Immunity & Ageing最新文献

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.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: All experiments have demonstrated that miRNA-144-5p has a significant impact on the regulation of autophagy and the development of senile sarcopenia.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Phytochemicals help mitigate skin aging by scavenging free radicals, modulating key enzymatic pathways, and promoting the skin's structural integrity. Carotenoids, vitamins, essential fatty acids, and phenolic compounds work by acting as antioxidants, inhibiting enzymes like hyaluronidase, collagenase, and elastase, which degrade skin structure, and reducing levels of inflammatory markers (IL-6, IL-8, etc.) and matrix metalloproteinases (MMP-1, MMP-2) linked to aging. Recent research highlights that plant-based phytochemicals can improve skin elasticity, reduce hyperpigmentation, prevent the breakdown of important skin proteins, and support wound healing, making them valuable components for skin care and treatments. This review explores the multifaceted roles of phytochemicals in maintaining and improving skin health, highlighting their mechanisms of action and potential in skin anti-aging innovations.

Background: The characteristics of ulcerative colitis (UC) in the elderly are quite different from the young population. Mitochondrial injury is a key mechanism regulating both aging and inflammation. This study aims to reveal the role of mitochondrial damage in the pathogenesis of adult- and elderly-onset UC.

Methods: RNA-sequencing of colonic mucosa from adult- and elderly-onset UC patients was performed. Mitochondria-related differentially expressive genes (mDEGs) and immune cell infiltration analysis were identified and performed in colonic tissues from UC patients. Mice aged 6-8 weeks and 20-24 months were administered 2% dextran sodium sulphate (DSS) for 7 days to induce colitis. Mitochondrial morphological changes and ATP levels were evaluated in the colons of mice. Mechanistically, we explored the association of key mDEG with reactive oxygen species (ROS), oxygen consumption rates, NLRP3/IL-1β pathway in HCT116 cell line.

Results: Thirty mDEGs were identified between adult- and elderly-onset UC, which were related primarily to mitochondrial respiratory function and also had significant correlation with different infiltrates of immune cells. Compared with young colitis mice, DSS-induced colitis in the aged mice exhibited more severe inflammation, damaged mitochondrial structure and lower ATP levels in colonic tissues. ALDH1L1 was identified as a hub DEG through protein-protein interaction networks of RNA-seq, which was downregulated in UC patients or colitis mice versus healthy controls. In tumor necrosis factor-alpha-stimulated HCT116 cells, mitochondrial ROS, NLRP3 and IL-1β expression increased less and mitochondrial respiration had an upregulated trend after knocking down ALDH1L1.

Conclusion: There are significant differences in mitochondrial structure, ATP production and mitochondria-related gene expression between adult- and elderly-onset UC, which have a potential link with cytokine pathways and immune microenvironment. The more prominent mitochondrial injury may be a key factor for more severe inflammatory response and poorer outcome in elderly-onset UC.

Background: Older people living with HIV-1 (PLWH) experience a dual burden from the combined effects of aging and HIV-1 infection, resulting in significant immune dysfunction. Despite receiving HAART, immune reconstitution is not fully optimized. The objective of this study was to investigate the impact of aging and HAART on T cell subsets and function in PLWH across different age groups, thereby providing novel insights into the prognosis of older PLWH.

Method: This study was conducted at Yunnan AIDS Care Center, China, to explore the immunological responses of old PLWH to HAART and compared with the middle-age and the younger. Blood samples were collected from 146 PLWH to analyze T cell subsets and their functions, with a particular emphasis on markers related to T cell differentiation, activation, exhaustion, inflammation, and cellular function, using multicolor flow cytometry analysis.

Results: Older age may have a greater effect on long-term CD4⁺T cell recovery. Compared with young and middle-aged PLWH, older PLWH presented distinct alterations in their immune profile, including a decline in the Naïve CD4⁺T and CD8⁺T cell subsets, an expansion of effector memory cells, and other potential immune risk phenotypes, such as activation, exhaustion, and up-regulation of aging markers. In addition, we observed a significant association between the CD4 + EM3 subset and the CD8 + EM2 subset with HIV-1 progression, independent of age, suggesting their potential as reliable markers for assessing immune reconstitution in all PLWH.

Conclusion: Our study extends previous findings showing that older participants exhibit a wide range of late differentiation, senescence, or exhaustion phenotypes in cells, including all the CD4⁺T and CD8⁺T subsets, consistent with an immunosenescent phenotype. This may accelerate poor immune recovery in older PLWH. Identifying new strategies to improve the immune risk phenotypes of older PLWH may help improve their immune reconstitution outcomes. The CD4 + EM3 subset and the CD8 + EM2 subset should be studied as additional markers of late presentation.

Background: Obesity and metabolic syndrome are major public health concerns linked to cognitive decline with aging. Prior work from our lab has demonstrated that short-term high fat diet (HFD) rapidly impairs memory function via a neuroinflammatory mechanism. However, the degree to which these rapid inflammatory changes are unique to the brain is unknown. Moreover, deviations in gut microbiome composition have been associated with obesity and cognitive impairment, but how diet and aging interact to impact the gut microbiome, or how rapidly these changes occur, is less clear. Thus, our study investigated the impact of HFD after two distinct consumption durations: 3 months (to model diet-induced obesity) or 3 days (to detect the rapid changes occurring with HFD) on memory function, anxiety-like behavior, central and peripheral inflammation, and gut microbiome profile in young and aged rats.

