Rapalink-1 reveals novel mTOR-dependent genes and the role of agmatinases in cellular growth and chronological lifespan DOI Creative Commons
Juhi Kumar, Charalampos Rallis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 22, 2024

The mechanistic Target of Rapamycin, mTOR, is a conserved pro-ageing pathway with characterised inhibitors such as rapamycin, rapalogues and torins. Bi-steric third-generation inhibitors, rapalink-1 have been developed, however, their effects on organismal gene expression lifespan not characterised. Here, we demonstrate that affects fission yeast spatial temporal growth prolongs chronological distinct TORC1 selectivity profile. Endosome vesicle-mediated transport homeostasis processes related to autophagy Pik3, the orthologue human PI3K, render cells resistant rapalink-1. Our study reveals mTOR-regulated genes unknown roles in ageing including all agmatinases, enzymes convert agmatine putrescine urea. Through genome-wide screens, identify sensitive mutants putrescine. Genetic interactome assays for agmatinase agm1 further cell molecular analyses, impairing agmatinergic branch arginine catabolism results mTOR activity levels are beneficial but detrimental ageing. anti-ageing action agmatinases within metabolic feedback circuit regulating possible implications other systems, cells.

Language: Английский

The role of colonic microbiota amino acid metabolism in gut health regulation DOI Creative Commons
Youli Chen, Jing‐Yuan Fang

Cell Insight, Journal Year: 2025, Volume and Issue: unknown, P. 100227 - 100227

Published: Jan. 1, 2025

The human gut microbiota plays a critical role in maintaining host homeostasis through metabolic activities. Among these, amino acid (AA) metabolism by the large intestine is highly heterogeneous and relevant to health. Despite increasing interest, microbial AA remains relatively unexplored. This review highlights recent advances colonic metabolism, including auxotrophies, synthesis, dissimilatory metabolites, their implications health, focusing on major gastrointestinal diseases colorectal cancer, inflammatory bowel disease, irritable syndrome.

Language: Английский

Citations

0
Biochemical and genomic evidence for converging metabolic routes of metformin and biguanide breakdown in environmental Pseudomonads DOI Creative Commons

Katie B. Wissbroecker,

Anthony J. Zmuda,

Harsheeth Karumanchi

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 107935 - 107935

Published: Oct. 1, 2024

Language: Английский

Citations

1
Caenorhabditis elegans as a Convenient Animal Model for Microbiome Studies DOI Open Access

Cheng-Yeu Wu,

Scott Davis,

Neekita Saudagar

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6670 - 6670

Published: June 18, 2024

Microbes constitute the most prevalent life form on Earth, yet their remarkable diversity remains mostly unrecognized. Microbial in vertebrate models presents a significant challenge for investigating host–microbiome interactions. The model organism Caenorhabditis elegans has many advantages delineating effects of host genetics microbial composition. In wild, C. gut contains various species, while laboratory it is usually single bacterial species. There potential host–microbe interaction between metabolites, drugs, and phenotypes. This mini-review aims to summarize current understanding regarding microbiome elegans. Examples using study host–microbe–metabolite interactions are discussed.

Language: Английский

Citations

0
Rapalink-1 reveals novel mTOR-dependent genes and the role of agmatinases in cellular growth and chronological lifespan DOI Creative Commons
Juhi Kumar, Charalampos Rallis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 22, 2024

The mechanistic Target of Rapamycin, mTOR, is a conserved pro-ageing pathway with characterised inhibitors such as rapamycin, rapalogues and torins. Bi-steric third-generation inhibitors, rapalink-1 have been developed, however, their effects on organismal gene expression lifespan not characterised. Here, we demonstrate that affects fission yeast spatial temporal growth prolongs chronological distinct TORC1 selectivity profile. Endosome vesicle-mediated transport homeostasis processes related to autophagy Pik3, the orthologue human PI3K, render cells resistant rapalink-1. Our study reveals mTOR-regulated genes unknown roles in ageing including all agmatinases, enzymes convert agmatine putrescine urea. Through genome-wide screens, identify sensitive mutants putrescine. Genetic interactome assays for agmatinase agm1 further cell molecular analyses, impairing agmatinergic branch arginine catabolism results mTOR activity levels are beneficial but detrimental ageing. anti-ageing action agmatinases within metabolic feedback circuit regulating possible implications other systems, cells.

Language: Английский

Citations

0