Age-related Gene Research Articles

A comparative study of metformin and nicotinamide riboside in alleviating tissue aging in rats

AbstractMetformin (MET) and nicotinamide riboside (NR) have both been reported to exert geroprotective effects in multiple species. However, the mechanism by which MET and NR regulate the aging program and delay aging in multiple tissues remains unclear. Here, we demonstrated that MET and NR attenuate aging features in human mesenchymal stem cells. Moreover, by systematically investigating the pathophysiological changes in different tissues from aged rats after oral administration of MET and NR, we showed that both MET and NR treatment alleviated various aging-related characteristics in multiple tissues, including inflammation, fibrosis, and protein aggregates. Consistently, MET or NR treatment partially rescued aging-related gene expression changes in aged rats. Collectively, we report that both MET and NR attenuate senescence phenotypes in human stem cells in vitro and in a variety of rodent tissues in vivo, thus providing a valuable resource and foundation for further evaluation of these two compounds against aging.

Selection of winter soft wheat for resistance to brown rust

The article presents the results of the phytopathological test and marker analysis of the selection material of winter wheat for resistance to the pathogen of brown rust (Puccinia recondita Rob. ex Desm f. sp. tritici.). The object of research was 10 cultivars of various ecological and geographical origin. Using molecular markers, the studied wheat varieties did not reveal the highly and partially effective genes Lr9, Lr19/Sr25, Lr24/Sr24, Lr41 and Lr47 in Russia, and the ineffective gene Lr20/Sr1. The combination of the Lr34 gene with ineffective genes can provide an increase in the level of field resistance of wheat varieties. In the variety type Leaf 25, the age-related resistance gene Lr37 is assumed to be partially effective in Russia. This type of stability is characterized by a longer latent period, a decrease in the number of pustules per unit leaf surface, their size and the number of spores in the pustule. According to the results of a comprehensive assessment of winter wheat cultivars to brown rust, the following cultivars showed a stable reaction type (R): Zhiva (Lr1, Lr3, Lr10, Lr26, Lr34) and Leaf 25 (Lr1, Lr3, Lr37;); a susceptible reaction type (S) in Malvina cultivars -(Lr1, Lr26;), Solara (Lr1, Lr34), Etude - Lr3. Genes in various combinations can provide field resistance of winter wheat to brown rust. Most cultivars were moderately susceptible to the disease.

Chemical composition and anti-aging effects of standardized herbal chicken essence on D-galactose- induced senescent mice.

This study aimed to examine the chemical and anti-aging properties of chicken essence (CE) prepared with Sesamum indicum, Angelica acutiloba, and Zingiber officinale (HCE). HCE was analyzed for nutritional and phytochemical composition, and its anti-aging effects were investigated on the D-galactose (Gal)-induced aging mice. Results showed that HCE possessed significantly higher calories and contents of valine and total phenols than CE; it also contained significant amounts of ferulic acid, sesamin, and sesamolin. HCE significantly decreased MDA and NO levels in serum and liver and increased liver GSH levels in the D-Gal-induced mice. HCE greatly enhanced SOD and CAT activities in serum and liver, and liver GPx activity, as well as upregulating SIRT1 expression and downregulating TNF-α, IL-1β, IL-6, iNOS, Cox-2, and MCP-1 expression in liver tissues. This study demonstrates that HCE was effective in suppressing the aging process through enhancing antioxidant and anti-inflammatory activities and modulating the aging-related gene expression.

The Zinc-sensing Receptor (GPR39) Modulates Declarative Memory and Age-related Hippocampal Gene Expression in Male Mice

As a neuromodulator, zinc regulates synaptic plasticity, learning and memory. Synaptic zinc is also a crucial factor in the development of toxic forms of amyloid beta protein and, subsequently, of Alzheimer’s dementia (AD). Therefore, efforts to pinpoint mechanisms underlying zinc-dependent cognitive functions might aid AD research, by providing potential novel targets for drugs. One of the most understudied proteins in this regard is a zinc-sensing metabotropic receptor: GPR39. In this study we investigated the impact of GPR39 knock-out (KO) on age-related memory decline in mice of both sexes, by comparing them to age-matched wild-type (WT) littermates. We also tested the effects of a GPR39 agonist (TC-G 1008) on declarative memory of old animals, and its disruption in adult mice. We observed episodic-like memory (ELM) and spatial memory (SM) deficits in male GPR39 KO mice, as well as intact procedural memory in GPR39 KO mice regardless of age and sex. ELM was also absent in old WT male mice, and all female mice regardless of their genotype. Acute application of TC-G 1008 (10 mg/kg) reversed a deficit in two of three ELM components in old WT male mice, and had no promnesic effect on consolidation interference of ELM in adult WT mice. We discuss the possible neurobiological mechanisms and the translational value of these results for potential add-on pharmacotherapy of AD aimed at the zinc-sensing receptor.

