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

收藏

页数：11

相关论文

共 101 条

[31] Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis [J].

Govaere, Olivier ;

Cockell, Simon ;

Tiniakos, Dina ;

Queen, Rachel ;

Younes, Ramy ;

Vacca, Michele ;

Alexander, Leigh ;

Ravaioli, Federico ;

Palmer, Jeremy ;

Petta, Salvatore ;

Boursier, Jerome ;

Rosso, Chiara ;

Johnson, Katherine ;

Wonders, Kristy ;

Day, Christopher P. ;

Ekstedt, Mattias ;

Oresic, Matej ;

Darlay, Rebecca ;

Cordell, Heather J. ;

Marra, Fabio ;

Vidal-Puig, Antonio ;

Bedossa, Pierre ;

Schattenberg, Joern M. ;

Clement, Karine ;

Allison, Michael ;

Bugianesi, Elisabetta ;

Ratziu, Vlad ;

Daly, Ann K. ;

Anstee, Quentin M. .

SCIENCE TRANSLATIONAL MEDICINE, 2020, 12 (572)

[32] Defined p16High Senescent Cell Types Are Indispensable for Mouse Healthspan [J].

Grosse, Laurent ;

Wagner, Nicole ;

Emelyanov, Alexander ;

Molina, Clement ;

Lacas-Gervais, Sandra ;

Wagner, Kay-Dietrich ;

Bulavin, Dmitry, V .

CELL METABOLISM, 2020, 32 (01) :87-+

[33] Adipose tissue macrophages and their role in obesity-associated insulin resistance: an overview of the complex dynamics at play [J].

Guria, Suktara ;

Hoory, Anupama ;

Das, Snehasis ;

Chattopadhyay, Dipanjan ;

Mukherjee, Sutapa .

BIOSCIENCE REPORTS, 2023, 43 (03)

[34] Type 2 Diabetes, Independent of Obesity and Age, Is Characterized by Senescent and Dysfunctional Mature Human Adipose Cells [J].

Gustafson, Birgit ;

Nerstedt, Annika ;

Spinelli, Rosa ;

Beguinot, Francesco ;

Smith, Ulf .

DIABETES, 2022, 71 (11) :2372-2383

[35] Reduced subcutaneous adipogenesis in human hypertrophic obesity is linked to senescent precursor cells [J].

Gustafson, Birgit ;

Nerstedt, Annika ;

Smith, Ulf .

NATURE COMMUNICATIONS, 2019, 10 (1)

[36] IMPAIRED ADIPOGENESIS AND DYSFUNCTIONAL ADIPOSE TISSUE IN HUMAN HYPERTROPHIC OBESITY [J].

Hammarstedt, Ann ;

Gogg, Silvia ;

Hedjazifar, Shahram ;

Nerstedt, Annika ;

Smith, Ulf .

PHYSIOLOGICAL REVIEWS, 2018, 98 (04) :1911-1941

[37] The Novel Adipokine Gremlin 1 Antagonizes Insulin Action and Is Increased in Type 2 Diabetes and NAFLD/NASH [J].

Hedjazifar, Shahram ;

Khatib Shahidi, Roxana ;

Hammarstedt, Ann ;

Bonnet, Laurianne ;

Church, Christopher ;

Boucher, Jeremie ;

Blueher, Matthias ;

Smith, Ulf .

DIABETES, 2020, 69 (03) :331-341

[38] Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease [J].

Hickson, LaTonya J. ;

Prata, Larissa G. P. Langhi ;

Bobart, Shane A. ;

Evans, Tamara K. ;

Giorgadze, Nino ;

Hashmi, Shahrukh K. ;

Herrmann, Sandra M. ;

Jensen, Michael D. ;

Jia, Qingyi ;

Jordan, Kyra L. ;

Kellogg, Todda. ;

Khosla, Sundeep ;

Koerber, Daniel M. ;

Lagnado, Anthony B. ;

Lawson, Donna K. ;

LeBrasseur, Nathan K. ;

Lerman, Lilach O. ;

McDonald, Kathleen M. ;

McKenzie, Travis J. ;

Passos, Joao F. ;

Pignolo, Robert J. ;

Pirtskhalava, Tamar ;

Saadiq, Ishran M. ;

Schaefer, Kalli K. ;

Textor, Stephen C. ;

Victorelli, Stella G. ;

Volkman, Tammie L. ;

Xue, Ailing ;

Wentworth, Mark A. ;

Gerdes, Erin O. Wissler ;

Zhu, Yi ;

Tchkonia, Tamara ;

Kirkland, James L. .

EBIOMEDICINE, 2019, 47 :446-456

[39] Understanding angiogenesis during aging: opportunities for discoveries and new models [J].

Hodges, Nicholas A. ;

Suarez-Martinez, Ariana D. ;

Murfee, Walter L. .

JOURNAL OF APPLIED PHYSIOLOGY, 2018, 125 (06) :1843-1850

[40] The impact of senescence on muscle wasting in chronic kidney disease [J].

Huang, Ying ;

Wang, Bin ;

Hassounah, Faten ;

Price, S. Russ ;

Klein, Janet ;

Mohamed, Tamer M. A. ;

Wang, Yanhua ;

Park, Jeanie ;

Cai, Hui ;

Zhang, Xuemei ;

Wang, Xiaonan H. .

JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE, 2023, 14 :126-141

← 1 2 3 4 5 6 7 8 9 10 →