Pharmacotherapies in Older Adults with COPD: Challenges and Opportunities

Drugs & Aging, Journal Year: 2023, Volume and Issue: 40(7), P. 605 - 619

Published: June 14, 2023

Older adults have a higher prevalence of chronic obstructive pulmonary disease (COPD), which will likely increase substantially in the coming decades owing to aging populations and increased long-term exposure risk factors for this disease. COPD older is characterized by low-grade systemic inflammation, known as inflamm-aging. It contributes age-associated changes that are clinically expressed reduced lung function, poor health status, limitations activities daily living. In addition, inflamm-aging has been associated with onset many comorbidities commonly encountered COPD. Furthermore, physiologic often seen can influence optimal treatment patients Therefore, variables such pharmacokinetics, pharmacodynamics, polypharmacy, comorbidities, adverse drug responses, interactions, method administration, social economic issues impact nutrition adherence therapy must be carefully evaluated when prescribing medication these because each them alone or together may affect outcome treatment. Current medications focus mainly on alleviating COPD-related symptoms, so alternative approaches target progression being investigated. Considering importance inflamm-aging, new anti-inflammatory molecules evaluated, focusing inhibiting recruitment activation inflammatory cells, blocking mediators inflammation thought important cells released cells. Potential therapies slow processes acting cellular senescence, cause it (senostatics), eliminating senescent (senolytics), targeting ongoing oxidative stress need evaluated.

Language: Английский

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Mechanism of Bazi Bushen capsule in delaying the senescence of mesenchymal stem cells based on network pharmacology and experimental validation

Heliyon, Journal Year: 2024, Volume and Issue: 10(6), P. e27646 - e27646

Published: March 1, 2024

Ageing is becoming an increasingly serious problem; therefore, there urgent need to find safe and effective anti-ageing drugs.AimsTo investigate the effects of Bazi Bushen capsule (BZBS) on senescence mesenchymal stem cells (MSCs) explore its mechanism action.MethodsNetwork pharmacology was used predict targets BZBS in delaying MSCs. For vitro studies, MSCs were treated with D-gal, BZBS, NMN, cell viability, senescence, stemness-related genes, cycle studied using counting kit-8 (CCK-8) assay, SA-β-galactosidase (SA-β-gal) staining, Quantitative Real-Time PCR (qPCR) flow cytometry (FCM), respectively. Alkaline phosphatase (ALP), alizarin red, oil red staining determine osteogenic lipid differentiation abilities Finally, expression senescence-related genes cyclin-related factors detected by qPCR western blotting.ResultsNetwork pharmacological analysis suggested that delayed interfering cycle. Our studies could significantly increase viability (P < 0.01), decrease quantity β-galactosidase+ downregulate p16 p21 0.05, P improve adipogenic differentiation, upregulate Nanog, OCT4 SOX2 0.01) senescent Moreover, reduced proportion G0/G1 phase enhanced CDK4, Cyclin D1, E2F1 0.01, respectively). Upon treatment HY-50767A, a CDK4 inhibitor, upregulation no longer observed group.ConclusionsBZBS can protect against D-gal-induced which may be associated regulation via D1/CDK4/E2F1 signalling pathway.

Language: Английский

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Role of Mesenchymal Stem/Stromal Cells (MSCs) and MSC-Derived Extracellular Vesicles (EVs) in Prevention of Telomere Length Shortening, Cellular Senescence, and Accelerated Biological Aging

Bioengineering, Journal Year: 2024, Volume and Issue: 11(6), P. 524 - 524

Published: May 21, 2024

Biological aging is defined as a progressive decline in tissue function that eventually results cell death. Accelerated biologic when the telomere length shortened prematurely secondary to damage from biological or environmental stressors, leading defective reparative mechanism. Stem cells therapy may have potential role influencing (counteract/ameliorate) and maintaining of organism. Mesenchymal stem cells, also called mesenchymal stromal (MSCs) are multipotent mesodermal origin can differentiate into other types such adipocytes, chondrocytes, osteocytes. MSCs influence resident through secretion paracrine bioactive components cytokines extracellular vesicles (EVs). This review examines changes length, cellular senescence, normal age, well factors contributing shortening accelerated aging. The MSCs-especially those derived gestational tissues-in prevention (TS) explored. In addition, strategies prevent MSC senescence improve antiaging therapeutic application MSC-derived EVs reviewed.

Language: Английский

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Cartilage-Specific Gene Expression and Extracellular Matrix Deposition in the Course of Mesenchymal Stromal Cell Chondrogenic Differentiation in 3D Spheroid Culture

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5695 - 5695

Published: May 23, 2024

Articular cartilage damage still remains a major problem in orthopedical surgery. The development of tissue engineering techniques such as autologous chondrocyte implantation is promising way to improve clinical outcomes. On the other hand, application chondrocytes has considerable limitations. Mesenchymal stromal cells (MSCs) from various tissues have been shown possess chondrogenic differentiation potential, although different degrees. In present study, we assessed alterations chondrogenesis-related gene transcription rates and extracellular matrix deposition levels before after MSCs 3D spheroid culture. were obtained three tissues: umbilical cord Wharton’s jelly (WJMSC—Wharton’s mesenchymal cells), adipose (ATMSC—adipose dental pulp deciduous teeth (SHEDs—stem human exfoliated teeth). Monolayer MSC cultures served baseline controls. Newly formed spheroids composed previously grown 2D precultured for 2 days growth medium, then, was induced by maintaining them TGF-β1-containing medium 21 days. Among types studied, WJMSCs showed most similarities with primary terms upregulation cartilage-specific expression. Interestingly, occurred some extent all spheroids, even prior addition TGF-β1. These results confirm that potential on par valuable cell source applications well treatment osteoarthritis. environment its own acts trigger MSCs.

