Citations 49
Bone Marrow Adiposity in Models of Radiation- and Aging-Related Bone Loss Is Dependent on Cellular Senescence
Chandra, Abhishek , Lagnado, Anthony B. , Farr, Joshua N. , Schleusner, Megan , Monroe, David G. , Saul, Dominik , Passos, João F. , Khosla, Sundeep , Pignolo, Robert J. , Khosla, Sundeep , Passos, João F , Monroe, David G , Farr, Joshua N , Saul, Dominik , Chandra, Abhishek
Journal of Bone and Mineral Research | March 5, 2022 | Volume: 37 | Issue: 5 | Pages: 997-1011
ABSTRACT Oxidative stress-induced reactive oxygen species, DNA damage, apoptosis, and cellular senescence have been associated with reduced osteoprogenitors in a reciprocal fashion to bone marrow adipocyte tissue (BMAT); however, a direct (causal) link between cellular senescence and BMAT is still elusive. Accumulation of senescent cells occur in naturally aged and in focally radiated bone tissue, but despite amelioration of age- and radiation-associated bone loss after senescent cell clearance, molecular events that precede BMAT accrual are largely unknown. Here we show by RNA-Sequencing data that BMAT-related genes were the most upregulated gene subset in radiated bones of C57BL/6 mice. Using focal radiation as a model to understand age-associated changes in bone, we performed a longitudinal assessment of cellular senescence and BMAT. Using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), RNA in situ hybridization of p21 transcripts and histological assessment of telomere dysfunction as a marker of senescence, we observed an increase in senescent cell burden of bone cells from day 1 postradiation, without the presence of BMAT. BMAT was significantly elevated in radiated bones at day 7, confirming the qRT-PCR data in which most BMAT-related genes were elevated by day 7, and the trend continued until day 42 postradiation. Similarly, elevation in BMAT-related genes was observed in bones of aged mice. The senolytic cocktail of Dasatinib (D) plus Quercetin (Q) (ie, D + Q), which clears senescent cells, reduced BMAT in aged and radiated bones. MicroRNAs (miRNAs or miRs) linked with senescence marker p21 were downregulated in radiated and aged bones, whereas miR-27a, a miR that is associated with increased BMAT, was elevated both in radiated and aged bones. D + Q downregulated miR-27a in radiated bones at 42 days postradiation. Overall, our study provides evidence that BMAT occurrence in oxidatively stressed bone environments, such as radiation and aging, is induced following a common pathway and is dependent on the presence of senescent cells. © 2022 American Society for Bone and Mineral Research (ASBMR). Abstract Schematic representing a senescent bone environment during aging and radiation. The schematic represents changes in an oxidatively stressed, senescent microenvironment in which mesenchymal progenitors are preferentially forming adipocytes, regulated by a common process shared between aging bone and radiation-induced bone damage, and with identical expression patterns of bone marrow adipocyte tissue (BMAT)-related genes and microRNAs (miRNAs or miRs). Increase in senescent markers p21 and p16Ink4a induce a cellular state in which production of the senescence-associated secretory phenotype (SASP) increases and influences the bone marrow environment. Secreted adipokines can promote mesenchymal stem cell (MSC) fate, switching to an adipocyte lineage. Several adipokines are also released in circulation, causing systemic effects. These changes in senescence markers and genes that regulate BMAT are in turn regulated by their corresponding miRNAs. These changes can be blocked or reversed by the clearance of senescent cells using senolytic drugs. The figure was created with BioRender.com.
Cellular senescence: all roads lead to mitochondria
Martini, Hélène , Passos, João F. , Passos, João F
The FEBS Journal | January 20, 2022 | Volume: 290 | Issue: 5 | Pages: 1186-1202
Senescence is a multi‐functional cell fate, characterized by an irreversible cell‐cycle arrest and a pro‐inflammatory phenotype, commonly known as the senescence‐associated secretory phenotype (SASP). Emerging evidence indicates that accumulation of senescent cells in multiple tissues drives tissue dysfunction and several age‐related conditions. This has spurred the academic community and industry to identify new therapeutic interventions targeting this process. Mitochondrial dysfunction is an often‐unappreciated hallmark of cellular senescence which plays important roles not only in the senescence growth arrest but also in the development of the SASP and resistance to cell‐death. Here, we review the evidence that supports a role for mitochondria in the development of senescence and describe the underlying mechanisms. Finally, we propose that a detailed road map of mitochondrial biology in senescence will be crucial to guide the future development of senotherapies.
A New Gene Set Identifies Senescent Cells and Predicts Senescence-Associated Pathways Across Tissues
Khosla, Sundeep , Saul, Dominik , Kosinsky, Robyn Laura , Atkinson, Elizabeth J. , LeBrasseur, Nathan K. , Pignolo, Robert J. , Robbins, Paul D. , Niedernhofer, Laura J. , Ikeno, Yuji , Jurk, Diana , Xue, Ailing, Kirkland, James L. , Khosla, Sundeep , Jurk, Diana , LeBrasseur, Nathan K , Niedernhofer, Laura J , Robbins, Paul D , Kosinsky, Robyn Laura , Saul, Dominik , Doolittle, Madison L. , Zhang, Xu , Passos, João F. , Hickson, LaTonya J. , Monroe, David G. , Tchkonia, Tamar , Farr, Joshua N.
No container title available | December 13, 2021 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Although cellular senescence is increasingly recognized as driving multiple age-related co-morbidities through the senescence-associated secretory phenotype (SASP), in vivo senescent cell identification, particularly in bulk or single cell RNA-sequencing (scRNA-seq) data remains challenging. Here, we generated a novel gene set (SenMayo) and first validated its enrichment in bone biopsies from two aged human cohorts. SenMayo also identified senescent cells in aged murine brain tissue, demonstrating applicability across tissues and species. For direct validation, we demonstrated significant reductions in SenMayo in bone following genetic clearance of senescent cells in mice, with similar findings in adipose tissue from humans in a pilot study of pharmacological senescent cell clearance. In direct comparisons, SenMayo outperformed all six existing senescence/SASP gene sets in identifying senescent cells across tissues and in demonstrating responses to senescent cell clearance. We next used SenMayo to identify senescent hematopoietic or mesenchymal cells at the single cell level from publicly available human and murine bone marrow/bone scRNA-seq data and identified monocytic and osteolineage cells, respectively, as showing the highest levels of senescence/SASP genes. Using pseudotime and cellular communication patterns, we found senescent hematopoietic and mesenchymal cells communicated with other cells through common pathways, including the Macrophage Migration Inhibitory Factor (MIF) pathway, which has been implicated not only in inflammation but also in immune evasion, an important property of senescent cells. Thus, SenMayo identifies senescent cells across tissues and species with high fidelity. Moreover, using this senescence panel, we were able to characterize senescent cells at the single cell level and identify key intercellular signaling pathways associated with these cells, which may be particularly useful for evolving efforts to map senescent cells (e.g., SenNet). In addition, SenMayo represents a potentially clinically applicable panel for monitoring senescent cell burden with aging and other conditions as well as in studies of senolytic drugs.
Cellular Senescence Related Protein and Gene Expression Patterns in Asthmatic Human Whole Lung Tissue
Aghali, A., Pabelick, C.M., Wicher, Sarah A. , Pabelick, C.M., Passos, João F. , Prakash, Y. S.
