Trends in Cell Biology, Год журнала: 2024, Номер unknown
Опубликована: Дек. 1, 2024
Язык: Английский
Mechanisms of Ageing and Development, Год журнала: 2023, Номер 211, С. 111797 - 111797
Опубликована: Март 1, 2023
Sexual dimorphism is a key factor to consider in the ageing process given impact that it has on life expectancy. The oxidative-inflammatory theory of states result establishment oxidative stress which, due interplay immune system, translates into inflammatory stress, and both processes are responsible for damage loss function an organism. We show there relevant gender differences number markers propose they may account differential lifespan between sexes, males display, general, higher oxidation basal inflammation. In addition, we explain significant role circulating cell-free DNA as marker inductor inflammation, connecting having potential become useful marker. Finally, discuss how changes take place differentially with each sex, which could also have sex-differential lifespan. Further research including sex essential variable needed understand grounds better comprehend itself.
Язык: Английский
Процитировано
75
Ageing Research Reviews, Год журнала: 2022, Номер 83, С. 101805 - 101805
Опубликована: Ноя. 21, 2022
Major depressive disorder (MDD) is characterized by psychological and physiological manifestations contributing to the disease severity outcome. In recent years, several lines of evidence have suggested that individuals with MDD an elevated risk age-related adverse outcomes across lifespan. This review provided a significant overlap between biological abnormalities in changes commonly observed during aging process (i.e., hallmarks aging). Based on such evidence, we formulate mechanistic model showing how can be common denominator mediate health MDD. Finally, proposed roadmap for novel studies investigate intersection biology MDD, including use geroscience-guided interventions, as senolytics, delay or improve major depression targeting aging.
Язык: Английский
Процитировано
59
Journal of Extracellular Vesicles, Год журнала: 2024, Номер 13(4)
Опубликована: Апрель 1, 2024
Abstract Extracellular vesicles (EVs), lipid‐enclosed structures released by virtually all life forms, have gained significant attention due to their role in intercellular and interorganismal communication. Despite recognized importance disease processes therapeutic applications, fundamental questions about primary function remain. Here, we propose a different perspective on the of EVs, arguing that they serve as essential elements providing membrane area for long‐distance, contact‐dependent cellular communication based protein‐protein interaction. While EVs been carriers genetic information, additional unique advantages could provide remain unclear. introduce concept substantial provided allows interactions be central function. This enables lateral diffusion sorting ligands like proteins, polysaccharides or lipids two dimensions, promoting avidity‐driven effects assembly co‐stimulatory architectures at EV‐cell interface. The vesicle‐induced receptor sequestration (VIRS), example, describes how confine focus receptors EV contact site, dense local concentration into signalosomes. process can increase signalling strength EV‐presented 10‐1000‐fold compared soluble counterparts. speculations this advance our understanding EV‐biology critical implications EV‐based applications therapeutics. We suggest shift from viewing merely transporters relevant nucleic acids proteins considering biophysical properties presentation platforms signalling. therefore highlight functional rather than content. further discuss mechanism might exploited virus‐transformed cancer cells enhance immune‐evasive mechanisms.
Язык: Английский
Процитировано
8
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Янв. 31, 2025
Abstract Altered mitochondria biology can accelerate biological aging, but scalable biomarkers of mitochondrial health for population studies are lacking. We examined two potential candidates: 1) cell-free DNA (cf-mtDNA), a marker signaling elevated with disease states accessible as distinct entities from plasma or serum; and 2) growth differentiation factor 15 (GDF15), an established biomarker aging downstream energy transformation defects stress signaling. In cohort 430 participants aged 24-84 (54.2% women), we measured serum cf-mtDNA, GDF15 levels at timepoints 5 years apart, then assessed their associations age, BMI, diabetes, sex, health-related behaviors, psychosocial factors. As expected, showed positive, exponential association age (r=0.66, p<0.0001) increased by 33% over five years. cf-mtDNA was not correlated age. BMI sex were also related to nor GDF15. Type 2 diabetes only positively associated Exploring drivers systemic signaling, report novel linking higher education lower age-adjusted (r=-0.14, p<0.0034), both baseline the 5-year follow up, highlighting influence factors on health. Overall, our findings among adults spanning six decades lifespan establish between GDF15, emerging Further needed determine if blood metabolic be moderated behaviors.
