Immunity & Ageing最新文献

{"title":"Chronic IL-21 drives neuroinflammation and promotes lipid accumulation in microglia.","authors":"Hugo Oyamada, Yinzhi Ying, Sudhanshu Agrawal, Aizhu Liu, Veedamali S Subramanian, Cleonice Alves de Melo Bento, Anshu Agrawal","doi":"10.1186/s12979-025-00510-2","DOIUrl":"https://doi.org/10.1186/s12979-025-00510-2","url":null,"abstract":"<p><p>Neuroinflammation is a key contributor to the onset and progression of neurodegenerative diseases, driven by factors such as viral infections, autoimmune disorders, and peripheral inflammation. However, the mechanisms linking peripheral inflammation or viral infections to neuroinflammation remain poorly understood, limiting the development of effective therapies. Proinflammatory cytokines are implicated in these processes but their effects on brain cells, including microglia, remain insufficiently characterized. Here, we demonstrate that IL-21, a proinflammatory cytokine elevated in autoimmune disorders, chronic viral infections, and Alzheimer's disease, activates microglia and promotes lipid accumulation within these cells. Young, healthy mice injected with IL-21 to mimic chronic exposure exhibited increased proinflammatory cytokine levels and microglial activation in the brain. Notably, microglia in these mice displayed enhanced lipid accumulation, accompanied by upregulation of lipid uptake receptors such as CD36 and TREM-2. These findings were corroborated using the human microglial cell line HMC-3, where IL-21 exposure similarly induced lipid accumulation and increased expression of CD36 and ApoE. Mechanistic investigations revealed that IL-21 upregulates HIF-1α, a transcription factor critical for lipid metabolism and lipid droplet formation. Additionally, we observed elevated IL-21 levels in the circulation of elderly individuals compared to younger counterparts, with IL-21 increases associated with CMV seropositivity. Aged mouse brains mirrored the microglial lipid accumulation and activation patterns seen in IL-21-injected mice. In summary, we identify a novel IL-21-driven mechanism involving lipid accumulation in microglia that contributes to neuroinflammation.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"15"},"PeriodicalIF":5.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Old hematopoietic stem cells retain competence to reconstitute a youthful B cell system that is highly responsive to protein-based vaccination.","authors":"Paul Kunath, Dominik Pflumm, Bettina Moehrle, Vadim Sakk, Alina Seidel, Jan Münch, Hartmut Geiger, Reinhold Schirmbeck","doi":"10.1186/s12979-025-00507-x","DOIUrl":"10.1186/s12979-025-00507-x","url":null,"abstract":"<p><strong>Background: </strong>Ageing-associated remodeling of the murine B cell system is accompanied with a reduction of CD19⁺ B cells such as follicular B cells (FOB) and an accumulation of age-associated B cells (ABC) or activated B cell subsets. This remodeling is thought to confer an attenuated antibody response, such as to SARS-CoV-2 spike (S) vaccines in both aged mice and humans. To gain insight into the de novo development and function of an old B cell system, we reconstituted young and old immune systems by transferring hematopoietic stem cells (HSCs) from immune-competent young (2-3 months) CD45.1⁺ donors (DY-HSC) or old (20-24 months) donors (DO-HSC) into T and B cell-deficient young recipient CD45.2⁺ RAG1^-/- mice, followed by protein-based vaccination.</p><p><strong>Results: </strong>In the same environment of young RAG1^-/- mice, transplanted DO-HSCs compared to DY-HSCs reconstituted lower numbers of CD19⁺ B cells and CD45.1⁺ cells, though the engraftment of donor-derived HSCs in the young bone marrow (BM) was very similar. Furthermore, indicative for youthful and unchallenged B cell systems, and in contrast to aged mice, very low levels of antigen-experienced memory B cells or age-associated B cells (ABC) developed in both DY-HSC and DO-HSC hosts. The commercially available recombinant SARS-CoV-2 S vaccine (NVX-CoV2373) induced lower IgG⁺ S-antibody titers and pseudovirus neutralization activity in old compared to young mice. In contrast, very similar high IgG⁺ S-antibody titers were induced in DO-HSC and DY-HSC hosts, and pseudovirus neutralization activity was even enhanced in DO-HSC compared with DY-HSC hosts.</p><p><strong>Conclusions: </strong>Both DO-HSCs and DY-HSCs established in the young recipient BM to a similar extend, suggesting that the concomitant reduction in the de novo reconstitution of CD19⁺ B cells in DO-HSC vs. DY-HSC transplanted animals is specifically related to old HSCs. DO-HSCs and DY-HSCs reconstitute very similar unchallenged B cell systems that efficiently elicit antigen-specific IgG antibodies by protein-based vaccination. Old HSCs thus retain competence to reconstitute a youthful and functional B cell system, at least in the young environment of transplanted RAG1^-/- mice. This suggests that it is primarily age-related factors, and not HSCs per se, that influence the composition and functionality of the old B cell system.