Interleukin-11 (IL-11) - Revision history

Dmitry Dzhagarov: /* IL11 can cause senescence */

2024-08-02T11:54:40Z

IL11 can cause senescence

← Older revision		Revision as of 11:54, 2 August 2024
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	== IL11 can cause senescence ==		== IL11 can cause senescence ==
	[[File:Female Il11-deleted mice are protected from age-associated obesity, frailty, and metabolic decline.jpg\|thumb\|Female Il11-deleted mice are protected from age-associated obesity, frailty, and metabolic decline.<ref name="Cook"> Widjaja, A. A., Lim, W. W., Viswanathan, S., Chothani, S., Corden, B., Goh, J. W. T., ... & Cook, S. A. (2023). Inhibition of an immunometabolic axis of mTORC1 activation extends mammalian healthspan. bioRxiv, 2023-07. https://doi.org/10.1101/2023.07.09.548250</ref>]]		[[File:Female Il11-deleted mice are protected from age-associated obesity, frailty, and metabolic decline.jpg\|thumb\|Female Il11-deleted mice are protected from age-associated obesity, frailty, and metabolic decline.<ref name="Cook"> Widjaja, A. A., Lim, W. W., Viswanathan, S., Chothani, S., Corden, B., Goh, J. W. T., ... & Cook, S. A. (2023). Inhibition of an immunometabolic axis of mTORC1 activation extends mammalian healthspan. bioRxiv, 2023-07. https://doi.org/10.1101/2023.07.09.548250</ref>]]
	As mice age, IL11 is progressively upregulated in liver, skeletal muscle, and fat to stimulate an ERK/AMPK/mTORC1 axis of cellular, tissue- and organismal-level ageing pathologies. In old mice, deletion of Il11 or Il11ra1 protects against metabolic multi-morbidity, sarcopenia, and frailty. Administration of anti-IL11 therapy to elderly mice for six months reactivates an age-repressed program of white fat beiging, reverses metabolic dysfunction, restores muscle function, and reduces frailty. Across studies, inhibition of IL11 lowers epigenetic age, reduces telomere attrition, and preserves mitochondrial function.<ref name="Cook" /> Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%.<ref>Widjaja, A.A., Lim, WW., Viswanathan, S. et al. (2024). Inhibition of IL-11 signalling extends mammalian healthspan and lifespan. Nature. https://doi.org/10.1038/s41586-024-07701-9</ref>		As mice age, IL11 is progressively upregulated in liver, skeletal muscle, and fat to stimulate an ERK/AMPK/mTORC1 axis of cellular, tissue- and organismal-level ageing pathologies. In old mice, deletion of Il11 or Il11ra1 protects against metabolic multi-morbidity, sarcopenia, and frailty. Administration of anti-IL11 therapy to elderly mice for six months reactivates an age-repressed program of white fat beiging, reverses metabolic dysfunction, restores muscle function, and reduces frailty. Across studies, inhibition of IL11 lowers epigenetic age, reduces telomere attrition, and preserves mitochondrial function.<ref name="Cook" /> Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%.<ref>Widjaja, A.A., Lim, WW., Viswanathan, S. et al. (2024). Inhibition of IL-11 signalling extends mammalian healthspan and lifespan. Nature. 632, 157–165 https://doi.org/10.1038/s41586-024-07701-9</ref>

	== Small moleculas and inhibitors ==		== Small moleculas and inhibitors ==

Dmitry Dzhagarov: /* Understanding interleukin 11 as a disease gene and therapeutic target */

2024-07-21T17:58:09Z

Understanding interleukin 11 as a disease gene and therapeutic target

← Older revision		Revision as of 17:58, 21 July 2024
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	<ref>Cook, S. A. (2023). Understanding interleukin 11 as a disease gene and therapeutic target. Biochemical journal, 480(23), 1987-2008. PMID: 38054591 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754292/ '''PMC10754292'''] DOI: 10.1042/BCJ20220160</ref>		<ref>Cook, S. A. (2023). Understanding interleukin 11 as a disease gene and therapeutic target. Biochemical journal, 480(23), 1987-2008. PMID: 38054591 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754292/ '''PMC10754292'''] DOI: 10.1042/BCJ20220160</ref>

