New Molecular Insights of Inflammation in Aging and Age-Related Disease

Editors

Qiulun Lu

Nanjing Medical University

Changhan Ouyang

Hubei University of Science and Technology

Yufeng Yao

Huazhong University of Science and Technology

Andréa Cristina Paula-Lima

University of Chile

Impact

* p<0.05, ** p<0.005, ns=not significant.

Original Research

07 December 2023

Fulvio Massaro

, 6 more and

Laurence Lagneaux

6,546 views

12 citations

Activation of AhR in aging and HIV causes disruption of bone homeostasis and fat deposition in skeletal muscle.

Review

08 September 2023

The kynurenine pathway in HIV, frailty and inflammaging

Shabiha Sultana

, 4 more and

Mark W. Hamrick

6,228 views

15 citations

5 W/cm2 protects against myocardial ischemia/reperfusion (MI/R) injury. With heterodimers comprised of the hypoxia-inducible factor-1α (HIF-1α) subunit and HIF-1β subunit, hypoxia-inducible factors coordinate cellular adaptations to reduced O2 availability by regulating transcriptional programs in metabolism, angiogenesis, and erythropoiesis. Hypoxia increases and stabilizes HIF-1α by reducing prolyl hydroxylation and increasing the dimerization of HIF-1α and HIF-1β. HIF-1α is quickly degraded with a sufficient supply of O2. The O2-mediated degradation of HIF-1α is inhibited because of the hypoxic condition suffering from MI/R. Accumulated HIF-1α upregulates NADPH oxidase 4 (Nox4) by binding to a core DNA sequence in the gene of NOX4, upregulating NOX4 and inducing the overproduction of reactive oxygen species (ROS). ROS, including O2.- and H2O2, are mainly hydrolyzed by superoxide dismutase (SOD) and catalase (CAT). The increased ROS stimulates cardiomyocytes to release inflammatory cytokines by ROS signaling. The released inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), further stimulated cardiomyocytes to generate ROS by upregulating Nox4 in cardiomyocytes, forming a chain reaction between the cardiac oxidative stress and inflammatory reaction in the cardiomyocytes with MI/R injury. Under oxidative stress, ROS induces cell death by upregulating an intrinsic apoptotic pathway in which ASK1 and JNK are activated within cardiomyocytes. In addition, the released TNF-α also promotes cell death by activating an extrinsic apoptotic pathway in which the receptor of TNF-α is activated on the cytomembrane of cardiomyocytes and subsequently increases the expression of Casp-3, a major executioner of programmed cell death. Both in vivo and in vitro, LIPUS of 0.5 W/cm2 alleviates the MI/R jury, cardiac inflammatory reaction, and cardiac oxidative stress while LIPUS of 2.5 W/cm2 aggravates the MI/R jury, cardiac inflammatory reaction, and cardiac oxidative stress. The activation of the ASK1/JNK pathway is inhibited by LIPUS of 2.5 W/cm2 in cardiomyocytes both in vivo and in vitro.

Original Research

07 September 2023

Low-intensity pulsed ultrasound of different intensities differently affects myocardial ischemia/reperfusion injury by modulating cardiac oxidative stress and inflammatory reaction

Quan Cao

, 8 more and

Qing Zhou

3,061 views

6 citations

Systematic Review

14 July 2023

Crosstalk between ferroptosis and chondrocytes in osteoarthritis: a systematic review of in vivo and in vitro studies

Siyang Cao

, 8 more and

Hui Zeng

5,552 views

21 citations

Systematic Review

13 July 2023

Markers of the ageing macrophage: a systematic review and meta-analysis

Charlotte E. Moss

, 2 more and

Endre Kiss-Toth

7,120 views

11 citations

Original Research

10 August 2023

Single-cell RNA-seq analysis reveals that immune cells induce human nucleus pulposus ossification and degeneration

Song Guo

, 8 more and

Qiang Fu

7,444 views

6 citations

Original Research

22 August 2023

The aging kidney is characterized by tubuloinflammaging, a phenotype associated with MHC-II gene expression