TP118. TP118 AIRWAY HYPERRESPONSIVENESS AND INFLAMMATION IN ASTHMA | May 4, 2021 | Volume: No volume available | Issue: No issue available | Pages: A4500-A4500
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
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Douglas , Falcó, Alberto , Fan, Daping , Fan, Jie , Fang, Evandro Fei , Fang, Yanshan , Fang, Yognqi, Farfel‐Becker, Tamar, Faure, Mathias , Fazeli, Gholamreza , Fedele, Anthony O., Feldman, Arthur M. , Feng, Jiachun , Feng, Lifeng , Feng, Wei , Araujo, Thaís Fenz , Ferguson, Thomas A., Fernández, Álvaro F. , Fernández‐Veledo, Sonia , Fernie, Alisdair R. , Ferrante, Anthony W. , Ferraresi, Alessandra , Ferrari, M , Ferreira, Julio Cesar Batista , Ferro‐Novick, Susan , Figueras, António , Filadi, Riccardo , Filigheddu, Nicoletta , Fimia, Gian María , Finetti, Francesca , Finkbeiner, Steven , Fisher, Edward A. , Fisher, Paul B. , Fliesler, Steven J. , Flo, Trude Helen , Florance, Ida , Florey, Oliver , Florio, Tullio , Fodor, Erika , Forlino, Antonella , Fortini, Paola , Fracassi, Anna , Franconi, Flavia , Frankel, Lisa B. , Fröhlich, Leopold F. , Fuentes, José M. , Fujiki, Yukio , Fulda, Simone , Furuya, Norihiko , Gack, Michaela U. , Gaffke, Lidia , Galadari, Sehamuddin , Galasso, Alessia , Galindo, Marı́a F. , Kankanamalage, Sachith Gallolu , Galluzzi, Lorenzo, Galy, Vincent , Gammoh, Noor , Ganley, Ian G. , Gao, Feng , Gao, Minghui , Gao, Ping , Gao, Wentao , Gao, Xiaobo , Garcerá, Ana , Garcia, María Noé , García, Verónica , Portillo, Francisco Garcı́a-del , García‐Escudero, Vega , García‐García, Aracely , García‐Macía, Marina , García‐Moreno, Diana , García‐Ruiz, Carmen , García‐Sanz, Patricia , Garg, Abhishek D. , Garofalo, Tina , Gassen, Nils C. , Gatica, Damián , Geiss‐Friedlander, Ruth , Genschik, Pascal , Gerbino, Valeria , Gerhardt, Christoph , Germain, Kyla , Germain, Marc , Afshar, Elham Ghasemipour, Ghavami, Saeid , Ghosh, Manosij , Giamas, Georgios , Giatromanolaki, Alexandra , Gibson, Gary E. , Ginet, Vanessa, Girardin, Stephen E. , Giridharan, Mridhula, Giuliano, Sandy , Giulivi, Cecilia , Giuriato, Sylvie , Giustiniani, Julien , Gluschko, Alexander , Goder, Veit , Goginashvili, Alexander , Gołąb, Jakub , Golebiewska, Anna , Gomes, Luciana Rodrigues, Gomez, Rodrigo Enrique, Gómez‐Sánchez, Rubén , Gómez‐Sintes, Raquel , Gong, Qingqiu , González‐Gallego, Javier , González‐Polo, Rosa A. , González‐Reyes, José A. , González-Rodríguez, Patricia , Goping, Ing Swie , Gorbunov, Nikolai V., Görgülü, Kıvanç , Gorojod, Roxana Mayra , Gorski, Sharon M. , Gotor, Cecilia , Gözüaçık, Devrim , Graef, Martin , Gräler, Markus H. , Granatiero, Veronica, Grasso, Daniel , Gray, Joshua P. , Greenhough, Alexander , Gregory, Stephen L. , Griffin, Edward F., Gros, Frédéric , Grose, Charles , Gross, Angelina S. , Грубер, Флориан , Grumati, Paolo , Gu, Xueyan , Guan, Jun‐Lin , Guardia, Carlos M. , Guda, Kishore , Guerra, Flora , Guerri, Consuelo , Guha, Prasun , Guillén, Carlos , Gujar, Shashi , Gukovskaya, Anna S. , Gukovsky, Ilya , Gunst, Jan , Günther, Andreas , Guo, Chuanyong , Guo, Chun , Guo, Hongqing , Guo, Ming , Gupta, Pawan , Gupta, Swapnil , Gupta, Veer Bala , Gupta, Vivek , Gutterman, David D. , H.B., Ranjitha, Haber, James E. , Hać, Aleksandra , Haidar, Mansour , Halldén, Gunnel , Hamacher‐Brady, Anne , Hamasaki, Maho , Hansen, Malene , Hao, Zijian, Harada, Masaru , Harhaji‐Trajkovic, Ljubica , Hariharan, Nirmala , Haspel, Jeffrey A. , Haucke, Volker , Hawkins, Wayne D. , Haynes, Cole M. , Hays, Thomas S. , He, Congcong , He, Qin , He, Rong‐Rong , He, You‐Wen , Heakal, Yasser, Heberle, Alexander Martin , Hejtmancik, J. Fielding , Henkel, Vanessa, Herb, Marc , Herman-Antosiewicz, Anna , Hernández, Agustín , Hernández, Carlos , Hernández-Díaz, Sergio , Hernández–Gea, Virginia , Herpin, Amaury , Herreros, Judit , Hervás, Javier H. , Hesselson, Daniel , Hetz, Claudio , Higuchi, Yujiro , Hilfiker, Sabine , Hill, Joseph A., Ho, Emmanuel A. , Ho, Idy H. T. , Ho, Philip Wing‐Lok , Ho, Shu‐Leong , Ho, Wan Yun, Hoet, Peter , Hofius, Daniel , Höhn, Annika , Hong, Yi-Ren Hong Chang-Won, Hooper, Lora V. , Hsin, I‐Lun , Hu, Bing , Hu, Dong , Hu, Wei , Hu, Zhuowei , Hua, Jinlian, Huan, Chongmin , Huang, Chuanshu , Huang, Chunling , Huang, Haishan , Huang, Michael , Huang, Shan , Huang, Tianzhi , Huang, Xing , Huang, Yuxiang , Hubert, Virginie , Hübner, Christian A. , Hughes, Stephanie M. , Hughes, William E. , Hummer, Gerhard , Hurley, James H. , Hussain, Sabah N. A. , Hussain, Salik , Hutabarat, Martina , Hwang, Hui-Yun, Ieni, Antonio , Ikeda, Fumiyo , Imagawa, Yusuke , Imbriano, Carol , Imoto, Masaya , Inman, Denise M. , Inoki, Ken , Iozzo, Renato V. , Iribarren, Pablo , Ishaq, Mohd , Ishimwe, Nestor , Ismail, Nahed , Issazadeh‐Navikas, Shohreh , Itakura, Eisuke , Ito, Daisuke , Ivankovic, Davor , Ivanova, Saška , Iyer, Anand Krishnan V. , Izquierdo, José M. , Jacobo‐Herrera, Nadia , Jacquin, Élise , Jadiya, Pooja , Jaeschke, Hartmut , Jagannath, Chinnaswamy, Jakobsson, Johan , Janji, Bassam , Jansen‐Dürr, Pidder , Jansson, Patric J. , Januszewski, Sławomir, Jeltsch‐David, Hélène , Jenny, Andreas , Jensen, Thomas E. , Jessen, Niels , Jia, Lijun , Jia, Rui , Jiang, Qing , Jiang, Richeng , Jiang, Teng , Jiang, Xuejun , Jiang, Yu , Jiménez-Sánchez, María , Jin, Fengyan , Jin, Li , Jin, Luqi, Jin, Si , Joffre, Carine , Johnston, Simon A. , Jokitalo, Eija , Juárez, Esmeralda , Juhász, Gábor , Jun, Youngsoo , Jung, Chang Hwa , Jung, Sung‐Chul , Jungbluth, Heinz , Jungverdorben, Johannes , Just, Steffen , Kaasik, Allen , Kaganovich, Daniel , Kain, Renate , Kajimura, Shingo , Kalamvoki, Maria , Kalia, Manjula , Kalinowski, Danuta S. , Kaludercic, Nina , Kalvari, Ioanna , Kamińska, Joanna , Kanamori, Hiromitsu , Kang, Chanhee , Kang, Rui , Kang, Sang Sun , Kaniyappan, Senthilvelrajan , Kanki, Tomotake , Kanneganti, Thirumala‐Devi , Kanthasamy, Arthi , Kantorow, Marc , Kapuy, Orsolya , Karim, Md. Razaul , Kato, Masaru , Kauppinen, Anu , Kaushal, Gur P. , Kawasaki, Kiyoshi, Kazan, Kemal , Keber, Ursula , Keller, Kate E. , Kenific, Candia M. , Kepp, Oliver , Kern, Andreas , Keulers, Tom G. , Khalfin, Boris , Khalil, Hany , Khan, Shahid Y. , Khandelwal, Vinoth Kumar Megraj, Khandia, Rekha , Kho, Widuri , Khobrekar, Noopur V. , Khuansuwan, Sataree , Khundadze, Mukhran , Killackey, Samuel A. , Kim, Dasol , Kim, Deok Ryong, Kim, Do‐Hyung , Kim, Dong‐Eun , Kim, Eun‐Kyoung , Kim, Hak-Rim, Kim, Hee-Sik , Kim, Hyung-Ryong, Kim, Jeong Hun , Kim, Joungmok , Kim, Seong‐Jun , Kimball, Scot R., Kimchi, Adi , Kimmelman, Alec , Kimura, Tomonori , King, Matthew, Kinsey, Conan G. , Kirshenbaum, Lorrie A. , Kishi, Shuji , Kitamoto, Katsuhiko , Kitaoka, Yasushi , Kitazato, Kaio, Kitsis, Richard N. , Kjærulff, Ole , Klein, Peter S. , Klopstock, Thomas , Klucken, Jochen , Knævelsrud, Helene , Ko, Fred , Kobayashi, Satoru, Koch, Ina , Koch, Jan Christoph , Kögel, Donat , Koh, Young Ho , Kocatürk, Nur Mehpare , Komatsu, Masaaki, König, Jeannette , Kono, Toru, Korkmaz, Gözde , Korsnes, Mónica Suárez , Koskela, Ali , Kota, Janaiah , Kotake, Yaichiro , Kotler, Monica L., Kou, Yanjun , Koukourakis, Michael I., Koustas, Evangelos , Kovács, Tibor , Kovács, Tibor, Kraft, Claudine , Krainc, Dimitri, Krämer, Helmut, Krasnodembskaya, Anna , Kretz‐Remy, Carole , Kroemer, Guido, Kuenen, Sabine , Kuerschner, Lars , Kukar, Thomas , Kumar, Ajay , Kumar, Deepak, Kumar, Dhiraj, Kumar, Sharad , Kume, Shinji , Kumsta, Caroline , Kundu, Chanakya Nath , Kundu, Mondira, Kunnumakkara, Ajaikumar B. , Kutlu, Özlem , Kwak, SeongAe , Kwon, Yong Tae , Spada, Albert La, Labonté, Patrick , Ladoire, Sylvain , Laface, Ilaria, Lafont, Frank , Lagace, Diane C. , Lahiri, Vikramjit , Lai, Zhibing, Laird, Angela S. , Lakkaraju, Aparna , Lan, Sheng‐Hui , Landajuela, Ane , Lane, Darius J.R. , Lange, Carsten , Langer, Rupert , Lapaquette, Pierre, Laporte, Jocelyn , Lastres-Becker, Isabel, Lau, Wilson Chun Yu , Laurie, Gordon W. , Le, Weidong, Stunff, Hervé Le , Leary, Alexandre Y , Lebrun, Jean-Jacques, Leck, Lionel , Lee, Changwook , Lee, Chung‐Pei , Lee, Da-Hye , Lee, Edward B., Lee, Erinna F. , Lee, Gyun Min, Lee, He-Jin, Lee, Heung Kyu , Lee, Jason S. , Lee, Jin-A, Lee, Joo‐Yong , Lee, Michael , Lee, Min Goo , Lee, Min Jae, Lee, Myung‐Shik , Lee, Sangyoon , Lee, Stella Y. , Lee, Sung, Lee, Won Hee , Lee, Yong‐ho , Lee, Youngil , Lei, Yu L., Lei, Yuchen , Leikin, Sergey , Lemus, Leticia , Leng, Shuilong, Lenoir, Olivia , Lenz, Guido , Lenz, Heinz Josef, Lenzi, Paola, León, Yolanda , Leschczyk, Christoph, Leskelä, Stina, Letellier, Elisabeth , Leung, Chi-Ting, Leung, Po Sing , Leventhal, Jeremy S. , Levine, Beth, Lewis, Patrick A. , Ley, Klaus , Li, Bin , Li, Da‐Qiang , Li, Jian‐Ming , Li, Jiong , Li, Liwu , Li, Mei , Li, Ming , Li, Mingchuan , Li, Pin‐Lan, Li, Ming‐Qing , Li, Qing , Li, Sheng , Li, Wei , Li, Wenming , Li, Xue , Li, Yi-Ping, Li, Yuan , Li, Zhiqiang, Li, Zhiyong , Li, Zhiyuan , Lian, Jiqin, Liang, Chengyu, Liang, Qiangrong, Liang, Weicheng , Liang, Yongheng, Liang, YongTian , Liao, Guanghong , Liao, Lujian , Liao, Yung-Feng, Librizzi, Mariangela, Lie, Pearl P.Y. , Lim, Hyunjung J., Lima, Thania Rios Rossi , Limana, Federica , Lin, Chao , Lin, Chih-Wen, Lin, Dar‐Shong , Lin, Fu‐Cheng , Lin, Jiandie D. , Lin, Kurt M., Lin, Kwang‐Huei , Lin, Qiong, Lin, Shaofeng , Lin, Su-Ju, Lin, Wenyu , Lin, Yao‐Xin , Lin, Yee‐Shin, Linden, Rafael, Lindner, Paula , Lipinski, Marta M. , Lipovšek, Saška, Lisiak, Natalia , Liton, Paloma B. , Liu, Chao , Liu, Ching‐Hsuan , Liu, Fang , Liu, Hua-feng , Liu, Huifang , Liu, Jia , Liu, Jing , Liu, Leyuan, Liu, Wei , Liu, Wende , Liu, Xiao-Hong, Liu, Xu , Liu, Yanfen , Liu, Yang, Liu, Yang, Liu, Yueyang , Liu, Yule , Livingston, J. 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H. , Ma, Ning-Fang, Ma, Quanhong , Ma, Xinliang , Ma, Yueyun , Ma, Zhenyi , MacDougald, Ormond A. , MacIntosh, Gustavo C. , Macleod, Kay F. , Maday, Sandra , Madeo, Frank , Madesh, Muniswamy , Madl, Tobias , Madrigal‐Matute, Julio , Maeda, Akiko, Maejima, Yasuhiro , Magariños, Marta , Mahavadi, Poornima , Maiani, Emiliano , Maiese, Kenneth , Maiti, Panchanan , Maiuri, Maria Chiara , Major, Michael Ben, Makareeva, Elena , Malik, Fayaz , Mallilankaraman, Karthik , Maloyan, Alina , Mammadova, Najiba, Man, Gene Chi Wai , Manai, Federico , Mancias, Joseph D. , Mandelkow, Eva‐Maria , Manfredi, Angelo A. , Manshian, Bella B. , Manzano, Raquel , Marchese, Chiara , Marchetti, Sandrine , Marcucci, F, Mardente, Stefania , Mareninova, Olga A. , Mari, Muriel , Marinelli, Sara , Mariño, Guillermo , Mariotto, Sofia , Martin, Alexandre , Martin, Katie R. , Martin, Sara L. , Martín‐Segura, Adrián , Martin-Burriel, Inmaculada, Martín-Rincón, Marcos , Martín‐Sanz, Paloma , Martinez, Aitor , Martı́nez, Ana , Martinez-Lopez, Nuria, Martínez‐Vicente, Marta , Martins, Daniel Oliveira , Martins, Joilson O. , Martins, Waleska K. , Martins-Marques, Tania, Marzetti, Emanuele , Masaldan, Shashank , Masclaux-Daubresse, Celine, Mashek, Douglas G. , Massa, Valentina , Massieu, Lourdes , Masyuk, Anatoliy I. , Masyuk, Tetyana V., Matheu, Ander , Matoba, Satoaki , Matsuzaki, Sachiko , Mattar, Pamela , Mattè, Alessandro , Mauriz, José L., Mauthe, Mario , Maycotte, Paola , Mayer, Johanna , Mazzoni, Cristina , Mazzulli, Joseph R. , McCarty, Nami , McGill, Mitchell R. , McKenna, Sharon L. , McLoughlin, Fionn , McNiven, Mark A., McWilliams, Thomas G. , Medeiros, Tania , Medina, Diego L., Megeney, Lynn A. , Megyeri, Klára , Mehrpour, Maryam , Mehta, Jawahar L. , Meijer, Alfred J., Mejlvang, Jakob , Meléndez, Alicia , Melk, Annette, Memişoğlu, Gönen , Mendes, A.F. , Meng, Delong , Meng, Fei, Mercier, A., Mergny, Jean‐Louis , Merkley, Seth D. , Meske, Volker, Mestre, Ana Cecilia, Metur, Shree Padma, Meyer, C., Meyer, Hemmo , Mi, Wenyi , Mialet‐Perez, Jeanne , Miao, Jun‐Ying, Micale, Lucia , Miki, Yasuo, Milan, Enrico , Milczarek, Małgorzata , Miller, Samuel I. , Millward, Steven W. , Mirzaei, Hamed, Mirzaei, Hamid Reza , Mirzaei, Mehdi , Mishra, Amit , Mishra, Nandita , Mishra, Paras Kumar, Misirkić, Maja , Misasi, Roberta, Misra, Amit , Misso, Gabriella , Mitchell, Claire H. , Mitou, Géraldine, Miura, Tetsuji , Miyazaki, Makoto, Miyazaki, Mitsunori , Miyazaki, Taiga , Miyazawa, Keisuke, Mizushima, Noboru , Mogensen, Trine H. , Mohammadinejad, Reza , Mohamud, Yasir , Mohanty, Abhishek , Möhlmann, Torsten , Moley, Kelle H. , Möller, Andreas, Mollereau, Bertrand , Mollinedo, Faustino, Montagna, Costanza , Monteiro, Mervyn J. , Montella, Andrea , Montes, L. Ruth , Montico, Barbara , Mony, Vinod K., Compagnoni, Giacomo Monzio , Moore, Michael N. , Moosavi, Mohammad Amin , Morales‐Álamo, David , Moratalla, Rosario , Moreira, Paula I. , Morelli, Elena , Moreno-Blas, Daniel , Morgan, Alwena H. , Morin, Fabrice , Morishita, Hideaki , Moriyama, Mariko , Moriyasu, Yuji, Morleo, Manuela , Morselli, Eugenia , Moruno-Manchon, Jose F. , Moscat, Jorge , Motori, Elisa , Moura, Andréa Felinto , Mrakovcic, Maria, Muciño-Hernández, Gabriel, Mukherjee, Anupam , Mukhopadhyay, Subhadip , Levy, Jean M. 