Relationships between the expression of adipose genes and profiles of hospitalized dogs

Obesity is one of the risk factors for the onset of various metabolic diseases in dogs. Energy expenditure in brown/beige adipocytes, which is partially regulated by the bone morphogenetic protein (BMP) pathway, is a key factor determining systemic energy balance. Here, we examined gene expression in the fat depots of 129 hospitalized dogs, and the relationship between the relative levels of gene expression and profiles of dogs. We evaluated the expression levels of 23 genes such as regulatory genes of adipocyte differentiation and function, adipokines, genes related to brown adipogenesis and uncoupling protein (Ucp), and genes involved in BMP signaling. A reliable equation of multiple regression was not obtained to explain the body condition score (BCS), which is an index of adiposity. Positive relationships were detected between the expression levels of many genes, except for Ucp1 or Ucp3. BCS was found to increase with age. BCS was negatively correlated to the expression levels of Pparγ and Fasn, and positively correlated to Leptin and Opn3 expression. Aging decreased the expression levels of genes related to adipocyte differentiation and function (Pparγ, Fabp4, Fasn, Hsl, and Insr) and Adipoq. In addition, age was negatively correlated with the expression of genes involved in brown adipogenesis and BMP signaling components (Prdm16, Bmp4, Alk3, Actr2a, and Actr2b). In contrast, the expression levels of Leptin and Ucp2 were found to increase with age. The present study clarifies BCS- and age-related gene expressions in the adipose tissue, which potentially contribute to elucidating the etiology of canine obesity.

A novel age-related gene expression signature associates with proliferation and disease progression in breast cancer

Background and objectiveBreast cancer (BC) diagnosed at ages <40 years presents with more aggressive tumour phenotypes and poorer clinical outcome compared to older BC patients. Here, we explored transcriptional BC alterations to gain a better understanding of age-related tumour biology, also subtype-stratified.MethodsWe studied publicly available global BC mRNA expression (n = 3999) and proteomics data (n = 113), exploring differentially expressed genes, enriched gene sets, and gene networks in the young compared to older patients.ResultsWe identified transcriptional patterns reflecting increased proliferation and oncogenic signalling in BC of the young, also in subtype-stratified analyses. Six up-regulated hub genes built a novel age-related score, significantly associated with aggressive clinicopathologic features. A high 6 Gene Proliferation Score (6GPS) demonstrated independent prognostic value when adjusted for traditional clinicopathologic variables and the molecular subtypes. The 6GPS significantly associated also with disease-specific survival within the luminal, lymph node-negative and Oncotype Dx intermediate subset.ConclusionsWe here demonstrate evidence of higher tumour cell proliferation in young BC patients, also when adjusting for molecular subtypes, and identified a novel age-based six-gene signature pointing to aggressive tumour features, tumour proliferation, and reduced survival—also in patient subsets with expected good prognosis.

Transcriptional modulation of inflammation, and aging in Indian obese adults following a 12-week yoga-based lifestyle intervention: A randomized controlled trial.

