Fat tissue, aging, and cellular senescence

Aging Cell - Tập 9 Số 5 - Trang 667-684 - 2010
Tamar Tchkonia1, Dean E. Morbeck1, Thomas von Zglinicki2, Jan van Deursen1, Joseph Lustgarten1, Heidi Scrable1, Sundeep Khosla1, Michael D. Jensen1, James L. Kirkland1
1Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, 55905, USA.
2Henry Wellcome Biogerontology Laboratory, Institute for Ageing and Health, University of Newcastle, Newcastle upon Tyne, UK

Tóm tắt

SummaryFat tissue, frequently the largest organ in humans, is at the nexus of mechanisms involved in longevity and age‐related metabolic dysfunction. Fat distribution and function change dramatically throughout life. Obesity is associated with accelerated onset of diseases common in old age, while fat ablation and certain mutations affecting fat increase life span. Fat cells turn over throughout the life span. Fat cell progenitors, preadipocytes, are abundant, closely related to macrophages, and dysdifferentiate in old age, switching into a pro‐inflammatory, tissue‐remodeling, senescent‐like state. Other mesenchymal progenitors also can acquire a pro‐inflammatory, adipocyte‐like phenotype with aging. We propose a hypothetical model in which cellular stress and preadipocyte overutilization with aging induce cellular senescence, leading to impaired adipogenesis, failure to sequester lipotoxic fatty acids, inflammatory cytokine and chemokine generation, and innate and adaptive immune response activation. These pro‐inflammatory processes may amplify each other and have systemic consequences. This model is consistent with recent concepts about cellular senescence as a stress‐responsive, adaptive phenotype that develops through multiple stages, including major metabolic and secretory readjustments, which can spread from cell to cell and can occur at any point during life. Senescence could be an alternative cell fate that develops in response to injury or metabolic dysfunction and might occur in nondividing as well as dividing cells. Consistent with this, a senescent‐like state can develop in preadipocytes and fat cells from young obese individuals. Senescent, pro‐inflammatory cells in fat could have profound clinical consequences because of the large size of the fat organ and its central metabolic role.

Từ khóa


Tài liệu tham khảo

10.1038/35055575

10.1038/nm0909-996

10.1371/journal.pgen.1000752

10.1093/gerona/63.5.447

10.1083/jcb.200507081

10.1038/ncb1744

10.1093/gerona/54.3.B89

10.2337/diabetes.48.1.94

10.1038/nature05221

10.1172/JCI200420663

10.1016/j.ghir.2004.02.005

10.1016/j.ghir.2008.05.005

Berryman DE, 2009, Two‐year body composition analyses of long‐lived GHR null mice, J. Gerontol. A Biol. Sci. Med. Sci., 65, 31

10.1126/science.151328

10.1093/geronj/35.6.827

Bjorntorp P, 1990, Obesity and adipose tissue distribution as risk factors for the development of disease. A review, Infusionstherapie, 17, 24

10.1126/science.1078223

Boney CM, 2001, Src family tyrosine kinases participate in insulin‐like growth factor I mitogenic signaling in 3T3‐L1 cells, Cell Growth Differ., 12, 379

10.1002/hep.510290245

Campisi J, 2000, Cancer, aging and cellular senescence, In Vivo, 14, 183

10.1016/S0531-5565(02)00152-3

10.1038/nm0304-231

10.1016/j.cell.2005.02.003

10.1016/j.bbalip.2005.03.005

10.1177/135965350801300103

10.2337/diabetes.53.8.2087

10.1016/j.exger.2007.03.003

10.1093/gerona/glp213

10.1152/ajpendo.2001.280.2.E238

10.1254/jphs.08215FP

10.1016/j.yexcr.2006.12.027

10.1074/jbc.M210811200

10.1016/j.yexcr.2006.06.034

10.1101/gad.1213104

10.1016/S0090-4295(00)00538-0

10.1210/en.2006-0536

10.1194/jlr.M500294-JLR200

10.1006/bbrc.1997.7627

10.7326/0003-4819-122-7-199504010-00001

10.1371/journal.pbio.0060301

10.1096/fasebj.13.2.305

10.1172/JCI28510

10.2337/diabetes.53.5.1285

10.1056/NEJMoa0810780

10.1111/j.1467-789X.2004.00115.x

10.1007/BF03344054

10.1111/j.1368-504X.2004.00389.x

Denke MA, 1993, Excess body weight. An underrecognized contributor to high blood cholesterol levels in white American men, Arch. Intern. Med., 153, 1093, 10.1001/archinte.1993.00410090045006

