, immunological memory, complement system, BCG vaccine

The research, led by Joaquim Pedro Brito-de-Sousa and senior authors Ana Carolina Campi-Azevedo, Karen Cecília de Lima Torres, and Olindo Assis Martins-Filho, draws on samples collected between 2011 and 2019 at primary care vaccination centers in southeastern and northeastern Brazil. Volunteers were recruited when they presented for routine vaccination, and the team excluded anyone recently vaccinated, pregnant, HIV-positive, living with chronic immune-mediated disease, or taking immunosuppressive therapy. The cohort — 926 women and 870 men — was divided into twelve consecutive age bands, from under one year of age through 50 to 65 years, allowing the investigators to track immune remodeling with unusual granularity across childhood, adolescence, adulthood, and the threshold of old age.

At the heart of the study is a technical tour de force in flow cytometry. Peripheral blood mononuclear cells were isolated by density-gradient centrifugation and cultured for 144 hours before being stained with monoclonal antibodies against CD3, CD4, CD8, CD45RO, CD27, and the chemokine receptor CXCR3 (CD183) for T-cells, and against CD19, CD27, and IgD for B-cells. This combination allowed the researchers to resolve eight distinct T-cell phenotypes — including naïve, early effector, central memory, effector memory, and both interferon-mediated and non-interferon-mediated memory compartments — alongside four B-cell subsets spanning naïve, double-negative, unswitched memory, and class-switched memory cells. At least 100,000 lymphocytes were acquired per sample on an LSRFortessa cytometer, and the long culture period was deliberately chosen to let cells recover from isolation stress and resume homeostatic behavior before phenotyping.

The results reveal that immune memory remodeling is anything but gradual. Statistically significant shifts between adjacent age groups clustered into three discrete windows: an early transition around 5 to 6 years, a pronounced and prolonged wave between 10 and 19 years — the most dramatic of the entire lifespan — and a more subdued recalibration between 20 and 29 years. During the adolescent wave, memory and interferon-mediated memory T-cell subsets expanded sharply while naïve subsets contracted, and the B-cell compartment followed suit, with double-negative and unswitched memory cells rising as naïve CD19+ cells fell. Beyond the late twenties, the pace of change slowed markedly, with only scattered subset shifts in the fourth, fifth, and sixth decades of life.

Sex emerged as a defining variable. Women showed an earlier onset of change: declines in naïve and early activated subsets began as early as one year of age in females, whereas comparable shifts in males did not appear until the 10-to-19-year window. Men, however, exhibited greater lifelong variability in differentiated subsets — most strikingly in early effector CD4+ cells — with elevated median values for central memory, effector memory, and interferon-mediated CD4+ and CD8+ populations concentrated between 10 and 39 years. Signature analyses, which converted continuous cell frequencies into proportions of individuals above global median cut-offs, confirmed that the two sexes reached their peaks of high-producer status at distinct ages, with the 10-to-19-year range serving as the pivotal turning point for the population as a whole.

Logistic regression modeling reinforced the picture of directional, lifelong drift. Naïve T- and B-cell subsets — NCD4, NCD4, NCD8, NCD8, and NCD19 — showed continuously decreasing predicted probabilities with age, while virtually every memory subset, from central and effector memory CD4+ and CD8+ T-cells through unswitched and class-switched memory B-cells, climbed steadily from birth onward. Notably, an increase in early effector CD4+ cells and a decrease in early activated CD4+ cells were observed selectively in males, underscoring that the male trajectory is defined less by earlier onset than by greater amplitude of differentiation and inflammatory polarization.

Perhaps the most striking findings came from the network analyses. Using Spearman correlations among all memory subsets, the team built integrative connectivity maps for each age band and sex. Naïve cells displayed the highest overall connectivity, anchoring the immune network’s architecture. Total connections followed a wave-like pattern, with a peak at two years, a long-lasting plateau from 5 to 19 years, and a continuous decline thereafter. But the sexes diverged dramatically: in women, B-cell network connectivity increased with age and correlation density remained relatively stable throughout life, whereas in men, connectivity collapsed sharply after age 20. Correlation axes — shared connections between adjacent age ranges — emerged earlier in men, concentrated between 2 and 19 years, but persisted longer and more intensely in women, spanning 5 to 49 years. Importantly, the upregulation of memory cell subsets was accompanied by an increase in global connectivity, suggesting that phenotypic diversification and network integration are tightly coupled processes.

The authors frame these patterns within the concept of immunobiography — the idea, introduced by Franceschi and colleagues, that the immune system carries a lifelong record of antigenic encounters, endocrine transitions, and environmental exposures, inscribed in waves rather than accumulated uniformly. The CD27/CD45RO axis in T-cells and the CD27/IgD axis in B-cells serve as molecular ledgers of this history: CD27+CD45RO− cells mark the naïve compartment sustained by thymic output, while progressive transitions toward central and effector memory reflect mounting antigenic experience. The addition of CXCR3 further refines the picture, separating Th1/Tc1-polarized inflammatory memory cells shaped by viral and intracellular pathogens from non-Th1 trajectories associated with barrier immunity and B-cell help. The team also notes that their cohort, drawn from a region hyperendemic for parasitic and infectious diseases, may exhibit accelerated immunological remodeling relative to chronological age — a phenomenon their earlier work has linked to epigenetic aging and compensatory innate immune mechanisms in uninfected residents.

