Ablation of telomerase reverse transcriptase inLeishmania majorresults in a senescent-like phenotype and loss of infectivity DOI Open Access
Mark Ewusi Shiburah, Beatriz C. D. de Oliveira, Habtye Bisetegn

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 10, 2023

Abstract The lack of efficient human vaccines and effective nontoxic drugs for leishmaniasis necessitates a search new therapeutic targets. telomere environment could provide potential targets against leishmaniasis. TERT, the telomerase reverse transcriptase component, has been on radar options several diseases more than two decades. In this study, we constructed full deletion ( Lm TERT-/-) an ORF disruption N420) gene encoding TERT component Leishmania major . TERT-/- N420 parasites showed replicative proliferative defects, growth impairment, cell cycle alterations, increased DNA damage, progressive shortening. Blockage parasite altruism presence autophagosomes characteristic senescent-like phenotype were also detected. caused either micro lesion development or no visible lesions in mouse footpads reduced infectivity macrophages. While our checks to see if erosion had reached SCG genes involved lipophosphoglycan modification changes, proteomic assessment revealed downregulation metacyclic-associated protein. Complementation knockout lineages using WT restored some lost phenotypes. Therefore, speculate that pleiotropic effects loss advance case it as drug target parasite.

Language: Английский

ALKBH5 SUMOylation-mediated FBXW7 m6A modification regulates alveolar cells senescence during 1-nitropyrene-induced pulmonary fibrosis DOI

Se-Ruo Li,

Ningning Kang,

Rongrong Wang

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 468, P. 133704 - 133704

Published: Feb. 9, 2024

Language: Английский

Citations

13
Bazi Bushen capsule improves the deterioration of the intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis through microbiota-gut-brain axis DOI Creative Commons
Shi-Xiong Zhang, Mengnan Li, Liping Chang

et al.

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Purpose The senescence-accelerated prone mouse 8 (SAMP8) is a widely used model for accelerating aging, especially in central aging. Mounting evidence indicates that the microbiota-gut-brain axis may be involved pathogenesis and progression of aging-related diseases. This study aims to investigate whether Bazi Bushen capsule (BZBS) attenuates deterioration intestinal function aging animal model. Methods In our study, SAMP8 mice were randomly divided into group, BZ-low group (0.5 g/kg/d BZBS), BZ-high (1 BZBS) RAPA (2 mg/kg/d rapamycin). Age-matched SAMR1 as control group. Next, cognitive was detected through Nissl staining two-photon microscopy. gut microbiota composition fecal samples analyzed by 16S rRNA gene sequencing. Ileum tissue morphology observed hematoxylin eosin staining, barrier immunofluorescence. expression senescence-associated secretory phenotype (SASP) factors, including P53, TNF-α, NF-κB, IL-4, IL-6, IL-10 measured real-time quantitative PCR. Macrophage infiltration proliferation differentiation cells assessed immunohistochemistry. We also inflammasome pyroptosis levels ileum western blotting. Results BZBS improved neuronal density mice. restored villus structure function, which damaged reduced SASP factors macrophages tissues, indicating lower level inflammation. enhanced cells, are essential maintaining homeostasis. modulated composition, inhibited activation inflammasomes intestine. Conclusion could restore dysbiosis prevent inhibiting NLRP3 inflammasome-mediated pyroptosis. These results suggested attenuated mice, at least partially, targeting axis.

Language: Английский

Citations

8
Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases DOI
Zeming Wu, Jing Qu, Guang‐Hui Liu

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(12), P. 979 - 1000

Published: Oct. 3, 2024

Language: Английский

Citations

8
Effects of senotherapeutics on gut microbiome dysbiosis and intestinal inflammation in Crohn's Disease: A Pilot Study DOI Creative Commons
Nannapat Sangfuang, Laura E. McCoubrey, Atheer Awad

et al.

Translational research, Journal Year: 2025, Volume and Issue: 278, P. 36 - 47

Published: Feb. 20, 2025

Language: Английский

Citations

1
Lack of telomerase reduces cancer incidence and increases lifespan of zebrafish tp53M214K mutants DOI Creative Commons

Naz Şerifoğlu,

Bruno Lopes-Bastos, Miguel Godinho Ferreira

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 5, 2024

Abstract Telomerase activity is restricted in humans and telomere attrition occurs several tissues accompanying natural aging. Critically short telomeres trigger DNA damage responses activate p53 which leads to apoptosis or replicative senescence. These processes reduce cell proliferation disrupt tissue homeostasis, thus contributing systemic Similarly, zebrafish have telomerase expression, shorten critical length during their lifespan. Telomerase-deficient ( tert −/− ) a premature model of aging that anticipates phenotypes due early shortening. impaired proliferation, accumulation markers response. cellular defects lead disruption resulting infertility, gastrointestinal atrophy, sarcopenia kyphosis. Such consequences contribute its death. Here we reveal genetic interdependence between tp53 function. Mutation abrogates zebrafish, prolonging male fertility However, it does not fully rescue healthspan. tp53mut retain high levels inflammation increased spontaneous cancer incidence. Conversely, loss prolongs the lifespan single mutants. Lack reduces two-fold incidence double mutants increases lifetime survival. Thus, observe reciprocal ameliorates but , likely higher inflammation.