10.1001/archinte.154.4.401

10.1172/JCI111075

10.1038/oby.2006.178

10.2337/diabetes.54.3.672

10.1074/jbc.274.12.7946

10.1038/oby.2009.335

10.1038/sj.ijo.0802907

10.1161/01.HYP.34.4.568

10.1038/nm.2002

10.1016/j.molmed.2010.03.003

Fried S, 1987, Sex differences in regional distribution of fat cell size and lipoprotein lipase activity in morbidly obese patients, Int. J. Obes., 11, 129

10.1210/jc.83.3.847

10.1152/ajpendo.1998.274.4.E726

10.1152/ajpregu.00494.2002

10.2337/diabetes.51.10.2951

10.1016/j.bbalip.2008.12.014

10.1093/geronj/49.4.B135

10.1152/ajpgi.90351.2008

10.1093/ajcn/70.3.405

10.1152/ajpendo.00557.2006

10.1152/ajpendo.00377.2009

10.1074/jbc.M100797200

10.1038/sj.ijo.0802314

10.1016/S0002-9343(99)00066-2

10.1038/nature08221

10.1016/0014-4827(61)90192-6

10.1093/jn/136.2.343

10.1074/jbc.272.8.5283

10.1096/fj.05-4295fje

10.2337/diab.43.11.1271

10.1093/gerona/54.5.B183

10.1073/pnas.92.21.9856

10.1016/j.bbagen.2009.01.008

10.1093/ajcn/80.2.475

10.1016/j.jaci.2006.12.066

10.1016/j.mad.2008.04.001

10.1172/JCI118600

10.1152/ajpregu.2001.280.6.R1772

10.1073/pnas.0600821103

10.1074/jbc.M513187200

10.1101/gad.342305

10.1172/JCI31021

10.1161/ATVBAHA.108.165100

10.1111/j.1532-5415.1984.tb02006.x

10.1111/j.1532-5415.1997.tb02967.x

10.1007/978-3-642-72149-6_9

10.1152/ajpcell.1990.258.2.C206

10.1139/o93-079

10.1093/geronj/49.1.B31

Kirkland JL, 1997, Decreasing preadipocyte differentiation capacity with aging is associated with blunted expression of the transcription factor, CCAAT enhancer binding protein a, Obes. Res., 5, 22S

10.1016/S0531-5565(02)00014-1

Kirkland JL, 2003, Adipose tissue as an endocrine organ: regional differences in adipocyte endocrine function, Prog. Obes. Res., 9, 87

10.1056/NEJMoa033179

10.1038/oby.2010.86

Kotani K, 1994, Sexual dimorphism of age‐related changes in whole‐body fat distribution in the obese, Int. J. Obes. Relat. Metab. Disord., 18, 207

