scholarly journals Transcriptomics analysis for the identification of potential age-related genes and cells associated with three major urogenital cancers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jinlong Cao ◽  
Jianpeng Li ◽  
Xin Yang ◽  
Pan Li ◽  
Zhiqiang Yao ◽  
...  

AbstractAge is one of the most important risk factors of the occurrence for tumor patients. The majority of patients with urogenital cancers are the elderly, whose clinical characteristics are greatly affected by age and ageing. Our study aimed to explore age-related genes, cells, and biological changes in three common urogenital cancers via integrative bioinformatics analysis. First, mRNA (count format) and clinical data for bladder cancer, prostate cancer and renal cell carcinoma were downloaded from the Cancer Genome Atlas (TCGA). Through the comparison of clinicopathological characteristics, genes expression and cells infiltration between the old group and the young group, it was found that the clinical characteristics, genes and cells in the tumor microenvironment of different ages were quite different. And 4 key cells, 14 hub genes and some potential pathways were identified and considered as important factors. More importantly, we analyzed the differential landscape of the genes and cells from different perspectives, and confirmed its importance. In conclusion, we identified genes and cell types associated with age-related changes in the tumour microenvironment in urogenital cancer patients. These genes and cell types may play a critical role in the age-associated differences in clinicopathological characteristics among urogenital cancers, thus providing a link between ageing and cancer occurrence. The findings of this study may pave the way for the development of age-tailored approaches to treat cancer and other age-related diseases.

Author(s):  
Gagan Chooramani ◽  
Pooja Singh

The World Health Organization has declared that the spread of tuberculosis is a global emergency. Despite the implementation of strong tuberculosis-control initiatives by WHO, this highly infectious disease continues to affect all vulnerable populations, including the elderly population. Adverse social factors and poor living conditions also affect the elderly much more than the young. The clinical characteristics of tuberculosis in older adults can be unusual and may be confused with age-related illnesses. Various factors related to old age can also cause complications in the diagnosis, treatment, and disease outcomes for tuberculosis patients. The contributory factors may be poor memory, deafness, mental confusion, or impairment of speech. In addition, therapy for tuberculosis in elderly individuals is challenging because of the increased incidence of adverse drug reactions. Hence, understanding the impact of these substantial aspects will help to overcome the problem of tuberculosis in the elderly population.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Hao Zhang ◽  
Fan Fan ◽  
Yuanqiang Yu ◽  
Zeyu Wang ◽  
Fangkun Liu ◽  
...  

Abstract Background Immunotherapies targeting glioblastoma (GBM) have led to significant improvements in patient outcomes. TOX is closely associated with the immune environment surrounding tumors, but its role in gliomas is not fully understood. Methods Using data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we analyzed the transcriptomes of 1691 WHO grade I-IV human glioma samples. The R language was used to perform most of the statistical analyses. Somatic mutations and somatic copy number variation (CNV) were analyzed using GISTIC 2.0. Results TOX was down-regulated in malignant gliomas compared to low grade gliomas, and upregulated in the proneural and IDH mutant subtypes of GBM. TOXlow tumours are associated with the loss of PTEN and amplification of EGFR, while TOXhigh tumours harbor frequent mutations in IDH1 (91%). TOX was highly expressed in leading edge regions of tumours. Gene ontology and pathway analyses demonstrated that TOX was enriched in multiple immune related processes including lymphocyte migration in GBM. Finally, TOX had a negative association with the infiltration of several immune cell types in the tumour microenvironment. Conclusion TOX has the potential to be a new prognostic marker for GBM.


2019 ◽  
Vol 20 (9) ◽  
pp. 903-918 ◽  
Author(s):  
Francesca Liva ◽  
Doretta Cuffaro ◽  
Elisa Nuti ◽  
Susanna Nencetti ◽  
Elisabetta Orlandini ◽  
...  

Background: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. The disease is characterized by photoreceptor loss in the macula and reduced Retinal Pigment Epithelium (RPE) function, associated with matrix degradation, cell proliferation, neovascularization and inflammation. Matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play a critical role in the physiology of extracellular matrix (ECM) turnover and, in turn, in ECM pathologies, such as AMD. A balance between the activities of MMPs and Tissue Inhibitors of Metalloproteinase (TIMPs) is crucial for the integrity of the ECM components; indeed, a dysregulation in the ratio of these factors produces profound changes in the ECM, including thickening and deposit formation, which eventually might lead to AMD development. Objective: This article reviews the relevance and impact of zinc metalloproteinases on the development of AMD and their roles as biomarkers and/or therapeutic targets. We illustrate some studies on several inhibitors of MMPs currently used to dissect physiological properties of MMPs. Moreover, all molecules or technologies used to control MMP and ADAM activity in AMD are analyzed. Conclusion: This study underlines the changes in the activity of MMPs expressed by RPE cells, highlights the functions of already used MMP inhibitors and consequently suggests their application as therapeutic agents for the treatment of AMD.