	Also see video from The Aging and Drug Discovery Conference (ARDD) 2022. Stuart Cook's report: [https://youtu.be/oNc5MxkWrms '''The IL-11/ERK/mTOR axis is a target for extending mammalian healthspan''']		Also see video from The Aging and Drug Discovery Conference (ARDD) 2022. Stuart Cook's report: [https://youtu.be/oNc5MxkWrms '''The IL-11/ERK/mTOR axis is a target for extending mammalian healthspan'''] and from AnaBios [https://youtu.be/niJO_S16epQ Antibody Mediated Blockade of Interleukin-11 Signaling for IPF & Other Fibrotic Diseases]

	== References ==		== References ==

Dmitry Dzhagarov: /* Small moleculas and inhibitors */

2024-07-20T13:11:56Z

Small moleculas and inhibitors

← Older revision		Revision as of 13:11, 20 July 2024
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	Current IL-11 signalling inhibitors include antibodies against either IL-11 or IL-11Rα and IL-11 mutants, especially a cytokine variant, '''IL-11 Mutein''', which potently inhibits IL-11 signaling in human cells.<ref>Metcalfe, R. D., Hanssen, E., Fung, K. Y., Aizel, K., Kosasih, C. C., Zlatic, C. O., ... & Griffin, M. D. (2023). Structures of the interleukin 11 signalling complex reveal gp130 dynamics and the inhibitory mechanism of a cytokine variant. Nature Communications, 14(1), 7543. PMID: 37985757 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662374/ PMC10662374] DOI: 10.1038/s41467-023-42754-w</ref>		Current IL-11 signalling inhibitors include antibodies against either IL-11 or IL-11Rα and IL-11 mutants, especially a cytokine variant, '''IL-11 Mutein''', which potently inhibits IL-11 signaling in human cells.<ref>Metcalfe, R. D., Hanssen, E., Fung, K. Y., Aizel, K., Kosasih, C. C., Zlatic, C. O., ... & Griffin, M. D. (2023). Structures of the interleukin 11 signalling complex reveal gp130 dynamics and the inhibitory mechanism of a cytokine variant. Nature Communications, 14(1), 7543. PMID: 37985757 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662374/ PMC10662374] DOI: 10.1038/s41467-023-42754-w</ref>

			One important next step would be to test candidate IL-11 drugs in mice with diverse genetic backgrounds and in multiple laboratories to be sure that the results are reproducible. Beyond that, determining the effect of anti-IL-11 drug candidates on longevity in people could be a challenge. Instead researchers might do well to focus on a specific condition associated with ageing.<ref>Ledford H. (2024). [https://doi.org/10.1038/d41586-024-02298-5 Mice live longer when inflammation-boosting protein is blocked. Humans also have the protein, called IL-11, offering hope for a future longevity treatment]. Nature (News)</ref>

	== Understanding interleukin 11 as a disease gene and therapeutic target ==		== Understanding interleukin 11 as a disease gene and therapeutic target ==

Dmitry Dzhagarov: /* Understanding interleukin 11 as a disease gene and therapeutic target */

2024-07-19T19:30:33Z

Understanding interleukin 11 as a disease gene and therapeutic target

← Older revision		Revision as of 19:30, 19 July 2024
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	== Understanding interleukin 11 as a disease gene and therapeutic target ==		== Understanding interleukin 11 as a disease gene and therapeutic target ==
	<ref>Cook, S. A. (2023). Understanding interleukin 11 as a disease gene and therapeutic target. Biochemical journal, 480(23), 1987-2008. PMID: 38054591 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754292/ '''PMC10754292'''] DOI: 10.1042/BCJ20220160</ref>		<ref>Cook, S. A. (2023). Understanding interleukin 11 as a disease gene and therapeutic target. Biochemical journal, 480(23), 1987-2008. PMID: 38054591 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754292/ '''PMC10754292'''] DOI: 10.1042/BCJ20220160</ref>

			Also see video from The Aging and Drug Discovery Conference (ARDD) 2022. Stuart Cook's report: [https://youtu.be/oNc5MxkWrms '''The IL-11/ERK/mTOR axis is a target for extending mammalian healthspan''']