10.1210/jc.2009-0165

10.1016/j.regpep.2009.02.010

10.1172/JCI22475

10.1016/S1357-2725(02)00053-5

10.1038/nrc2560

10.1016/j.cell.2008.03.039

10.1016/j.arr.2009.06.001

10.1038/sj.ejcn.1601198

10.1210/en.2006-0687

10.1017/S0029665100000379

10.1038/sj.ijo.0802854

10.1038/oby.2009.232

10.1073/pnas.91.19.8757

10.1074/jbc.M002137200

10.1073/pnas.0630588100

10.1038/nm.1994

10.1096/fsb2fasebj.12.1.57

10.1016/S0092-8674(00)81654-2

10.1038/nm0809-846

10.1038/nature06516

10.1152/ajpendo.90851.2008

10.1111/j.1474-9726.2009.00515.x

10.1074/jbc.M311980200

10.1093/gerona/61.1.14

10.1002/j.1550-8528.1995.tb00462.x

10.1023/A:1005404708710

10.1097/00003086-197110000-00021

10.1038/ijo.2008.214

10.1167/iovs.05-1199

10.1038/nm.2014

10.1093/gerona/52A.4.B190

10.1093/gerona/59.2.M139

10.1002/jcp.1041650324

10.1111/j.1474-9726.2008.00391.x

10.1073/pnas.97.21.11371

10.1007/s00125-005-1868-2

10.1038/nm0905-920

10.1016/S0092-8674(03)00401-X

10.1038/nm.1964

10.1089/scd.2008.0189

10.1210/en.2008-1199

10.1242/jcs.01635

10.1038/msb.2010.5

10.1371/journal.pbio.0050110

10.1007/s11357-009-9108-1

10.1016/j.cmet.2008.08.015

10.1152/ajpendo.00544.2003

10.1038/nm1001-1138

10.1056/NEJMoa0801891

10.1007/s00125-009-1261-7

10.1111/j.1467-789X.2006.00293.x

10.1016/j.clnu.2005.10.013

10.1111/j.1532-5415.2010.02773.x

10.1016/j.plefa.2005.04.004

10.1615/CritRevEukarGeneExpr.v19.i2.20

10.1016/j.cmet.2009.09.006

10.1172/JCI118404

10.1007/BF03401666

10.1073/pnas.95.13.7591

10.1038/oby.2009.443

10.1073/pnas.1133870100

10.1097/SAP.0b013e3181723bbe

10.1007/978-1-4020-9063-9_46

10.1210/me.2004-0481

10.1096/fj.07-9261com

10.1126/science.1177221

10.1038/sj.ijo.0802482

10.1016/S0092-8674(00)00046-5

Shillabeer G, 1990, Paradoxically slow preadipocyte replication and differentiation in corpulent rats, Am. J. Physiol., 258, E368

10.1111/j.1532-5415.1993.tb06693.x

10.1016/j.arr.2006.03.004

10.4161/cc.6.18.4682

10.1093/gerona/glp046

10.1111/j.1365-2265.2009.03742.x

10.1111/j.0105-2896.2005.00260.x

10.2337/db07-0767

10.1161/01.ATV.0000183883.72263.13

10.1074/jbc.M309895200

10.1126/science.1156232

10.1016/S0047-6374(01)00411-0

10.1097/00060793-200110000-00001

10.1152/ajpregu.00653.2001

10.1152/ajpendo.00265.2004

10.1007/978-0-387-32164-6_6

10.2337/db06-0540

10.1152/ajpendo.00295.2007

10.1152/ajpendo.00202.2006

Tchkonia T, 2009, Cellular senescence and inflammation in obesity, Obesity, 17, S57

10.1007/s00125-006-0496-9

10.1002/9783527629527.ch2

10.1016/j.cmet.2008.04.004

Turkenkopf IJ, 1988, Regional and genotypic differences in stromal‐vascular cells from obese and lean Zucker rats, Int. J. Obes. Relat. Metab. Disord., 12, 515

10.1038/nature02866

10.1146/annurev.med.53.082901.104057

10.1016/j.biochi.2004.11.014

10.1152/ajpendo.00340.2004

10.1089/rej.2007.0626

10.1096/fj.00-0051com

10.1210/jcem.82.5.3950

10.1001/jama.282.22.2131

10.1152/japplphysiol.00124.2002

10.1038/oby.2008.25

10.1172/JCI114075

10.1111/j.1474-9726.2009.00481.x

10.1126/scisignal.2000143

10.1093/ajcn/86.5.1339

10.1152/ajpregu.2000.279.3.R936

10.1172/JCI200319246

10.1016/S0021-9150(01)00626-8

10.1038/nm.2001

10.1101/gad.9.19.2350

10.1128/MCB.16.8.4128

10.1016/S1097-2765(00)80306-8

10.4049/jimmunol.179.7.4829

10.1007/s11745-006-5096-4

10.2337/diabetes.51.6.1876

10.1172/JCI200319451

10.1038/nature05529

10.1038/oby.2009.512

10.1101/gad.9.2.168

Yki‐Jarvinen H, 1986, Insulin binding and action in adipocytes in vitro in relation to insulin action in vivo in young and middle‐aged subjects, Acta Endocrinol., 113, 88

10.1093/geronj/37.2.130

10.1096/fj.08-110296

Thông tin
Thông tin xuất bản

Aging Cell

Tập 9 Số 5

667-684

Thông tin tác giả