Senescent cells as a target for anti-aging interventions: From senolytics to immune therapies DOI
Tao Fu, Zhongjun Zhou

Journal of Translational Internal Medicine, Год журнала: 2025, Номер 13(1), С. 33 - 47

Опубликована: Фев. 1, 2025

Aging and age-related diseases are major drivers of multimorbidity mortality worldwide. Cellular senescence is a hallmark aging. The accumulation senescent cells causally associated with pathogenesis various age-associated disorders. Due to their promise for alleviating disorders extending healthspan, therapeutic strategies targeting (senotherapies) as means combat aging have received much attention over the past decade. Among conventionally used approaches, one usage small-molecule compounds specifically exhibit cytotoxicity toward or inhibit deleterious effects senescence-associated secretory phenotype (SASP). Alternatively, there immunotherapies directed at surface antigens upregulated in (seno-antigens), including chimeric antigen receptor (CAR) therapies senolytic vaccines. This review gives an update current status discovery development therapies, translational progress from preclinical clinical trials. We highlight challenges faced by senotherapeutic context heterogeneity, aim offering novel perspectives future anti-aging interventions aimed enhancing healthy longevity.

Язык: Английский

Mitochondrial dysfunction: a new molecular mechanism of intervertebral disc degeneration DOI
Chao Song, Yulin Xu, Qinghua Peng

и другие.

Inflammation Research, Год журнала: 2023, Номер 72(12), С. 2249 - 2260

Опубликована: Ноя. 5, 2023

Язык: Английский

Процитировано

25
Injectable Ozone‐Rich Nanocomposite Hydrogel Loaded with D‐Mannose for Anti‐Inflammatory and Cartilage Protection in Osteoarthritis Treatment DOI

Hangtian Wu,

Jun Wang,

Yanpeng Lin

и другие.

Small, Год журнала: 2024, Номер 20(25)

Опубликована: Янв. 26, 2024

Abstract Osteoarthritis (OA) is a dynamic condition characterized by cartilage damage and synovial inflammation. Ozone (O 3 ) shows potential therapeutic effects owing to its anti‐inflammatory properties; however, high reactivity short half‐life substantially limit effectiveness in OA treatment. In this study, an ozone‐rich thermosensitive nanocomposite hydrogel loaded with D‐mannose developed for Briefly, O encapsulated nanoparticles (NPs) composed of perfluorotributylamine fluorinated hyaluronic acid improve stability. Next, conjugated α‐amino the hydroxypropyl chitin (HPCH) via Schiff base prepare MHPCH. These are MHPCH produce NPs@MHPCH. vitro cell experiments demonstrate that NPs@MHPCH treatment significantly reduced VEGF inflammation levels, accompanied decrease inflammatory factors such as IL‐1β, IL‐6, TNF‐α, iNOS. Furthermore, promotes expression collagen II aggrecan stimulates chondrocyte proliferation. Additionally, vivo studies show alleviated reducing inflammation, destruction, subchondral bone remodeling. offers promising option improving efficacy therapy risk degeneration OA.

Язык: Английский

Процитировано

11
Senolytic treatment for low back pain DOI Creative Commons
Matthew Mannarino, Hosni Cherif, Saber Ghazizadeh Darband

и другие.

Science Advances, Год журнала: 2025, Номер 11(11)

Опубликована: Март 14, 2025

Senescent cells (SnCs) accumulate because of aging and external cellular stress throughout the body. They adopt a senescence-associated secretory phenotype (SASP) release inflammatory degenerative factors that actively contribute to age-related diseases, such as low back pain (LBP). The senolytics, o -vanillin RG-7112, remove SnCs in human intervertebral discs (IVDs) reduce SASP release, but it is unknown whether they can treat LBP. sparc −/− mice, with LBP, were treated orally RG-7112 single or combination treatments. Treatment reduced LBP factor removed from IVD spinal cord. also lowered degeneration scores IVDs, improved vertebral bone quality, expression markers Together, our data suggest potential disease-modifying drugs for other painful disorders linked cell senescence.

Язык: Английский

Процитировано

1
Senescence-associated alterations in the extracellular matrix: deciphering their role in the regulation of cellular function DOI
Eleni Mavrogonatou,

Adamantia Papadopoulou,

Harris Pratsinis

и другие.

AJP Cell Physiology, Год журнала: 2023, Номер 325(3), С. C633 - C647

Опубликована: Июль 24, 2023

The extracellular matrix (ECM) is a dynamic structural network that provides physical scaffolding, as well biochemical factors maintain normal tissue homeostasis and thus its disruption implicated in many pathological conditions. On the other hand, senescent cells express particular secretory phenotype, affecting composition organization of surrounding ECM modulating their microenvironment. As accumulation may be linked to manifestation several age-related conditions, senescence-associated alterations serve targets for novel anti-aging treatment modalities. Here, we will review characteristic changes elicited by cellular senescence discuss complex interplay between cells, relation aging selected age-associated pathologies.

Язык: Английский

Процитировано

19
FSTL1 Accelerates Nucleus Pulposus Cell Senescence and Intervertebral Disc Degeneration Through TLR4/NF-κB Pathway DOI

Xu Yan,

Jing-Yu Ding,

Renjie Zhang

и другие.

Inflammation, Год журнала: 2024, Номер 47(4), С. 1229 - 1247

Опубликована: Фев. 6, 2024

Язык: Английский

Процитировано

7
An anti-senescence hydrogel with pH-responsive drug release for mitigating intervertebral disc degeneration and low back pain DOI Creative Commons

Wantao Wang,

Lei Liu,

Wenzheng Ma

и другие.