The study is not without limitations, which the authors acknowledge candidly. The observational design, non-probabilistic convenience sampling, and unequal sample sizes across age groups — particularly the small male cohorts in the 20-to-29 and 50-to-65-year ranges — constrain generalizability. The analysis was not adjusted for lifetime infectious exposure, cumulative vaccination, nutritional status, or endocrine transitions, though the authors argue that within the immunobiographical framework these factors are not mere confounders but intrinsic components of the biological record. No soluble immune mediators were measured alongside the cellular phenotyping, leaving the inflammatory dimension of the remodeling to be inferred rather than directly quantified.

Even so, the implications are considerable. The identification of discrete, sex-dependent remodeling windows — with early life and puberty emerging as critical periods — suggests that the foundation of immune resilience, and the susceptibility to chronic inflammatory disease in later life, may be set decades before old age arrives. The divergent network strategies adopted by male and female immune systems, with men losing connectivity as women sustain it, offer a mechanistic thread connecting cellular phenotype to lifelong inflammatory tone. As the authors conclude, the balance between central and late effector memory in both T- and B-cell compartments may prove to be a key determinant of immune flexibility versus inflammatory burden — a ledger written in childhood, balanced in adolescence, and cashed out across the decades that follow.

Subject of Research: Age- and sex-dependent remodeling of memory T- and B-cell immunophenotypes across the human lifespan

Article Title: Comprehensive profiling of phenotypic features of memory T- and B-cells from birth to the onset of old age

Article References: Brito-de-Sousa, J. P., Reis, L. R., Costa-Rocha, I. A. D., Peruhype-Magalhães, V., Costa-Pereira, C., Martins, J. P., Antonelli, L. R. D. V., Garcia, C. C., Gomes, A. O., Coelho-dos-Reis, J. G. A., Faria, A. M. D. C., Teixeira-Carvalho, A., Campi-Azevedo, A. C., Torres, K. C. D. L., & Martins-Filho, O. A. (2026). Comprehensive profiling of phenotypic features of memory T- and B-cells from birth to the onset of old age. Frontiers in Aging, 7, Article 1890974. https://doi.org/10.3389/fragi.2026.1890974

Image Credits: AI Generated

DOI: 10.3389/fragi.2026.1890974

Keywords: immunobiography, memory T-cells, memory B-cells, immunosenescence, flow cytometry, inflammaging, adaptive immunity, sex differences, immune network connectivity, naive T-cells, CXCR3, aging

Immunosenescence, the term researchers use for the structural and functional reorganization of immunity over a lifetime, is closely tied to increased vulnerability to infections, weaker vaccine responses, and a heavier burden of chronic disease. While flow cytometric profiling of blood lymphocyte subsets has become a standard tool for characterizing this process, systematic age-related data on natural killer cell subsets and B cell subsets in healthy Chinese adults have remained scarce. Quantitative trends for CD57 and TEMRA cells, widely accepted markers of terminal T cell differentiation, have also been incompletely described in this population. The new study was designed to fill that gap with two complementary 12-color flow cytometry panels applied across a broad age range.

The researchers prospectively enrolled 146 healthy adults attending the hospital’s annual health examination center between 2023 and 2024. Panel 1 included 103 participants aged 20 to 82 years, while Panel 2 included 43 participants aged 25 to 92 years, deliberately enriched for older individuals to strengthen statistical power at the upper end of the age spectrum. Eligibility required no clinically significant abnormalities on routine examination, and the team excluded anyone with autoimmune disease, chronic infections including HIV, hepatitis B, or hepatitis C, hematological disorders, recent immunosuppressive treatment, acute infection within the preceding four weeks, pregnancy, or evidence of malignancy or severe organ dysfunction.

Panel 1 was a single-tube 12-color assay that simultaneously covered T cells, including CD57 expression, the three-way classification of NK cells by CD56 and CD16 intensity, and the four-way classification of B cells by IgD and CD27. Panel 2 was a dual-tube 12-color assay focused on detailed T cell differentiation, incorporating CD45RA and CD62L to resolve naive, central memory, effector memory, and TEMRA subsets, along with CD28, CD31, CD38, and HLA-DR. At least 100,000 lymphocyte events were acquired per tube on a BD LSRFortessa instrument. Statistical analysis employed Spearman rank correlation, Kruskal-Wallis testing, and Mann-Whitney U tests, with multivariate models controlling for sex.

