Chronic inflammation and the hallmarks of aging

Molecular Metabolism, Journal Year: 2023, Volume and Issue: 74, P. 101755 - 101755

Published: June 16, 2023

Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, low-grade inflammation during aging, without overt infection, is defined as "inflammaging," which associated with increased morbidity mortality in population. Emerging evidence suggests a bidirectional cyclical relationship between development age-related conditions, such cardiovascular diseases, neurodegeneration, cancer, frailty. How crosstalk other underlies biological mechanisms disease thus particular interest current geroscience research.

Language: Английский

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Epigenetic modifications of inflammation in intervertebral disc degeneration

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 87, P. 101902 - 101902

Published: March 4, 2023

Intervertebral disc degeneration (IDD) is a common cause of joint-related chronic disability in elderly individuals worldwide. It seriously impacts the quality life and inflicts substantial social economic burden. The pathological mechanisms underlying IDD have not been fully revealed, leading to less satisfactory clinical treatment outcomes. More studies are urgently needed reveal its precise mechanisms. Numerous revealed that inflammation closely related various processes IDD, including continuous loss extracellular matrix, cell apoptosis, senescence, indicating important role mechanism IDD. Epigenetic modifications affect functions characteristics genes mainly through DNA methylation, histone modification, non-coding RNA regulation, other mechanisms, thus having major effect on survival state body. Recently, epigenetic during has attracting research interest. In this review, we summarize roles different types recent years, improve our understanding etiology transform basic strategy into clinically effective for individuals.

Language: Английский

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Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging

Aging Cell, Journal Year: 2024, Volume and Issue: 23(4)

Published: Jan. 29, 2024

Abstract Osteoarthritis (OA), a chronic degenerative joint disease, is highly prevalent among the aging population, and often leads to pain, disability, diminished quality of life. Although considerable research has been conducted, precise molecular mechanisms propelling OA pathogenesis continue be elusive, thereby impeding development effective therapeutics. Notably, recent studies have revealed subchondral bone lesions precede cartilage degeneration in early stage OA. This marked by escalated osteoclast‐mediated resorption, subsequent imbalances metabolism, accelerated turnover, decrease volume, contributing significantly pathological changes. While role hallmarks extensively elucidated from perspective chondrocytes, their connection with osteoclasts not yet fully understood. There compelling evidence suggest that age‐related abnormalities such as epigenetic alterations, proteostasis network disruption, cellular senescence, mitochondrial dysfunction, can stimulate osteoclast activity. review intends systematically discuss how contribute pathogenesis, placing particular emphasis on age‐induced shifts It also aims future probing into therapeutic approaches targeting during aging.

Language: Английский

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Novel insights into the interaction between N6‐methyladenosine methylation and noncoding RNAs in musculoskeletal disorders

Cell Proliferation, Journal Year: 2022, Volume and Issue: 55(10)

Published: June 23, 2022

Abstract Background Musculoskeletal disorder (MSD) are a class of inflammatory and degener‐ative diseases, but the precise molecular mechanisms still poorly understood. Noncoding RNA (ncRNA) N6‐methyladenosine (m6A) modification plays an essential role in pathophysiological process MSD. This review summarized interaction between m6A methylation ncRNAs regulatory mechanism It provides new perspective for ncRNA targeted therapy Methods A comprehensive search databases was conducted with musculoskeletal disorders, noncoding RNA, N6‐methyladenosine, intervertebral disc degeneration, osteoporosis, osteosarcoma, osteoarthritis, skeletal muscle, bone, cartilage as key‐words. Then, all relevant articles. Results Intervertebral degeneration (IDD), osteoporosis (OP), osteosarcoma (OS), osteoarthritis (OA) common MSDs that affect cartilage, joint, leading to limited movement, pain, disability. However, pathogenesis remains unclear, no effective treatment drug is available at present. Numerous studies confirmed mutual regulation (i.e., microRNAs, long ncRNAs, circular RNAs) found MSD, can regulate also target regulators. by regulating homeostasis cartilage. Conclusion interacts multiple biological processes important roles IDD, OP, OS, OA. These provide insights into MSD targeting m6A‐modified may be promising approach.

Language: Английский

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CircGNB1 drives osteoarthritis pathogenesis by inducing oxidative stress in chondrocytes

Clinical and Translational Medicine, Journal Year: 2023, Volume and Issue: 13(8)

Published: Aug. 1, 2023

Circular RNAs (circRNAs) have risen to prominence as important regulators of biological processes. This study investigated whether circGNB1 functions a competitive endogenous RNA regulate the pathological process oxidative stress in age-related osteoarthritis (OA).The relationship between expression and stress/OA severity was determined cartilages from OA patients at different ages. The roles progression, its downstream targets were using gain- loss-of-function experiments various biochemical assays human chondrocytes (HCs). vivo effects overexpression knockdown also destabilization medial meniscus (DMM) mouse model.Increased detected HCs under inflammatory cartilage older individuals. Mechanistically, sponged miR-152-3p thus blocked interaction with mRNA target, ring finger protein 219 (RNF219), which turn stabilized caveolin-1 (CAV1) by preventing ubiquitination K47 residue. CircGNB1 inhibited IL-10 signalling antagonizing miR-152-3p-mediated RNF219 CAV1 inhibition. Consequently, promoted progression enhancing catabolic factor suppressing anabolic genes vitro vivo. Furthermore, alleviated OA, whereas had opposite effect DMM model OA.CircGNB1 regulated via miR-152-3p/RNF219/CAV1 axis. Modulating could be an effective strategy for treating OA.

