Senescence markers in subcutaneous preadipocytes differ in childhood- versus adult-onset obesity before and after weight loss

Objective: The aim of this study was to determine the effect of age of obesity onset on senescence-related markers in abdominal (AB) and femoral (FEM) subcutaneous adipose tissue (SAT) before and after moderate (~10%) weight loss. Methods: AB and FEM SAT were collected from human females with childhood-onset obesity (CO) or adult-onset obesity (AO) before and after diet- and exercise-induced weight loss. Immunofluorescence analysis of γH2AX/RAD51 (DNA damage/repair markers) and p53/p21 (senescence markers) was conducted in cultured preadipocytes, and senescence-associated β-galactosidase (SA-β-gal) activity was measured in SAT. Results: CO had proportionately more AB and FEM preadipocytes with DNA damage (γH2AX⁺) and senescence markers (p53⁺ and/or p21⁺) than AO at baseline. The proportion of γH2AX⁺ FEM preadipocytes declined with weight loss in CO and was similar between groups after weight loss. The number of γH2AX foci in γH2AX⁺ preadipocytes decreased similarly between groups and regions with weight loss in parallel with an increase in RAD51. The proportion of p53⁺ and p21⁺ preadipocytes and SA-β-gal⁺ cells in SAT did not change with weight loss, but the total p21 intensity in p53⁺/p21⁺ FEM preadipocytes declined in AO. Conclusions: These results provide preliminary evidence that females with CO have an accelerated preadipocyte aging state that improves with weight loss in terms of DNA damage but not senescence.