Increased cell senescence in human metabolic disorders

被引：52

作者：

Spinelli, Rosa ^{[1
,2
,3
]}

Baboota, Ritesh Kumar ^{[1
,4
]}

Gogg, Silvia ^{[1
]}

Beguinot, Francesco ^{[2
,3
]}

Bluher, Matthias ^{[5
,6
]}

Nerstedt, Annika ^{[1
,4
]}

Smith, Ulf ^{[1
,7
]}

机构：

[1] Univ Gothenburg, Sahlgrenska Acad, Dept Mol & Clin Med, Lundberg Lab Diabet Res, Gothenburg, Sweden

[2] Federico II Univ Naples, Dept Translat Med Sci, Naples, Italy

[3] CNR, Inst Expt Endocrinol & Oncol, URT Genom Diabet, Naples, Italy

[4] Evotec Int GmbH, Gottingen, Germany

[5] Univ Leipzig, Helmholtz Inst Metab Obes & Vasc Res HI MAG, Leipzig, Germany

[6] Univ Hosp Leipzig, Leipzig, Germany

[7] Sahlgrens Univ Hosp, Dept Mol & Clin Med, Lundberg Lab Diabet Res, Bla Straket 5, SE-41345 Gothenburg, Sweden

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2023年 / 133卷 / 12期

基金：

瑞典研究理事会;

关键词：

ADIPOSE-TISSUE; ENDOTHELIAL-CELLS; P53; HYPERINSULINEMIA; ADIPOCYTES; MECHANISMS; OBESITY; DEPOTS; AGE;

D O I：

10.1172/JCI169922

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Cell senescence (CS) is at the nexus between aging and associated chronic disorders, and aging increases the burden of CS in all major metabolic tissues. However, CS is also increased in adult obesity, type 2 diabetes (T2D), and nonalcoholic fatty liver disease independent of aging. Senescent tissues are characterized by dysfunctional cells and increased inflammation, and both progenitor cells and mature, fully differentiated and nonproliferating cells are afflicted. Recent studies have shown that hyperinsulinemia and associated insulin resistance (IR) promote CS in both human adipose and liver cells. Similarly, increased CS promotes cellular IR, showing their interdependence. Furthermore, the increased adipose CS in T2D is independent of age, BMI, and degree of hyperinsulinemia, suggesting premature aging. These results suggest that senomorphic/senolytic therapy may become important for treating these common metabolic disorders.

引用

页数：11

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