Obesity Increases Vascular Senescence and Susceptibility to Ischemic Injury Through Chronic Activation of Akt and mTOR
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Chronic activation of Akt and mammalian target of rapamycin (mTOR) links diet-induced obesity with cardiovascular disease.
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Preadipocytes, mature adipocytes, and endothelial cells can become senescent during obesity.
“Surprisingly, preadipocytes and mature adipocytes as well as endothelial cells can become senescent during obesity (105-109).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [108]
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Cites
Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor
Brunet, A., Bonni, A., Zigmond, M. J., Lin, M. Z., Juo, P., Hu, L. S., Anderson, M. J., Arden, K. C., Blenis, J., & Greenberg, M. E. (1999) · Cell · doi:10.1016/s0092-8674(00)80595-4 · Cited by 6,535 · see citing works
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216 · see citing works
Hubert, H. B., Feinleib, M., McNamara, P. M., & Castelli, W. P. (1983) · Circulation · doi:10.1161/01.cir.67.5.968 · Cited by 4,241 · see citing works
Cellular survival: a play in three Akts
Datta, S. R., Brunet, A., & Greenberg, M. E. (1999) · Genes & Development · doi:10.1101/gad.13.22.2905 · Cited by 4,216 · see citing works
Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation
Dimmeler, S., Fleming, I., Fisslthaler, B., Hermann, C., Busse, R., & Zeiher, A. M. (1999) · Nature · doi:10.1038/21224 · Cited by 3,591 · see citing works
Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB
Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,645 · see citing works
Regulation of endothelium-derived nitric oxide production by the protein kinase Akt
Fulton, D. J., Gratton, J., McCabe, T. J. D., Fontana, J. T., Fujio, Y., Walsh, K. X., Franke, T. F., Papapetropoulos, A., & Sessa, W. C. (1999) · Nature · doi:10.1038/21218 · Cited by 2,585 · see citing works
Self-citationRb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
Narita, M., Nuñez, S., Heard, E., Narita, M., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., & Lowe, S. W. (2003) · Cell · doi:10.1016/s0092-8674(03)00401-x · Cited by 2,278 · cited 1× · see citing works
“5 as previously described for endothelial cells and en face aortas (53).”
BackgroundTOR, a Central Controller of Cell Growth
Schmelzle, T., & Hall, M. N. (2000) · Cell · doi:10.1016/s0092-8674(00)00117-3 · Cited by 1,914 · see citing works
Cho, H., Mu, J., Kim, J. K., Thorvaldsen, J. L., Chu, Q., Crenshaw, E. B., Kaestner, K. H., Bartolomei, M. S., Shulman, G. I., & Birnbaum, M. J. (2001) · Science · doi:10.1126/science.292.5522.1728 · Cited by 1,837 · see citing works
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
Um, S. H., Frigerio, F., Watanabe, M., Picard, F., Joaquin, M., Sticker, M., Fumagalli, S., Allegrini, P. R., Kozma, S. C., Auwerx, J., et al. (2004) · Nature · doi:10.1038/nature02866 · Cited by 1,677 · see citing works
Guertin, D. A., Stevens, D. M., Thoreen, C. C., Burds, A. A., Kalaany, N. Y., Moffat, J., Brown, M., Fitzgerald, K. J., & Sabatini, D. M. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.10.007 · Cited by 1,409 · see citing works
The plasticity of aging: insights from long-lived mutants
Kenyon, C. (2005) · Cell · doi:10.1016/j.cell.2005.02.002 · Cited by 1,338 · see citing works
Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients
Kaeberlein, M., Powers, R. W., Steffen, K. K., Westman, E. A., Hu, D., Dang, N., Kerr, E. O., Kirkland, K. T., Fields, S., & Kennedy, B. K. (2005) · Science · doi:10.1126/science.1115535 · Cited by 1,293 · see citing works
Hypothalamic mTOR Signaling Regulates Food Intake
Cota, D., Proulx, K., Smith, K. A. B., Kozma, S. C., Thomas, G., Woods, S. C., & Seeley, R. J. (2006) · Science · doi:10.1126/science.1124147 · Cited by 1,278 · see citing works
Oncogene-induced senescence as an initial barrier in lymphoma development
Braig, M., Lee, S., Loddenkemper, C., Rudolph, C., Peters, A. H. F. M., Schlegelberger, B., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2005) · Nature · doi:10.1038/nature03841 · Cited by 1,220 · see citing works
Epidemiology of coronary heart disease: the Framingham study.