IntroductionObesity is one of the major global problems in today's world, both in children, and the adult age group. Current evidence suggests obesity alters the expression of various genes related to oxidative stress, inflammation, and aging. In recent times complementary therapy like yoga-based lifestyle intervention (YBLI) is used as an adjunct therapy to modern medicine. This study examines the efficacy of 12 weeks of yoga-based lifestyle intervention with standard care (SC) on the expression of genes related to oxidative stress, inflammation, and aging in obese adults.MethodsThis was a two-arm parallel randomized control trial implemented at Integral Health Clinic (IHC), an outpatient facility that regularly conducted YBLI programs for the prevention of lifestyle diseases like obesity and diabetes in the Department of Physiology, All India Institute of Medical Sciences (AIIMS), New Delhi. Blood samples at baseline and weeks 2,4, and 12 were collected from 72 adults (male n = 21; female n = 51) of age 20–45 years with a body–mass index (BMI) of 25–35 kg/m2 who were randomized to receive either a 12-week SC (n = 36) or YBLI (n = 36). SC included recommendations for the management of obesity as per Indian guidelines including a low-calorie individualized diet and physical activity. Asana (physical postures), pranayama (breathing exercises), and meditation were all part of the YBLI. Primary outcomes were relative fold change in the expression of genes associated with oxidative stress [Nuclear factor-kappa B (NF-Kappa B)], inflammation [Tumor necrosis factor-α (TNFα), interleukin-6 (IL-6)], and aging [human telomerase reverse transcriptase (TERT)] in peripheral blood mononuclear cells between the two groups at week-12.ResultsThere were no significant changes in fold change of TERT, IL-6, and NF-kappa B between the groups at week 12. The relative fold change of TERT was significantly greater in the YBLI group (p = <0.0001) vs the SC group at 2 weeks. The relative fold change of TNF α was significantly lower at week 12 in YBLI though the change was not continuous and reliable. Within both groups, TERT expression was significantly increased at week 2 though the change was greater in the YBLI group (p < 0.0001). TNF α gene expression was significantly lower at weeks 2 and 4, compared to baseline level, in the SC group but it increased at week 12.ConclusionThe results while did not confirm our hypothesis, are important to share with the scientific society, to be able to improve prospective study designs and find optimal time/intervention/biological marker settings for this highly important scientific field. The results are suggestive of a positive impact of YBLI and SC on the fold change of aging-related TERT gene in obesity, though the benefit was not evident till week 12. However, the results should be evaluated with caution and in light of other published studies. To better understand the positive effects of YBLI on oxidative stress, inflammation, and aging-related gene expression in obesity, larger studies are recommended.

Differential effects of calorie restriction and rapamycin on age-related molecular and functional changes in skeletal muscle.

Aging is a multifactorial process associated with progressive degradation of physiological integrity and function. One of the greatest factors contributing to the deleterious effects of aging is the decline of functional ability due to loss of muscle mass, strength, and function, a condition termed sarcopenia. Calorie restriction (CR) has consistently been shown to extend lifespan and delay the onset and progression of various age-related diseases, including sarcopenia. Additional anti-aging interventions that are receiving scientific attention are CR mimetics. Of these pharmacological compounds, rapamycin has shown similar CR-related longevity benefits without the need for diet restrictions. To investigate the potential role of rapamycin as an anti-sarcopenic alternative to CR, we conducted a study in male and female C57BL/6J mice to assess the effects of rapamycin on age-related gene expression changes in skeletal muscle associated with loss of muscle mass, strength, and function, relative to control. We hypothesize that the effects of rapamycin will closely align with CR with respect to physical function and molecular indices associated with muscle quality. Our results indicate CR and rapamycin provide partial protection against age-related decline in muscle, while engaging uniquely different molecular pathways in skeletal muscle. Our preclinical findings of the therapeutic potential of rapamycin or a CR regimen on geroprotective benefits in muscle should be extended to translational studies towards the development of effective strategies for the prevention and management of sarcopenia.

Identification and validation of a siglec-based and aging-related 9-gene signature for predicting prognosis in acute myeloid leukemia patients