2020 ◽  
Author(s):  
Zhang Hao ◽  
Fan Fan ◽  
Yu Yuanqiang ◽  
Wang Zeyu ◽  
Liu Fangkun ◽  
...  

Abstract Background: Immunotherapies targeting glioblastoma (GBM) have led to significant improvements in patient outcomes. TOX is closely associated with the immune environment surrounding tumors, but its role in gliomas is not fully understood. Methods: Using data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we analyzed the transcriptomes of 1691 WHO grade I-IV human glioma samples. The R language was used to perform most of the statistical analyses. Somatic mutations and somatic copy number variation (CNV) were analyzed using GISTIC 2.0. Results: TOX was down-regulated in malignant gliomas compared to low grade gliomas, and upregulated in the proneural and IDH mutant subtypes of GBM. TOXlow tumours are associated with the loss of PTEN and amplification of EGFR, while TOXhigh tumours harbor frequent mutations in IDH1 (91%). TOX was highly expressed in leading edge regions of tumours. Gene ontology and pathway analyses demonstrated that TOX was enriched in multiple immune related processes including lymphocyte migration in GBM. Finally, TOX had a negative association with the infiltration of several immune cell types in the tumour microenvironment. Conclusion: TOX has the potential to be a new prognostic marker for GBM.


2010 ◽  
Vol 298 (2) ◽  
pp. H671-H678 ◽  
Author(s):  
Anthony J. Donato ◽  
Abhimanyu Uberoi ◽  
Damian M. Bailey ◽  
D. Walter Wray ◽  
Russell S. Richardson

Aging, vascular function, and exercise are thought to have a common link in oxidative stress. Of the 28 subjects studied (young, 26 ± 2 yr; old, 71 ± 6 yr), 12 took part in a study to validate an antioxidant cocktail (AOC: vitamins C, E, and α-lipoic acid), while the remaining 8 young and 8 old subjects performed submaximal forearm handgrip exercise with placebo or AOC. Old subjects repeated forearm exercise with placebo or AOC following knee-extensor (KE) exercise training. Brachial arterial diameter and blood velocity (Doppler ultrasound) were measured at rest and during exercise. During handgrip exercise, brachial artery vasodilation in the old subjects was attenuated compared with that in young subjects following placebo (maximum = ∼3.0 and ∼6.0%, respectively). In contrast to the previously documented attenuation in exercise-induced brachial artery vasodilation in the young group with AOC, in the old subjects the AOC restored vasodilation (maximum = ∼7.0%) to match the young. KE training also improved exercise-induced brachial artery vasodilation. However, in the trained state, AOC administration no longer augmented brachial artery vasodilation in the elderly, but rather attenuated it. These data reveal an age-related pro-/antioxidant imbalance that impacts vascular function and show that exercise training is capable of restoring equilibrium such that vascular function is improved and the AOC-mediated reduction in free radicals now negatively impacts brachial artery vasodilation, as seen in the young.


2020 ◽  
Author(s):  
Fucai Tang ◽  
Zechao Lu ◽  
Chengwu He ◽  
Hanbin Zhang ◽  
Weijia Wu ◽  
...  

Abstract Background: The objectives of this study were to screen out cut-off age value and age-related differentially expressed genes (DEGs) in clear cell renal cell carcinoma (CCRCC) from Surveillance Epidemiology and End Results (SEER) database and The Cancer Genome Atlas (TCGA) database. Methods: We selected 45,974 CCRCC patients from SEER and 530 RNA-seq data from TCGA database. The age cut-off value was defined using the X-tile program. Propensity score matching (PSM) was used to balance the differences between young and old groups. Hazard ratio (HR) was applied to evaluate prognostic risk of age in different subgroups. Age-related DEGs were identified via RNA-seq data. Survival analysis was used to assess the relationship between DEGs and prognosis.Results: In this study, we divided the patients into young (n=14276) and old (n=31698) subgroups according to cut-off value (age=53). Age >53 years was indicated as independent risk factor for overall survival (OS) and cancer specific survival (CSS) of CCRCC before and after PSM. The prognosis of old group was worse than that in young group. Eleven gene were differential expression between the younger and older groups in CCRCC. The expression levels of PLA2G2A and SIX2 were related to prognosis of the elderly. Conclusion: 53 years old was cut-off value in CCRCC. The prognosis of the elderly was worse than young people. It remind clinicians that more attention and better treatment should be given to CCRCC patients who are over 53 years old. PLA2G2A and SIX2 were age-related differential genes which might play an important role in the poor prognosis of elderly CCRCC patients.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Tobias Fehlmann ◽  
Benoit Lehallier ◽  
Nicholas Schaum ◽  
Oliver Hahn ◽  
Mustafa Kahraman ◽  
...  