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"14"},"PeriodicalIF":5.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing flu vaccine responses in older adults: preliminary insights from the ISOLDA study on immunosenescence and antioxidant and anti-inflammatory approaches.","authors":"Anna Aiello, Anna Calabrò, Mattia Emanuela Ligotti, Giulia Accardi, Mojtaba Shekarkar Azgomi, Nadia Caccamo, Calogero Caruso, Francesco Dieli, Marco Pio La Manna, Antonio Procopio, Giuseppina Candore","doi":"10.1186/s12979-025-00506-y","DOIUrl":"10.1186/s12979-025-00506-y","url":null,"abstract":"<p><p>Aging is frequently characterized by an inadequate primary vaccine response, likely due to immunosenescence and inflamm-aging, a low-level, chronic inflammatory state. Both aspects increase the susceptibility of older adults to viral and bacterial infections, resulting in a higher frequency and severity of infectious diseases. In this preliminary study, a cohort of 52 individuals was recruited and divided into two groups: young (age range 21-35) and older adults (> 60 years old). Peripheral blood mononuclear cells (PBMCs) were collected before (time 0, T0) and after (time 1, T1) the immunization with a tetravalent influenza vaccine. Then, T cell immunophenotyping analysis was conducted to investigate how aging and influenza vaccination influence T cell responses. Additionally, the anti-inflammatory and antioxidant effects of oleuropein (OLE), a secoiridoid extracted from extra virgin olive oil, alone or in combination with BIRB 796, a potent inhibitor of p38 MAPK, were explored to enhancing the impact of influenza virus on T cell activation, aiming to identify potential alternatives or complementary strategies to improve traditional flu-vaccine formulations. Statistically significant observations were noted for a decrement in CD8 + T naïve and an increase of effector memory between the young and older adults after flu-vaccination. Moreover, preliminary findings indicate anti-inflammatory and antioxidant properties of OLE and BIRB 796 on T cell responses, particularly regarding Reactive Oxygen Species/Reactive Nitrogen Species modulation, with a trend toward the decrease of pro-inflammatory cytokines (i.e., Interferon-γ (INF-γ), Tumor Necrosis Factor-α (TNF-α)), αalthough without statistical significance.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"13"},"PeriodicalIF":5.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed viral clearance and altered inflammatory responses affect severity of SARS-CoV-2 infection in aged mice.","authors":"Émile Lacasse, Isabelle Dubuc, Leslie Gudimard, Ana Claudia Dos S P Andrade, Annie Gravel, Karine Greffard, Alexandre Chamberland, Camille Oger, Jean-Marie Galano, Thierry Durand, Éric Philipe, Marie-Renée Blanchet, Jean-François Bilodeau, Louis Flamand","doi":"10.1186/s12979-025-00503-1","DOIUrl":"10.1186/s12979-025-00503-1","url":null,"abstract":"<p><p>Epidemiological investigations consistently demonstrate an overrepresentation of the elderly in COVID-19 hospitalizations and fatalities, making the advanced age as a major predictor of disease severity. Despite this, a comprehensive understanding of the cellular and molecular mechanisms explaining how old age represents a major risk factor remain elusive. To investigate this, we compared SARS-CoV-2 infection outcomes in young adults (2 months) and geriatric (15-22 months) mice. Both groups of K18-ACE2 mice were intranasally infected with 500 TCID₅₀ of SARS-CoV-2 Delta variant with analyses performed on days 3, 5, and 7 post-infection (DPI). Analyses included pulmonary cytokines, lung RNA-seq, viral loads, lipidomic profiles, and histological assessments, with a concurrent evaluation of the percentage of mice reaching humane endpoints. The findings unveiled notable differences, with aged mice exhibiting impaired viral clearance, reduced survival, and failure to recover weight loss due to infection. RNA-seq data suggested greater lung damage and reduced respiratory function in infected aged mice. Additionally, elderly-infected mice exhibited a deficient antiviral response characterized by reduced Th1-associated mediators (IFNγ, CCL2, CCL3, CXCL9) and diminished number of macrophages, NK cells, and T cells. Furthermore, mass-spectrometry analysis of the lung lipidome indicated altered expression of several lipids with immunomodulatory and pro-resolution effects in aged mice such as Resolvin, HOTrEs, and NeuroP, but also DiHOMEs-related ARDS. These findings indicate that aging affects antiviral immunity, leading to prolonged infection, greater lung damage, and poorer clinical outcomes. This underscores the potential efficacy of immunomodulatory treatments for elderly subjects experiencing symptoms of severe COVID-19.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"11"},"PeriodicalIF":5.