Julius Sinning

, 8 more and

Roland Schmitt

5,293 views

5 citations

Original Research

06 September 2023

A role of inflammaging in aortic aneurysm: new insights from bioinformatics analysis

Shilin Wang

, 5 more and

Shu Chen

4,652 views

6 citations

Original Research

12 July 2023

Identification of aging-related biomarkers and immune infiltration characteristics in osteoarthritis based on bioinformatics analysis and machine learning

JiangFei Zhou

, 5 more and

QingQi Meng

Background: Osteoarthritis (OA) is a degenerative disease closely related to aging. Nevertheless, the role and mechanisms of aging in osteoarthritis remain unclear. This study aims to identify potential aging-related biomarkers in OA and to explore the role and mechanisms of aging-related genes and the immune microenvironment in OA synovial tissue.

Methods: Normal and OA synovial gene expression profile microarrays were obtained from the Gene Expression Omnibus (GEO) database and aging-related genes (ARGs) from the Human Aging Genomic Resources database (HAGR). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO), and Gene set variation analysis (GSVA) enrichment analysis were used to uncover the underlying mechanisms. To identify Hub ARDEGs with highly correlated OA features (Hub OA-ARDEGs), Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning methods were used. Furthermore, we created diagnostic nomograms and receiver operating characteristic curves (ROC) to assess Hub OA-ARDEGs’ ability to diagnose OA and predict which miRNAs and TFs they might act on. The Single sample gene set enrichment analysis (ssGSEA) algorithm was applied to look at the immune infiltration characteristics of OA and their relationship with Hub OA-ARDEGs.

Results: We discovered 87 ARDEGs in normal and OA synovium samples. According to functional enrichment, ARDEGs are primarily associated with inflammatory regulation, cellular stress response, cell cycle regulation, and transcriptional regulation. Hub OA-ARDEGs with excellent OA diagnostic ability were identified as MCL1, SIK1, JUND, NFKBIA, and JUN. Wilcox test showed that Hub OA-ARDEGs were all significantly downregulated in OA and were validated in the validation set and by qRT-PCR. Using the ssGSEA algorithm, we discovered that 15 types of immune cell infiltration and six types of immune cell activation were significantly increased in OA synovial samples and well correlated with Hub OA-ARDEGs.

Conclusion: Synovial aging may promote the progression of OA by inducing immune inflammation. MCL1, SIK1, JUND, NFKBIA, and JUN can be used as novel diagnostic biomolecular markers and potential therapeutic targets for OA.

11,791 views

27 citations

After binding with cytoplasmic dsDNA, cGAS catalyzes the synthesis of cGAMP, which is an active ligand of STING. Activation of STING results in the upregulation of autophagy and the expression of inflammatory factors, which in turn leads to SASP. Furthermore, the cGAS-STING pathway indirectly promotes cell cycle arrest.

Review

10 July 2023

STING signaling in inflammaging: a new target against musculoskeletal diseases

Chenyu Song

, 9 more and

Yinghua Li

7,955 views

10 citations

Review

05 July 2023

The effect of cytokines on osteoblasts and osteoclasts in bone remodeling in osteoporosis: a review

Jie Xu

, 3 more and

Zhenhua Deng

The complicated connections and cross talk between the skeletal system and the immune system are attracting more attention, which is developing into the field of Osteoimmunology. In this field, cytokines that are among osteoblasts and osteoclasts play a critical role in bone remodeling, which is a pathological process in the pathogenesis and development of osteoporosis. Those cytokines include the tumor necrosis factor (TNF) family, the interleukin (IL) family, interferon (IFN), chemokines, and so on, most of which influence the bone microenvironment, osteoblasts, and osteoclasts. This review summarizes the effect of cytokines on osteoblasts and osteoclasts in bone remodeling in osteoporosis, aiming to providing the latest reference to the role of immunology in osteoporosis.

15,703 views

85 citations