Castelli, W. (1984) · American Journal of Medicine · doi:10.1016/0002-9343(84)90952-5 · Cited by 1,106 · see citing works
Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a
Janzen, V., Forkert, R., Fleming, H. E., Saito, Y., Waring, M. T., Dombkowski, D. M., Cheng, T., DePinho, R. A., Sharpless, N. E., & Scadden, D. T. (2006) · Nature · doi:10.1038/nature05159 · Cited by 1,106 · see citing works
Cellular Senescence in Aging Primates
Herbig, U., Ferreira, M., Condel, L., Carey, D., & Sedivy, J. M. (2006) · Science · doi:10.1126/science.1122446 · Cited by 1,101 · see citing works
Handschin, C., & Spiegelman, B. M. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0037 · Cited by 1,090 · see citing works
The role of exercise and PGC1α in inflammation and chronic disease
Handschin, C., & Spiegelman, B. M. (2008) · Nature · doi:10.1038/nature07206 · Cited by 1,083 · see citing works
Role of Akt Signaling in Vascular Homeostasis and Angiogenesis
Shiojima, I., & Walsh, K. (2002) · Circulation Research · doi:10.1161/01.res.0000022200.71892.9f · Cited by 1,011 · see citing works
Self-citationMammalian TOR: a homeostatic ATP sensor
Dennis, P. B., Jaeschke, A., Saitoh, M., Fowler, B., Kozma, S. C., & Thomas, G. (2001) · Science · doi:10.1126/science.1063518 · Cited by 962 · see citing works
Cho, H., Thorvaldsen, J. L., Chu, Q., Feng, F., & Birnbaum, M. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100462200 · Cited by 959 · see citing works
Phosphorylation of the Translational Repressor PHAS-I by the Mammalian Target of Rapamycin
Brunn, G. J., Hudson, C. C., Sekulić, A., Williams, J. M., Hosoi, H., Houghton, P. J., Lawrence, J. C., & Abraham, R. T. (1997) · Science · doi:10.1126/science.277.5322.99 · Cited by 959 · see citing works
Growth retardation and increased apoptosis in mice with homozygous disruption of the akt1 genePreprint
Chen, W. S., Xu, P.-Z., Gottlob, K., Chen, M.-L., Sokol, K. A., Shiyanova, T., Roninson, I. B., Weng, W., Suzuki, R., Tobe, K., et al. (2001) · Genes & Development · doi:10.1101/gad.913901 · Cited by 926 · see citing works
Regulation of Longevity and Stress Resistance by Sch9 in Yeast
Fabrizio, P., Pozza, F., Pletcher, S. D., Gendron, C. M., & Longo, V. D. (2001) · Science · doi:10.1126/science.1059497 · Cited by 874 · see citing works
Bhaskar, P. T., & Hay, N. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.03.020 · Cited by 798 · see citing works
mSin1 Is Necessary for Akt/PKB Phosphorylation, and Its Isoforms Define Three Distinct mTORC2s
Frías, M. A., Thoreen, C. C., Jaffe, J. D., Schroder, W. A., Sculley, T. B., Carr, S. A., & Sabatini, D. M. (2006) · Current Biology · doi:10.1016/j.cub.2006.08.001 · Cited by 690 · see citing works
Cristofalo, V. J., Allen, R. G., Pignolo, R. J., Martin, B. G., & Beck, J. C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.18.10614 · Cited by 554 · see citing works
Akt Signaling--Linking Membrane Events to Life and Death Decisions
Hemmings, B. A. (1997) · Science · doi:10.1126/science.275.5300.628 · Cited by 517 · see citing works
The expanding TOR signaling network
Martin, D. E., & Hall, M. N. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.02.008 · Cited by 496 · see citing works
Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1α transcription coactivator
Li, X., Monks, B., Ge, Q., & Birnbaum, M. J. (2007) · Nature · doi:10.1038/nature05861 · Cited by 487 · see citing works
Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo
Chen, J., Somanath, P. R., Razorenova, O. V., Chen, W. S., Hay, N., BORNSTEIN, P. K., & Byzova, T. V. (2005) · Nature Medicine · doi:10.1038/nm1307 · Cited by 450 · see citing works
Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin
Phung, T. L., Ziv, K., Dabydeen, D. A., Eyiah-Mensah, G., Riveros, M., Perruzzi, C. A., Sun, J., Monahan-Earley, R. A., Shiojima, I., Nagy, J. A., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.07.003 · Cited by 439 · see citing works
Self-citationReplicative Senescence: An Old Lives' Tale?