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compositional analysis of lymphocytes and their relationship with health outcomes: findings from the health and retirement study.","authors":"Lantian Xu, Chihua Li, Allison E Aiello, Kenneth M Langa, Jennifer B Dowd, Rebecca C Stebbins, Helen C S Meier, Ziman Jiang, Grace A Noppert, Gen Li","doi":"10.1186/s12979-025-00505-z","DOIUrl":"10.1186/s12979-025-00505-z","url":null,"abstract":"<p><strong>Background: </strong>Immunosenescence, the gradual deterioration of the immune system, is critical for aging-related diseases. However, the lack of detailed population-level immune data has limited our understanding, underscoring the need for innovative analytical approaches. The Health and Retirement Study (HRS) in the United States provides a unique opportunity to examine T and B lymphocyte subsets using compositional data analysis and dimension reduction techniques.</p><p><strong>Methods: </strong>We constructed a hierarchical tree structure to map relationships among T and B subset cells in HRS. Network analysis examined conditional dependence across 16 immune subset cells, while stepwise redundancy analysis (SRDA) identified a subset of pairwise logratio measures that capture main variance in immune composition. We conducted two sets of supervised learning analyses: first, linear penalized log-contrast models to examine the associations between subset cells and three health outcomes (chronic disease index, self-reported health, and frailty level); second, linear regressions to examine the associations between the top selected logratios and health outcomes.</p><p><strong>Findings: </strong>Our study included 6,250 participants from the HRS with a median age of 68. Network analysis showed some dependence among 16 immune subset cells, including associations between central memory CD4 + T cells and both other CD4 + T cells and other lymphocytes, as well as between central memory CD8 + T cells and other CD8 + T cells. SRDA identified nine key log-ratio measures, explaining over 90% of the variance in immune composition. Linear penalized log-contrast models showed that a lower proportion of naïve CD4 + T cells and higher proportions of other CD4 + and central memory CD8 + T cells were significantly associated with greater chronic disease burden, poorer self-reported health, and higher frailty levels. Linear regression models using log-ratios reinforced these patterns, showing that a higher ratio of other lymphocytes over naïve CD4 + T cells and terminally differentiated effector memory CD4 + T cells over other CD8 + T cells were associated with greater chronic disease burden, poorer self-reported health, and higher frailty levels. In contrast, a higher ratio of other lymphocytes over central memory CD4 + T cells was associated with better health outcomes.</p><p><strong>Interpretation: </strong>Our findings highlight the value of a systems-based approach and compositional analysis in understanding immunosenescence and its impact on health. The identified subset cells and logratio measures provide meaningful insights into immune aging and warrant further investigation to explore their long-term relationships with health outcomes.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"12"},"PeriodicalIF":5.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD31 + naïve T cells associate with immunosenescence and responsiveness to multiple vaccines in older adults.","authors":"Alper Cevirgel, Martijn Vos, Elske Bijvank, Josine van Beek, Marieke van der Heiden, Anne-Marie Buisman, Debbie van Baarle","doi":"10.1186/s12979-025-00504-0","DOIUrl":"10.1186/s12979-025-00504-0","url":null,"abstract":"<p><strong>Background: </strong>The T cell compartment undergoes significant age-related changes, contributing to the decline of the adaptive immune system and increasing the risk of suboptimal antibody responses to vaccines in older adults. To better understand the association between T cell phenotypes and vaccine responsiveness, we conducted an in-depth analysis of CD4+, CD8+, and γδ + T cells on VITAL cohort participants who are low or high responders to multiple vaccines (influenza, pneumococcal, and SARS-CoV-2).</p><p><strong>Results: </strong>Using spectral cytometry and FlowSOM, we identified detailed phenotypes of naïve, regulatory, and terminally differentiated T cells. We observed that the percentages of CD31 + naïve CD4+, CD31 + naïve CD8+, and CD38 + naïve CD8 + T cells were significantly lower in low vaccine responders. Notably, CD31 + naïve T cell subsets showed a stronger correlation with immune entropy, a measure of cumulative immune system perturbations, than with age itself.</p><p><strong>Conclusions: </strong>These findings suggest that subsets of naïve cells could be associated with weak vaccine responsiveness and immunosenescence. Furthermore, these naive T cell signatures could help predict weak vaccine responses, potentially informing targeted vaccination strategies in older adults.