Language: Английский

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Insights into the underlying pathogenesis and therapeutic potential of endoplasmic reticulum stress in degenerative musculoskeletal diseases

Military Medical Research, Journal Year: 2023, Volume and Issue: 10(1)

Published: Nov. 9, 2023

Degenerative musculoskeletal diseases are structural and functional failures of the system, including osteoarthritis, osteoporosis, intervertebral disc degeneration (IVDD), sarcopenia. As global population ages, degenerative becoming more prevalent. However, pathogenesis is not fully understood. Previous studies have revealed that endoplasmic reticulum (ER) stress a response occurs when impairment protein folding capacity ER leads to accumulation misfolded or unfolded proteins in ER, contributing diseases. By affecting cartilage degeneration, synovitis, meniscal lesion, subchondral bone remodeling angiogenesis nucleus pulposus annulus fibrosus rupture, cartilaginous endplate IVDD, sarcopenia, involved Preclinical found regulation can delay progression multiple These pilot provide foundations for further evaluation feasibility, efficacy, safety modulators treatment clinical trials. In this review, we integrated up-to-date research findings into future perspective, also discussed possible directions investigation disease, potential therapeutic strategies using modulators, as well underlying challenges obstacles bench-to-beside research.

Language: Английский

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Epigenetic modifications in spinal ligament aging

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 77, P. 101598 - 101598

Published: Feb. 24, 2022

Spinal stenosis is a common degenerative spine disorder in the aged population and spinal ligament aging main contributor to this chronic disease. However, underlying mechanisms of remain unclear. Epigenetics study heritable reversible changes function gene or genome that occur without any alteration primary DNA sequence. Epigenetic alterations have been demonstrated play crucial roles age-related diseases conditions, they are recently studied as biomarkers therapeutic targets field cancer research. The epigenetic modifications, including methylation alteration, histone modifications well dysregulated noncoding RNA modulation, all implicated diseases. modulates expression critical genes WNT5A, GDNF, ACSM5, miR-497 miR-195 during degeneration. Histone widely affect obvious modification abnormalities found aging. MicroRNAs (miRNAs), long RNAs (lncRNAs) circular (circRNAs) exert regulating effects on conditions via targeting various osteogenic fibrogenic differentiation related genes. To our knowledge, there no systematic review yet summarize involvement In study, we systematically discussed different their potential functions process.

Language: Английский

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Circular RNA CircFOXO3 Functions as a Competitive Endogenous RNA for Acid-Sensing Ion Channel Subunit 1 Mediating Oxeiptosis in Nucleus Pulposus

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 678 - 678

Published: March 18, 2024

Oxeiptosis is a reactive oxygen species (ROS)-induced pathway of cell death. The involvement circular RNAs (circRNAs) has been confirmed in the incidence and progression intervertebral disc degeneration (IVDD). However, whether oxeiptosis occurs IVDD how circRNAs regulate still unclear. In this study, we discovered that could be induced nucleus pulposus cells (NPCs), circFOXO3 was significantly upregulated after induction. Transfection using small interfering RNA (siRNA) inhibited NPCs. Mechanistically, acid-sensing ion channel subunit 1 (ASIC1) expression by functioning as molecular sponge for miR-185-3p miR-939-5p. Subsequent rescue experiments validated NPCs via miR-185-3p/miR-939-5p-ASIC1 axis. Further research on ASIC1 functions indicated regulation achieved affecting Calcium (Ca2+) influx mediated ASIC1. A mouse model established, silencing vivo found to inhibit development activation oxeiptosis-related pathway. Overall, one factors contributing mediating oxeiptosis.

Language: Английский

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High-order graph convolutional networks for circular Ribonucleic Acid and disease association prediction incorporating multiple biological relationships

Engineering Applications of Artificial Intelligence, Journal Year: 2025, Volume and Issue: 146, P. 110303 - 110303

Published: Feb. 21, 2025

Language: Английский

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Muscle atrophy in osteoarthritis: clinical features, pathological changes, underlying mechanisms, and exercise‐based interventions

Deleted Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 29, 2025

Abstract Background Osteoarthritis (OA) is a common degenerative disease with cartilage injury as the core pathological phenotype, which has become leading cause of disability in elderly. Skeletal muscle an important organ to maintain structure and motor function joints, highly related OA progress. Patients typically exhibit abnormalities skeletal muscles surrounding such reduced mass strength. We refer this condition OA‐related atrophy (hereafter referred OAMA). The mechanisms OAMA are multifactorial unclear. Methods In narrative review, we summarized relevant research progress (i) review changes patients OA, (ii) underlying biological OAMA, (iii) effects on (iv) provide perspectives current potential strategies clinical treatment based muscle, especially exercise training. Results may lead destruction joint stability homeostasis then promote occurrence development OA. Clinical manifestations decline strength abnormal movement pattern. include chronic inflammation, oxidative stress, ion metabolism, glycolipid epigenetics. muscle‐mediated damage via biomechanics, muscle‐derived secretions, stem cells. Conclusions More preclinical studies imperative study develop strategies. hope that more can focus during process, will be beneficial for delaying progression improving future.

Language: Английский

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