AbstractAging is a key risk factor for chronic diseases of the elderly. MicroRNAs regulate post-transcriptional gene silencing through base-pair binding on their target mRNAs. We identified nonlinear changes in age-related microRNAs by analyzing whole blood from 1334 healthy individuals. We observed a larger influence of the age as compared to the sex and provide evidence for a shift to the 5’ mature form of miRNAs in healthy aging. The addition of 3059 diseased patients uncovered pan-disease and disease-specific alterations in aging profiles. Disease biomarker sets for all diseases were different between young and old patients. Computational deconvolution of whole-blood miRNAs into blood cell types suggests that cell intrinsic gene expression changes may impart greater significance than cell abundance changes to the whole blood miRNA profile. Altogether, these data provide a foundation for understanding the relationship between healthy aging and disease, and for the development of age-specific disease biomarkers.


2013 ◽  
Vol 115 (4) ◽  
pp. 456-467 ◽  
Author(s):  
Tarkeshwar Singh ◽  
Vladimir M. Zatsiorsky ◽  
Mark L. Latash

We investigated the effects of fatigue produced by timed maximal voluntary contraction (MVC) of the index finger of the right hand on performance in MVC and accurate cyclic force production tasks in right-handed young (Young group) and strength-matched elderly (Elderly group) participants. We hypothesized that, before fatigue, the Elderly group would show weaker force-stabilizing synergies and smaller adaptive changes in the synergy index during fatigue. Synergies were defined as covaried adjustments of neural commands to fingers (finger modes) across trials that stabilize total force. Fatigue caused a significant reduction in the MVC, which was larger in the Young group compared with the Elderly group for both fatigued finger (index finger) and four fingers (index, middle, ring, and little fingers pressing together). Indexes of finger enslaving (lack of individuation) increased with fatigue in both groups. The index of force-stabilizing synergies was similar for the two groups before fatigue, while its increase with fatigue was significantly larger in the Elderly group compared with the Young group. We infer that changes in the indexes of finger interaction (enslaving) and coordination (synergy) with age seem to be correlated with changes in muscle strength. This correlation may be causally related to the progressive death of neurons at different levels of the neuromotor hierarchy. The surprisingly large changes in the synergy index with fatigue in older adults suggest that, by itself, aging does not necessarily lead to impairment in synergic control. Strength training may be a method to avoid age-related decrement in finger interaction and coordination.


2019 ◽  
Author(s):  
Fucai Tang ◽  
Zechao Lu ◽  
Chengwu He ◽  
Hanbin Zhang ◽  
Weijia Wu ◽  
...  

Abstract Background The objectives of this study were to screen out cut-off age value and age-related differentially expressed genes (DEGs) in clear cell renal cell carcinoma (CCRCC) from Surveillance Epidemiology and End Results (SEER) database and The Cancer Genome Atlas (TCGA) database. Methods We selected 45,974 CCRCC patients from SEER and 530 RNA-seq data from TCGA database. The age cut-off value was defined using the X-tile program. Propensity score matching (PSM) was used to balance the differences between young and old groups. Hazard ratio (HR) was applied to evaluate prognostic risk of age in different subgroups. Age-related DEGs were identified via RNA-seq data. Survival analysis was used to assess the relationship between DEGs and prognosis. Results In this study, we divided the patients into young (n=14276) and old (n=31698) subgroups according to cut-off value (age=53). Age >53 years was indicated as independent risk factor for overall survival (OS) and cancer specific survival (CSS) of CCRCC before and after PSM. The prognosis of old group was worse than that in young group. 176 age-related DEGs were obtained by 530 CCRCC RNA-seq analysis result. The expression levels of KCNE5, CLDN6 and CACNG6 were related to prognosis of the elderly. Conclusion 53 years old was cut-off value in CCRCC. The prognosis of the elderly was worse than young people. KCNE5, CLDN6 and CACNG6 were age-related differential genes which might play an important role in the poor prognosis of elderly CCRCC patients.


2021 ◽  
Vol 22 (16) ◽  
pp. 9045
Author(s):  
Nicholas A. Foreman ◽  
Anton S. Hesse ◽  
Li Li Ji

Sarcopenia, the age-related decline in muscle mass and function, derives from multiple etiological mechanisms. Accumulative research suggests that reactive oxygen species (ROS) generation plays a critical role in the development of this pathophysiological disorder. In this communication, we review the various signaling pathways that control muscle metabolic and functional integrity such as protein turnover, cell death and regeneration, inflammation, organismic damage, and metabolic functions. Although no single pathway can be identified as the most crucial factor that causes sarcopenia, age-associated dysregulation of redox signaling appears to underlie many deteriorations at physiological, subcellular, and molecular levels. Furthermore, discord of mitochondrial homeostasis with aging affects most observed problems and requires our attention. The search for the primary suspect of the fundamental mechanism for sarcopenia will likely take more intense research for the secret of this health hazard to the elderly to be unlocked.


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