	== References ==		== References ==

Dmitry Dzhagarov: /* Small moleculas */

2024-07-19T01:36:28Z

Small moleculas

← Older revision		Revision as of 01:36, 19 July 2024
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	As mice age, IL11 is progressively upregulated in liver, skeletal muscle, and fat to stimulate an ERK/AMPK/mTORC1 axis of cellular, tissue- and organismal-level ageing pathologies. In old mice, deletion of Il11 or Il11ra1 protects against metabolic multi-morbidity, sarcopenia, and frailty. Administration of anti-IL11 therapy to elderly mice for six months reactivates an age-repressed program of white fat beiging, reverses metabolic dysfunction, restores muscle function, and reduces frailty. Across studies, inhibition of IL11 lowers epigenetic age, reduces telomere attrition, and preserves mitochondrial function.<ref name="Cook" /> Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%.<ref>Widjaja, A.A., Lim, WW., Viswanathan, S. et al. (2024). Inhibition of IL-11 signalling extends mammalian healthspan and lifespan. Nature. https://doi.org/10.1038/s41586-024-07701-9</ref>		As mice age, IL11 is progressively upregulated in liver, skeletal muscle, and fat to stimulate an ERK/AMPK/mTORC1 axis of cellular, tissue- and organismal-level ageing pathologies. In old mice, deletion of Il11 or Il11ra1 protects against metabolic multi-morbidity, sarcopenia, and frailty. Administration of anti-IL11 therapy to elderly mice for six months reactivates an age-repressed program of white fat beiging, reverses metabolic dysfunction, restores muscle function, and reduces frailty. Across studies, inhibition of IL11 lowers epigenetic age, reduces telomere attrition, and preserves mitochondrial function.<ref name="Cook" /> Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%.<ref>Widjaja, A.A., Lim, WW., Viswanathan, S. et al. (2024). Inhibition of IL-11 signalling extends mammalian healthspan and lifespan. Nature. https://doi.org/10.1038/s41586-024-07701-9</ref>

	== Small moleculas ==		== Small moleculas and inhibitors ==
	Blockage of sgp130Fc (by TJ301 (sgp130Fc)) or inhibition of the JAK2/STAT3 pathway (by WP1066 (a JAK2/STAT3 inhibitor)) could ameliorate the profibrotic effect of IL-11.<ref>Ye, W., Wang, Q., Zhao, L., Wang, C., Zhang, D., Zhou, M., ... & Xue, Y. (2023). Blockade of IL-11 Trans-Signaling or JAK2/STAT3 Signaling Ameliorates the Profibrotic Effect of IL-11. Immunological Investigations, 52(6), 703-716. PMID: 37401665 DOI: 10.1080/08820139.2023.2222746</ref>		Blockage of sgp130Fc (by TJ301 (sgp130Fc)) or inhibition of the JAK2/STAT3 pathway (by WP1066 (a JAK2/STAT3 inhibitor)) could ameliorate the profibrotic effect of IL-11.<ref>Ye, W., Wang, Q., Zhao, L., Wang, C., Zhang, D., Zhou, M., ... & Xue, Y. (2023). Blockade of IL-11 Trans-Signaling or JAK2/STAT3 Signaling Ameliorates the Profibrotic Effect of IL-11. Immunological Investigations, 52(6), 703-716. PMID: 37401665 DOI: 10.1080/08820139.2023.2222746</ref>

			Current IL-11 signalling inhibitors include antibodies against either IL-11 or IL-11Rα and IL-11 mutants, especially a cytokine variant, '''IL-11 Mutein''', which potently inhibits IL-11 signaling in human cells.<ref>Metcalfe, R. D., Hanssen, E., Fung, K. Y., Aizel, K., Kosasih, C. C., Zlatic, C. O., ... & Griffin, M. D. (2023). Structures of the interleukin 11 signalling complex reveal gp130 dynamics and the inhibitory mechanism of a cytokine variant. Nature Communications, 14(1), 7543. PMID: 37985757 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662374/ PMC10662374] DOI: 10.1038/s41467-023-42754-w</ref>

	== Understanding interleukin 11 as a disease gene and therapeutic target ==		== Understanding interleukin 11 as a disease gene and therapeutic target ==

