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MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation
Open accessAbstract
The TOR (target of rapamycin) kinase limits longevity by poorly understood mechanisms. Rapamycin suppresses the mammalian TORC1 complex, which regulates translation, and extends lifespan in diverse species, including mice. We show that rapamycin selectively blunts the pro-inflammatory phenotype of senescent cells. Cellular senescence suppresses cancer by preventing cell proliferation. However, as senescent cells accumulate with age, the senescence-associated secretory phenotype (SASP) can disrupt tissues and contribute to age-related pathologies, including cancer. MTOR inhibition suppressed the secretion of inflammatory cytokines by senescent cells. Rapamycin reduced IL6 and other cytokine mRNA levels, but selectively suppressed translation of the membrane-bound cytokine IL1A. Reduced IL1A diminished NF-κB transcriptional activity, which controls much of the SASP; exogenous IL1A restored IL6 secretion to rapamycin-treated cells. Importantly, rapamycin suppressed the ability of senescent fibroblasts to stimulate prostate tumour growth in mice. Thus, rapamycin might ameliorate age-related pathologies, including late-life cancer, by suppressing senescence-associated inflammation.
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“the secretome of senescent tumor cells can also drive tumor progression by promoting inflammation and potentially stimulating the growth and invasiveness of nearby tumor cells [148,154,163].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [163]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The NF- κB, p38, mTOR and C/EBPβ signalling pathways are major components of the SASP 63-67 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [66]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Rapamycin, an immunosuppressant, decreases the SASP and maintains cell cycle arrest but does not kill Sncs (24).”
From Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span (2021) · cites this paper as [24]
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In the citing paper
“Treatment with rapamycin (and its analogue RAD001)232 attenuated the protumorigenic SASP230, prevented senescence233, impaired SASP-mediated immune recognition of oncogene-expressing cells and ameliorated liver dysfunction in naturally aged mice231.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [231]
The cited source says what the claim attributes to it.
In the citing paper
“In addition, the nutrient sensing pathways, mTOR and NAD, are involved in SASP regulation.56, 57, 58”
From Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer (2020) · cites this paper as [56]
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In the citing paper
“In various preclinical studies, the mTOR inhibitor rapamycin might have the context-dependent potential to induce senescence 45 , diminish NF-κB activity 65,66 , suppress the pro-inflammatory SASP at the translational level, and limit the growth-promoting effect of senescent bystander fibroblasts on prostate tumours 66 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [66]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“and the serine/threonine kinase MK2, which indirectly stabilizes many cytokine-encoding transcripts231.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [231]
Experimental — accuracy not yet measuredIn the citing paper
“It also differentially regulates translation of IL-1A, the master regulator of SASP that subsequently engages IL-6/IL-8 (Orjalo et al., 2009; Laberge et al., 2015) and MAP kinase-activated protein kinase 2 (MAPKAP2) through 4EBP1, a translation repressor protein (Herranz et al., 2015).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Laberge et al., 2015
In the citing paper
“Inhibition of mTOR by rapamycin suppresses the secretion of inflammatory cytokines by senescent cells (Herranz et al., 2015; Laberge et al., 2015).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Laberge et al., 2015
In the citing paper
“IL-1α is the key driver of the SASP 79,80 , with upstream expression controlled in part by ATM/ATRmediated liberation of GATA4 from p62-directed autophagy 81 and/or an mTORC1-dependent pathway 82 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [82]
In the citing paper
“As an alternative approach, reduction of the SASP through “senostatic” or “senomorphic” approaches may be less toxic and has been shown to be effective in animal models (Birch and Passos, 2017; Georgilis et al., 2018; Laberge et al., 2015; Laberge et al., 2012; Niedernhofer and Robbins, 2018; Xu et al., 2015; Yoshimoto et al., 2013).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Laberge et al., 2015
In the citing paper
“Hypoxia impairs mammalian target of rapamycin (mTOR) activity, leading to reduced IL-1α translation to support NF-κB activity and SASP induction [162,163].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [163]
In the citing paper
“The increase in mTORC1 activity is essential for implementing the SASP by modulating the translation of IL-1α and MAP kinase-activated protein kinase 2 (MAPKAPK2) [162,163].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [163]
In the citing paper
“SASP inhibition by the mTOR inhibitor rapamycin can suppress the capacity of senescent fibroblasts to stimulate prostate tumor growth in mice [163].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [163]
In the citing paper
“inhibition of mTOR by rapamycin selectively inhibits the SASP and SA β‐gal staining of senescent cells without affecting their cell cycle arrest”
From Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism (2017) · cites this paper as Laberge et al., 2015
In the citing paper
“Rapamycin treatment suppressed SA-βgal activity (~ 50%) in irradiated cells (Fig. 5H), as expected [68]”
From Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis (2018) · cites this paper as [68]
In the citing paper
“The mTOR pathway is a negative regulator of autophagy and is implicated in cellular senescence [67], most notably through SA-βgal activity and the expression of p16 and p21 markers [67], [68].”
From Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis (2018) · cites this paper as [68]
In the citing paper
“These factors are commonly described as the mediator of the pro-disease functions of senescent cells in vivo59.”
From Algorithmic assessment of cellular senescence in experimental and clinical specimens (2021) · cites this paper as [59]
In the citing paper
“These in vitro observations have been further substantiated in vivo, where co-injection of senescent fibroblasts has been shown to increase tumourigenicity in xenograft models, including primary breast cancer tissues.26,45–47”
From Paracrine roles of cellular senescence in promoting tumourigenesis (2018) · cites this paper as [46]
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Citations
Cites
Immunity, Inflammation, and Cancer
Grivennikov, S. I., Greten, F. R., & Karin, M. (2010) · Cell · doi:10.1016/j.cell.2010.01.025 · Cited by 10,755
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206
Self-citationCellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
Self-citationRapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766
Self-citationClearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670
Mechanisms underlying inflammation in neurodegeneration
Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., & Gage, F. H. (2010) · Cell · doi:10.1016/j.cell.2010.02.016 · Cited by 3,580
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473
Paradoxical roles of the immune system during cancer development
de Visser, K. E., Eichten, A., & Coussens, L. M. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1782 · Cited by 2,299
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mTOR at the nexus of nutrition, growth, ageing and disease
Liu, G. Y., & Sabatini, D. M. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0199-y · Cited by 2,737
Hallmarks of Cellular Senescence
Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.001 · Cited by 2,605
Self-citationCellular senescence in ageing: from mechanisms to therapeutic opportunities
Di Micco, R., Krizhanovsky, V., Baker, D., & d’Adda di Fagagna, F. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00314-w · Cited by 2,277
Sarcopenia: Aging-Related Loss of Muscle Mass and Function
Larsson, L., Degens, H., Li, M., Salviati, L., Lee, Y. I., Thompson, W., Kirkland, J. L., & Sandri, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00061.2017 · Cited by 1,797
Senescence in Health and Disease
He, S., & Sharpless, N. E. (2017) · Cell · doi:10.1016/j.cell.2017.05.015 · Cited by 1,766
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
Kumari, R., & Jat, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.645593 · Cited by 1,622
Cellular senescence promotes adverse effects of chemotherapy and cancer relapse
Demaria, M., O'Leary, M. N., Chang, J., Shao, L., Liu, S., Alimirah, F., Koenig, K., Le, C., Mitin, N., Deal, A. M., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0241 · Cited by 1,338
Self-citationCellular Senescence: Aging, Cancer, and Injury
Calcinotto, A., Kohli, J., Zagato, E., Pellegrini, L., Demaria, M., & Alimonti, A. (2019) · Physiological Reviews · doi:10.1152/physrev.00020.2018 · Cited by 1,270
Self-citationAgeing and the pathogenesis of osteoarthritis
Loeser, R. F., Collins, J. A., & Diekman, B. O. (2016) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2016.65 · Cited by 1,344
Senescent cells: an emerging target for diseases of ageing
Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R.-M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.116 · Cited by 1,284
Self-citationSenescence and aging: Causes, consequences, and therapeutic avenues
McHugh, D., & Gil, J. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201708092 · Cited by 1,233
Mechanisms and functions of cellular senescence
Herranz, N., & Gil, J. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95148 · Cited by 1,232
Senescence and the SASP: many therapeutic avenues
Birch, J., & Gil, J. (2020) · Genes & Development · doi:10.1101/gad.343129.120 · Cited by 1,177
“Given the intricate correlation between cGAS-STING, inflammation, senescence, and disease, several inhibitors of cGAS (Lama et al. 2019) and STING (Haag et al. 2018) have been developed.”