BackgroundAcute myeloid leukemia (AML) is a group of highly heterogenous and aggressive blood cancer. Despite recent progress in its diagnosis and treatment, patient outcome is variable and drug resistance results in increased mortality. The siglec family plays an important role in tumorigenesis and aging. Increasing age is a risk factor for AML and cellular aging contributes to leukemogenesis via various pathways.MethodsThe differential expression of the siglec family was compared between 151 AML patients and 70 healthy controls, with their information downloaded from TCGA and GTEx databases, respectively. How siglec expression correlated to AML patient clinical features, immune cell infiltration, drug resistance and survival outcome was analyzed. Differentially expressed genes in AML patients with low- and high-expressed siglec9 and siglec14 were analyzed and functionally enriched. The aging-related gene set was merged with the differentially expressed genes in AML patients with low and high expression of siglec9, and merged genes were subjected to lasso regression analysis to construct a novel siglec-based and aging-related prognostic model. The prediction model was validated using a validation cohort from GEO database (GSE106291).ResultsThe expression levels of all siglec members were significantly altered in AML. The expression of siglecs was significantly correlated with AML patient clinical features, immune cell infiltration, drug resistance, and survival outcome. Based on the differentially expressed genes and aging-related gene set, we developed a 9-gene prognostic model and decision curve analysis revealed the net benefit generated by our prediction model. The siglec-based and aging-related 9-gene prognostic model was tested using a validation data set, in which AML patients with higher risk scores had significantly reduced survival probability. Time-dependent receiver operating characteristic curve and nomogram were plotted and showed the diagnostic accuracy and predictive value of our 9-gene prognostic model, respectively.ConclusionsOverall, our study indicates the important role of siglec family in AML and the good performance of our novel siglec-based and aging-related 9-gene signature in predicting AML patient outcome.

Over-Expression of Larch DAL1 Accelerates Life-Cycle Progression in Arabidopsis

Homologs of Larix kaempferiDEFICIENS-AGAMOUS-LIKE 1 (LaDAL1) promote flowering in Arabidopsis. However, their functional role in the whole life-cycle is limited. Here, we analyzed the phenotypes and transcriptomes of Arabidopsis plants over-expressing LaDAL1. With respect to the defined life-cycle stage of Arabidopsis based on the meristem state, the results showed that LaDAL1 promoted seed germination, bolting, flower initiation, and global proliferative arrest, indicating that LaDAL1 accelerates the meristem reactivation, the transitions of vegetative meristem to inflorescence and flower meristem, and meristem arrest. As a marker gene of meristem, TERMINAL FLOWER 1 was down-regulated after LaDAL1 over-expression. These results reveal that LaDAL1 accelerates the life-cycle progression in Arabidopsis by promoting the transition of meristem fate, providing more and novel functional information about the conifer age-related gene DAL1.

Age-Related Increase of Collagen/Fibrin Deposition and High PAI-1 Production in Human Nasal Polyps.

Objective: Our previous studies showed an age-related increased prevalence of nasal polyps (NP) and reduced production of S100A8/9 in elderly patients with chronic rhinosinusitis with NP (CRSwNP). In this study, we investigated an unbiased age-related gene expression profile in CRSwNP subjects and healthy controls, and further identified the differences in their tissue remodeling. Methods: Microarrays using NP and uncinate tissues from health controls (elderly, age ≥65 vs. non-elderly, age 18–49) were performed, and differentially regulated genes were analyzed. Quantitative real-time PCR (qPCR), Immunostaining, Periodic acid-Schiff (PAS), trichrome staining, Western blot, and ELISA were performed for further investigation. Results: Microarrays identified differentially expressed genes according to disease and age; 278 in NP vs. controls, 75 in non-elderly NP vs. non-elderly controls, and 32 in elderly NP vs. elderly controls. qPCR confirmed that the PLAT gene was downregulated and the SERPINB2 gene upregulated in NP vs. controls. The serous glandular cell-derived antimicrobial protein/peptide-related genes such as BPIFB3, BPIFB2, LPO, and MUC7 were remarkably reduced in NP, regardless of age. SERPINE1 gene (plasminogen activator inhibitor-1, PAI-1) expression was significantly increased in elderly NP versus elderly controls. IHC and western blot confirmed significantly decreased production of MUC7 and LPO in NP versus controls. There was a trend of age-related reduction of submucosal gland cells in normal controls. Trichrome and immunofluorescence staining demonstrated an age-related increase of collagen and fibrin deposition in NP, consistent with increased PAI-1 production. Conclusion: This study demonstrated age-related differential glandular remodeling patterns and fibrosis in NP and normal controls. PAI-1 expression was significantly increased in elderly NP versus elderly controls, suggesting PAI-1 as a potential treatment target in elderly NP.

