AbstractObjectiveThe 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.MethodsAB 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.ResultsCO 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.ConclusionsThese 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.