Язык: Английский
Процитировано
1
Aging Cell, Год журнала: 2023, Номер 22(8)
Опубликована: Май 15, 2023
Abstract Identifying metabolic biomarkers of frailty, an age‐related state physiological decline, is important for understanding its underpinnings and developing preventive strategies. Here, we systematically examined 168 nuclear magnetic resonance‐based metabolomic 32 clinical their associations with frailty. In up to 90,573 UK Biobank participants, identified 59 robustly independently associated the frailty index (FI). Of these, 34 were replicated in Swedish TwinGene study ( n = 11,025) Finnish Health 2000 Survey 6073). Using two‐sample Mendelian randomization, showed that genetically predicted level glycoprotein acetyls, inflammatory marker, was statistically significantly increased FI β per SD increase 0.37%, 95% confidence interval: 0.12–0.61). Creatinine several lipoprotein lipids also FI, yet effects mostly driven by kidney cardiometabolic diseases, respectively. Our findings provide new insights into causal metabolites on highlight role chronic inflammation underlying development.
Язык: Английский
Процитировано
14
Oncotarget, Год журнала: 2025, Номер 16(1), С. 29 - 38
Опубликована: Янв. 21, 2025
Approximately two-thirds of patients with colorectal cancer (CRC) undergo resection curative intent; however, 30% to 50% these experience recurrence. The concentration cell-free DNA (cfDNA) before and after surgery may be related the prognosis CRC, but there is limited information regarding cfDNA levels at time surgery. Here, we analyzed surgical release using plasma samples from 30 three key points during surgery: preoperative (immediately surgery), intraoperative (during postoperative (at end surgery). Automated electrophoresis was used analyze concentrations fragment sizes, which were then correlated clinical variables. Our findings indicate a significant increase in (2.8- 2.2-fold higher respectively, p < 0.01). Characteristic fragments (<400 bp) predominated all stages; genomic material (>400 also observed. We found that increases over 60 years old (2.9-fold intraoperatively than preoperatively 2.3 folds postoperatively preoperatively, 0.01); comorbidities (3.0-fold 2.3-fold postoperatively, CEA >5 ng/mL (3.1-fold 1.3-fold Interestingly, significantly adverse characteristics. Patients bearing locally advanced tumors or metastasis had 3.1-fold 2.4-fold 0.01. high score tumor buds (2.6 higher, 0.02), perineural invasion (3.4-fold 0.02) lymphovascular 0.05). Furthermore, observed rise correlation duration surgery, highlighting its potential as marker quality. Taken together, our results suggest addition physiological age, unfavorable traits, intense manipulation tumor's extent, result greater tissue damage elevated release.
Язык: Английский
Процитировано
0
Vavilov Journal of Genetics and Breeding, Год журнала: 2025, Номер 28(8), С. 993 - 1007
Опубликована: Янв. 26, 2025
In this part of the study, first component concept “natural genome reconstruction” is being proven. It was shown with mouse and human model organisms that CD34+ hematopoietic bone marrow progenitors take up fragments extracellular double-stranded DNA through a natural mechanism. known process internalization involves glycocalyx structures, which include glycoproteins/protein glycans, glycosylphosphatidylinositol-anchored proteins scavenger receptors. The bioinformatic analysis conducted indicates main surface marker stem cells belong to indicated groups factors contain specific binding sites, including heparin-binding domain clusters positively charged amino acid residues. A direct interaction CD34 CD84 (SLAMF5) glycoproteins, markers cells, demonstrated using an electrophoretic mobility shift assay system. negative for CD34, also internalize fragments, concatemerization delivered into cell occurs. case, five oligonucleotide monomers containing 9 telomeric TTAGGG repeats are stitched together one structure. Extracellular initiate division original in such way daughter becomes committed terminal differentiation, second retains its low-differentiated status. After treatment hDNA gr , number colonies increases 3 % (humans as organism). At same time, induces proliferation blood their immediate descendants stimulates colony formation (mouse, rat humans organisms). Most often, granulocyte-macrophage lineage hematopoiesis activated result processing DNA. commitment manifested by appearance repair pangenomic single-strand breaks. transition time direction differentiation (the it takes breaks appear be repaired) about 7 days. assumed at moment initiation breaks, “recombinogenic situation” ensues molecular recombination mechanisms activated. all experiments individual molecules, recombinant angiogenin used comparison factor. other experiments, experimental consisted treated angiogenin.