Language: Английский

Citations

4
Fecal Microbiota Transplantation, a tool to transfer healthy longevity DOI Creative Commons
Marta G. Novelle,

Beatriz Naranjo-Martínez,

Juan L López-Cánovas

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 103, P. 102585 - 102585

Published: Nov. 23, 2024

The complex gut microbiome influences host aging and plays an important role in the manifestation of age-related diseases. Restoring a healthy via Fecal Microbiota Transplantation (FMT) is receiving extensive consideration to therapeutically transfer longevity. Herein, we comprehensively review benefits microbial rejuvenation - FMT promote aging, with few studies documenting life length properties. This explores how preconditioning donors standard lifestyle pharmacological antiaging interventions reshape microbiome, resulting being also FMT-transferable. Finally, expose current clinical uses context therapy address challenges regulatory landscape, protocol standardization, health risks that require refinement effectively utilize elderly.

Language: Английский

Citations

4
Establishment and application of a zebrafish model of Werner syndrome identifies sapanisertib as a potential antiaging drug DOI Creative Commons
Jianlong Ma, Yang Chen, Jingmei Song

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(5)

Published: Jan. 30, 2025

Aging is a complex process that affects multiple organs, and the discovery of pharmacological approach to ameliorate aging considered Holy Grail medicine. Here, we performed an N-ethyl-N-nitrosourea forward genetic screening in zebrafish identified accelerated mutant named meteor ( met ), harboring mutation Werner syndrome RecQ - like helicase wrn ) gene. Loss leads short lifespan age-related characteristics intestine embryos, such as cellular senescence, genomic instability, epigenetic alteration. Therefore, conducted antiaging drugs using revealed sapanisertib effectively ameliorated most phenotypes mutant. Mechanistically, geroprotective effects may be attributed inhibition mTORC1/2. Furthermore, also attenuated chronological wild-type aged replicative-senescence human foreskin fibroblasts. Taken together, our study introduces unique efficient model for large-scale drug vertebrates suggests potential therapeutic option treating premature promoting healthy aging.

Language: Английский

Citations

0
Zbtb48 is a regulator of Mtfp1 expression in zebrafish DOI Creative Commons

Soon Pang Goh,

Albert Fradera-Sola, Nadine Wittkopp

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Feb. 22, 2025

Language: Английский

Citations

0
Zebrafish genetic model of neuromuscular degeneration associated with Atrogin-1 expression DOI Creative Commons

Romain Menard,

Elena Morin,

D.C. Morse

et al.

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

Published: March 10, 2025

ABSTRACT The degenerative loss of muscle associated with aging leading to muscular atrophy is called sarcopenia. Currently, practicing regular physical exercise the only efficient way delay sarcopenia onset. Identification therapeutic targets alleviate symptoms requires in vivo model organisms accelerated degeneration and atrophy. zebrafish undergoes aging, hallmarks including mitochondrial dysfunction, telomere shortening, accumulation senescent cells. However, age slowly, no specific models molecular events are currently available. We have developed a new genetic tool efficiently accelerate muscle-fiber muscle-tissue larvae adults. used gain-of-function strategy molecule that has been shown be necessary sufficient induce phenotype mammals: Atrogin-1 (also named Fbxo32). report generation, validation, characterization neuromuscular atrophy, atrofish. demonstrated expression specifically skeletal tissue induces atrophic locomotion dysfunction both adult fish. identified degradation myosin light chain as an event occurring prior degeneration. Biological processes such proteolysis, inflammation, stress response, extracellular matrix (ECM) remodeling, apoptosis upregulated Surprisingly, we observed strong correlation between reduced numbers junctions peripheral nervous system, well neuronal cell bodies spinal cord, suggesting could underly neurodegenerative central system. Finally, while atrofish can recover locomotive functions, impaired regenerative capacities, mammals during aging. In future, serve platform for testing molecules aimed at treating or alleviating thereby opening avenues fight against

Language: Английский

Citations

0
Hexavalent Chromium and Cellular Senescence: A Comprehensive Analysis from Chromate-Exposed Occupational Population and Chromate-Inhaled Mouse Model DOI
Zhiqiang Ji, Yali Zhang, Guiping Hu

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: 493, P. 138387 - 138387

Published: April 22, 2025

Language: Английский

Citations

0