1 Department of Health, Kinesiology, and Applied Physiology, Concordia University, Montréal, Québec, Canada.
2 Metabolism, Obesity, and Nutrition Laboratory, PERFORM Centre, Concordia University, Montréal, Québec, Canada.
3 Centre de recherche-Axe maladies chroniques, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Ile-de-Montréal, Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada.
4 Department of Sport, Physical Education, and Health, Faculty of Social Sciences, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
5 Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA.
6 Division of Endocrinology and Metabolism, Department of Medicine, McGill University, Royal Victoria Hospital, McGill University Health Centre Glen Site, Montréal, Québec, Canada.
7 Division of Geriatric Medicine, Department of Medicine, McGill University, McGill University Health Centre-Montréal General Hospital, Montréal, Québec, Canada.

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 ?H2AX/RAD51 (DNA damage/repair markers) and p53/p21 (senescence markers) was conducted in cultured preadipocytes, and senescence-associated ß-galactosidase (SA-ß-gal) activity was measured in SAT.

Results: CO had proportionately more AB and FEM preadipocytes with DNA damage (?H2AX⁺ ) and senescence markers (p53⁺ and/or p21⁺ ) than AO at baseline. The proportion of ?H2AX⁺ FEM preadipocytes declined with weight loss in CO and was similar between groups after weight loss. The number of ?H2AX foci in ?H2AX⁺ 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-ß-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.