Campisi, J. (1996) · Cell · doi:10.1016/s0092-8674(00)81023-5 · Cited by 434 · see citing works
Akt1/protein kinase B is critical for ischemic and VEGF-mediated angiogenesis
Ackah, E. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24726 · Cited by 386 · see citing works
Rapid nongenomic actions of thyroid hormone
Hiroi, Y., Kim, H.-H., Ying, H., Furuya, F., Huang, Z., Simoncini, T., Noma, K., Ueki, K., Nguyen, N.-H., Scanlan, T. S., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601600103 · Cited by 380 · see citing works
Self-citationRapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML
Zeng, Z., Sarbassov, D. D., Samudio, I. J., Yee, K. W. L., Munsell, M. F., Jackson, C. E., Giles, F. J., Sabatini, D. M., Andreeff, M., & Konopleva, M. Y. (2006) · Blood · doi:10.1182/blood-2006-06-030833 · Cited by 339 · see citing works
Miyauchi, H., Minamino, T., Tateno, K., Kunieda, T., Toko, H., & Komuro, I. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600045 · Cited by 332 · see citing works
PRAK Is Essential for ras-Induced Senescence and Tumor Suppression
Sun, P., Yoshizuka, N., New, L., Moser, B. A., Li, Y., Liao, R., Xie, C., Chen, J., Deng, Q., Yamout, M., et al. (2007) · Cell · doi:10.1016/j.cell.2006.11.050 · Cited by 321 · see citing works
Loss of Akt1 Leads to Severe Atherosclerosis and Occlusive Coronary Artery Disease
Fernandez-Hernando, C. F., Ackah, E., Yu, J., Suárez, Y., Murata, T., Iwakiri, Y., Prendergast, J., Miao, R. Q., Birnbaum, M. J., & Sessa, W. C. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.007 · Cited by 283 · see citing works
Requirement of Rac1 in the development of cardiac hypertrophy
Satoh, M., Ogita, H., Takeshita, K., Mukai, Y., Kwiatkowski, D. J., & Liao, J. K. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510444103 · Cited by 271 · see citing works
Self-citationCritical role of endothelial Notch1 signaling in postnatal angiogenesis
Takeshita, K., Satoh, M., Ii, M., Silver, M., Limbourg, F. P., Mukai, Y., Rikitake, Y., Radtke, F., Gridley, T., Losordo, D. W., et al. (2007) · Circulation Research · doi:10.1161/01.res.0000254788.47304.6e · Cited by 232 · see citing works
Self-citationHayashi, T., Matsui‐Hirai, H., Miyazaki, A., Fukatsu, A., Funami, J., Ding, Q., Sumitra, K., Hattori, Y., Ignarro, L. J., & Iguchi, A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607873103 · Cited by 222 · see citing works
Interaction of RAFT1 with Gephyrin Required for Rapamycin-Sensitive Signaling
Sabatini, D. M., Barrow, R. K., Blackshaw, S., Burnett, P. E., Lai, M. M.-S., Field, M. E., Bahr, B. A., Kirsch, J., Betz, H., & Snyder, S. H. (1999) · Science · doi:10.1126/science.284.5417.1161 · Cited by 182 · see citing works
Requirement for p27<sup>KIP1</sup> in Retinoblastoma Protein-Mediated Senescence
Alexander, K., & Hinds, P. W. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.11.3616-3631.2001 · Cited by 164 · see citing works
Novel glycogen synthase kinase 3 and ubiquitination pathways in progressive myoclonus epilepsy
Lohi, H., Ianzano, L., Zhao, X.-C., Chan, E. M., Turnbull, J., Scherer, S. W., Ackerley, C. A., & Minassian, B. A. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi306 · Cited by 153 · see citing works