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Celeste, Nicoli, Francesco , Nieto‐Díaz, Manuel , Niranjan, Rituraj , Nishimune, Hiroshi , Niso-Santano, Mireia, Nixon, Ralph A. , Nobili, Annalisa , Noda, Takeshi , Nogueira-Recalde, Uxía , Nombela, Iván , Novak, Ivana, Novoa, Beatriz , Nukina, Nobuyuki , Nussbaum-Krammer, Carmen, Nylandsted, Jesper , O’Donovan, Tracey R. , O’Leary, Seónadh M. , O’Rourke, Eyleen J. , O’Sullivan, Mary P. , O’Sullivan, Timothy E., Oddo, Salvatore , Oehme, Ina, Ogawa, Michinaga , Ogier‐Denis, Éric , Ögmundsdóttir, Margrét H. , Öğretmen, Besim , Oh, Goo Taeg , Oh, Seon‐Hee , Oh, Young J. , Ohama, Takashi, Ohashi, Yohei , Ohmuraya, Masaki, Oikonomou, Vasileios , Ojha, Rani , Okazawa, Hitoshi , Oku, M., Oliván, Sara , Oliveira, Jorge M.A. , Ollmann, Michael, Olzmann, James A. , Omari, Shakib , Önal, Gizem, Ondrej, Martin , Ong, Sang‐Bing , Onnis, Anna , Orellana, Juan , Orellana‐Muñoz, Sara , Ortega-Villaizán, María del Mar , Ortiz‐González, Xilma R. , Osiewacz, Heinz D. , Osman, Abdel‐Hamid K. , Otsu, Kinya, Ott, Christiane , Ou, Jing-hsiung James, Outeiro, Tiago F., Öztürk, Melek , Pagès, Gilles, Pahari, Susanta , Pajares, Marta, Pal, Rituraj, Paladino, Simona , Palmieri, Michela , Palmisano, Giuseppe , Pan, Qingjun , Pan, Xin , Panasyuk, Ganna , Pandey, Rahul , Pandey, Udai B., Pandya, Vrajesh , Paneni, Francesco , Pang, Shirley Yin-Yu, Papademetrio, Daniela L. , Papinski, Daniel, Papp, Diana , Park, Hwan Tae , Park, Ji-Man, Park, Jong‐In , Park, Junsoo, Park, Sang-Youel, Pasquier, Adrien , Pasquier, Benoit , Passos, João F. , Pastore, Nunzia , Patschan, Daniel , Pattingre, Sophie , Pedraza‐Alva, Gustavo , Pedraza-Chaverri, Jose, Pedrozo, Zully , Pei, Gang , Pei, Jianming , Peled-Zehavi, Hadas, Pellegrini, Joaquín Miguel , Pelletier, Joffrey , Peñalva, Miguel A., Peng, Di , Peng, Ying , Pennuto, Maria , Pentimalli, Francesca , Pereira, Cláudia MF, Pereira, Gustavo J.S. , Pereira, Lílian Cristina , Almeida, Luís Pereira de , Perera, Nirma D. , Pérez-Lara, Ángel, Pérez‐Oliva, Ana B. , Perl, András , Pestell, Richard G. , Petrache, I., Petrovski, Goran , Pfirrmann, Thorsten , Pfister, Astrid S., Pi, Huifeng , Pickrell, Alicia M. , Picot, Sandy, Pierantoni, Giovanna Maria , Pierre, Philippe , Pierrefite‐Carle, Valérie , Pierzynowska, Karolina , Pietruczuk, Mirosława , Pimentel-Muiños, Felipe X., Pinar, Mario , Pinheiro, Roberta Olmo , Pinkas‐Kramarski, Ronit , Pircs, Karolina , Piya, Sujan , Pizzo, Paola , Platta, Harald W. , Plomann, Markus , Pocock, Roger , Pöggeler, Stefanie , Pohl, Christian, Poirot, Marc , Poletti, Angelo , Ponpuak, Marisa , Popelka, Hana , Popova, Bilyana , Porta, Helena, Alcón, Soledad Porte , Portilla-Fernández, Eliana , Potts, Malia B. , Powers, Ted, Prahlad, Veena , Prajsnar, Tomasz K. , Praticò, Domenico , Prencipe, Rosaria, Priault, Muriel , Proikas‐Cezanne, Tassula , Puertollano, Rosa , Puglielli, Luigi, Pulinilkunnil, Thomas , Puri, Deepika , Puri, Rajat, Puyal, Julien , Qi, Yongmei , Quadrilatero, Joe , Quarleri, Jorge, Raben, Nina, Rabinowich, Hannah, Ragona, Debora, Rahmati, Marveh , Raia, Valeria, Raimundo, Nuno , Rajasekaran, Namakkal-Soorappan, Rao, Sriganesh Ramachandra , Rami, Abdelhaq, Ramírez‐Pardo, Ignacio , Ramsden, D. , Randow, Felix , Ranieri, Danilo , Rao, Hai , Rao, Rekha , Rathore, Sumit , Ratnayaka, J. 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M. , Soldati, Thierry , Soler, Rosa M. , Somarelli, Jason A. , Sonawane, Avinash , Song, Fuyong, Song, Hyun Kyu , Song, Kunhua , Sorice, Maurizio , Soukas, Alexander A. , Soukup, Sandra‐Fausia , Sousa, Diana , Sousa, Nadia, Bharath, M. M. Srinivas , Clair, Daret St., Stagni, Venturina, Staiano, Leopoldo , Stankov, Metodi V. , Stathopulos, Peter B. , Stefan, Katja, Stefan, Sven Marcel , Stefanis, Leonidas, Steffan, Joan S. , Steinkasserer, Alexander , Stenmark, Harald, Sterneckert, Jared , Stevens, Craig , Storch, Stephan , Strappazzon, Flavie , Strohecker, Anne M. , Stupack, Dwayne G., Su, Huanxing , Su, Ling‐Yan , Suarez-Fontes, Ana Márcia , Subirada, Paula V., Sudhandiran, Ganapasam, Sue, Carolyn M. , Sui, Xinbing , Summers, Corey M., Sun, Guangchao , Sun, Zhongjie , Sunahara, Karen K. S. , Susztak, Katalin, Šutovský, Peter , Suzuki, Hidekazu , Sweeney, Gary , Symons, J. David , Sze, Stephen Cho Wing , Szewczyk, Nathaniel J. , Tabęcka-Łonczynska, Anna, Tabolacci, Claudio , Taegtmeyer, Heinrich, Tagaya, Mitsuo , Tai, Haoran , Tait, Stephen W. G., Takahashi, Yoshinori , Tam, Chit , Tam, Shing Yau , Tampellini, Davide , Tamura, Atsushi , Tan, Eng-King, Tan, Ya‐Qin , Tanaka, Masaki , Tang, Daolin , Tang, Jingfeng , Tang, Tie-Shan , Tao, Zhipeng , Taouis, Mohammed , Tavernarakis, Nektarios, Taylor, Allen, Teixeira, Natércia , Tekirdağ, Kumsal Ayşe, Tencomnao, Tewin , Tenreiro, Sandra , Tharaux, Pierre‐Louis , Thedieck, Kathrin , Thekkinghat, Arvind A. , Thinwa, Josephine , Thirumalaikumar, Venkatesh P. , Thomes, Paul G. , Thorburn, Andrew , Thum, Thomas, Thumm, Michael , Tian, Ling, Tichý, Aleš , Timmerman, Vincent , Titorenko, Vladimir I. , Toivonen, Janne M. , Tomaipitinca, Luana , Tomar, Dhanendra , Tomás‐Zapico, Cristina , Tomić, Sergej , Tong, Chao, Tong, Xin , Torgersen, Maria L., Torii, Satoru , Torres-López, Liliana , Torriglia, Alicia , Towers, Christina G. , Towns, Roberto, Tran, Quynh‐Giao , Travassos, Leonardo H. , Tremel, Shirley , Trougakos, Ioannis P., Tsao, Betty P. , Tse, Tak Fu, Tsvetkov, Andrey S. , Tumbarello, David A. , Tyler, Jessica K., Tyutereva, Elena V. , Uchiyama, Yasuo , Ugun‐Klusek, Aslihan , Uhlig, Holm H. , Ułamek-Kozioł, Marzena, Ulasov, Ilya V. , Umekawa, Midori, Ungermann, Christian , Urbe, Sylvie, Uribe-Carretero, Elisabet , Uversky, Vladimir N. , Vaccaro, María I. , Vahsen, Björn F. , Vakifahmetoglu-Norberg, Helin, Valdor, Rut , Valente, Maria João , Valko, Ayelén , Vallée, Richard, Valverde, Ángela M. , Berghe, Greet Van den, Veen, Stijn van der , Kaer, Luc Van , Loosdregt, Jorg van , Wijk, Sjoerd J. L. van , Vandenberghe, Wim , Vanhorebeek, Ilse , Vannier-Santos, Marcos A., Vannini, Nicola , Vanrell, M. Cristina, Vantaggiato, Chiara , Varela‐Nieto, Isabel , Varga, Máté , Vasconcelos, M. Helena , Vats, Somya , Vega-Rubín-de-Celis, Silvia , Velasco, Guillermo , Velázquez, Ariadna P., Vellai, Tibor , Vellenga, Edo , Verdier, Mireille , Verginis, Panayotis , Vergne, Isabelle , Verkade, Paul , Verma, Manish , Verstreken, Patrik , Vervliet, Tim , Vervoorts, Jörg , Víctor, Víctor M., Vidoni, Chiara , Vieira, Otília V. , Vierstra, Richard D., Viganò, Sonia , Vihinen, Helena , Vijayan, Vinoy, Vila, Miquel , Villalba, José M., Villalobo, Antonio , Villarejo‐Zori, Beatriz , Vincent, Olivier , Vindis, Cécile , Viret, Christophe , Vocadlo, David J. , Voitsekhovskaja, Olga V. , Volonté, Cinzia , Volta, Mattia , Vomero, Marta , Haefen, Clarissa von, Vooijs, Marc , Voos, Wolfgang , Vučićević, Ljubica , Waguri, Satoshi , Waite, Kenrick A., Wakatsuki, Shuji , Walker, David W., Walker, Mark J. , Walter, Jochen, Wandosell, Francisco , Wang, Bo , Wang, Chao-Yung, Wang, Chen , Wang, Chenran, Wang, Chenwei , Wang, Cun-Yu, Wang, Fengming, Wang, Han, Wang, Hexiang , Wang, Hong‐Gang , Wang, Jianrong, Wang, Jigang , Wang, Jun-Dong , Wang, Kui , Wang, Lianrong, Wang, Liming , Wang, Maggie Haitian, Wang, Meiqing , Wang, Nanbu , Wang, Pengwei , Wang, Ping , Wang, Ping, Wang, Q., Wang, Qiong , Wang, Wentao , Wang, Xinnan, Wang, Xuejun , Wang, Yan, Wang, Yanchang , Wang, Yanzhuang , Wang, Yihua , Wang, Yu , Wang, Yuqi , Wang, Zhe, Wang, Zhenyu , Wang, Zhouguang , Watanabe, Eizo, Watchon, Maxinne , Wawrzyńska, Anna , Weaver, Timothy E., Węgrzyn, Grzegorz, Wehman, Ann M. , Wei, Huafeng , Wei, Taotao , Wei, Yongjie, Weiergräber, Oliver H. , Weihl, Conrad C., Weindl, Günther , Weiskirchen, Ralf , Wen, Runxia H. , Werner, Antonia, Weykopf, Beatrice , Whitton, J. Lindsay , Wiktorska, Katarzyna , Wildenberg, Manon E. , Wileman, Tom, Wilkinson, Simon , Williams, Brett, Williams, Robin S. B. , Williamson, Peter R. , Wilson, Richard A. , Winsor, Nathaniel J. , Wodrich, Harald , Woehlbier, Ute , Wollert, Thomas , Wong, Richard W., Wong, Vincent Kam Wai , Wong, W. Wei-Lynn, Wu, Anguo , Wu, Kenneth K., Wu, Shan‐Ying , Wu, William Ka Kei , Wu, Shufang, Wu, Xiaoqing , Wu, Yao‐Wen , Wu, Yihua , Xavier, Ramnik J. , Xia, Hongguang , Xia, Lixin , Xia, Zhengyuan , Ge, Xiang , Xiang, Jin , Xiang, Mingliang , Xiang, Wei , Xiao, Guozhi , Xiao, Hengyi , Xiao, Hongtao , Xiao, Jian, Xiao, Lan , Xiao, Shi , Xiao, Yin , Xie, Baoming, Xie, Zhiping , Xie, Min , Xie, Yuxiang , Xie, Zhonglin, Xilouri, Maria , Xu, En , Xu, Jin‐Rong , Xu, Liang , Xu, Xiulong , Xue, Yu , Yakhine-Diop, Sokhna M. S. , Yamaguchi, Masamitsu , Yamamoto, Ai , Yamashina, Shunhei, Yan, Shengmin , Yan, Shian-Jang, Yan, Zhen , Yang, Chuanbin , Yang, Dun-Sheng, Yang, Huan , Yang, Huang-Tian, Yang, Hui , Yang, Jing , Yang, Jingyu , Yang, Ling , Liu, Yang , Yang, Ming , Yang, Seungwon, Yang, Shu , Yang, Shun-Fa , Yang, Wannian, Yang, Wei , Yang, Xiaoyong , Yang, Yi , Yao, Xiaoqiang , Yao, Yong-Gang , Yao, Yong-ming, Yasui, Takahiro , Yazdankhah, Meysam, Yi, Cong , Yin, Xiao-Ming , Yin, Yanhai , Yin, Zhangyuan , Yin, Ziyi , Ying, Meidan , Ying, Zheng, Yip, Calvin K. , Yiu, Stephanie Pei Tung , Yoo, Young Hyun , Yoshimori, Tamotsu, Yousefi, Bahman, Yu, Boxuan , Yu, Haiyang , Yu, Jun, Li, Yu , Yu, Ming‐Lung , Yu, Seong-Woon, Yu, Victor C. , Yu, Zhengping, Yuan, Junying , Yuan, Ling‐Qing , Yuan, Shilin , Yuan, Yanggang , Yuan, Zengqiang , Yue, Jianbo , Yue, Zhenyu , Yung, Raymond , Zacks, David, Zaffagnini, Gabriele , Zambelli, Vanessa O. , Zanella, Isabella , Zang, Qun S. , Zanivan, Sara , Zappavigna, Silvia , Zaragoza, P. , Zarbalis, Konstantinos S., Zarebkohan, Amir , Zarrouk, Amira , Zeitlin, Scott, Zeng, Jialiu , Zeng, Judeng , Žerovnik, Eva , Zhan, Lixuan , Zhang, Donna D., Zhang, Hong , Zhang, Honghe , Zhang, Huafeng , Zhang, Huaye, Zhang, Huiling , Zhang, Jianbin , Zhang, Jingpu , Zhang, Kalin Yanbo , Zhang, Leshuai W. , Zhang, Lu , Zhang, Luoying , Zhang, Menghuan, Zhang, Peng , Zhang, Sheng , Zhang, Xiangnan, Zhang, Xiao-Wei, Zhang, Xiaolei , Zhang, Xiaoyan , Zhang, Xin , Zhang, Xinxin , Zhang, Yang, Zhang, Yi , Zhang, Yingdong , Zhang, Yuanyuan , Zhang, Yuchen , Zhang, Zhe , Zhang, Zhibing , Zhang, Zili , Zhao, Haobin, Zhao, Lei , Zhao, Shuang , Zhao, Tongbiao , Zhao, Ying, Zhao, Yongchao , Zhao, Yongliang , Zhao, Yuting , Zheng, Guoping , Zheng, Kai, Zheng, Ling , Zheng, Shizhong , Zheng, Xi‐Long , Zheng, Zu‐Guo , Zhivotovsky, Boris, Zhong, Qing , Zhou, Ao, Zhou, Ben , Zhou, Cefan , Zhou, Gang , Zhou, Hongbo , Zhou, Kailiang, Zhou, Rongjia , Zhou, Yanshuang, Zhou, Yinghong , Zhou, Yubin , Zhou, Zhengyu, Zhou, Zhou , Zhu, Binglin , Zhu, Changlian , Zhu, Guo‐Qing , Zhu, Haining , Zhu, Hongxin, Zhu, Yanping , Zhu, Yushan , Zhuang, Haixia , Zhuang, Xiaohong , Zimmermann, Christine , Żołądek, Teresa , Zong, Wei‐Xing, Zorov, Dmitry B. , Zorzano, Antonio, Zou, Weiping, Zou, Zhen , Zou, Zhengzhi, Zuryn, Steven , Kenchappa, Chandra Shekar, Li, Zuguo , Lin, Yong , Sluimer, Judith C. , Stallings, Christina L. , Tong, Chun-Kit, Wang, Ping , Hu, Bo , Lee, Edward B. , Tse, Hung‐Fat , Suszták, Katalin , Lei, Yu Leo , Yu, M-L , Dai, Yun , Bartolome, Alberto , Brown, Rhoderick E , Passos, João F , Paneni, Francesco , Sahin, Özgür , Pereira de Almeida, Luis , Ren, Jun , Bornhauser, Beat , Kumar, Sharad , Sampaio-Marques, Belém , Ludovico, Paula , Luftig, Micah , Begun, Jakob , Krasnodembskaya, Anna D , Dafsari, Hormos Salimi , Chevet, Eric , Tse, Hung-Fat , Barmada, Sami , Ebrahimi-Fakhari, Darius , Cavadas, Claudia , Sue, Carolyn M , Cardenal-Muñoz, Elena , Lee, Edward B , Golebiewska, Anna , Calbet, Jose A L , Boya, Patricia , Maday, Sandra , Klionsky, Daniel J. , Abdelfatah, Sara , Abdoli, Asghar , Agarwal, Anupam , Ahmed, Zubair M. , Alcocer‐Gómez, Elísabet , Ali, Muhammad , Al‐Bari, Md. Abdul Alim , Aliwaini, Saeb H. , Alizadeh, Javad , Almacellas, Eugènia , Almasan, Alexandru , Alonso, G. , Altieri, Dario C. , Andersen, Stig Uggerhøj , Andrade-Silva, Magaiver , Angelini, Sabrina , Apostolova, Nadezda , Arasaki, Kohei , Araújo, Wagner