Journal: Signal Transduction and Targeted Therapy

Article Title: Hyperglutaminolysis drives senescence and aging through arginine-mTORC1 axis activation

doi: 10.1038/s41392-026-02576-w

Figure Lengend Snippet: Hyperglutaminolysis enhances arginine biosynthesis in senescent cells and aged flies. a Venn diagram of metabolites detected by LC-MS/MS-based metabolomics assay ( n = 5 per group). These metabolites are classified into three subsets: the upregulated ones in senescent NIH3T3 cells (green, H vs C UP, p ≤ 0.05, fold change ≥ 1), the downregulated ones in CB-839 (1 μM, 36 hours)-treated senescent cells (red, HCB vs H DOWN, p ≤ 0.05, fold change ≤ 1), and those engaged in the “GLS-related pathway” (blue, GLS-related). 12 metabolites situated in the intersection of these 3 subsets are listed on the right side. b A sketch map of the arginine synthesis pathway linked to glutaminolysis. c – n Levels of metabolites involved in arginine synthesis detected by LC-MS/MS assays and CB-839-caursed alterations (delta levels) of these metabolites, in proliferating (Pro) and senescent (Sen) cells. These metabolites are glutamine (Gln, c , d ), arginine (Arg, e , f ), glutamate (Glu, g , h ), ammonia (NH 4 + , i , j ), aspartate (Asp, k , l ) and citrulline (Cit, m , n ). Levels of arginine, aspartate and citrulline in naturally aged ( o ) and H 2 O 2 -stressed ( p ) flies, with young and unstressed controls. Arginine ( q ) and NH 4 + ( r ) levels in the control and H 2 O 2 -stressed flies treated without or with DON (0.1 μM, 3 days). s Levels of arginine, aspartate and citrulline in wild-type and Gls -KD flies. All metabolite assays used pooled homogenates of at least 20 flies per group and were executed with three technical replicates. Histogram data are shown as mean ± SD. Student’s t-test: * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, n.s . non-significant

Article Snippet: Adriamycin HCl (ADR, S1208), Bafilomycin A1 (BafA1, S1413) were purchased from Selleck (Houston, USA); ammonium chloride (NH 4 Cl) and hydrogen peroxide (H 2 O 2 ) were purchased from CHRON Chemical (Chengdu, China); 6-Diazo-5-oxo-L-nor-leucine (DON, HY-108357) was purchased from MedChemExpress (NJ, USA); CB-839 (Telaglenastat, T6797) was purchased from TargetMol (Massachusetts, USA); L-glutamine (Gln, G8540) was purchased from Merck (Darmstadt, Germany); sodium glutamate hydrate (glutamate, Glu, A602012), L-aspartic acid sodium salt monohydrate (aspartate, Asp, A601178), L-citrulline (Cit, A604057) and L-arginine (Arg, A600205) were purchased from Sangon Biotech (Shanghai, China).

Techniques: Liquid Chromatography with Mass Spectroscopy, Control