Bioactive Materials, Год журнала: 2024, Номер 41, С. 355 - 370

Опубликована: Июль 27, 2024

Язык: Английский

Процитировано

7
Dynamics of N6‐methyladenosine modification during aging and their potential roles in the degeneration of intervertebral disc DOI Creative Commons
Libangxi Liu,

Hong Sun,

Yang Zhang

и другие.

JOR Spine, Год журнала: 2024, Номер 7(1)

Опубликована: Янв. 25, 2024

Abstract Background The N6‐methyladenosine (m6A) dynamics in the progression of intervertebral disc (IVD) aging remain largely unknown. This study aimed to explore distribution and pattern m 6 A modification nucleus pulpous (NP) tissues rats at different ages. Methods Histological staining MRI were performed evaluate degeneration IVD. expression m6A modifiers was analyzed using qRT‐PCR western blot. Subsequently, methylated RNA immunoprecipitation next generation sequencing RNA‐seq conducted identify differences methylome transcriptome NP tissues. Results Compared 2‐month‐old rats, we found significant changes global level Mettl3 FTO from 20‐month‐old rats. During aging, there 1126 persistently differentially peaks within 931 genes, 51 expressed genes. GO KEGG analyses showed that these modified genes mainly engaged biological processes pathways degermation (IDD), such as extracellular matrix metabolism, angiogenesis, inflammatory response, mTOR AMPK signaling pathways. Meanwhile, conjoint Venn diagram revealed a total 405 related contained methylation levels contrast 10‐month‐old Moreover, it four with hypermethylated including BUB1, CA12, Adamts1, Adamts4 depicted protein level, which BUB1 CA12 decreased, while Adamts1 increased during aging. Conclusion Collectively, this elucidated Furthermore, involved IDD These findings may provide novel insights into mechanisms therapies perspective

Язык: Английский

Процитировано

6
Gut microbiota and intervertebral disc degeneration: a bidirectional two-sample Mendelian randomization study DOI Creative Commons

Ziming Geng,

Jian Wang, Guangdong Chen

и другие.

Journal of Orthopaedic Surgery and Research, Год журнала: 2023, Номер 18(1)

Опубликована: Авг. 14, 2023

Although previous studies have suggested a close association between gut microbiota (GM) and intervertebral disc degeneration (IVDD), the causal relationship them remains unclear. Hence, we thoroughly investigate their by means of two-sample Mendelian randomization (MR) study, aiming to determine impact on risk developing degeneration.Summary data from genome-wide GM (the MiBioGen) IVDD FinnGen biobank) been acquired. The inverse variance weighted (IVW) method was utilized as primary MR analysis approach. Weighted median, MR-Egger regression, mode, simple mode were used supplements. pleiotropy residual sum outlier (MR-PRESSO) regression performed assess horizontal pleiotropy. Cochran's Q test evaluated heterogeneity. Leave-one-out sensitivity further conducted reliability relationship. A reverse potential causation.We identified nine microbial taxa that causally associated with (P < 0.05). Following Benjamini-Hochberg corrected test, phylum Bacteroidetes higher remained significant (IVW FDR-corrected P = 0.0365). results Cochrane did not indicate heterogeneity > Additionally, both intercept MR-PRESSO global revealed our influenced Furthermore, leave-one-out substantiated In analysis, no evidence found suggest has an microbiota.Our validate particular IVDD, thus providing fresh insights into microbiota-mediated mechanism laying groundwork for research targeted preventive measures.

Язык: Английский

Процитировано

13
PGC1α‐Inducing Senomorphic Nanotherapeutics Functionalized with NKG2D‐Overexpressing Cell Membranes for Intervertebral Disc Degeneration DOI Creative Commons
Sheng Liu,

Kanglu Li,

Yuxin He

и другие.

Advanced Science, Год журнала: 2024, Номер 11(22)

Опубликована: Март 30, 2024

Abstract Cellular senescence is a significant contributor to intervertebral disc aging and degeneration. However, the application of senotherapies, such as senomorphics targeting markers senescence‐associated secretory phenotype (SASP), remains limited due challenges in precise delivery. Given that natural killer group 2D (NKG2D) ligands are increased on surface senescent nucleus pulposus (NP) cells, NKG2D‐overexpressing NP cell membranes (NNPm) constructed, which expected achieve dual effect toward cells based homologous membrane fusion NKG2D‐mediated immunosurveillance mechanism. Then, mesoporous silica nanoparticles carrying peroxisome proliferator‐activated receptor‐ɣ coactivator 1α (PGC1α)inducer (SP) coated with NNPm (SP@NNPm) it found SP@NNPm selectively targets SP cores exhibit pH‐responsive drug release. Moreover, effectively induces PGC1α‐mediated mitochondrial biogenesis mitigates induced by oxidative stress SASP, thereby alleviating puncture‐induced This dual‐targeting nanotherapeutic system represents novel approach delivery for degeneration treatment.

Язык: Английский

Процитировано

5
Dysregulated lipid metabolism and intervertebral disc degeneration: the important role of ox-LDL/LOX-1 in endplate chondrocyte senescence and calcification DOI Creative Commons

Tan Bing,

Xiang Shanlin,

Jisheng Wang

и другие.

Molecular Medicine, Год журнала: 2024, Номер 30(1)

Опубликована: Авг. 9, 2024

Lipid metabolism disorders are associated with degeneration of multiple tissues and organs, but the mechanism crosstalk between lipid disorder intervertebral disc (IDD) has not been fully elucidated. In this study we aim to investigate regulatory abnormal signal on endplate chondrocyte (EPC) senescence calcification.

Язык: Английский

Процитировано

5