Language: Английский

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LncRNA NEAT1-206 regulates autophagy of human umbilical cord mesenchymal stem cells through the WNT5A/Ca2+ signaling pathway under senescence stress

Non-coding RNA Research, Journal Year: 2025, Volume and Issue: 11, P. 234 - 248

Published: Jan. 5, 2025

Stem cells are crucial for maintaining bodily stability, but their regenerative abilities decline with age. This is marked by reduced proliferation and differentiation capacities of stem cells, as well exhaustion the cell pool. The accumulation aged mesenchymal (MSCs) can reduce tissue regeneration, molecular mechanisms influencing MSCs aging remain unclear. Moreover, collecting from elderly individuals not suitable observing early response to senescence stress, factors involved in In our previous study, we established a fast MSC model using D-galactose. We discovered that, while affecting "stemness" markers expression LncRNA NEAT1-206 was notably increased during stages induction (within 4 days). And observed be localized cytoplasmic matrix due enhanced nuclear export. found that could trigger autophagy through WNT5A/Ca2+ signaling pathway, thereby decreasing enhancing osteogenic MSCs. study elucidated role potential key factor conferring resistance D-galactose-induced at stage promoting may provide foundational understanding delaying process.

Language: Английский

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Injectable DAT-ALG Hydrogel Mitigates Senescence of Loaded DPMSCs and Boosts Healing of Perianal Fistulas in Crohn’s Disease

ACS Biomaterials Science & Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Perianal fistulas (PAFs) are a severe complication of Crohn's disease that significantly impact patient prognosis and quality life. While stem-cell-based strategies have been widely applied for PAF treatment, their efficacy remains limited. Our study introduces an injectable, temperature-controlled decellularized adipose tissue-alginate hydrogel loaded with dental pulp mesenchymal stem cells (DPMSCs) in vivo fistula treatment. The experimental group demonstrated higher healing rates compared to surgical DPMSCs groups, as evidenced by magnetic resonance imaging, multiplex immunohistochemical, ELISA analyses. KEGG enrichment differential genes suggested cellular senescence involvement cell therapy efficacy, further confirmed β-galactosidase staining markers (p21 p53). Collectively, our research provides novel PAFs illuminates underlying mechanisms.

Language: Английский

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Accumulation of advanced oxidation protein products aggravates bone-fat imbalance during skeletal aging

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 51, P. 24 - 36

Published: Jan. 21, 2025

Language: Английский

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PIK3R3 regulates differentiation and senescence of periodontal ligament stem cells and mitigates age-related alveolar bone loss by modulating FOXO1 expression

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Periodontal diseases are prevalent among middle-aged and elderly individuals. There's still no satisfactory solution for tooth loss caused by periodontal diseases. Human ligament stem cells (hPDLSCs) is a distinctive subgroup of mesenchymal cells, which play crucial role in supportive tissues, but their application value hasn't been fully explored yet. As regulatory subunit PI3K, PIK3R3's cell regulation remains poorly comprehended. This study aims to explore the effect PIK3R3 on differentiation senescence hPDLSCs underlying mechanism, as well whether overexpression mitigate alveolar bone aged rats. PDLSC lines with both knockdown established. Osteogenic, adipogenic, chondrogenic senescent induction used test vitro. Model mice reveal vivo. FOXO1 siRNA mechanism exploration. Knockdown inhibits mRNA protein expression markers osteogenic, promotes vitro hPDLSCs, including proliferation, expression, telomerase density reactive oxygen species. Overexpression has opposite effect. Furthermore, result Micro-CT tissue section shows that elder rats mitigates loss. Mechanistically, regulates through modulating expression. Expression altered when knocked down or overexpressed medium. promoting knocking weakened highly expressed. These findings indicate modulates MSCs regulating promise therapeutic target mitigating age-related

Language: Английский

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Single-cell transcriptional profiling reveals a novel RAB13+ endothelial subpopulation and profibrotic mesenchymal cells in the aged human bone marrow

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

ABSTRACT The bone marrow (BM) microenvironment plays a crucial role in regulating hematopoiesis, yet the molecular and functional changes associated with aging humans remain poorly understood. Using single-cell RNA sequencing (scRNA-seq), we uncovered transcriptional shifts BM endothelial cells (EC) mesenchymal stem (MSC) during aging. Our analysis revealed that aged sinusoidal EC adopt prothrombotic, exhibit mitochondrial dysfunction, have compromised vascular function. Additionally, identified unique arterial subset, present only individuals, elongation senescence processes characterized by RAB13 expression. MSC from subjects displayed an impaired matrix remodeling epithelial-mesenchymal transition, driven partly subpopulation of THY1 + profibrotic stromal absent young subjects. Aged were also increased ATP-oxidative metabolism reduced protein folding capacity. Finally, using immunofluorescent imaging spatial transcriptomics, confirmed presence senescent samples significant age-related cell-cell communication within niche. In summary, this work provides comprehensive view diversity, cellular interactions, organization MSC, offering novel insights potential targets could be exploited for preventing aged-associated humans.

Language: Английский

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Quiescence modulates age-related changes in the functional capacity of highly proliferative canine lung mesenchymal stromal cell populations

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 9, 2025

Abstract The functional capacity of highly proliferative cell populations changes with age. Here, we report that the canine lung mesenchymal stromal cells (LMSCs) declines increasing age donor. However, other such as reduced autophagy, migration/wound healing, increased production reactive oxygen species, and senescence are not significantly altered Furthermore, transcriptomic profiling suggests minimal age-related changes. These data suggest LMSCs isolated from aging donors may be associated reversible cycle arrest (quiescence), rather than irreversible (senescence). Similar findings have been reported in systems, including neural muscle stem low turnover-rate tissues.

Language: Английский

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