p53 Mediates the Accelerated Onset of Senescence of Endothelial Progenitor Cells in Diabetes
Rosso, A., Balsamo, A., Gambino, R., Dentelli, P., Falcioni, R., Cassader, M., Pegoraro, L., Pagano, G., & Brizzi, M. F. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509293200 · Cited by 152 · see citing works
Wang, C., Wen, M., Wang, H., Hsieh, C., Li, Y., Liu, P., Lin, F., & Liao, J. K. (2008) · Circulation · doi:10.1161/circulationaha.108.790469 · Cited by 141 · see citing works
Self-citationHypoxia-Induced Endothelial Proliferation Requires Both mTORC1 and mTORC2
Li, W., Petrimpol, M., Molle, K. D., Hall, M. N., Battegay, E., & Humar, R. (2006) · Circulation Research · doi:10.1161/01.res.0000253094.03023.3f · Cited by 134 · see citing works
Re-evaluating AKT regulation: role of TOR complex 2 in tissue growthPreprint
Hietakangas, V., & Cohen, S. M. (2007) · Genes & Development · doi:10.1101/gad.416307 · Cited by 134 · see citing works
Cloning, chromosomal localization and expression analysis of the mouse Akt2 oncogene.
Altomare, D., Guo, K., Cheng, J., Sonoda, G., Walsh, K., & Testa (1995) · PubMed · Cited by 98 · see citing works
Self-citationMukai, Y. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26223 · Cited by 79 · see citing works
Nishi, J.-I., Minamino, T., Miyauchi, H., Nojima, A., Tateno, K., Okada, S., Orimo, M., Moriya, J., Fong, G., Sunagawa, K., et al. (2008) · Circulation Research · doi:10.1161/circresaha.108.174128 · Cited by 55 · see citing works
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- Authors
- Wang, C.-Y., Kim, H.-H., Hiroi, Y., Sawada, N., Salomone, S., Benjamin, L. E., Walsh, K., Moskowitz, M. A., & Liao, J. K.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Beth Israel Deaconess Medical Center (US)
- Boston University (US)
- Corresponding author
- Liao, James K.
- ORCID
- Venue
- Science Signaling
- Published
- 2009-03-17
- Volume
- 2
- Issue
- 62
- Pages
- ra11-ra11
- ISSN
- 1937-9145 (ISSN-L)
- 1945-0877
- PMC
- PMC2667954
- OpenAlex
- W2122554904
- Cited by
- 177
- References
- 55
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 6 · 2023: 11 · 2022: 8 · 2021: 13 · 2020: 9 · 2019: 11 · 2018: 8 · 2017: 12 · 2016: 11 · 2015: 8 · 2014: 21 · 2013: 10 · 2012: 9
- FWCI
- 8.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Signaling (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL080187, R01HL070274, R01HL052233)
- National Institute of Neurological Disorders and Stroke (P50NS010828)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- obesity, vascular aging, Akt signaling, mTOR, Rictor, high-fat diet, diet-induced obesity, ischemic injury, limb ischemia, cerebral ischemia, ischemic stroke, vascular dysfunction, rapamycin, cardiovascular disease, aging
- MeSH terms
- Animals, Cardiovascular Diseases, Carrier Proteins, Disease Susceptibility, Eating, Enzyme Activation, Ischemia, Mice, Transgenic, Obesity, Signal Transduction, Cellular Senescence, Phosphotransferases (Alcohol Group Acceptor), Sirolimus, Proto-Oncogene Proteins c-akt, Mice, TOR Serine-Threonine Kinases
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