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

Abstract

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.

DNA damage, obesity and obesity-related health complications: what are new data telling us?

“…Recently, it was reported that preadipocytes isolated from abdominal and femoral subcutaneous adipose tissue explants of women with childhoodonset obesity had higher levels of damaged DNA and more senescent cells (assessed as p53þ/p21þ cells) than preadipocytes isolated from women with adult-onset obesity [19]. After moderate (10%) weight loss, DNA damage decreased in all studied patients and no difference between groups was recognized.…”

Cellular senescence in cancer: molecular mechanisms and therapeutic targets

“…Two important tumor suppressor pathways, p16 ink4a ‐pRb and p53‐p21, are engaged to initiate and maintain persistent cell cycle arrest in senescence. 68 , 72 , 73 These four crucial factors can induce senescence by prolonged overexpression of any one of them, and they essentially sustain the senescent state by causing extensive alterations in gene expression through p53, which is an important transcription factor, and Rb, which participates in regulating the expression of a variety of genes. 74 The Rb family is a primary target of cyclin–CDK complexes, and it functions by sequestering E2F complexes and thus inhibiting the expression of E2F target genes.…”