Evaluation of photoreceptor-directed fibroblasts derived from retinitis pigmentosa patients with defects in the EYS gene: a possible cost-effective cellular model for mechanism-oriented drug

BackgroundThe most common gene responsible for autosomal recessive retinitis pigmentosa (RP) is EYS. The manner of decay of genetically defective EYS gene transcripts varies depending on the type of mutation using our cellular model, which consists of induced photoreceptor-directed fibroblasts from EYS-RP patients (EYS-RP cells). However, disease-specific profiles have not been clarified in EYS-RP cells. Herein we investigated comprehensive gene expression patterns and restoration of altered expression by low molecular weight molecules in EYS-RP cells.MethodsUsing induced photoreceptor-like cells by CRX, RAX, NeuroD, and OTX2, we employed qRT-PCR and DNA microarray analysis to compare expression levels of disease-related genes in EYS-RP cells. We investigated the effect of antiapoptotic or anti-endoplasmic reticulum (ER) stress/antioxidant reagents on the restoration of altered gene expression.ResultsExpression levels of phototransduction-related genes (blue opsin, rhodopsin, S-antigen, GNAT1, GNAT2) were lower in EYS-RP cells. CRYGD was extracted by global gene expression analysis, as a downregulated, retina-related and apoptosis-, endoplasmic reticulum (ER) stress- or aging-related gene. Pathway enrichment analysis suggested that “complement and coagulation cascades,” “ECM-receptor interaction” and “PI3K-Akt signaling pathway” could be involved in EYS-RP-associated pathogenesis. Among the matching/overlapping genes involved in those pathways, F2R was suggested as an EYS-RP-associated gene. The downregulation of CRYGD and F2R was completely restored by additional 4-PBA, an inhibitor of ER stress, and partially restored by metformin or NAC. In addition, 4-PBA normalized the expression level of cleaved caspase-3.ConclusionsOur cellular model may reflect the ER stress-mediated degenerative retina and serve as a pathogenesis-oriented cost-effective rescue strategy for RP patients.

Evolution of gene expression signature in mammary gland stem cells from neonatal to old mice

During the lifetime of females, mammary epithelial cells undergo cyclical expansion and proliferation depending on the cyclical activation of mammary gland stem/progenitor cells (MaSCs) in response to the change of hormone level. The structural shrink of mammary duct tree and the functional loss of mammary gland occur along with inactivation of MaSCs in old females, even leading to breast cancer occasionally. However, the gene expression signature in MaSCs across the lifespan remains unclear. Herein, we tested the tissue regeneration ability of CD24+CD49fhigh MaSCs over six time points from neonatal (4-day-old) to aged mice (360-day-old). Further RNA-seq analyses identified four clusters of gene signatures based on the gene expression patterns. A subset of stemness-related genes was identified, showing the highest level at day 4 of the neonatal age, and the lowest level at the old age. We also identified an aging-related gene signature showing significant change in the old mice, in which an association between aging process and stemness loss was indicated. The aging-related gene signature showed regulation of cancer signaling pathways, as well as aging-related diseases including Huntington disease, Parkinson disease, and Alzheimer disease. Moreover, 425, 1056, 418, and 1107 gene variants were identified at D20, D40, D90, and D180, respectively, which were mostly reported to associated with tumorigenesis and metastasis in cancer. In summary, the current study is the first to demonstrate the gene expression shift in MaSCs from neonatal to aging, which leads to stemness loss, aging, aging-related diseases, and even breast cancer in old mice.

Characterization of Aging-Related Genes to Predict Prognosis and Evaluate the Tumor Immune Microenvironment in Malignant Melanoma.

Objective Malignant melanoma (MM) is one of the most malignant types of skin cancer and its incidence and mortality rates are increasing worldwide. Aging is well recognized as a significant risk factor for cancer. However, few studies have analyzed in depth the association between aging-related genes (AGs) and malignant melanoma prognosis with tumor immune microenvironment. Methods Here, we downloaded 471 MM patients from The Cancer Genome Atlas (TCGA) with RNA sequence and clinicopathological data. 58 AGs from the TCGA dataset were examined using Cox regression and the LASSO assay. As a result, a gene signature for aging-related genes was created. The time-dependent ROC curve and Kaplan–Meier analysis were calculated to determine its predictive capability. Moreover, we created a nomogram for the clinicopathologic variables and the AGs gene signature to determine overall survival (OS). We also explored the association between three immune checkpoints, immune cell infiltration, and the aging-related gene signature. Results We established an aging risk model to identify and predict the immune microenvironment in malignant melanoma. Then we developed and validated a prognosis risk model using three AGs (CSNK1E, C1QA, and SOD-2) in the GSE65904 dataset. The aging signature was positively associated with clinical and molecular characteristics and can be used as a prognostic factor for malignant melanoma. The low aging risk score was associated with a poor prognosis and indicated an immunosuppressive microenvironment. Conclusions To summarize, we established and validated a model of aging risk based on three aging-related genes that acted as an independent prognostic predictor of overall survival. Besides, it also characterized the immune response in the malignant melanoma microenvironment and could provide a potential indicator of individualized immunotherapy in malignant melanoma.