The strongest age-related signals emerged in the CD8-positive T cell compartment. TEMRA accumulation showed a correlation coefficient of +0.532, CD28 loss reached -0.552, and naive cell depletion reached -0.534, all with p values below 0.001. Together these three changes form a coherent triad representing the hallmarks of replicative senescence in CD8 T cells, painting a picture of progressive, co-stimulation-independent terminal differentiation that dominates this compartment in older individuals. Activation and proliferation markers reinforced the pattern: CD8 cells expressing HLA-DR, CD38 together with HLA-DR, and Ki67 all rose significantly with age, indicating that despite their differentiated phenotype, CD8 T cells in older adults remain in a state of chronic activation.

In the CD4 compartment, two significant age-related changes stood out. CD4-positive CD31-positive cells, which serve as a marker of recent thymic emigrants, declined with age at a correlation of -0.361, consistent with thymic involution progressively curtailing the output of new naive T cells. CD4-positive naive cells also showed a significant decline at -0.303. In Panel 1, the two strongest correlations were both CD57-related: CD4-positive CD57-positive cells rose at +0.421 and CD8-positive CD57-positive cells at +0.338, both highly significant, reflecting progressive accumulation of terminally differentiated T cells across both major subsets. When all 146 participants were pooled for shared markers, both CD4-positive and CD8-positive PD-1 expression became significantly positive, suggesting that exhaustion-like checkpoint upregulation accompanies terminal differentiation as a co-occurring feature of immune aging.

The NK cell findings revealed a more nuanced picture. Total NK cell frequency increased with age, yet within that expanding pool the CD56-high CD16-negative regulatory subset contracted significantly, while the cytotoxic CD56-dim CD16-positive fraction showed no significant proportional change. NK cell PD-1 expression also rose with age, a less commonly reported observation suggesting that NK cells, like T cells, may undergo progressive phenotypic exhaustion. In segmented analysis of the combined dataset, the atypical CD56-negative CD16-positive subset showed no significant overall age correlation but became significantly positively associated with age in participants aged 65 and above, reaching a correlation of +0.482. The researchers caution that the formal slope-change test did not reach significance, so this pattern is best described as a late-life tendency requiring replication rather than a confirmed threshold effect.

B cell aging followed a different timeline. In Panel 1, total B cell frequency was stable across the age range, and among the four IgD/CD27 subsets only the IgD-positive CD27-positive marginal zone-like population showed a significant decline at -0.257. This subset represents antigen-experienced but unswitched B cells, and its contraction may reflect reduced T-independent responses with aging. The more dramatic changes emerged in Panel 2, where total B cell frequency declined significantly at -0.381 and switched memory B cells contracted at -0.379. That these changes appeared in an older-enriched cohort with a median age of 70 but not in the broader Panel 1 sample suggests that substantial B cell contraction may be a relatively late phenomenon, becoming apparent mainly in the oldest age ranges.

Sex was a meaningful source of variation throughout the study. Women tended to have higher CD8-positive fractions and lower CD4-to-CD8 ratios than men of the same age, a pattern consistent with established sex differences in immune aging. Both panels showed higher CD31-positive fractions in women, consistent with greater thymic output or slower naive T cell attrition. Men had higher NK frequency in Panel 2. Critically, however, multivariate analysis showed that sex did not explain the primary age effects; all ten significant age correlations in Panel 1 survived adjustment for sex, and the three core CD8 markers remained strongly significant regardless. The researchers note that the male-heavy composition of Panel 1, at 83.5 percent, introduces some interpretive caution and encourage sex-stratified reporting when these data are used as clinical reference ranges.

To integrate the multidimensional age signal into a single summary measure, the team constructed an Immunological Composite Score from nine parameters showing consistent, sex-independent age associations across both panels. Each parameter was z-scored and combined with directional signs aligned to the age correlation direction. Across all 146 participants, the composite score correlated strongly with chronological age at +0.575, and Kruskal-Wallis testing demonstrated highly significant group separation between young, middle-aged, and older cohorts. The older group differed significantly from both the young and middle-aged groups, while the young and middle-aged groups did not differ significantly from each other. The authors emphasize that the score is presented as a proof-of-concept instrument, derived from and validated in the same dataset, and that external prospective validation in an independent cohort with longitudinal follow-up and clinical endpoints such as infection susceptibility or vaccine immunogenicity is required before any clinical application.

Subject of Research: Age-related changes in T cell, NK cell, and B cell subsets measured by multicolor flow cytometry in healthy Chinese adults

Article Title: Age-associated remodeling of NK cell subsets, B cell subsets, and T cell surface markers in peripheral blood of healthy Chinese adults: a prospective multicolor flow cytometry study

Article References: Zheng, L., Cao, W., Wang, Y., Xu, T., Wang, F., Zhang, L., Liu, X., & Li, T. (2026). Age-associated remodeling of NK cell subsets, B cell subsets, and T cell surface markers in peripheral blood of healthy Chinese adults: a prospective multicolor flow cytometry study. Frontiers in Aging, 7, Article 1847033. https://doi.org/10.3389/fragi.2026.1847033

Image Credits: AI Generated

DOI: 10.3389/fragi.2026.1847033

Keywords: immunosenescence, flow cytometry, T cells, NK cells, B cells, TEMRA, CD57, PD-1, aging, healthy Chinese adults, Peking Union Medical College Hospital, immune aging