BackgroundVascular smooth muscle cells in atherosclerosis
Basatemur, G. L., Jørgensen, H. F., Clarke, M. C. H., Bennett, M. R., & Mallat, Z. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-019-0227-9 · Cited by 1,099
ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age‐Related Diseases
Davalli, P., Mitic, T., Caporali, A., Lauriola, A., & D’Arca, D. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3565127 · Cited by 1,059
Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL
Yosef, R., Pilpel, N., Tokarsky-Amiel, R., Biran, A., Ovadya, Y., Cohen, S., Vadai, E., Dassa, L., Shahar, E., Condiotti, R., et al. (2016) · Nature Communications · doi:10.1038/ncomms11190 · Cited by 1,032
Cellular senescence: a translational perspective
Kirkland, J. L., & Tchkonia, T. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.04.013 · Cited by 1,013
Xu, M., Tchkonia, T., Ding, H., Ogrodnik, M., Lubbers, E. R., Pirtskhalava, T., White, T. A., Johnson, K. O., Stout, M. B., Mezera, V., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515386112 · Cited by 915
Exploiting senescence for the treatment of cancer
Wang, L., Lankhorst, L., & Bernards, R. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-022-00450-9 · Cited by 867
Unmasking senescence: context-dependent effects of SASP in cancer
Faget, D. V., Ren, Q., & Stewart, S. A. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0156-2 · Cited by 863
The senescence-associated secretory phenotype and its physiological and pathological implications
Wang, B., Han, J., Elisseeff, J. H., & Demaria, M. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00727-x · Cited by 948
Self-citationMechanisms and therapeutic implications of cellular senescence in osteoarthritis
Coryell, P. R., Diekman, B. O., & Loeser, R. F. (2021) · Nature Reviews Rheumatology · doi:10.1038/s41584-020-00533-7 · Cited by 761
Mitochondria are required for pro-ageing features of the senescent phenotype
Correia‐Melo, C., Marques, F. D., Anderson, R., Hewitt, G., Hewitt, R., Cole, J., Carroll, B. M., Miwa, S., Birch, J., Merz, A., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201592862 · Cited by 796
Senescence and cancer — role and therapeutic opportunities
Schmitt, C. A., Wang, B., & Demaria, M. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00668-4 · Cited by 794
Self-citationTumor biomarkers for diagnosis, prognosis and targeted therapy
Zhou, Y., Tao, L., Qiu, J., Xu, J., Yang, X., Zhang, Y., Tian, X., Guan, X., Cen, X., & Zhao, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01823-2 · Cited by 836
Identification of HSP90 inhibitors as a novel class of senolytics
Fuhrmann-Stroissnigg, H., Ling, Y. Y., Zhao, J., McGowan, S. J., Zhu, Y., Brooks, R. W., Grassi, D., Gregg, S. Q., Stripay, J. L., Dorronsoro, A., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00314-z · Cited by 701
mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review
Weichhart, T. (2018) · Gerontology · doi:10.1159/000484629 · Cited by 596
Targeting cellular senescence with senotherapeutics: senolytics and senomorphics
Zhang, L. J., Pitcher, L. E., Prahalad, V., Niedernhofer, L. J., & Robbins, P. D. (2022) · FEBS Journal · doi:10.1111/febs.16350 · Cited by 674
The senescence-associated secretory phenotype and its regulation
Lopes-Paciencia, S., Saint-Germain, E., Rowell, M.-C., Ruiz, A. F., Kalegari, P., & Ferbeyre, G. (2019) · Cytokine · doi:10.1016/j.cyto.2019.01.013 · Cited by 601
Cancer-Cell-Intrinsic Mechanisms Shaping the Tumor Immune Landscape
Wellenstein, M. D., & de Visser, K. E. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.004 · Cited by 592
Interleukin 1α and the inflammatory process
Di Paolo, N. C., & Shayakhmetov, D. M. (2016) · Nature Immunology · doi:10.1038/ni.3503 · Cited by 568
Cellular Senescence as a Mechanism and Target in Chronic Lung Diseases
Barnes, P. J., Baker, J. R., & Donnelly, L. (2019) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201810-1975tr · Cited by 571
The role of cellular senescence in ageing and endocrine disease
Khosla, S., Farr, J. N., Tchkonia, T., & Kirkland, J. L. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0335-y · Cited by 523
Senescent Cells in Cancer Therapy: Friends or Foes?