L. , Arden, Catherine , Arimoto, Hirokazu , Armstrong-James, Darius P. H. , Pelloquin, Laetitia , Aschner, Michael , Ashrafizadeh, Milad , Autelli, Riccardo , Aveic, Sanja , Avin‐Wittenberg, Tamar , Ayton, Scott , Backues, Steven K. , Bae, Dong-Hun , Bae, Ok‐Nam , Baek, Ahruem , Baek, Seung‐Hoon , Baek, Sung Hee , Bai, Jie , Bai, Yidong , Baldari, Cosima T. , Balduini, Walter , Ballabio, Andrea , Banerjee, Sreeparna , Bao, Yan , Baptista, Maurı́cio S. , Barreto, George Emilio , Basagoudanavar, Suresh H. , Bast, Robert C. , Basu, Alakananda , Batoko, Henri , Batten, Isabella , Behrens, Georg M. N. , Bei, Roberto , Behl, Christian , Bello‐Morales, Raquel , Beltrán, Sebastián , Bergami, Matteo , Bergmann, Andreas , Berthoux, Lionel , Bhattacharya, Resham , Bhattacharyya, Shalmoli , Bhutia, Sujit Kumar , Bi, Lanrong , Birgisdottir, Åsa Birna , Bjørkøy, Geir , Blomgren, Klas , Boada-Romero, Emilio , Boesze‐Battaglia, Kathleen , Bonifacino, Juan S. , Boone, Brian A. , Borthakur, Gautam , Bosch, Jürgen , Bose, Santanu , Botana, Luis Miguel , Boulton, Michael E. , Bourdenx, Mathieu , Brackney, Doug E. , Brandts, Christian , Braun, Ralf J. , Braus, Gerhard H. , Bravo, Roberto , Brody, Steven L. , Brown, Carolyn Nicole , Brumell, John Hunter , Brunetti‐Pierri, Nicola , Buitrago‐Molina, Laura Elisa , Buraschi, Simone , Buch, Shilpa J. , Butturini, Elena , Cairó, Montserrat , Caldwell, Kim A. , Campbell‐Valois, François‐Xavier , Campello, Silvia , Campesi, Ilaria , Almeida, Danilo Cândido de , Canesi, Laura , Caraglia, Michele , Carchman, Evie H. , Carmona‐Gutiérrez, Didac , Carnevali, Oliana , Carrier, Lucie , Carroll, Bernadette , Carter, A. Brent , Casas, Caty , Castillo, Eliseo F. , Castro‐Caldas, Margarida , Castro‐Obregón, Susana , Catz, Sergio , Cayuela, María Luisa , Cecarini, Valentina , Cecconi, Francesco , Cenci, Simone , Ceperuelo‐Mallafré, Victòria , Cervia, Davide , Chae, Han–Jung , Chakrabarti, Oishee , Chan, Edmond Y. W., Chan, Edward D. , Chandra, Partha Kumar , Chang, Chih‐Peng , Chang, Chunmei , Chapman, Tracey , Chen, Guang‐Chao , Chen, Leilei , Chen, Lin , Chen, Quan , Chen, Ruey‐Hwa , Chen, Shi , Chen, Wei‐Qiang , Chen, Xu , Chen, Yu-Jen , Chen, Yujie , Chen, Zhi , Chen, Zhijian J. , Chen, Zhixiang , Cheng, Hanhua , Cheng, Jun , Cheng, Shi‐Yuan , Cheng, Wei Nee , Cheng, Xiaodong , Chen, Zhong , Cheong, Heesun , Chernyak, Boris V. , Chi, Richard J., Chiang, Aks , Chiarelli, Roberto , Chu, Charleen T. , Chung, Seockhoon , Cianfanelli, Valentina , Cifuentes, Mariana , Cirone, Mara , Clague, Michael J. , Cohen, Ehud , Cohen, Mickaël M. , Čolić, Miodrag J , Combaret, Lydie , Comincini, Sergio , Conte, Andrea, Conti, Fabrizio , Coppens, Isabelle , Corasaniti, Maria Tiziana , Corkery, Dale , Cordes, Nils , Cortese, Katia , Coto‐Montes, Ana M. , Crack, Peter John , Crespo, José L. , Cuadrado, Antonio , Cui, Jun , Cui, Yong , D’Arcangelo, Daniela , D’Lugos, Andrew C. , Dagda, Ruben Karim , Dagdas, Yasin , Daμμe, Markus , Dantuma, Nico P. , Darling, April L. , Dasarathy, Srinivasan , Daumke, Oliver , Davis, Tanja , Amicis, Francesca De , Felice, Francesca De , Franceschi, Lucia De , Milito, Angelo De , Nunzio, Cosimo De , Santi, Mauro De , Debnath, Jayanta , DeBosch, Brian J. , DeGregori, James V. , Rio, Gabriel del , Delbridge, Lea M.D. , Delpino, M. Victoria , Demarchi, Francesca , Dembitz, Vilma , Deng, Zhiqiang , Denton, Donna , Der, Channing J , Deretić, Vojo , Dhiman, Rohan , Bernardo, Diego di , Cristina, Manlio Di , Nardo, Alessia Di, Sano, Federica Di , Diallinas, George , Diaz-Araya, Guillermo, Đikić, Ivan , Ding, Wen‐Xing , Dini, Luciana , Dionne, Marc , Diwan, Abhinav , Dixon, Ian , Djavaheri‐Mergny, Mojgan , Dobrinski, Ina , Dobrovinskaya, Oxana R. , Dobrowolski, Radek , Dobson, Renwick C. J. , Donadelli, Massimo , Dong, Bo, Dötsch, Volker , Dou, Huan , Dridi, Sami , Du, Caigan , Du, Li‐Lin , Dubrovska, Anna , Dunlop, Elaine A. , Dwarakanath, Bilikere Srinivasa Rao , Eftekharpour, Eftekhar , Eichinger, Ludwig , Eissa, N. Tony , Eissa, Sanaa , El‐Naggar, Shahenda , Eliopoulos, Aristides G. , Elks, Philip M. , Emerling, Brooke M. , Engelbrecht, Anna‐Mart , Escobar‐Henriques, Mafalda , Fabriàs, Gemma , Fabrizi, Cinzia , Falkenburger, Björn H. , Fan, Yanbo , Fanto, Manolis , Feng, Du , Feng, Yibin , Feng, Yuchen , Fernández-Checa, José Carlos , Filippi‐Chiela, Eduardo Cremonese , Filomeni, Giuseppe , Fineschi, Vittorio , Flamigni, Flavio , Follo, Carlo , Fon, Edward A , Fornai, Francesco , Fraldi, Alessandro , Franco, Brunella , Franco, Rodrigo , Friedman, Scott L. , Frühbeck, Gema , Fujita, Naonobu , Fujiwara, Yuuki , Fukuda, Mitsunori , Furic, Luc , Fusco, Carmela , Galluzzi, Lorenzo, Gan, Boyi , Gao, Hui , Gao, Shou‐Jiang , Gargini, Ricardo , Garry, Robert F. , Ge, Liang , Ge, Wanzhong , Gelfi, Cecilia , Gentle, Ian Edward , Gewirtz, David A , Ghigo, Alessandra , Giampietri, Claudia , Gibson, Spencer B. , Giniger, Edward , Giorgi, Carlotta , Girão, Henrique , Goldstone, David C. , Gomez‐Puerto, Maria Catalina , Goñi, Félix M. , González‐Hernández, Tomás , Gorbatyuk, Marina S. , Goruppi, Sandro , Gottlieb, Roberta A. , Gozes, Illana , Green, Douglas R. , Grinstaff, Mark W. , Grune, Tilman , Guntur, Anyonya R. , Guo, Lian‐Wang , Gupta, Shashi Kumar , Gustafsson, Åsa B. , Haapasalo, Annakaisa , Hadano, Shinji , Hafrén, Anders , Hall, Belinda S. , Hamann, Andréa , Han, Weidong , Hanson, Phyllis I. , Haroon, Nigil , Harris, James , Hasegawa, Takafumi , Nagoor, Noor Hasima , Hay, Bruce A. , Hayrabedyan, Soren , He, Yu‐Ying , Helgason, G. Vignir , Hergovich, Alexander , Hernández–Gea, Virginia , Heussler, Volker Theo , Hlavacek, William S. , Hobbs, G. Aaron , Hochstrasser, Mark , Hofman, Paul , Holmberg, Carina I. , Hombrebueno, José R. , Hoppe, Thorsten , Horos, Rastislav , Hoshida, Yujin , Hsu, Hsin‐Yun , Hu, Li‐Fang , Hu, Ming Chang , Hu, Ronggui , Hu, Yu‐Chen , Hua, Fang , Hua, Jinlian, Hua, Yingqi , Huang, Canhua , Huang, Chuanxin , Huang, Kun , Huang, Rui , Huber, Tobias Bruno , Humbert, Magali , Hussey, Patrick J. , Hwang, Hui‐Yun , Hwang, Seungmin , Imai, Yuzuru , Iovanna, Juan , Ippolito, Giuseppe , Irazoqui, Javier E. , Ishaq, Mohd, Ishikawa, Makoto , Isidoro, Ciro , Izumi, Masanori , Jäättelä, Marja , Jabir, Majid Sakhi , Jackson, William T. , Jacomin, Anne‐Claire , Jakobi, Arjen