Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 14, 2023

Abstract The ageing process is a systemic decline from cellular dysfunction to organ degeneration, with more predisposition deteriorated disorders. Rejuvenation refers giving aged cells or organisms youthful characteristics through various techniques, such as reprogramming and epigenetic regulation. great leaps in rejuvenation prove that not one-way street, many rejuvenative interventions have emerged delay even reverse the process. Defining mechanism by which roadblocks signaling inputs influence complex programs essential for understanding developing strategies. Here, we discuss intrinsic extrinsic factors counteract cell rejuvenation, targeted core mechanisms involved this Then, critically summarize latest advances state-of-art strategies of rejuvenation. Various methods also provide insights treating specific ageing-related diseases, including reprogramming, removal senescence (SCs) suppression senescence-associated secretory phenotype (SASP), metabolic manipulation, stem cells-associated therapy, dietary restriction, immune heterochronic transplantation, etc. potential applications therapy extend cancer treatment. Finally, analyze detail therapeutic opportunities challenges technology. Deciphering will further into anti-ageing disease treatment clinical settings.

Language: Английский

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Melatonin and bone-related diseases: an updated mechanistic overview of current evidence and future prospects

Osteoporosis International, Journal Year: 2023, Volume and Issue: 34(10), P. 1677 - 1701

Published: July 2, 2023

Language: Английский

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Circadian Rhythm‐Regulated ADSC‐Derived sEVs and a Triphasic Microneedle Delivery System to Enhance Tendon‐to‐Bone Healing

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 9, 2024

Modulating the inflammatory microenvironment to reconstruct fibrocartilaginous layer while promoting tendon repair is crucial for enhancing tendon-to-bone healing in rotator cuff (RCR), a persistent challenge orthopedics. Small extracellular vesicles (sEVs) hold significant potential modulate inflammation, yet efficient production of highly bioactive sEVs remains substantial barrier their clinical application. Moreover, achieving minimally invasive local delivery interface presents technical difficulties. Herein, circadian rhythm adipose-derived stem cells modulated increase yield and enhance regulatory capacity sEVs. Circadian rhythm-regulated (CR-sEVs) cyclic adenosine monophosphate signaling pathway macrophage (Mφ) via platelet factor 4 delivery, thereby inhibiting Mφ M1 polarization. Subsequently, triphasic microneedle (MN) scaffold with tip, stem, base designed CR-sEVs (CR-sEVs/MN) at junction, incorporating tendon-derived decellularized matrix facilitate repair. CR-sEVs/MN mitigates promotes fibrocartilage regeneration, enhances healing, improving biomechanical strength shoulder joint function rat RCR model. Combining this system promising strategy settings.

Language: Английский

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The Diurnal Variation in Mitochondrial Gene in Human Type 2 Diabetic Mesenchymal Stem Cell Grafts

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 719 - 719

Published: Jan. 16, 2025

The application of regenerative therapy through stem cell transplantation has emerged as a promising avenue for the treatment diabetes mellitus (DM). Transplanted tissue homeostasis is affected by disturbances in clock genes cells. aim this study to investigate diurnal variation mitochondrial and function after adipose-derived mesenchymal cells (T2DM-ADSCs) from type 2 diabetic patients into immunodeficient mice. Diurnal was assessed next-generation sequencing. As result, showing troughs at ZT10 ZT22 observed group transplanted with derived healthy individuals (N-ADSC). On other hand, T2DM-ADSCs, indicative ZT18, large phase amplitude deviation between two groups. To evaluate function, we quantified DNA copy number using Human mtDNA Monitoring Primer Set, measured membrane potential JC-1, evaluated mitophagy staining. results showed number, mitophagy, potential, NF-kB signaling N-ADSC transplant group. In contrast, no T2DM-ADSC transplants. revealed may be new marker efficiency transplantation.

Language: Английский

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Signaling pathway mechanisms of circadian clock gene Bmal1 regulating bone and cartilage metabolism: a review

Bone Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 27, 2025

Abstract Circadian rhythm is ubiquitous in nature. clock genes such as Bmal1 and Clock form a multi-level transcription-translation feedback network, regulate variety of physiological pathological processes, including bone cartilage metabolism. Deletion the core gene leads to alterations, while phenotypes are not consistent. Studies have shown that multiple signaling pathways involved process regulating metabolism, but exact regulatory mechanisms remain unclear. This paper reviews by which regulates bone/cartilage upstream factors control , current knockout mouse models for research. We hope provide new insights prevention treatment diseases related circadian rhythms.

Language: Английский

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Rhythms in Remodeling: Posttranslational Regulation of Bone by the Circadian Clock

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 705 - 705

Published: March 13, 2025

The circadian clock is a fundamental timekeeping system that regulates rhythmic biological processes in response to environmental light–dark cycles. In mammals, core genes (CLOCK, BMAL1, PER, and CRY) orchestrate these rhythms through transcriptional–translational feedback loops, influencing various physiological functions, including bone remodeling. Bone homeostasis relies on the coordinated activities of osteoblasts, osteoclasts, osteocytes, with increasing evidence highlighting role regulation maintaining skeletal integrity. Disruptions are linked disorders such as osteoporosis. Posttranslational modifications (PTMs), phosphorylation, acetylation, ubiquitination, serve crucial regulators both mechanisms metabolism. However, specific PTMs integrating timing remodeling remains underexplored. This review examines intersection biology, elucidating their impact cell function homeostasis. Understanding interactions may uncover novel therapeutic targets for diseases associated disruptions.