</p><p><strong>Clinical trial number: </strong>EudraCT: 2019-000836-24.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"10"},"PeriodicalIF":5.2,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secreted IgM deficiency alters the retinal landscape enhancing neurodegeneration associated with aging.","authors":"Sarah E Webster, Sydney M Les, Nico Deleon, Daken M Heck, Naomi L Tsuj, Michael J Clemente, Prentiss Jones, Nichol E Holodick","doi":"10.1186/s12979-025-00502-2","DOIUrl":"10.1186/s12979-025-00502-2","url":null,"abstract":"<p><strong>Background: </strong>Maintenance of the retina, part of the central nervous system, and other structures in the eye is critical for vision preservation. Aging increases the prevalence of vision impairment, including glaucoma, macular degeneration, and diabetic retinopathy. The retina is primarily maintained by glial cells; however, recent literature suggests that lymphocytes may play a role in the homeostasis of central nervous system tissues. Natural antibodies are produced by B cells without infection or immunization and maintain tissue homeostasis. Here, we explored the potential role of natural immunoglobulin M (IgM) produced by B lymphocytes in maintaining retinal health during aging in mice.</p><p><strong>Results: </strong>Our results indicate that the vitreous humor of both mice and humans contains IgM and IgG, suggesting that these immunoglobulins may play a role in ocular function. Furthermore, we observed that aged mice lacking secreted IgM (µs-/-) exhibited pronounced retinal degeneration, accompanied by reactive gliosis, and a proinflammatory cytokine environment. This contrasts with the aged wild-type counterparts, which retain their ability to secrete IgM and maintain a better retinal structure and anti-inflammatory environment. In addition to these findings, the absence of secreted IgM was associated with significant alterations in the retinal pigment epithelium, including disruptions to its morphology and signs of increased stress. This was further observed in changes to the blood-retinal-barrier, which is critical for regulation of retinal homeostasis.</p><p><strong>Conclusions: </strong>These data suggest a previously unrecognized association between a lack of secreted IgM and alterations in the retinal microenvironment, leading to enhanced retinal degeneration during aging. Although the precise mechanism remains unclear, these findings highlight the potential importance of secreted IgM in processes that support retinal health over time. By increasing our understanding of ocular aging, these results show that there is a broader role for the immune system in retinal function and integrity in advanced age, opening new areas for the exploration of immune-related interventions in age-associated retinal conditions.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"9"},"PeriodicalIF":5.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the link between fat-soluble vitamins and aging-associated immune system status: a literature review.","authors":"Hendrik Schmieder, Christian Leischner, Alban Piotrowsky, Luigi Marongiu, Sascha Venturelli, Markus Burkard","doi":"10.1186/s12979-025-00501-3","DOIUrl":"10.1186/s12979-025-00501-3","url":null,"abstract":"<p><p>The importance of vitamin D for a well-functioning immune system is becoming increasingly evident. Nevertheless, the other fat-soluble vitamins A, E and K also seem to play a central role regarding the adequate function of immune cells and to counteract excessive immune reactions and inflammatory processes. However, recognizing hidden hunger, particularly micronutrient deficiencies in vulnerable groups like the elderly, is crucial because older adults often lack sufficient micronutrients for various reasons. This review summarizes the latest findings on the immune modulating functions of fat-soluble vitamins in a physiological and pathophysiological context, provides a graphical comparison of the Recommended Daily Allowances between Deutschland, Austria, Confoederatio Helvetica (D-A-CH; eng. GSA, Germany, Switzerland, Austria), Deutsche Gesellschaft für Ernährung (DGE; eng. German Nutrition Society) and National Institutes of Health (NIH) across all age groups and, in particular, addresses the question regarding the benefits of supplementation of the respective micronutrients for the aging population of industrialized nations to strengthen the immune system. The following review highlights the importance of fat-soluble vitamins A, D, E and K which play critical roles in maintaining immune system function and, in some cases, in preventing excessive immune activation. Therefore, a better understanding of the relevance of adequate blood levels and consequently potential supplementation strategies may contribute to the prevention and management of infectious diseases as well as better overall health of the elderly.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"8"},"PeriodicalIF":5.