J. , Jantsch, Jonathan , Jassey, Alagie , Jean, Steve , Jendelová, Pavla , Jewell, Jenna L. , Ji, Jing , Jiang, Liwen , Jin, Eun‐Jung , Jin, Hongchuan , Jin, Meiyan , Jo, Eun‐Kyeong , Johansen, Terje , Johnson, Gail V.W. , Jolly, Mohit Kumar , Joosten, Leo A. B. , Jordán, Joaquı́n , Joseph, Bertrand , Ju, Dianwen , Ju, Jeong-Sun , Ju, Jingfang , Judith, Delphine , Jung, Yong‐Keun , Kaarniranta, Kai , Kabuta, Tomohiro , Kahana, Alon , Kaminskyy, Vitaliy O. , Kanasaki, Keizo , Kanthasamy, Anumantha G. , Karamouzis, Michalis V. , Karmakar, Parimal , Katare, Rajesh , Kaufmann, Stefan H. E. , Kaushik, Susmita , Kawasaki, Kiyoshi, Ke, Po‐Yuan , Keating, Damien J. , Kehrl, John H. , Keller, Christian W. , Kemper, Jongsook Kim , Kermorgant, Stéphanie , Ketteler, Robin , Khambu, Bilon , Kim, Deok Ryong, Kim, Eun Young , Kim, Jin Kyung , Kim, Jin‐Hoi , Kim, Ju Hwan , Kim, Keun Il , Kim, Peter Kijun , Kinghorn, Kerri J. , Kirkin, Vladimir , Киселев, С. Л. , Kittler, Josef T. , Knorr, Roland L. , Ko, Ben C.B. , Ko, Jiunn‐Liang , Kobayashi, Hotaka , Koenig, Ulrich , Koike, Masato , Kohlwein, Sepp Dieter , Komatsu, Masaaki , Kopp, Benjamin T. , Korcsmaros, Tamas Douglas , Korolchuk, Viktor I. , Kotler, Mónica L. , Koukourakis, Michael Ioannis , Kovács, Tibor, Koya, Daisuke , Kozako, Tomohiro , Krämer, Helmut , Kroemer, Guido , Ktistakis, Nicholas T. , Kuchitsu, Kazuyuki , Kumar, Ashok , Kumar, Deepak, Kundu, Mondira , Kurgan, Lukasz , Kutateladze, Tatiana G. , Kwon, Ho Jeong , Kwon, Taeg Kyu , Kyrmizi, Irene , Spada, Albert R. La , Lai, Zhibing, Lamark, Trond , Lane, Jon D. , Lang, Charles H. , Lange, Carsten, Langel, Ülo , Lapaquette, Pierre , LaRusso, Nicholas F. , Lastres‐Becker, Isabel , Lavandero, Sergio , Law, Hkw , Layfield, Robert , Leduc‐Gaudet, Jean‐Philippe , Lee, He-Jin, Lee, Jae Man , Lee, Jun Hee , Lee, Seung‐Jae , Lee, Ying‐Ray , Lefebvre, Christophe , Legouis, Renaud , Leitinger, Gerd , Lenz, Heinz Josef, León, Yolanda, Leopoldino, Andréia Machado , Leung, Chi-Ting, Levine, Beth , Li, Jing , Li, Ke, Li, Min , Li, Min , Li, Pin‐Lan , Li, Tiangang , Li, Zhiqiang, Lian, Jiqin , Liang, Chengyu, Liang, Qiangrong , Liao, Mingzhi , Lilly, Mary A. , Lin, Liang , Lin, Pei‐Hui , Lin, Xueying , Linden, Rafael , Ling, Shuo‐Chien , Lingor, Paul , Linnemann, Amelia K , Liou, Yih‐Cherng , Lira, Vitor Agnew , Liu, Chunfeng , Liu, Cui Hua , Liu, Hao , Liu, Hsiao‐Sheng , Liu, Julia C. , Liu, Longhua , Liu, Meilian , Liu, Qin , Liu, Xiao-Hong, Liu, Xiaodong , Liu, Xingguo , Liu, Xuedong , Liu, Yang, Liu, Yang, Lizard, Gérard , Llorente, Alicia , Long, Qi , Long, Yun Chau, López, Manuela G. , Lőrincz, Péter , Lovat, Penny E. , Lu, Jin‐Jian , Lum, Julian J., Lünemann, Jan D. , Luo, Shouqing , Ma, Changle , Ma, Mengxiao , Ma, Ning‐Fang , Macián, Fernando , MacKeigan, Jeffrey P. , Majello, Barbara , Malorni, Walter , Mandell, Michael A. , Manjili, Masoud H. , Manjithaya, Ravi R. , Manque, Patrício , Manzoni, Claudia , Mao, Kai, Marconi, Anna Maria , Margeta, Marta , Marinelli, Oliviero , Marshall, Richard Scott , Marten, Mark R. , Martens, Sascha , Martin, Sara, Martín-Acebes, Miguel A. , Martín‐Burriel, Inmaculada , Martina, José A. , Martinet, Wim , Martinez, Jennifer , Martínez‐Velázquez, Moisés , Martinez-Lopez, Nuria, Martins‐Marques, Tânia , Masclaux‐Daubresse, Céline , Masson, Glenn Robert , Masuelli, Laura , Masyuk, Tetyana V., Matarrese, Paola , Mattoscio, Domenico , Mauriz, Jose Luis , Mauvezin, Caroline , Maverakis, Emanual Michael , Mazzoccoli, Gianluigi , McDonald, Christine , McLaughlin, BethAnn , Mechta‐Grigoriou, Fatima , Meijer, Annemarie H. , Meng, Tian, Menna‐Barreto, Rubem F. S. , Menon, Manoj B., Mercer, Carol A. , Mercier, Anne E., Merighi, Adalberto , Merla, Giuseppe , Miller, Dana L. , Miller, Silke , Milošević, Ira , Minina, Elena A. , Mirzaei, Mehdi, Mishra, Paras Kumar , Miyamoto, Shigeki, Miyazawa, Keisuke, Mograbi, Baharia , Mohanty, Abhishek , Mohapatra, Sipra , Mohmmed, Asif , Moles, Anna , Molinari, Maurizio , Mollace, Vincenzo , Møller, Andreas Buch , Mora, Ana Lucia , Mora, Marina, Morelli, Elena, Moreno, Sandra , Moresi, Viviana , Morga, Benjamín , Moritz, Orson L. , Moriyama, Mariko, Mostowy, Serge , Moustaïd‐Moussa, Naïma , Muller, Sylviane , Munjal, Ashok Kumar , Muñoz‐Cánoves, Pura , Münz, Christian , Muratori, Claudia, Murphy, John Patrick , Nabissi, Massimo , Nah, Jihoon , Nakagawa, Ichiro, Nakatogawa, Hitoshi , Nardacci, Roberta , Narita, Masashi , Neri, Luca Maria , Neufeld, Thomas P. , Nezis, Ioannis P. , Ni, Hong‐Min , Nicolao, María Celeste , Nilsson, Per Gunnar , Ning, Shunbin , Nóbrega, Clévio , Nolan, Trevor M. , Novak, Ivana, Nozawa, Takashi , Nussbaum-Krammer, Carmen I. , O’Sullivan, Timothy E., Oehme, Ina , Ohmuraya, Masaki , Okamoto, Koji , Oku, Masahide, Omary, M. 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Thomas , Sandri, Marco F. , Santaguida, Stefano , Sanz, Alberto, Sanz, Pascual , Sathyanarayanan, Ranganayaki, Schaefer, Liliana , Scharl, Michael M. , Schätzl, Hermann M. , Scheper, Wiep , Scheuring, David , Schott, Micah B. , Schramm, Michael, Schröder, Bernd, Schüller, Christoph, Scialò, Filippo , Sciarretta, Sebastiano , Scovassi, Anna Ivana , Segatori, Laura , Seiliez, Iban , Seki, Ekihiro , Sellke, Frank W. , Sergi, Consolato Maria , Settembre, Carmine , Shao, Changshun , Sheng, Zhi , Shi, Xiaobing , Shimozawa, Makoto, Shoji, Ikuo, Shridhar, Viji , Shu, Hong‐Bing , Sierra, Amanda , Sierra‐Torre, Virginia , Sil, Payel , Simon, Anna Katharina , Simon, Hans‐Uwe , Simons, Matias , Singh, Lalit Pukhrambam , Sirohi, Kapil , Sivridis, Efthimios , Skirycz, Aleksandra , Slaninová, Iva , Smaili, Soraya Soubhi , Smertenko, Andrii , Smith, Matthew D., Soenen, Stefaan J. , Solaini, Giancarlo , Soleimanpour, Scott A. , Solovchenko, Alexei E. , Song, Fuyong, Song, Ju‐Xian , Song, Zhiyin , Soria, Leandro R. , Spagnuolo, Paul A. , Spector, Stephen A. , Stalnecker, Clint A. , Stefan, Katja, Stefanis, Leonidas , Stenmark, Harald , Stevens, Craig, Stoka, Veronika , Stork, Björn , Su, Longxiang , Subauste, Carlos S. , Subbian, Selvakumar , Sun, Jun , Sun, Kang, Sun, Meng‐Xiang , Sun, Qiming , Sun, Yi Ning , Sundberg, Eva , Tabęcka-Łonczyńska, Anna , Tacke, Frank , Tafani, Marco , Tait, Stephen W. 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G.