Wang, B., Kohli, J., & Demaria, M. (2020) · Trends in Cancer · doi:10.1016/j.trecan.2020.05.004 · Cited by 508
Self-citationRecent Developments in Radiotherapy
Citrin, D. E. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1608986 · Cited by 515
From Ancient Pathways to Aging Cells—Connecting Metabolism and Cellular Senescence
Wiley, C. D., & Campisi, J. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.010 · Cited by 440
Self-citationChronic inflammation and the hallmarks of aging
Baechle, J. J., Chen, N., Makhijani, P., Winer, S., Furman, D., & Winer, D. A. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101755 · Cited by 471
Masaldan, S., Clatworthy, S. A. S., Gamell, C., Meggyesy, P. M., Rigopoulos, A.-T., Haupt, S., Haupt, Y., Denoyer, D., Adlard, P. A., Bush, A. I., et al. (2018) · Redox Biology · doi:10.1016/j.redox.2017.08.015 · Cited by 452
mTOR as a central regulator of lifespan and aging
Papadopoli, D. J., Boulay, K., Kazak, L., Pollak, M., Mallette, F. A., Topisirović, I., & Hulea, L. (2019) · F1000Research · doi:10.12688/f1000research.17196.1 · Cited by 447
BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance
Tasdemir, N., Banito, A., Roe, J.-S., Alonso-Curbelo, D., Camiolo, M., Tschaharganeh, D. F., Huang, C.-H., Aksoy, O., Bolden, J. E., Chen, C.-C., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0217 · Cited by 415
“Thus, these results indicate that BRD4 inactivation uncouples the SASP from the cell-cycle arrest during senescence, and imply that BET inhibitors may be valuable at modulating SASP activity in vivo, such as has been recently reported for the mTOR inhibitor rapamycin (28, 29).”
Maier, P., Hartmann, L., Wenz, F. K., & Herskind, C. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17010102 · Cited by 449
Cai, Y., Song, W., Li, J., Jing, Y., Liang, C., Zhang, L., Zhang, X., Zhang, W., Liu, B., An, Y., et al. (2022) · Science China Life Sciences · doi:10.1007/s11427-022-2161-3 · Cited by 450
Self-citationMechanisms and Regulation of Cellular Senescence
Roger, L., Tomas, F., & Gire, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313173 · Cited by 395
Zhenyukh, O., Civantos, E., Ruiz‐Ortega, M., Pizarro-Sánchez, M. S., Vázquez, C., Peiró, C., Egido, J., & Mas, S. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.01.009 · Cited by 417
Zhu, X., Chen, Z., Shen, W., Huang, G., Sedivy, J. M., Wang, H., & Ju, Z. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00646-9 · Cited by 425
Ageing and the telomere connection: An intimate relationship with inflammation
Zhang, J., Rane, G., Dai, X., Shanmugam, M. K., Arfuso, F., Samy, R. P., Lai, M. K. P., Kappei, D., Kumar, A. P., & Sethi, G. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.11.006 · Cited by 396
Tumor microenvironment and cancer therapy resistance
Sun, Y. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.07.044 · Cited by 391
Self-citationVizioli, M. G., Liu, T., Miller, K. N., Robertson, N. A., Gilroy, K., Lagnado, A. B., Perez-Garcia, A., Kiourtis, C., Dasgupta, N., Lei, X., et al. (2020) · Genes & Development · doi:10.1101/gad.331272.119 · Cited by 359
Takahashi, A., Loo, T. M., Okada, R., Kamachi, F., Watanabe, Y., Wakita, M., Watanabe, S., Kawamoto, S., Miyata, K., Barber, G. N., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03555-8 · Cited by 350
Redox control of senescence and age-related disease.