Age-related differential gene expression in granulosa cells and its effects on fertility using high-throughput transcriptomics

More couples worldwide, delay their childbearing years. The increase in age causes a gradual decrease in female ovarian function and fertility, leading to an exponential decrease in women over 35 years of age having children. Although promising for some, assisted reproductive technology (ART) is not promising for older women. Decreased fertility in advanced age has become a growing concern in the field of reproduction. In this study, high-throughput transcriptome sequencing was used to identify the differentially expressed genes (DEGs) in the ovarian granulosa cells (GCs) of older women (aged 35–44) with infertility and younger women (aged 25–34). The enriched functions and signaling pathways of DEGs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The function of DEGs were analyzed and predicted combined with clinical ART data. Sequencing results were verified by quantitative reverse transcription-polymerase chain reaction. Retrospective clinical data and bioinformatics analyses revealed marked reductions in the retrieved oocyte, metaphase II oocyte, 2PN fertilization, and effective embryo numbers in older women. Although the clinical pregnancy and live birth rates did not differ notably between the groups, the miscarriage rate increased significantly in older women. In total, 620 DEGs were identified, of which 246 were upregulated, and 374 were downregulated in the older group. GO, and KEGG analyses indicated that the mechanism of fertility decline in older women was probably related to chronic inflammation, cytokine receptor interaction, and oxidative stress. In conclusion, combined with basic clinical ART data and pregnancy outcomes, we tried to provide a more intuitive and in-depth understanding of age-related reduction in ovarian function and pathogenesis of infertility with regard to chronic inflammation and oxidative stress.

Effects of dietary macronutrients on the hepatic transcriptome and serum metabolome in mice.

Dietary macronutrient composition influences both hepatic function and aging. Previous work suggested that longevity and hepatic gene expression levels were highly responsive to dietary protein, but almost unaffected by other macronutrients. In contrast, we found expression of 4005, 4232, and 4292 genes in the livers of mice were significantly associated with changes in dietary protein (5%–30%), fat (20%–60%), and carbohydrate (10%–75%), respectively. More genes in aging‐related pathways (notably mTOR, IGF‐1, and NF‐kappaB) had significant correlations with dietary fat intake than protein and carbohydrate intake, and the pattern of gene expression changes in relation to dietary fat intake was in the opposite direction to the effect of graded levels of caloric restriction consistent with dietary fat having a negative impact on aging. We found 732, 808, and 995 serum metabolites were significantly correlated with dietary protein (5%–30%), fat (8.3%–80%), and carbohydrate (10%–80%) contents, respectively. Metabolomics pathway analysis revealed sphingosine‐1‐phosphate signaling was the significantly affected pathway by dietary fat content which has also been identified as significant changed metabolic pathway in the previous caloric restriction study. Our results suggest dietary fat has major impact on aging‐related gene and metabolic pathways compared with other macronutrients.

An Aging-Related Gene Signature-Based Model for Risk Stratification and Prognosis Prediction in Lung Squamous Carcinoma.