Dmitry Dzhagarov: /* IL-11 in the lung */

2024-07-19T01:16:01Z

IL-11 in the lung

← Older revision		Revision as of 01:16, 19 July 2024
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	== IL-11 in the lung ==		== IL-11 in the lung ==
	IL-11 plays a role in viral airway disorders; human stromal cells stimulated with respiratory syncytial virus, rhinovirus, and parainfluenza virus type 3 secrete high levels of IL-11. However, IL-11 activity does not alter the initial immune responses and bacterial clearance in the context of acute respiratory infections.<ref>Einarsson, O., Geba, G. P., Zhu, Z., Landry, M., & Elias, J. A. (1996). Interleukin-11: stimulation in vivo and in vitro by respiratory viruses and induction of airways hyperresponsiveness. The Journal of clinical investigation, 97(4), 915-924. PMID: 8613544 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507136/ PMC507136] DOI: 10.1172/JCI118514</ref>		IL-11 plays a role in viral airway disorders; human stromal cells stimulated with respiratory syncytial virus, rhinovirus, and parainfluenza virus type 3 secrete high levels of IL-11. However, IL-11 activity does not alter the initial immune responses and bacterial clearance in the context of acute respiratory infections.<ref>Einarsson, O., Geba, G. P., Zhu, Z., Landry, M., & Elias, J. A. (1996). Interleukin-11: stimulation in vivo and in vitro by respiratory viruses and induction of airways hyperresponsiveness. The Journal of clinical investigation, 97(4), 915-924. PMID: 8613544 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507136/ PMC507136] DOI: 10.1172/JCI118514</ref>
	Interleukin-11 (IL-11) is linked to the pathogenesis of idiopathic pulmonary fibrosis (IPF), since IL-11 induces myofibroblast differentiation and stimulates their excessive collagen deposition in the lung.<ref>Ng, B., Dong, J., D’Agostino, G., Viswanathan, S., Widjaja, A. A., Lim, W. W., ... & Cook, S. A. (2019). Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. Science Translational Medicine, 11(511), eaaw1237.PMID: 37228276 PMC10204861 DOI: 10.1183/23120541.00679-2022</ref> IL-11 and and its cognate receptor IL-11Rα are overexpressed in pulmonary arteries of pulmonary hypertension associated to IPF patients, and contributes to pulmonary artery remodeling and pulmonary hypertension.<ref>Milara, J., Roger, I., Montero, P., Artigues, E., Escrivá, J., & Cortijo, J. (2022). IL-11 system participates in pulmonary artery remodeling and hypertension in pulmonary fibrosis. Respiratory Research, 23(1), 1-18. PMID: 36376885 PMC9664718 DOI: 10.1186/s12931-022-02241-0</ref><ref>Ng, B., Dong, J., D’Agostino, G., Viswanathan, S., Widjaja, A. A., Lim, W. W., ... & Cook, S. A. (2019). Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. Science Translational Medicine, 11(511), eaaw1237. PMID: 31554736 DOI: 10.1126/scitranslmed.aaw1237</ref> Interleukin-11 negatively impacts lung epithelial regeneration by inhibiting progenitor cell activation and suppressing alveolar differentiation.