The trend of aging of the global population is becoming more and more significant, and the incidence of age-related diseases continues to rise.This phenomenon makes the problem of aging gradually attracted wide attention of the society, and gradually developed into an independent research field.As a vital defense mechanism of the human body, the immune system changes significantly during the aging process.Age-induced changes in the body\'s immune system are considered harmful and are commonly referred to as immune aging, which may represent the beginning of systemic aging.Immune cells, especially T cells, are the biggest influencers and participants in age-related deterioration of immune function, making older people more susceptible to different age-related diseases.More and more evidence shows that T cells play an important role in the change of human tissue structure after aging, which fundamentally affects the health and survival of the elderly.In this review, we discuss the general characteristics of age-related T cell immune alterations and the possible effects of aging T cells in various tissue structures in the human body.

BACKGROUND: Immunoglobulin G (IgG) N-glycosylation is considered a potential biomarker for aging and various pathological conditions. However, whether these changes in IgG N-glycosylation are a consequence or a contributor to the aging process remains unclear. This study aims to investigate the causality between IgG N-glycosylation and aging using Mendelian randomization (MR) analysis.
METHODS: We utilized genetic variants associated with IgG N-glycosylation traits, the frailty index (FI), and leukocyte telomere length (LTL) from a previous genome-wide association study (GWAS) on individuals of European ancestry. Two-sample and multivariable MR analyses were conducted, employing the inverse-variance weighted (IVW) method. Sensitivity analyses were performed to assess potential confounding factors.
RESULTS: Using the IVW method, we found suggestive evidence of a causal association between GP14 and FI (β 0.026, 95% CI 0.003 to 0.050, p = 0.027) and LTL (β -0.020, 95% CI -0.037 to -0.002, p = 0.029) in the two-sample MR analysis. In the multivariable MR analysis, suggestive evidence was found for GP23 and FI (β -0.119, 95% CI -0.219 to -0.019, p = 0.019) and GP2 and LTL (β 0.140, 95% CI 0.020 to 0.260, p = 0.023).
CONCLUSIONS: In conclusion, our results supported a potentially causal effect of lower GP23 levels on an advanced aging state. Additional verification is required to further substantiate the causal relationship between glycosylation and aging.

Adipose tissue is a widely distributed organ that plays a critical role in age-related physiological dysfunctions as an important source of chronic sterile low-grade inflammation. Adipose tissue undergoes diverse changes during aging, including fat depot redistribution, brown and beige fat decrease, functional decline of adipose progenitor and stem cells, senescent cell accumulation, and immune cell dysregulation. Specifically, inflammaging is common in aged adipose tissue. Adipose tissue inflammaging reduces adipose plasticity and pathologically contributes to adipocyte hypertrophy, fibrosis, and ultimately, adipose tissue dysfunction. Adipose tissue inflammaging also contributes to age-related diseases, such as diabetes, cardiovascular disease and cancer. There is an increased infiltration of immune cells into adipose tissue, and these infiltrating immune cells secrete proinflammatory cytokines and chemokines. Several important molecular and signaling pathways mediate the process, including JAK/STAT, NFκB and JNK, etc. The roles of immune cells in aging adipose tissue are complex, and the underlying mechanisms remain largely unclear. In this review, we summarize the consequences and causes of inflammaging in adipose tissue. We further outline the cellular/molecular mechanisms of adipose tissue inflammaging and propose potential therapeutic targets to alleviate age-related problems.

Despite the well-known senolytic effects of physical exercise on immune cells in older adults, the effect of physical activity (PA) on premature immune senescence in sedentary adults with obesity remains largely unknown. This pilot study aimed to investigate the role of objectively measured physical behaviors and Fitbit watch-based free-living PA intervention in premature senescence of immune cells in sedentary adults with obesity. Forty-five participants were recruited in the cross-sectional analysis, and forty of them further participated in the randomized controlled trial. We found that objectively measured moderate-vigorous PA was independently and inversely correlated with the expression of p16INK4a and p21Cip1 in the peripheral blood mononuclear cell (PBMCs) of adults with obesity; however, chronological age, body mass index, body fat, maximal oxygen consumption, light PA, sedentary behaviors, and sleep duration were not. More importantly, the 12-week PA intervention mitigated the elevated p16INK4a levels in PBMCs, though it showed no effect on p21Cip1 and senescence-associated secretory phenotypes. Taken together, physical inactivity is an independent determinant of premature senescence in immune cells, while the 12-week PA intervention is a promising strategy to alleviate premature immune senescence in adults with obesity.

