衰老
传出细胞增多
骨桥蛋白
脂肪组织
炎症
骨重建
生物
医学
巨噬细胞
内分泌学
细胞生物学
内科学
生物化学
体外
作者
Daigo Sawaki,Yanyan Zhang,Amel Mohamadi,Maria Silvia Pini,Zaineb Mezdari,Larissa Lipskaia,Suzain Naushad,Lucille Lamendour,Dogus Murat Altintas,Marielle Bréau,Hao Liang,Maissa Halfaoui,Thaïs Delmont,Mathieu Surénaud,Denis Rousseau,Takehiko Yoshimitsu,Fawzia Louache,Serge Adnot,Corneliu Hénégar,Philippe Gual,Gabor Czibik,Geneviève Dérumeaux
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2023-04-24
卷期号:8 (8)
被引量:4
标识
DOI:10.1172/jci.insight.145811
摘要
Adipose tissue macrophages (ATMs) play an important role in obesity and inflammation, and they accumulate in adipose tissue (AT) with aging. Furthermore, increased ATM senescence has been shown in obesity-related AT remodeling and dysfunction. However, ATM senescence and its role are unclear in age-related AT dysfunction. Here, we show that ATMs (a) acquire a senescence-like phenotype during chronological aging; (b) display a global decline of basic macrophage functions such as efferocytosis, an essential process to preserve AT homeostasis by clearing dysfunctional or apoptotic cells; and (c) promote AT remodeling and dysfunction. Importantly, we uncover a major role for the age-associated accumulation of osteopontin (OPN) in these processes in visceral AT. Consistently, loss or pharmacologic inhibition of OPN and bone marrow transplantation of OPN–/– mice attenuate the ATM senescence-like phenotype, preserve efferocytosis, and finally restore healthy AT homeostasis in the context of aging. Collectively, our findings implicate pharmacologic OPN inhibition as a viable treatment modality to counter ATM senescence-mediated AT remodeling and dysfunction during aging.
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