Chandrasekaran, A., Idelchik, M. D. P. S., & Melendez, J. A. (2017) · Redox Biology · doi:10.1016/j.redox.2016.11.005 · Cited by 360
Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism
Wang, R., Yu, Z., Sunchu, B., Shoaf, J., Dang, I., Zhao, S., Caples, K., Bradley, L., Beaver, L. M., Ho, E., et al. (2017) · Aging Cell · doi:10.1111/acel.12587 · Cited by 360
Cellular senescence: all roads lead to mitochondria
Martini, H., & Passos, J. F. (2023) · The FEBS Journal · doi:10.1111/febs.16361 · Cited by 334
The integration of inflammaging in age-related diseases
Fülöp, T., Witkowski, J. M., Olivieri, F., & Larbi, A. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2018.09.003 · Cited by 368
Therapy-Induced Senescence: Opportunities to Improve Anticancer Therapy
Prasanna, P. G. S., Citrin, D. E., Hildesheim, J., Ahmed, M. M., Venkatachalam, S., Riscuta, G., Xi, D., Zheng, G., van Deursen, J., Goronzy, J. J., et al. (2021) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djab064 · Cited by 359
Self-citationCellular senescence in renal ageing and disease
Sturmlechner, I., Durik, M., Sieben, C. J., Baker, D. J., & van Deursen, J. M. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.183 · Cited by 345
NKG2D ligands mediate immunosurveillance of senescent cells
Sagiv, A., Burton, D. G. A., Moshayev, Z., Vadai, E., Wensveen, F., Ben-Dor, S., Golani, O., Polic, B., & Krizhanovsky, V. (2016) · Aging · doi:10.18632/aging.100897 · Cited by 345
Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span
Robbins, P. D., Jurk, D., Khosla, S., Kirkland, J. L., LeBrasseur, N. K., Miller, J. D., Passos, J. F., Pignolo, R. J., Tchkonia, T., & Niedernhofer, L. J. (2021) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-050120-105018 · Cited by 360
“Rapamycin, an immunosuppressant, decreases the SASP and maintains cell cycle arrest but does not kill Sncs (24).”
BackgroundStress, cell senescence and organismal ageing
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Mitochondrial dysfunction and cell senescence: deciphering a complex relationship
Chapman, J., Fielder, E., & Passos, J. F. (2019) · FEBS Letters · doi:10.1002/1873-3468.13498 · Cited by 325
Function and regulation of IL ‐1α in inflammatory diseases and cancer
Malik, A., & Kanneganti, T. (2017) · Immunological Reviews · doi:10.1111/imr.12615 · Cited by 331
Borghesan, M., Fafián-Labora, J., Eleftheriadou, O., Carpintero-Fernández, P., Paez-Ribes, M., Vizcay-Barrena, G., Swisa, A., Kolodkin-Gal, D., Ximénez-Embún, P., Lowe, R., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.095 · Cited by 315
“Torin-2 (25 and 50 nM), an mTOR inhibitor that suppresses the SASP (Herranz et al., 2015; Laberge et al., 2015), was used as a control.”
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Aging and adipose tissue: potential interventions for diabetes and regenerative medicine
Palmer, A. K., & Kirkland, J. L. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.02.013 · Cited by 324
Watanabe, S., Kawamoto, S., Ohtani, N., & Hara, E. (2017) · Cancer Science · doi:10.1111/cas.13184 · Cited by 321
Advances in PET imaging of cancer
Schwenck, J., Sonanini, D., Cotton, J. M., Rammensee, H., la Fougère, C., Zender, L., & Pichler, B. J. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00576-4 · Cited by 343
Effect of rapamycin on aging and age-related diseases—past and future
Selvarani, R., Mohammed, S., & Richardson, A. (2021) · GeroScience · doi:10.1007/s11357-020-00274-1 · Cited by 290
Interconnections between Inflammageing and Immunosenescence during Ageing
Teissier, T., Boulanger, É., & Cox, L. S. (2022) · Cells · doi:10.3390/cells11030359 · Cited by 323
Cytoplasmic DNA: sources, sensing, and role in aging and disease
Miller, K. N., Victorelli, S. G., Salmonowicz, H., Dasgupta, N., Liu, T., Passos, J. F., & Adams, P. D. (2021) · Cell · doi:10.1016/j.cell.2021.09.034 · Cited by 288
Targeting senescent cells in translational medicine
Paez‐Ribes, M., González‐Gualda, E., Doherty, G. J., & Muñoz‐Espín, D. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201810234 · Cited by 293
Cuollo, L., Antonangeli, F., Santoni, A., & Soriani, A. (2020) · Biology · doi:10.3390/biology9120485 · Cited by 291
Toward targeting inflammasomes: insights into their regulation and activation
Christgen, S. L., Place, D. E., & Kanneganti, T. (2020) · Cell Research · doi:10.1038/s41422-020-0295-8 · Cited by 290
Lagoumtzi, S. M., & Chondrogianni, N. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.05.003 · Cited by 279
Ito, T., Teo, Y. V., Evans, S. A., Neretti, N., & Sedivy, J. M. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.002 · Cited by 265
Bird, T. G., Müller, M., Boulter, L., Vincent, D. F., Ridgway, R. A., Lopez-Guadamillas, E., Lu, W.-Y., Jamieson, T., Govaere, O., Campbell, A. D., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aan1230 · Cited by 261
“In addition, study of other SASP components, which may also promote paracrine senescence after liver injury, may be worthwhile (15, 41, 42).”