Язык: Английский
Процитировано
0
Aging Cell, Год журнала: 2025, Номер unknown
Опубликована: Март 4, 2025
ABSTRACT Physical exercise has been associated with healthier aging trajectories, potentially preventing or mitigating age‐related declines. This occurs through a complex, yet poorly characterized network of multi‐organ interactions involving mitochondrial, inflammatory, and cell death/survival pathways. Here, we comprehensively evaluated the 12‐week VIVIFRAIL multicomponent protocol in physically frail ( n = 16, mean age 81.4 ± 5.6) robust 50, mean‐age 73.6 4.7) old individuals. Before (T0) after (T1) protocol, functional outcomes were assessed alongside detailed exploratory analysis apoptotic, neuro‐muscular mediators concerning their plasmatic/serum concentrations, and/or mRNA expression from peripheral blood mononuclear cells (PBMCs). Besides significant improvements across both groups, our findings highlighted unique overlapping modulations key biological Both groups showed refined mitochondrial integrity/turnover (upregulated mt‐ND1 , downregulated TFAM ULK1 ), anti‐inflammatory responses IL10 TGF‐B IL6/IL10 ratio), as well reduced cellular damage/apoptosis (reduced plasmatic ccf‐nDNA, BAX upregulated BCL‐2/BAX ratio). Plasmatic ccf‐mtDNA was significantly subjects, while IL6 ratio subjects uniquely. Spearman correlations between physical pathway variations also suggested different adaptation mechanisms influenced not only by chronological but frailty status. In conclusion, this study confirms benefits activity older population provides novel insights into specific mitochondria‐inflammation axis players such effects. Moreover, establish PBMCs valuable tool for monitoring trajectories health‐promoting lifestyle interventions.
Язык: Английский
Процитировано
0
Journal of Hematology & Oncology, Год журнала: 2025, Номер 18(1)
Опубликована: Март 11, 2025
Lymphoma, a malignant tumor derived from lymphocytes and lymphoid tissues, presents with complex heterogeneous clinical manifestations, requiring accurate patient classification for appropriate treatment. While invasive pathological examination of lymph nodes or tissue remains the gold standard lymphoma diagnosis, its utility is limited in cases deep-seated tumors such as intraperitoneal central nervous system lymphomas. In addition, biopsy procedures carry an inherent risk complications. Computed tomography (CT) positron emission tomography/computed (PET/CT) imaging are essential treatment assessment monitoring, but lack ability to detect early clonal evolution minimal residual disease (MRD). Liquid biopsy-based analysis circulating DNA (ctDNA) offers non-invasive alternative that allows repeated sampling overcomes limitations spatial heterogeneity biopsies. ctDNA provides genetic epigenetic insights into serves dynamic, quantifiable biomarker stratification, response. This review comprehensively summarizes common variations systematically evaluates detection technologies, including PCR-based assays next-generation sequencing (NGS). Applications noninvasive genotyping, therapeutic response MRD discussed across various subtypes, diffuse large B-cell lymphoma, Hodgkin follicular T-cell lymphoma. By integrating recent research findings, highlights role profiling advancing precision medicine, enabling personalized strategies, improving outcomes
Язык: Английский
Процитировано
0
Seminars in Immunopathology, Год журнала: 2023, Номер 45(3), С. 411 - 425
Опубликована: Май 1, 2023
Abstract Stroke is the second leading cause of death worldwide and a disability. Clinical experimental studies highlighted complex role immune system in pathophysiology stroke. Ischemic brain injury leads to release cell-free DNA, damage-associated molecular pattern, which binds pattern recognition receptors on cells such as toll-like cytosolic inflammasome sensors. The downstream signaling cascade then induces rapid inflammatory response. In this review, we are highlighting characteristics DNA how these can affect local well systemic response after For purpose, screened literature clinical investigating concentration properties ischemia. We report current understanding for mechanisms uptake sensing context post-stroke inflammation. Moreover, compare possible treatment options targeting DNA-sensing pathways, mediators. Finally, describe implications pathway stroke patients, open questions, potential future research directions.
Язык: Английский
Процитировано
10