<ref>Kortekaas, R. K., Geillinger-Kästle, K. E., Borghuis, T., Belharch, K., Webster, M., Timens, W., ... & Gosens, R. (2023). Interleukin-11 disrupts alveolar epithelial progenitor function. ERJ Open Research, 9(3). PMID: 37228276 PMC10204861 DOI: 10.1183/23120541.00679-2022</ref>		Interleukin-11 (IL-11) is linked to the pathogenesis of idiopathic pulmonary fibrosis (IPF), since IL-11 induces myofibroblast differentiation and stimulates their excessive collagen deposition in the lung.<ref>Ng, B., Dong, J., D’Agostino, G., Viswanathan, S., Widjaja, A. A., Lim, W. W., ... & Cook, S. A. (2019). Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. Science Translational Medicine, 11(511), eaaw1237.PMID: 37228276 PMC10204861 DOI: 10.1183/23120541.00679-2022</ref> IL-11 and and its cognate receptor IL-11Rα are overexpressed in pulmonary arteries of pulmonary hypertension associated to IPF patients, and contributes to pulmonary artery remodeling and pulmonary hypertension.<ref>Milara, J., Roger, I., Montero, P., Artigues, E., Escrivá, J., & Cortijo, J. (2022). IL-11 system participates in pulmonary artery remodeling and hypertension in pulmonary fibrosis. Respiratory Research, 23(1), 1-18. PMID: 36376885 PMC9664718 DOI: 10.1186/s12931-022-02241-0</ref><ref>Ng, B., Dong, J., D’Agostino, G., Viswanathan, S., Widjaja, A. A., Lim, W. W., ... & Cook, S. A. (2019). Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. Science Translational Medicine, 11(511), eaaw1237. PMID: 31554736 DOI: 10.1126/scitranslmed.aaw1237</ref> Interleukin-11 negatively impacts lung epithelial regeneration by inhibiting progenitor cell activation and suppressing alveolar differentiation.<ref>Kortekaas, R. K., Geillinger-Kästle, K. E., Borghuis, T., Belharch, K., Webster, M., Timens, W., ... & Gosens, R. (2023). Interleukin-11 disrupts alveolar epithelial progenitor function. ERJ Open Research, 9(3). PMID: 37228276 PMC10204861 DOI: 10.1183/23120541.00679-2022</ref>
	Arachidonic acid (AA) increased mRNA expression and secretion of IL-11 in lung fibroblasts in a dose-dependent manner that was dependent on the activation of the p38 or ERK MAPK signaling pathways.<ref>Sasaki, K., Komamura, S., & Matsuda, K. (2023). Extracellular stimulation of lung fibroblasts with arachidonic acid increases interleukin 11 expression through p38 and ERK signaling. Biological Chemistry, 404(1), 59-69. PMID: 36268909 DOI: 10.1515/hsz-2022-0218</ref>		Arachidonic acid (AA) increased mRNA expression and secretion of IL-11 in lung fibroblasts in a dose-dependent manner that was dependent on the activation of the p38 or ERK MAPK signaling pathways.<ref>Sasaki, K., Komamura, S., & Matsuda, K. (2023). Extracellular stimulation of lung fibroblasts with arachidonic acid increases interleukin 11 expression through p38 and ERK signaling. Biological Chemistry, 404(1), 59-69. PMID: 36268909 DOI: 10.1515/hsz-2022-0218</ref>