Results: Our data indicated that both short-term and long-term HFD consumption impaired memory function and increased anxiety-like behavior in aged, but not young adult, rats. These behavioral changes were accompanied by pro- and anti-inflammatory cytokine dysregulation in the hippocampus and amygdala of aged HFD-fed rats at both time points. However, changes to fasting glucose, insulin, and inflammation in peripheral tissues such as the distal colon and visceral adipose tissue were increased in young and aged rats only after long-term, but not short-term, HFD consumption. Furthermore, while subtle HFD-induced changes to the gut microbiome did occur rapidly, robust age-specific effects were only present following long-term HFD consumption.

Conclusions: Overall, these data suggest that HFD-evoked neuroinflammation, memory impairment, and anxiety-like behavior in aging develop quicker than, and separately from the peripheral hallmarks of diet-induced obesity.

Background: As older age and having certain comorbidities can influence humoral responses to vaccination, we studied antibody responses after the COVID-19 booster campaigns in nursing home (NH) residents.

Methods: In a two year longitudinal study with Dutch NH residents (n = 107), aged 50 years and over, we monitored antibody responses in serum prior to and after vaccination with a third, fourth BNT162b2 (wild-type; WT), and a BNT162b2 bivalent (WT/OMI BA.1) fifth vaccine. Data on vaccinations, infections, comorbidities, and, for some participants, clinical symptoms after infection were obtained with questionnaires. Data were compared to antibody responses of BNT162b2-vaccinated, healthier community-dwelling older adults (n = 32) from the general population.

Results: The booster vaccinations substantially increased anti-WT and anti-Omicron SARS-CoV-2 Spike S1 (S1) and Spike protein receptor binding domain (RBD)-antibody concentrations of NH residents. This resulted in comparable antibody levels between NH residents and healthier community-dwelling older adults and between infection-naïve and infected NH residents, and in a decline in treatment duration and clinical symptom severity in SARS-CoV-2-infected NH residents. Between one and twelve months after the bivalent fifth dose, anti-Omicron BA.1 antibody levels of the NH residents waned faster than those against the WT strain.

Conclusions: The booster vaccinations upheld humoral responses of NH residents to WT and Omicron SARS-CoV-2. This, in addition to the less virulent circulating strains, decreased symptom severity and treatment durations for SARS-CoV-2-infected NH residents. Boosting this vulnerable group should, therefore, be continued to prevent waning of humoral immunity and achieve sufficient protection especially against newly emerging variants of concern.

The increased incidence of inflammatory diseases, infectious diseases, autoimmune disorders, and tumors in elderly individuals is closely associated with several well-established features of immunosenescence, including reduced B cell genesis and dampened immune responses. Recent studies have highlighted the critical role of dual receptor lymphocytes in tumors and autoimmune diseases. This study utilized shared data generated through scRNA-seq + scBCR-seq technology to investigate the presence of dual receptor-expressing B cells in the peritoneum of mouse and peripheral blood of healthy volunteers, and whether there are age-related differences in dual receptor B cell populations. In the peritoneum of mice, a high proportion of B cells expressing dual receptors, predominantly dual κ chains, was observed. Notably, there was an increase in dual BCR B cells in elderly mice. Subsequent analysis revealed that the elevated dual BCR B cells in elderly mice primarily originated from B1 cells.Consistent with the results we observed in healthy volunteers of different ages. Furthermore, these cells exhibited differential expressed genes compared to single BCR B cells, including Vim, Ucp2, and Zcwpw1.These findings support a hypothesis that age-related immune changes encompass not only alterations in B cell numbers but also qualitative changes in BCR diversity. Further exploration of the elevated dual BCR B cells in the elderly population can elucidate their function and their association with immune tolerance, revealing their potential role in maintaining immune surveillance and responding to age-related immune challenges.

Background: Immune ageing complicates cancer treatment in older individuals. While immunotherapy targeting the PD-1/PD-L1 pathway can reinvigorate T cells, these cells tend to become senescent with age. This study investigates different CD8⁺ T cell subsets usually associated with senescence, in cancer patients over 70 years old who are undergoing anti-PD-1/PD-L1 immunotherapy, and examines the relationship between these senescent cells and prior chemotherapy exposure. We analyzed data from the Elderly Cancer Patient (ELCAPA) cohort, which included 35 patients enrolled between March 2018 and March 2021.

Results: Flow cytometry and unsupervised analysis were employed to characterize Effector Memory CD45RA⁺ (EMRA) and CD8⁺ T cell senescence at baseline, before initiating PD-1/PD-L1 therapy. EMRA cells were found to overexpress CD57 and KLRG1 compared to overall CD8⁺ T cells. Chemotherapy prior to anti-PD-1/PD-L1 was associated with an increased proportion of CD57⁺ EMRA CD8⁺ T cells (p = 0.009) and its granzyme B (GRZB) subset (p = 0.007). Using a 10% cut-off to define positivity, the six-month non-response tends to be associated with the CD57⁺ GRZB⁺ EMRA positivity (p = 0.097). Other CD8⁺ T cell subsets (EMRA, CD57⁺, or KLRG1⁺), usually associated with senescence, showed no significant association with previous chemotherapy or response to anti-PD-1/anti-PD-L1 therapy.

Conclusions: These findings underscore the impact of prior chemotherapy on expanding the pool of senescent T cells, particularly CD57⁺ EMRA CD8⁺ T and CD57⁺ GRZB⁺ EMRA CD8⁺ T cells, whose expansion could potentially affect the effectiveness of anti-PD-1/PD-L1 immunotherapy in elderly patients. This highlights the need for tailored approaches in this population.