Progressive immune dysfunction associated with aging is known as immunosenescence. The age-related deterioration of immune function is accompanied by chronic inflammation and microenvironment changes. Immunosenescence can affect both innate and acquired immunity. Sepsis is a systemic inflammatory response that affects parenchymal organs, such as the respiratory system, cardiovascular system, liver, urinary system, and central nervous system, according to the sequential organ failure assessment (SOFA). The initial immune response is characterized by an excess release of inflammatory factors, followed by persistent immune paralysis. Moreover, immunosenescence was found to complement the severity of the immune disorder following sepsis. Furthermore, the immune characteristics associated with sepsis include lymphocytopenia, thymus degeneration, and immunosuppressive cell proliferation, which are very similar to the characteristics of immunosenescence. Therefore, an in-depth understanding of immunosenescence after sepsis and its subsequent effects on the organs may contribute to the development of promising therapeutic strategies. This paper focuses on the characteristics of immunosenescence after sepsis and rigorously analyzes the possible underlying mechanism of action. Based on several recent studies, we summarized the relationship between immunosenescence and sepsis-related organs. We believe that the association between immunosenescence and parenchymal organs might be able to explain the delayed consequences associated with sepsis.

Human immune system functions over an entire lifetime, yet how and why the immune system becomes less effective with age are not well understood. Here, we characterize peripheral blood mononuclear cell transcriptome from 132 healthy adults with 21-90 years of age using the weighted gene correlation network analyses. In our study, 113 Caucasian from the 10KIP database and RNA-seq data of 19 Asian (Chinese) are used to explore the differential co-expression genes in PBMC aging. These two dataset reveal a set of insightful gene expression modules and representative gene biomarkers for human immune system aging from Asian and Caucasian ancestry, respectively. Among them, the aging-specific modules may show an age-related gene expression variation spike around early-seventies. In addition, we find the top hub genes including NUDT7, CLPB, OXNAD1, and MLLT3 are shared between Asian and Caucasian aging related modules and further validated in human PBMCs from different age groups. Overall, the impact of age and race on transcriptional variation elucidated from this study may provide insights into the transcriptional driver of immune aging.

Aging leads to functional dysregulation of the immune system, especially T cell defects. Previous studies have shown that the accumulation of co-inhibitory molecules plays an essential role in both T cell exhaustion and aging. In the present study, we showed that CD244 and CD160 were both up-regulated on CD8+ T cells of elderly individuals. CD244+CD160- CD8+ T cells displayed the increased activity of β-GAL, higher production of cytokines, and severe metabolic disorders, which were characteristics of immune aging. Notably, the functional dysregulation associated with aging was reversed by blocking CD244 instead of CD160. Meanwhile, CD244+CD160+ CD8+ T cells exhibited features of exhaustion, including lower levels of cytokine, impaired proliferation, and intrinsic transcriptional regulation, compared to CD244+CD160- population. Collectively, our findings demonstrated that CD244 rather than CD160 acts as a prominent regulator involved in T cell aging, providing a solid therapeutic target to improve disorders and comorbidities correlated to immune system aging.

Immunosenescence, also known as immune aging, refers to the degeneration, compensation, and reconstruction of the immune system with aging. Immune aging is an important factor in the increased susceptibility of the elderly to infectious diseases, malignant tumors, and a variety of chronic diseases and has long been a hotspot in geriatrics and immunology research. In this paper, the characteristics and progression of immune aging are briefly reviewed for clinicians\' reference.

The characteristic accumulation of late-stage differentiated CD8+ T cells is enhanced by lifelong latent cytomegalovirus (CMV) persistence, which makes it challenging to screen for subclinical biomarkers of immune aging in the elderly. We systematically identified predominantly preformed, long, noncoding RNAs (lncRNAs) as integrative biomarkers of CD8+ T cell aging in 14 elderly CMV carriers over 80 years of age. After sorting the CD28nullCD8+ T cell subset and its CD28bearingCD8+ counterpart in five nonagenarians, we profiled the differential expression of lncRNAs and genes in CD28nullCD8+ T cells via array detection. We focused on 11 differentially expressed antisense lncRNAs and cross-referenced them with previously identified age-accumulated lncRNAs to create a set of candidates in CD28nullCD8+T cells. We performed intracellular validation on the age-accumulated candidate lncRNAs paired with their antisense target genes using quantitative polymerase chain reaction (qPCR). Simultaneously, we sorted the CMVpp65-specific CD8+ T cell subset and its counterpart from participant cells with the HLA-A-*0201 genotype. The validated age-accumulated lncRNAs in CD28nullCD8+ T cells were intracellularly cross-validated in CMVpp65CD8+ T cells. Finally, we identified the immunity-related gene(s) that acted as potential target(s) to the cross-validated age-accumulated lncRNA(s), using bioinformatics techniques. The potential regulation of the final identified lncRNA-gene pair(s) was simultaneously predicted in two pathway-integrated networks. We concluded that expression of an age-accumulated lncRNA (NRON) was decreased, whereas that of its immunity-related target gene (NFAT) was increased, in both CD28nullCD8+ T cells and CMVpp65CD8+ T cells of elderly individuals with persistent CMV infection. The identification of NRON as a potential biomarker suggests that NRON contributes to CMV-enhanced CD28nullCD8+ T cell aging by modulating phosphorylation and/or IL-4-dependent NFAT signaling.