Fig. 9
Chronic exposure to obesogenic milieu modulates adipose-derived stem cells (ADSC) to a senescent phenotype associated with the p38MAPK/NF-kB axis. In our model, the inflammatory environment observed in obesity triggers a senescent phenotype in ADSC. The exposure to obesogenic milieu stimulated an increase in SASP cytokines IL-6 and IL-8 through p38MAPK/NF-kB activation, as well as promoted mitochondrial remodeling. ADSC exhibited G2/M cycle arrest and up-regulation of CDKN1A (p21WAF1/Cip1), along with increased SA-β-gal activity positively correlated with TRF1 protein expression at day 10. After 18 days, ADSC showed persistent cycle arrest by increased CDKN2A (p16INK4A) expression, cumulative nuclear enlargement, and SASP amplification. These findings highlight the phenotypic and functional alterations in ADSC exposed to plasma from obesity and suggest a link between obesity-induced inflammation and cellular senescence