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect and mechanism of miRNA-144-5p-regulated autophagy in older adults with Sarcopenia.","authors":"Mengdie Hu, Ying Zhang, Hong Ding, Rui Chao, Zhidong Cao","doi":"10.1186/s12979-025-00499-8","DOIUrl":"10.1186/s12979-025-00499-8","url":null,"abstract":"<p><strong>Background: </strong>Advanced aging invariably triggers an overabundance of apoptosis, stemming from diminished autophagy or a disarray in cellular autophagic processes. This, in turn, leads to an accelerated breakdown of muscle proteins, which exacerbates the ongoing deterioration of skeletal muscle and intensifies the severity of senile sarcopenia. This study aimed to investigate the role and mechanism of miRNA-regulated autophagy in senile sarcopenia.</p><p><strong>Methods: </strong>The miRNAs associated with sarcopenia were screened, and the target genes of significant miRNAs were predicted. The effects of significantly differentially expressed miRNA-144-5p on cell aging and autophagy were validated in vivo and in vitro.</p><p><strong>Results: </strong>The inhibition of miR-144-5p enhanced the multiplication of mouse myoblasts, increased the expression of MHC and autophagic markers LC3II/LC3I and Beclin-1, facilitated the formation of autophagosomes in mouse myoblasts, and reduced the number of aging cells and the expression of senescence-related proteins acetylated p53, p53, and p21 expression in mouse myoblasts. miR-144-5p affects myoblast senescence, myogenic differentiation, and autophagy by regulating the downstream target gene, Atg2A. Inhibiting miR-144-5p markedly increased the grip strength of the posterior limb in old mice, and the CSA of old mice and young mice was also markedly increased.</p><p><strong>Conclusion: </strong>All experiments have demonstrated that miRNA-144-5p has a significant impact on the regulation of autophagy and the development of senile sarcopenia.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"7"},"PeriodicalIF":5.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between biological aging and psoriasis: evidence from three observational studies.","authors":"Zheng Lin, Hong-Fei Wang, Lu-Yan Yu, Jia Chen, Cheng-Cheng Kong, Bin Zhang, Xuan Wu, Hao-Nan Wang, Yi Cao, Ping Lin","doi":"10.1186/s12979-025-00500-4","DOIUrl":"10.1186/s12979-025-00500-4","url":null,"abstract":"<p><strong>Background: </strong>The relationship between psoriasis and aging remains unclear. Biological age is considered as a tool for strong association with aging, but there is a lack of reports on the relationship between biological age and psoriasis. Therefore, this study aimed to explore the relationship between biological age and psoriasis.</p><p><strong>Methods: </strong>Patients with psoriasis and non-psoriasis were recruited from National Health and Nutrition Examination Survey (NHANES) (12,973 cases), Medical Information Mart for Intensive Care (MIMIC-IV) (558 cases) and The First Clinical Medical College of Zhejiang Chinese Medical University (206 cases). Biological age was calculated using Klemera-Doubal method age (KDM-age) and phenotypic age (PhenoAge). Linear regression and logistic regression were used to explore the association between psoriasis and biological age advance. Cox regression was used to investigate the association between biological age advance and mortality. Finally, biological age advance was used to predict the death of psoriasis patients.</p><p><strong>Results: </strong>In NHANES, linear regression showed that psoriasis led to a 0.54 advance in PhenoAge (Adjust Beta: 0.54, 95CI: 0.12-0.97, p = 0.018). The KDM-age advance due to psoriasis was not statistically significant (p = 0.754). Using data from China, we came to the new conclusion that for every unit rise in Psoriasis Area and Severity Index, PhenoAge advance rose by 0.12 (Beta: 0.12, 95CI: 0.01-0.22, p = 0.031). Using NHANES data, cox regression shows for every unit rise in PhenoAge advance patients had an 8% rise in mortality (Adjust hazard ratio: 1.08, 95CI: 1.04-1.12, p < 0.001). Using MIMIC-IV, logistic regression showed a 13% increase in mortality within 28 days of admission for every 1 unit rise in PhenoAge advance (odds ratio: 1.13, 95CI: 1.09-1.18, P < 0.001). Finally, we used PhenoAge advance to predict death, with an AUC of 0.71 in the NHANES, an ACU of 0.79 for predicting death within 1 years in the general ward of MIMIC-IV. In the ICU of MIMIC-IV, the AUC for predicting death within 28 days was 0.71.</p><p><strong>Conclusion: </strong>Psoriasis leads to accelerated biological aging in patients, which is associated with the severity of psoriasis and more comorbidities. In addition, PhenoAge has the potential to monitor the health status of patients with psoriasis.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"6"},"PeriodicalIF":5.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11816997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}