Dmitry Dzhagarov: /* IL-11 in the lung */

2024-07-19T01:14:06Z

IL-11 in the lung

← Older revision		Revision as of 01:14, 19 July 2024
Line 8:		Line 8:

	== IL-11 in the lung ==		== IL-11 in the lung ==
			IL-11 plays a role in viral airway disorders; human stromal cells stimulated with respiratory syncytial virus, rhinovirus, and parainfluenza virus type 3 secrete high levels of IL-11. However, IL-11 activity does not alter the initial immune responses and bacterial clearance in the context of acute respiratory infections.<ref>Einarsson, O., Geba, G. P., Zhu, Z., Landry, M., & Elias, J. A. (1996). Interleukin-11: stimulation in vivo and in vitro by respiratory viruses and induction of airways hyperresponsiveness. The Journal of clinical investigation, 97(4), 915-924. PMID: 8613544 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507136/ PMC507136] DOI: 10.1172/JCI118514</ref>
	Interleukin-11 (IL-11) is linked to the pathogenesis of idiopathic pulmonary fibrosis (IPF), since IL-11 induces myofibroblast differentiation and stimulates their excessive collagen deposition in the lung.<ref>Ng, B., Dong, J., D’Agostino, G., Viswanathan, S., Widjaja, A. A., Lim, W. W., ... & Cook, S. A. (2019). Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. Science Translational Medicine, 11(511), eaaw1237.PMID: 37228276 PMC10204861 DOI: 10.1183/23120541.00679-2022</ref> IL-11 and and its cognate receptor IL-11Rα are overexpressed in pulmonary arteries of pulmonary hypertension associated to IPF patients, and contributes to pulmonary artery remodeling and pulmonary hypertension.<ref>Milara, J., Roger, I., Montero, P., Artigues, E., Escrivá, J., & Cortijo, J. (2022). IL-11 system participates in pulmonary artery remodeling and hypertension in pulmonary fibrosis. Respiratory Research, 23(1), 1-18. PMID: 36376885 PMC9664718 DOI: 10.1186/s12931-022-02241-0</ref><ref>Ng, B., Dong, J., D’Agostino, G., Viswanathan, S., Widjaja, A. A., Lim, W. W., ... & Cook, S. A. (2019). Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. Science Translational Medicine, 11(511), eaaw1237. PMID: 31554736 DOI: 10.1126/scitranslmed.aaw1237</ref> Interleukin-11 negatively impacts lung epithelial regeneration by inhibiting progenitor cell activation and suppressing alveolar differentiation.<ref>Kortekaas, R. K., Geillinger-Kästle, K. E., Borghuis, T., Belharch, K., Webster, M., Timens, W., ... & Gosens, R. (2023). Interleukin-11 disrupts alveolar epithelial progenitor function. ERJ Open Research, 9(3). PMID: 37228276 PMC10204861 DOI: 10.1183/23120541.00679-2022</ref>		Interleukin-11 (IL-11) is linked to the pathogenesis of idiopathic pulmonary fibrosis (IPF), since IL-11 induces myofibroblast differentiation and stimulates their excessive collagen deposition in the lung.<ref>Ng, B., Dong, J., D’Agostino, G., Viswanathan, S., Widjaja, A. A., Lim, W. W., ... & Cook, S. A. (2019). Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. Science Translational Medicine, 11(511), eaaw1237.PMID: 37228276 PMC10204861 DOI: 10.1183/23120541.00679-2022</ref> IL-11 and and its cognate receptor IL-11Rα are overexpressed in pulmonary arteries of pulmonary hypertension associated to IPF patients, and contributes to pulmonary artery remodeling and pulmonary hypertension.<ref>Milara, J., Roger, I., Montero, P., Artigues, E., Escrivá, J., & Cortijo, J. (2022). IL-11 system participates in pulmonary artery remodeling and hypertension in pulmonary fibrosis. Respiratory Research, 23(1), 1-18. PMID: 36376885 PMC9664718 DOI: 10.1186/s12931-022-02241-0</ref><ref>Ng, B., Dong, J., D’Agostino, G., Viswanathan, S., Widjaja, A. A., Lim, W. W., ... & Cook, S. A. (2019). Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. Science Translational Medicine, 11(511), eaaw1237. PMID: 31554736 DOI: 10.1126/scitranslmed.aaw1237</ref> Interleukin-11 negatively impacts lung epithelial regeneration by inhibiting progenitor cell activation and suppressing alveolar differentiation.<ref>Kortekaas, R. K., Geillinger-Kästle, K. E., Borghuis, T., Belharch, K., Webster, M., Timens, W., ... & Gosens, R. (2023). Interleukin-11 disrupts alveolar epithelial progenitor function. ERJ Open Research, 9(3). PMID: 37228276 PMC10204861 DOI: 10.1183/23120541.00679-2022</ref>
	Arachidonic acid (AA) increased mRNA expression and secretion of IL-11 in lung fibroblasts in a dose-dependent manner that was dependent on the activation of the p38 or ERK MAPK signaling pathways.<ref>Sasaki, K., Komamura, S., & Matsuda, K. (2023). Extracellular stimulation of lung fibroblasts with arachidonic acid increases interleukin 11 expression through p38 and ERK signaling. Biological Chemistry, 404(1), 59-69. PMID: 36268909 DOI: 10.1515/hsz-2022-0218</ref>		Arachidonic acid (AA) increased mRNA expression and secretion of IL-11 in lung fibroblasts in a dose-dependent manner that was dependent on the activation of the p38 or ERK MAPK signaling pathways.<ref>Sasaki, K., Komamura, S., & Matsuda, K. (2023). Extracellular stimulation of lung fibroblasts with arachidonic acid increases interleukin 11 expression through p38 and ERK signaling. Biological Chemistry, 404(1), 59-69. PMID: 36268909 DOI: 10.1515/hsz-2022-0218</ref>

Dmitry Dzhagarov: /* IL11 as a component of the SASP that can cause senescence */