Cellular senescence and SASP in tumor progression and therapeutic opportunities
Dong, Z., Luo, Y., Yuan, Z., Tian, Y., Jin, T., & Feng, X. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02096-7 · Cited by 315
Senescence in COPD and Its Comorbidities
Barnes, P. J. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022516-034314 · Cited by 278
Özeş, A., Miller, D. F., Özeş, O. N., Fang, F., Liu, Y., Matei, D. E., Huang, T. H. ‐., & Nephew, K. P. (2016) · Oncogene · doi:10.1038/onc.2016.75 · Cited by 271
Oxidative Stress in Pulmonary Fibrosis
Otoupalova, E., Smith, S., Cheng, G., & Thannickal, V. J. (2020) · Comprehensive physiology · doi:10.1002/cphy.c190017 · Cited by 312
The Dual Role of Cellular Senescence in Developing Tumors and Their Response to Cancer Therapy
Schosserer, M., Grillari, J., & Breitenbach, M. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00278 · Cited by 270
Georgilis, A., Klotz, S., Hanley, C. J., Herranz, N., Weirich, B., Morancho, B., Leote, A. C., D'Artista, L., Gallage, S., Seehawer, M., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.06.007 · Cited by 237
“Preliminary evidence indicates that uncoupling cell arrest and the SASP is feasible (Herranz et al., 2015; Laberge et al., 2015; Tasdemir et al., 2016; Wall et al., 2013).”
BackgroundZhu, Y., Liu, X., Ding, X., Wang, F., & Geng, X. (2019) · Biogerontology · doi:10.1007/s10522-018-9769-1 · Cited by 255
Protective Role of Polyphenols against Vascular Inflammation, Aging and Cardiovascular Disease
Serino, A., & Salazar, G. (2018) · Nutrients · doi:10.3390/nu11010053 · Cited by 263
Melanocytic nevi and melanoma: unraveling a complex relationship
Damsky, W., & Bosenberg, M. (2017) · Oncogene · doi:10.1038/onc.2017.189 · Cited by 263
Inflammageing and metaflammation: The yin and yang of type 2 diabetes
Prattichizzo, F., Nigris, V. D., Spiga, R., Mancuso, E., Sala, L. L., Antonicelli, R., Testa, R., Procopio, A. D., Olivieri, F., & Ceriello, A. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.10.003 · Cited by 255
Malaquin, N., Martinez, A., & Rodier, F. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.05.010 · Cited by 247
Mitochondrial Homeostasis and Cellular Senescence
Vasileiou, P. V. S., Evangelou, K., Vlasis, K. G., Fildisis, G., Panayiotidis, M. I., Chronopoulos, E., Passias, P.-G., Kouloukoussa, M., Gorgoulis, V. G., & Havaki, S. (2019) · Cells · doi:10.3390/cells8070686 · Cited by 255
Cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents
Wang, Z., Chen, Z., Jiang, Z., Luo, P., Liu, L., Huang, Y., Wang, H., Wang, Y., Long, L., Tan, X., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10386-8 · Cited by 219
Loo, T. M., Miyata, K., Tanaka, Y., & Takahashi, A. (2020) · Cancer Science · doi:10.1111/cas.14266 · Cited by 232
Nicaise, A. M., Wagstaff, L. J., Willis, C. M., Paisie, C. A., Chandok, H., Robson, P., Fossati, V., Williams, A., & Crocker, S. J. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1818348116 · Cited by 228
Aging in the dermis: Fibroblast senescence and its significance
Zhang, J., Yu, H., Man, M., & Hu, L. (2023) · Aging Cell · doi:10.1111/acel.14054 · Cited by 258
Cellular Senescence and the Senescence-Associated Secretory Phenotype as Drivers of Skin Photoaging
Fitsiou, E., Pulido, T., Campisi, J., Alimirah, F., & Demaria, M. (2020) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.09.031 · Cited by 237
Self-citationClassical and Nonclassical Intercellular Communication in Senescence and Ageing
Fafián‐Labora, J., & O’Loghlen, A. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.05.003 · Cited by 244
