biostudies-literatureTerron-Puig MGeneralitat de CatalunyaInstituto de Salud Carlos IIIMinisterio de Ciencia e InnovaciónFundació la Marató de TV3e13667https://www.ebi.ac.uk/biostudies/studies/S-EPMC9381900biostudies-literatureUnknown21(8)Dysfunctional adipocyte precursors have emerged as key determinants for obesity- and aging-related inflammation, but the mechanistic basis remains poorly understood. Here, we explored the dysfunctional adipose tissue of elderly and obese individuals focusing on the metabolic and inflammatory state of human adipose-derived mesenchymal stromal cells (hASCs), and on sirtuins, which link metabolism and inflammation. Both obesity and aging impaired the differentiation potential of hASCs but had a different impact on their proliferative capacity. hASCs from elderly individuals (≥65 years) showed an upregulation of glycolysis-related genes, which was accompanied by increased lactate secretion and glycogen storage, a phenotype that was exaggerated by obesity. Multiplex protein profiling revealed tAging cellGlycogen accumulation in adipocyte precursors from elderly and obese subjects triggers inflammation via SIRT1/6 signaling.PMC9381900RTI2018‐093919SAF2015‐65019‐R225/C/2016FI18/00151SLT002/16/00120CPII16/00008CP10/00438CM18/00029PI20/00338RYC2013‐13186PI17/0153Nunez-Roa CHuber-Ruano IVendrell JJorba RTerron-Puig MMaymo-Masip EFernandez-Veledo SSerena CEjarque MSabadell-Basallote JfalseGlycogen accumulation in adipocyte precursors from elderly and obese subjects triggers inflammation via SIRT1/6 signaling.Dysfunctional adipocyte precursors have emerged as key determinants for obesity- and aging-related inflammation, but the mechanistic basis remains poorly understood. Here, we explored the dysfunctional adipose tissue of elderly and obese individuals focusing on the metabolic and inflammatory state of human adipose-derived mesenchymal stromal cells (hASCs), and on sirtuins, which link metabolism and inflammation. Both obesity and aging impaired the differentiation potential of hASCs but had a different impact on their proliferative capacity. hASCs from elderly individuals (≥65 years) showed an upregulation of glycolysis-related genes, which was accompanied by increased lactate secretion and glycogen storage, a phenotype that was exaggerated by obesity. Multiplex protein profiling revealed t2022-01-01T00:00:00Z2022 Aug2025-04-26T22:10:24.366Z2024-11-19T18:23:16.588ZS-EPMC93819003581145710.1111/acel.13667