2024-07-19T01:04:39Z

IL11 as a component of the SASP that can cause senescence

← Older revision		Revision as of 01:04, 19 July 2024
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	== IL-11 can increase the tumorigenic capacity of cells ==		== IL-11 can increase the tumorigenic capacity of cells ==

	== IL11 ~~as a component of the SASP that~~ can cause senescence ==		== IL11 can cause senescence ==
	[[File:Female Il11-deleted mice are protected from age-associated obesity, frailty, and metabolic decline.jpg\|thumb\|Female Il11-deleted mice are protected from age-associated obesity, frailty, and metabolic decline.<ref name="Cook"> Widjaja, A. A., Lim, W. W., Viswanathan, S., Chothani, S., Corden, B., Goh, J. W. T., ... & Cook, S. A. (2023). Inhibition of an immunometabolic axis of mTORC1 activation extends mammalian healthspan. bioRxiv, 2023-07. https://doi.org/10.1101/2023.07.09.548250</ref>]]		[[File:Female Il11-deleted mice are protected from age-associated obesity, frailty, and metabolic decline.jpg\|thumb\|Female Il11-deleted mice are protected from age-associated obesity, frailty, and metabolic decline.<ref name="Cook"> Widjaja, A. A., Lim, W. W., Viswanathan, S., Chothani, S., Corden, B., Goh, J. W. T., ... & Cook, S. A. (2023). Inhibition of an immunometabolic axis of mTORC1 activation extends mammalian healthspan. bioRxiv, 2023-07. https://doi.org/10.1101/2023.07.09.548250</ref>]]
	As mice age, IL11 is progressively upregulated in liver, skeletal muscle, and fat to stimulate an ERK/AMPK/mTORC1 axis of cellular, tissue- and organismal-level ageing pathologies. In old mice, deletion of Il11 or Il11ra1 protects against metabolic multi-morbidity, sarcopenia, and frailty. Administration of anti-IL11 therapy to elderly mice for six months reactivates an age-repressed program of white fat beiging, reverses metabolic dysfunction, restores muscle function, and reduces frailty. Across studies, inhibition of IL11 lowers epigenetic age, reduces telomere attrition, and preserves mitochondrial function.<ref name="Cook" /> Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%.<ref>Widjaja, A.A., Lim, WW., Viswanathan, S. et al. (2024). Inhibition of IL-11 signalling extends mammalian healthspan and lifespan. Nature. https://doi.org/10.1038/s41586-024-07701-9</ref>		As mice age, IL11 is progressively upregulated in liver, skeletal muscle, and fat to stimulate an ERK/AMPK/mTORC1 axis of cellular, tissue- and organismal-level ageing pathologies. In old mice, deletion of Il11 or Il11ra1 protects against metabolic multi-morbidity, sarcopenia, and frailty. Administration of anti-IL11 therapy to elderly mice for six months reactivates an age-repressed program of white fat beiging, reverses metabolic dysfunction, restores muscle function, and reduces frailty. Across studies, inhibition of IL11 lowers epigenetic age, reduces telomere attrition, and preserves mitochondrial function.<ref name="Cook" /> Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%.<ref>Widjaja, A.A., Lim, WW., Viswanathan, S. et al. (2024). Inhibition of IL-11 signalling extends mammalian healthspan and lifespan. Nature. https://doi.org/10.1038/s41586-024-07701-9</ref>

Dmitry Dzhagarov: /* Small moleculas */

2024-07-18T10:17:36Z

Small moleculas

← Older revision		Revision as of 10:17, 18 July 2024
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	== Small moleculas ==		== Small moleculas ==
	Blockage of sgp130Fc (by TJ301 (sgp130Fc)) or inhibition of the JAK2/STAT3 pathway (by WP1066 (a JAK2/STAT3 inhibitor)) could ameliorate the profibrotic effect of IL-11.<ref>Ye, W., Wang, Q., Zhao, L., Wang, C., Zhang, D., Zhou, M., ... & Xue, Y. (2023). Blockade of IL-11 Trans-Signaling or JAK2/STAT3 Signaling Ameliorates the Profibrotic Effect of IL-11. Immunological Investigations, 52(6), 703-716. PMID: 37401665 DOI: 10.1080/08820139.2023.2222746</ref>		Blockage of sgp130Fc (by TJ301 (sgp130Fc)) or inhibition of the JAK2/STAT3 pathway (by WP1066 (a JAK2/STAT3 inhibitor)) could ameliorate the profibrotic effect of IL-11.<ref>Ye, W., Wang, Q., Zhao, L., Wang, C., Zhang, D., Zhou, M., ... & Xue, Y. (2023). Blockade of IL-11 Trans-Signaling or JAK2/STAT3 Signaling Ameliorates the Profibrotic Effect of IL-11. Immunological Investigations, 52(6), 703-716. PMID: 37401665 DOI: 10.1080/08820139.2023.2222746</ref>