Aging is an inevitable process characterized by a decline in many physiological activities, and has been known as a significant risk factor for many kinds of malignancies, but there are few studies about aging-related genes (ARGs) in lung squamous carcinoma (LUSC). We designed this study to explore the prognostic value of ARGs and establish an ARG-based prognosis signature for LUSC patients. RNA-sequencing and corresponding clinicopathological data of patients with LUSC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The ARG risk signature was developed on the basis of results of LASSO and multivariate Cox analysis in the TCGA training dataset (n = 492). Furthermore, the GSE73403 dataset (n = 69) validated the prognostic performance of this ARG signature. Immunohistochemistry (IHC) staining was used to verify the expression of the ARGs in the signature. A five ARG-based signature, including A2M, CHEK2, ELN, FOS, and PLAU, was constructed in the TCGA dataset, and stratified patients into low- and high-risk groups with significantly different overall survival (OS) rates. The ARG risk score remained to be considered as an independent indicator of OS in the multivariate Cox regression model for LUSC patients. Then, a prognostic nomogram incorporating the ARG risk score with T-, N-, and M-classification was established. It achieved a good discriminative ability with a C-index of 0.628 (95% confidence interval [CI]: 0.586–0.671) in the TCGA cohort and 0.648 (95% CI: 0.535–0.762) in the GSE73403 dataset. Calibration curves displayed excellent agreement between the actual observations and the nomogram-predicted survival. The IHC staining discovered that these five ARGs were overexpression in LUSC tissues. Besides, the immune infiltration analysis in the TCGA cohort represented a distinctly differentiated infiltration of anti-tumor immune cells between the low- and high-risk groups. We identified a novel ARG-related prognostic signature, which may serve as a potential biomarker for individualized survival predictions and personalized therapeutic recommendation of anti-tumor immunity for patients with LUSC.

Gene Expression Analysis Reveals Age and Ethnicity Signatures Between Young and Old Adults in Human PBMC.

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.

The physiology of plant seed aging: a review

Seed quality plays an important role in the agricultural and animal husbandry production, the effective utilization of genetic resources, the conservation of biodiversity and the restoration and reconstruction of plant communities. Seed aging is a common physiological phenomenon during storage. It is a natural irreversible process that occurs and develops along with the extension of seed storage time. It is not only related to the growth, yield and quality of seed and seedling establishment, but also has an important effect on the conservation, utilization and development of plant germplasm resources. The physiological mechanisms of seed aging are complex and diverse. Most studies focus on conventional physiological characterization, while systematic and comprehensive in-depth studies are lacking. Here we review the recent advances in understanding the physiology of seed aging process, including the methods of seed aging, the effect of aging on seed germination, and the physiological and molecular mechanisms of seed aging. The change of multiple physiological parameters, including seed vigor, electrical conductivity, malondialdehyde content and storage material in the seed, antioxidant enzyme activity and mitochondrial structure, were summarized. Moreover, insights into the mechanism of seed aging from the aspects of transcriptome, proteome and aging related gene function were summarized. This study may facilitate the research of seed biology and the conservation and utilization of germplasm resources.

Characterization of an Aging-Based Diagnostic Gene Signature and Molecular Subtypes With Diverse Immune Infiltrations in Atherosclerosis.

Objective: Advancing age is a major risk factor of atherosclerosis (AS). Nevertheless, the mechanism underlying this phenomenon remains indistinct. Herein, this study conducted a comprehensive analysis of the biological implications of aging-related genes in AS. Methods: Gene expression profiles of AS and non-AS samples were curated from the GEO project. Differential expression analysis was adopted for screening AS-specific aging-related genes. LASSO regression analysis was presented for constructing a diagnostic model, and the discriminatory capacity was evaluated with ROC curves. Through consensus clustering analysis, aging-based molecular subtypes were conducted. Immune levels were estimated based on the expression of HLAs, immune checkpoints, and immune cell infiltrations. Key genes were then identified via WGCNA. The effects of CEBPB knockdown on macrophage polarization were examined with western blotting and ELISA. Furthermore, macrophages were exposed to 100 mg/L ox-LDL for 48 h to induce macrophage foam cells. After silencing CEBPB, markers of cholesterol uptake, esterification and hydrolysis, and efflux were detected with western blotting. Results: This study identified 28 AS-specific aging-related genes. The aging-related gene signature was developed, which could accurately diagnose AS in both the GSE20129 (AUC = 0.898) and GSE43292 (AUC = 0.685) datasets. Based on the expression profiling of AS-specific aging-related genes, two molecular subtypes were clustered, and with diverse immune infiltration features. The molecular subtype–relevant genes were obtained with WGCNA, which were markedly associated with immune activation. Silencing CEBPB triggered anti-inflammatory M2-like polarization and suppressed foam cell formation. Conclusion: Our findings suggest the critical implications of aging-related genes in diagnosing AS and modulating immune infiltrations.