Language: Английский

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The mutual impacts of stem cells and sleep: opportunities for improved stem cell therapy

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 29, 2025

Abstract Sleep is an indispensable physiological function regulated by circadian rhythms, which influence the biological pathways and overall health of body. crucial for maintenance restoration bodily systems, disturbances can lead to various sleep disorders, impair both mental physical health. Treatment options these disorders encompass lifestyle modifications, psychotherapy, medications, therapies such as light therapy surgery. Not only deprivation has a significant impact on essential organs, but it also influences types stem cells in In this review, we explore connection between cells, highlighting how rhythms regulate cell activities that are vital tissue regeneration homeostasis. Disruptions hinder self-renewal, homing, proliferation, function, differentiation, thereby affecting We discuss transplantation their products may help improve quality affects behavior, implications therapies. Notably, while certain transplantations disrupt sleep, enhancing efficacy Finally, be utilized model offering valuable insights into underlying mechanisms.

Language: Английский

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Core Molecular Clock Factors Regulate Osteosarcoma Stem Cell Survival and Behavior via CSC/EMT Pathways and Lipid Droplet Biogenesis

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 517 - 517

Published: March 31, 2025

The circadian clock, an intrinsic 24 h cellular timekeeping system, regulates fundamental biological processes, including tumor physiology and metabolism. Cancer stem cells (CSCs), a subpopulation of cancer with self-renewal tumorigenic capacities, are implicated in initiation, recurrence, metastasis. Despite growing evidence for the clock’s involvement regulating CSC functions, its precise regulatory mechanisms remain largely unknown. Here, using human osteosarcoma (OS) model (143B), we have shown that core molecular clock factors critical OS cell survival behavior via direct modulation lipid metabolic pathways. In single-cell-derived spheroid formation assays, 143B exhibited robust spheroid-forming capacity under 3D culture conditions. Furthermore, siRNA-mediated depletion components (i.e., BMAL1, CLOCK, CRY1/2, PER1/2)—essential positive negative elements feedback loop—significantly reduced CSCs isolated from vivo xenografts. contrast, knockdown secondary clock-stabilizing factor genes NR1D1 NR1D2 had little effect. We also found or CRY1/2 markedly impaired migration invasion capacities CSCs. At level, silencing distinctly altered expression associated properties epithelial–mesenchymal transition (EMT) addition, disruption significantly droplet by downregulating involved lipogenesis (e.g., DGAT1, FASN, ACSL4, PKM2, CHKA, SREBP1), which closely linked to CSC/EMT processes. transcriptomic analysis patient samples revealed compared other genes, CRY1 was highly expressed tumors relative controls, strong correlations prognosis, survival, LD biogenesis gene expression. These findings highlight role metabolism, underscoring therapeutic potential targeting machinery enhance treatment outcomes.

Language: Английский

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BMAL1‐downregulation drives PANoptosis and the osteogenic differentiation impairment of PDLSCs by ERK/AP‐1 signaling pathway

Journal of Periodontology, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Abstract Background One strategy to delay bone loss in periodontitis involves maintaining the osteogenic differentiation function of periodontal ligament stem cells (PDLSCs). The core circadian gene BMAL1 influences fate mesenchymal and is essential for regulating pyroptosis, apoptosis, necroptosis. PANoptosis, a novel form programmed cell death, simultaneously activates all 3 pathways. This study focuses on role BMAL1, process impairment PDLSCs. Methods A mouse model was established evaluate expression factors. We stimulated PDLSCs with lipopolysaccharide (LPS) used Western blot detect PANoptosis‐related Osteogenic factors were assessed using real‐time quantitative polymerase chain reaction (RT‐qPCR), blot, alkaline phosphatase, alizarin red staining. ERK pathway proteins examined by immunofluorescence investigate how regulates PANoptosis under inflammatory conditions. Results Treatment LPS leads downregulation expression, which subsequently induces RIPK1‐PANoptosome‐mediated PDLSCs, impairing their function. Inhibition RIPK1‐PANoptosome Nec‐1S improved differentiation‐related genes proteins. Overexpression synthetic ligand SR1078 alleviated these detrimental effects. U0126 reduced its downstream target AP‐1, effectively reversing impact PANoptosis. Conclusions triggers leading impaired provides new insights into pathogenesis suggests targets prevention treatment. Plain language summary Periodontitis chronic condition oral cavity marked destruction attachment resorption alveolar bone. rhythm cells, playing crucial encompassing necroptosis, may play activity Our aims elucidate underlying relationship between found that treatment Notably, inhibition Mechanistic exploration revealed through ERK/AP‐1 signaling pathway. highlights potential therapeutic mitigating periodontitis.

Language: Английский

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“Time Is out of Joint” in Pluripotent Stem Cells: How and Why

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2063 - 2063

Published: Feb. 8, 2024

The circadian rhythm is necessary for the homeostasis and health of living organisms. Molecular clocks interconnected by transcription/translation feedback loops exist in most cells body. A puzzling exemption to this, otherwise, general biological hallmark given cell physiology pluripotent stem (PSCs) that lack oscillations gradually acquired following their vivo programmed differentiation. This process can be nicely phenocopied vitro commitment reversed during reprogramming somatic induce PSCs. current understanding how why pluripotency “time-uncoupled” largely incomplete. complex picture emerging where core clockwork negatively regulated PSCs at post-transcriptional/translational, epigenetic, other-clock-interaction levels. Moreover, non-canonical functions core-work components balance between identity metabolic-driven are emerging. review selects discusses results relevant recent investigations providing major insights into this context.

Language: Английский

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