Work

Aged mice overexpressing cellular repressor of E1A-stimulated genes 1 in adipose tissues exhibited increased liposarcoma incidence and shortened lifespan

Year: 2025

Type: article

Abstract: Cellular repressor of E1A-stimulated genes 1 (CREG1) is a multifunctional secreted glycoprotein that regulates p16-dependent cellular senescence and cell differentiation and accelerates brown adipogenesis. We recently demonstrated that the CREG1 levels in serum, liver, and kidney were significantly increased in aged wild-type (WT) mice, where age-related renal impairment was further aggravated by promoting cellular senescence. Based on these findings, we hypothesized that the constitutive regulation of CREG1 expression in vivo may affect lifespan. In this study, we revealed that the average lifespan of adipocyte P2-CREG1 transgenic (Tg) mice was shorter than that of WT mice. Moreover, we determined that this reduced lifespan was associated with an increased incidence of liposarcoma (LPS). Our findings indicated that the development of LPS in Tg mice may be driven by chronic inflammation induced by the p19 Arf -mouse double minute 2 pathway in white adipose tissue (WAT). These findings indicate that long-term alterations in CREG1 expression in vivo may affect tumor development in the WAT. • Lifespans of the high expression aP2-CREG1-Tg mice were shortened. • Long-term CREG1 overexpression may promote liposarcoma in white adipose tissue. • CREG1 induces cellular senescence through p19 Arf -MDM2 pathway. • Chronic increase in SASP may elevate liposarcoma likelihood in old mice.

Source: Biochemical and Biophysical Research Communications

DOI: 10.1016/j.bbrc.2025.151454

Authors: Michihiro Hashimoto, Ayumi Goto, Shanlou Qiao, Hitoshi Yamashita

Institutions: Asahikawa Medical University, Toyohashi SOZO University, Chubu University

Language: English

Topic: Telomeres, Telomerase, and Senescence

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,110