Obesity and Type-2 Diabetes As Inducers of Premature Cellular Senescence and Ageing

Overview

Journal Biogerontology

Specialty Geriatrics

Date 2018 Jul 29

PMID 30054761

Citations 87

Authors

Dominick G A Burton

Richard G A Faragher

Affiliations

Soon will be listed here.

Abstract

Cellular senescence is now considered as a major mechanism in the development and progression of various diseases and this may include metabolic diseases such as obesity and type-2 diabetes. The presence of obesity and diabetes is a major risk factor in the development of additional health conditions, such as cardiovascular disease, kidney disease and cancer. Since senescent cells can drive disease development, obesity and diabetes can potentially create an environment that accelerates cell senescence within other tissues of the body. This can consequently manifest as age-related biological impairments and secondary diseases. Cell senescence in cell types linked with obesity and diabetes, namely adipocytes and pancreatic beta cells will be explored, followed by a discussion on the role of obesity and diabetes in accelerating ageing through induction of premature cell senescence mediated by high glucose levels and oxidised low-density lipoproteins. Particular emphasis will be placed on accelerated cell senescence in endothelial progenitor cells, endothelial cells and vascular smooth muscle cells with relation to cardiovascular disease and proximal tubular cells with relation to kidney disease. A summary of the potential strategies for therapeutically targeting senescent cells for improving health is also presented.

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References

Wang J, Bai Y, Zhao X, Ru J, Kang N, Tian T . oxLDL-mediated cellular senescence is associated with increased NADPH oxidase p47phox recruitment to caveolae. Biosci Rep. 2018; 38(3). PMC: 5997791. DOI: 10.1042/BSR20180283. View

Laberge R, Zhou L, Sarantos M, Rodier F, Freund A, de Keizer P . Glucocorticoids suppress selected components of the senescence-associated secretory phenotype. Aging Cell. 2012; 11(4):569-78. PMC: 3387333. DOI: 10.1111/j.1474-9726.2012.00818.x. View

Coleman M, Marshall C, Olson M . Ras promotes p21(Waf1/Cip1) protein stability via a cyclin D1-imposed block in proteasome-mediated degradation. EMBO J. 2003; 22(9):2036-46. PMC: 156064. DOI: 10.1093/emboj/cdg189. View

Shahbazian H, Rezaii I . Diabetic kidney disease; review of the current knowledge. J Renal Inj Prev. 2014; 2(2):73-80. PMC: 4206005. DOI: 10.12861/jrip.2013.24. View

Carlos Acosta J, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton J . A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol. 2013; 15(8):978-90. PMC: 3732483. DOI: 10.1038/ncb2784. View

Burton D, Giles P, Sheerin A, Smith S, Lawton J, Ostler E . Microarray analysis of senescent vascular smooth muscle cells: A link to atherosclerosis and vascular calcification. Exp Gerontol. 2009; 44(10):659-65. DOI: 10.1016/j.exger.2009.07.004. View

Childs B, Gluscevic M, Baker D, Laberge R, Marquess D, Dananberg J . Senescent cells: an emerging target for diseases of ageing. Nat Rev Drug Discov. 2017; 16(10):718-735. PMC: 5942225. DOI: 10.1038/nrd.2017.116. View

Chen Y, Lin S, Lin F, Wu T, Tsao C, Huang P . High glucose impairs early and late endothelial progenitor cells by modifying nitric oxide-related but not oxidative stress-mediated mechanisms. Diabetes. 2007; 56(6):1559-68. DOI: 10.2337/db06-1103. View

Laberge R, Awad P, Campisi J, Desprez P . Epithelial-mesenchymal transition induced by senescent fibroblasts. Cancer Microenviron. 2011; 5(1):39-44. PMC: 3343197. DOI: 10.1007/s12307-011-0069-4. View

10.

Burton D, Stolzing A . Cellular senescence: Immunosurveillance and future immunotherapy. Ageing Res Rev. 2018; 43:17-25. DOI: 10.1016/j.arr.2018.02.001. View

11.

Burton D, Faragher R . Cellular senescence: from growth arrest to immunogenic conversion. Age (Dordr). 2015; 37(2):27. PMC: 4365077. DOI: 10.1007/s11357-015-9764-2. View

12.

Matsui-Hirai H, Hayashi T, Yamamoto S, Ina K, Maeda M, Kotani H . Dose-dependent modulatory effects of insulin on glucose-induced endothelial senescence in vitro and in vivo: a relationship between telomeres and nitric oxide. J Pharmacol Exp Ther. 2011; 337(3):591-9. DOI: 10.1124/jpet.110.177584. View

13.

Krishnamurthy J, Ramsey M, Ligon K, Torrice C, Koh A, Bonner-Weir S . p16INK4a induces an age-dependent decline in islet regenerative potential. Nature. 2006; 443(7110):453-7. DOI: 10.1038/nature05092. View

14.

Xu M, Palmer A, Ding H, Weivoda M, Pirtskhalava T, White T . Targeting senescent cells enhances adipogenesis and metabolic function in old age. Elife. 2015; 4:e12997. PMC: 4758946. DOI: 10.7554/eLife.12997. View

15.

Melk A, Kittikowit W, Sandhu I, Halloran K, Grimm P, Schmidt B . Cell senescence in rat kidneys in vivo increases with growth and age despite lack of telomere shortening. Kidney Int. 2003; 63(6):2134-43. DOI: 10.1046/j.1523-1755.2003.00032.x. View

16.

McHugh D, Gil J . Senescence and aging: Causes, consequences, and therapeutic avenues. J Cell Biol. 2017; 217(1):65-77. PMC: 5748990. DOI: 10.1083/jcb.201708092. View

17.

Larsen S, Kassem M, Rattan S . Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells. Chem Cent J. 2012; 6(1):18. PMC: 3325881. DOI: 10.1186/1752-153X-6-18. View

18.

Malaquin N, Martinez A, Rodier F . Keeping the senescence secretome under control: Molecular reins on the senescence-associated secretory phenotype. Exp Gerontol. 2016; 82:39-49. DOI: 10.1016/j.exger.2016.05.010. View

19.

Mitterberger M, Lechner S, Mattesich M, Zwerschke W . Adipogenic differentiation is impaired in replicative senescent human subcutaneous adipose-derived stromal/progenitor cells. J Gerontol A Biol Sci Med Sci. 2013; 69(1):13-24. DOI: 10.1093/gerona/glt043. View

20.

Alimbetov D, Davis T, Brook A, Cox L, Faragher R, Nurgozhin T . Suppression of the senescence-associated secretory phenotype (SASP) in human fibroblasts using small molecule inhibitors of p38 MAP kinase and MK2. Biogerontology. 2015; 17(2):305-15. PMC: 4819486. DOI: 10.1007/s10522-015-9610-z. View