			== Understanding interleukin 11 as a disease gene and therapeutic target ==
			<ref>Cook, S. A. (2023). Understanding interleukin 11 as a disease gene and therapeutic target. Biochemical journal, 480(23), 1987-2008. PMID: 38054591 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754292/ '''PMC10754292'''] DOI: 10.1042/BCJ20220160</ref>

	== References ==		== References ==

Dmitry Dzhagarov: /* IL11 as a component of the SASP that can cause senescence */

2024-07-18T10:05:48Z

IL11 as a component of the SASP that can cause senescence

← Older revision		Revision as of 10:05, 18 July 2024
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	== IL11 as a component of the SASP that can cause senescence ==		== IL11 as a component of the SASP that can cause senescence ==
	[[File:Female Il11-deleted mice are protected from age-associated obesity, frailty, and metabolic decline.jpg\|thumb\|Female Il11-deleted mice are protected from age-associated obesity, frailty, and metabolic decline.<ref name="Cook"> Widjaja, A. A., Lim, W. W., Viswanathan, S., Chothani, S., Corden, B., Goh, J. W. T., ... & Cook, S. A. (2023). Inhibition of an immunometabolic axis of mTORC1 activation extends mammalian healthspan. bioRxiv, 2023-07. https://doi.org/10.1101/2023.07.09.548250</ref>]]		[[File:Female Il11-deleted mice are protected from age-associated obesity, frailty, and metabolic decline.jpg\|thumb\|Female Il11-deleted mice are protected from age-associated obesity, frailty, and metabolic decline.<ref name="Cook"> Widjaja, A. A., Lim, W. W., Viswanathan, S., Chothani, S., Corden, B., Goh, J. W. T., ... & Cook, S. A. (2023). Inhibition of an immunometabolic axis of mTORC1 activation extends mammalian healthspan. bioRxiv, 2023-07. https://doi.org/10.1101/2023.07.09.548250</ref>]]
	As mice age, IL11 is progressively upregulated in liver, skeletal muscle, and fat to stimulate an ERK/AMPK/mTORC1 axis of cellular, tissue- and organismal-level ageing pathologies. In old mice, deletion of Il11 or Il11ra1 protects against metabolic multi-morbidity, sarcopenia, and frailty. Administration of anti-IL11 therapy to elderly mice for six months reactivates an age-repressed program of white fat beiging, reverses metabolic dysfunction, restores muscle function, and reduces frailty. Across studies, inhibition of IL11 lowers epigenetic age, reduces telomere attrition, and preserves mitochondrial function.<ref name="Cook" />		As mice age, IL11 is progressively upregulated in liver, skeletal muscle, and fat to stimulate an ERK/AMPK/mTORC1 axis of cellular, tissue- and organismal-level ageing pathologies. In old mice, deletion of Il11 or Il11ra1 protects against metabolic multi-morbidity, sarcopenia, and frailty. Administration of anti-IL11 therapy to elderly mice for six months reactivates an age-repressed program of white fat beiging, reverses metabolic dysfunction, restores muscle function, and reduces frailty. Across studies, inhibition of IL11 lowers epigenetic age, reduces telomere attrition, and preserves mitochondrial function.<ref name="Cook" /> Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%.<ref>Widjaja, A.A., Lim, WW., Viswanathan, S. et al. (2024). Inhibition of IL-11 signalling extends mammalian healthspan and lifespan. Nature. https://doi.org/10.1038/s41586-024-07701-9</ref>

	== Small moleculas ==		== Small moleculas ==