Chung, C. L., Lawrence, I., Hoffman, M., Elgindi, D., Nadhan, K., Potnis, M., Jin, A., Sershon, C., Binnebose, R., Lorenzini, A., et al. (2019) · GeroScience · doi:10.1007/s11357-019-00113-y · Cited by 219
Two-Step Senescence-Focused Cancer Therapies
Sieben, C. J., Sturmlechner, I., van de Sluis, B., & van Deursen, J. M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.04.006 · Cited by 222
mTOR pathway activation drives lung cell senescence and emphysema
Houssaini, A., Breau, M., Kebe, K., Abid, S., Marcos, É., Lipskaia, L., Rideau, D., Parpaleix, A., Huang, J. L., Amsellem, V., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.93203 · Cited by 229
Changes in Regenerative Capacity through Lifespan
Yun, M. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161025392 · Cited by 216
Key proteins and pathways that regulate lifespan
Pan, H., & Finkel, T. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r116.771915 · Cited by 228
Cellular senescence: the sought or the unwanted?
Sun, Y., Coppé, J.-P., & Lam, E. W.-F. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.08.002 · Cited by 208
Self-citationCellular senescence: Molecular mechanisms and pathogenicity
Wei, W., & Ji, S. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26956 · Cited by 214
Immunosenescence, aging and successful aging
Wang, Y., Chen, D., Han, Y., Gu, Z., & Sun, C. C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.942796 · Cited by 237
Metadata
- Authors
- Laberge, R.-M., Sun, Y., Orjalo, A. V., Patil, C. K., Freund, A., Zhou, L., Curran, S. C., Davalos, A. R., Wilson-Edell, K. A., Liu, S., Limbad, C., Demaria, M., Li, P., Hubbard, G. B., Ikeno, Y., Javors, M., Desprez, P.-Y., Benz, C. C., Kapahi, P., Nelson, P. S., & Campisi, J.
- Affiliations
- Chinese Academy of Sciences (CN)
- Buck Institute for Research on Aging (US)
- The University of Texas at San Antonio Health Science Center (US)
- Fred Hutch Cancer Center (US)
- Corresponding author
- Campisi, Judith
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2015-07-06
- Volume
- 17
- Issue
- 8
- Pages
- 1049-1061
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC4691706
- OpenAlex
- W1033197108
- Cited by
- 1,160
- References
- 72
- Citations by year
- 2026: 119 · 2025: 114 · 2024: 109 · 2023: 99 · 2022: 137 · 2021: 122 · 2020: 112 · 2019: 87 · 2018: 89 · 2017: 78 · 2016: 72 · 2015: 22
- FWCI
- 64.11
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-04-06)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG041122, R56AG009909, AG017242, AG-09909, RL1AG032113, AG045288, P01AG025901, R01AG045835, R37AG009909, P01AG041122, K99AG045288, AG032113, P01AG017242, AG000266-16, AG025901, P30AG013319, P30AG044271, T32AG000266)
- National Cancer Institute (CA097186, CA155679, R21CA155679, U24CA143858, CA165573, R01CA165573, CA071468, CA164188, R01CA071468, CA143858, U01CA164188, P50CA097186)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- mTOR, TORC1, rapamycin, senescence-associated secretory phenotype, cellular senescence, interleukin-6, NF-κB, senescence-associated inflammation, age-related cancer, longevity, translational regulation
- MeSH terms
- Animals, Anti-Inflammatory Agents, Antineoplastic Agents, Dose-Response Relationship, Drug, Fibroblasts, Humans, Male, Mitoxantrone, Phenotype, Prostatic Neoplasms, RNA, Messenger, Time Factors, Transcription, Genetic, Transfection, Interleukin-6, Up-Regulation, Gene Expression Regulation, Neoplastic, NF-kappa B, Mice, SCID, Cellular Senescence, Inflammation Mediators, Sirolimus, Xenograft Model Antitumor Assays, RNA Interference, Cell Line, Tumor, Tumor Burden, Cell Proliferation, Interleukin-1alpha, TOR Serine-Threonine Kinases
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