Autophagy | March 24, 2021 | Volume: 17 | Issue: 1 | Pages: 1-382
Duodenal mucosal mitochondrial gene expression is associated with delayed gastric emptying in diabetic gastroenteropathy
Narayanan, Susrutha Puthanmadhom, O’Brien, Daniel R. , Sharma, Mayank , Miller, Karl N. , Adams, Peter D. , Passos, João F. , Eirin, Alfonso , Ördög, Tamás , Bharucha, Adil E. , Puthanmadhom Narayanan, Susrutha, Passos, João F , Eirin, Alfonso , Adams, Peter
JCI Insight | January 24, 2021 | Volume: 6 | Issue: 2 | Pages: No page available
Hindered by a limited understanding of the mechanisms responsible for diabetic gastroenteropathy (DGE), management is symptomatic. We investigated the duodenal mucosal expression of protein-coding genes and microRNAs (miRNA) in DGE and related them to clinical features. The diabetic phenotype, gastric emptying, mRNA, and miRNA expression and ultrastructure of duodenal mucosal biopsies were compared in 39 DGE patients and 21 controls. Among 3175 differentially expressed genes (FDR < 0.05), several mitochondrial DNA–encoded (mtDNA-encoded) genes (12 of 13 protein coding genes involved in oxidative phosphorylation [OXPHOS], both rRNAs and 9 of 22 transfer RNAs) were downregulated; conversely, nuclear DNA–encoded (nDNA-encoded) mitochondrial genes (OXPHOS) were upregulated in DGE. The promoters of differentially expressed genes were enriched in motifs for transcription factors (e.g., NRF1), which regulate mitochondrial biogenesis. Seventeen of 30 differentially expressed miRNAs targeted differentially expressed mitochondrial genes. Mitochondrial density was reduced and correlated with expression of 9 mtDNA OXPHOS genes. Uncovered by principal component (PC) analysis of 70 OXPHOS genes, PC1 was associated with neuropathy ( P = 0.01) and delayed gastric emptying ( P < 0.05). In DGE, mtDNA- and nDNA-encoded mitochondrial genes are reduced and increased — associated with reduced mitochondrial density, neuropathy, and delayed gastric emptying — and correlated with cognate miRNAs. These findings suggest that mitochondrial disturbances may contribute to delayed gastric emptying in DGE.
Whole‐body senescent cell clearance alleviates age‐related brain inflammation and cognitive impairment in mice
Ogrodnik, Mikołaj , Evans, Shane A., Fielder, Edward , Victorelli, Stella , Krüger, Patrick, Salmonowicz, Hanna , Weigand, Bettina M., Patel, Ayush , Pirtskhalava, Tamar , Inman, Christine, Johnson, Kurt O. , Dickinson, Stephanie , Rocha, Azucena, Schafer, Marissa , Zhu, Yi , Passos, João F. , Kirkland, James L. , Jurk, Diana , Patel, Ayush D, Inman, Christine L, Schafer, Marissa J, Jurk, Diana , Passos, João F , Schafer, Marissa J , Zhu, Yi , Allison, David B. , Zglinicki, Thomas von , LeBrasseur, Nathan K. , Tchkonia, Tamar , Neretti, Nicola
Aging Cell | January 20, 2021 | Volume: 20 | Issue: 2 | Pages: No page available
Abstract Cellular senescence is characterized by an irreversible cell cycle arrest and a pro‐inflammatory senescence‐associated secretory phenotype (SASP), which is a major contributor to aging and age‐related diseases. Clearance of senescent cells has been shown to improve brain function in mouse models of neurodegenerative diseases. However, it is still unknown whether senescent cell clearance alleviates cognitive dysfunction during the aging process. To investigate this, we first conducted single‐nuclei and single‐cell RNA‐seq in the hippocampus from young and aged mice. We observed an age‐dependent increase in p16 Ink4a senescent cells, which was more pronounced in microglia and oligodendrocyte progenitor cells and characterized by a SASP. We then aged INK ‐ ATTAC mice, in which p16 Ink4a ‐positive senescent cells can be genetically eliminated upon treatment with the drug AP20187 and treated them either with AP20187 or with the senolytic cocktail Dasatinib and Quercetin. We observed that both strategies resulted in a decrease in p16 Ink4a exclusively in the microglial population, resulting in reduced microglial activation and reduced expression of SASP factors. Importantly, both approaches significantly improved cognitive function in aged mice. Our data provide proof‐of‐concept for senolytic interventions' being a potential therapeutic avenue for alleviating age‐associated cognitive impairment.
Moderate Exercise Inhibits Age-Related Inflammation, Liver Steatosis, Senescence, and Tumorigenesis
Bianchi, Arianna, Marchetti, Letizia , Lemos, Henrique , Vacca, Michèle , Paish, Hannah L. , Green, Kile , Elliott, Bronte, Passos, João F. , Jurk, Diana , Mann, Derek A. , Wilson, Caroline, Lemos, Henrique , Vacca, Michele , Jurk, Diana , Wilson, Caroline L , Passos, João F , Hall, Zoe , Tiniakos, Dina
The Journal of Immunology | January 13, 2021 | Volume: 206 | Issue: 4 | Pages: 904-916
Abstract Age-related chronic inflammation promotes cellular senescence, chronic disease, cancer, and reduced lifespan. In this study, we wanted to explore the effects of a moderate exercise regimen on inflammatory liver disease and tumorigenesis. We used an established model of spontaneous inflammaging, steatosis, and cancer (nfkb1−/− mouse) to demonstrate whether 3 mo of moderate aerobic exercise was sufficient to suppress liver disease and cancer development. Interventional exercise when applied at a relatively late disease stage was effective at reducing tissue inflammation (liver, lung, and stomach), oxidative damage, and cellular senescence, and it reversed hepatic steatosis and prevented tumor development. Underlying these benefits were transcriptional changes in enzymes driving the conversion of tryptophan to NAD+, this leading to increased hepatic NAD+ and elevated activity of the NAD+-dependent deacetylase sirtuin. Increased SIRT activity was correlated with enhanced deacetylation of key transcriptional regulators of inflammation and metabolism, NF-κB (p65), and PGC-1α. We propose that moderate exercise can effectively reprogram pre-established inflammatory and metabolic pathologies in aging with the benefit of prevention of disease.
On the evolution of cellular senescence
Kowald, Axel , Passos, João F. , Kirkwood, Thomas B. L. , Passos, João F
Aging Cell | November 9, 2020 | Volume: 19 | Issue: 12 | Pages: No page available
AbstractThe idea that senescent cells are causally involved in aging has gained strong support from findings that the removal of such cells alleviates many age‐related diseases and extends the life span of mice. While efforts proceed to make therapeutic use of such discoveries, it is important to ask what evolutionary forces might have been behind the emergence of cellular senescence, in order better to understand the biology that we might seek to alter. Cellular senescence is often regarded as an anti‐cancer mechanism, since it limits the division potential of cells. However, many studies have shown that senescent cells often also have carcinogenic properties. This is difficult to reconcile with the simple idea of an anti‐cancer mechanism. Furthermore, other studies have shown that cellular senescence is involved in wound healing and tissue repair. Here, we bring these findings and ideas together and discuss the possibility that these functions might be the main reason for the evolution of cellular senescence. Furthermore, we discuss the idea that senescent cells might accumulate with age because the immune system had to strike a balance between false negatives (overlooking some senescent cells) and false positives (destroying healthy body cells).
Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span
Jurk, Diana , Kirkland, James L. , Passos, João F. , Pignolo, Robert J. , Niedernhofer, Laura J. , Zhang, Lei , Miller, Jordan D. , Jurk, Diana , Passos, João F , Niedernhofer, Laura J , Zhang, Lei , Robbins, Paul D. , Khosla, Sundeep , LeBrasseur, Nathan K. , Tchkonia, Tamar
Annual Review of Pharmacology and Toxicology | September 30, 2020 | Volume: 61 | Issue: 1 | Pages: 779-803
10.1146/annurev-pharmtox-050120-105018
Senescence is the consequence of a signaling mechanism activated in stressed cells to prevent proliferation of cells with damage. Senescent cells (Sncs) often develop a senescence-associated secretory phenotype to prompt immune clearance, which drives chronic sterile inflammation and plays a causal role in aging and age-related diseases. Sncs accumulate with age and at anatomical sites of disease. Thus, they are regarded as a logical therapeutic target. Senotherapeutics are a new class of drugs that selectively kill Sncs (senolytics) or suppress their disease-causing phenotypes (senomorphics/senostatics). Since 2015, several senolytics went from identification to clinical trial. Preclinical data indicate that senolytics alleviate disease in numerous organs, improve physical function and resilience, and suppress all causes of mortality, even if administered to the aged. Here, we review the evidence that Sncs drive aging and disease, the approaches to identify and optimize senotherapeutics, and the current status of preclinical and clinical testing of senolytics.