Article
Geriatrics & Gerontology
Yaqun Huang, Ming-Xia Ge, Yu-Hong Li, Jing-Lin Li, Qin Yu, Fu-Hui Xiao, Hong-Shun Ao, Li-Qin Yang, Ji Li, Yonghan He, Qing-Peng Kong
Summary: This study found that long-lived individuals have lower inflammation levels and higher expression of ATF7. Loss of ATF7 leads to cellular senescence, while its overexpression delays senescence progress and secretion of senescence-associated secretory phenotype. These findings suggest that ATF7 is a longevity-promoting factor that lowers cellular senescence and inflammation in long-lived individuals.
Article
Geriatrics & Gerontology
Yaqun Huang, Ming-Xia Ge, Yu-Hong Li, Jing-Lin Li, Qin Yu, Fu-Hui Xiao, Hong-Shun Ao, Li-Qin Yang, Ji Li, Yonghan He, Qing-Peng Kong
Summary: This study found that long-lived individuals have lower inflammation levels and up-regulation of ATF7. Overexpression of ATF7 can delay cellular senescence and inhibit inflammation, thus promoting longevity.
Article
Cell Biology
Lichao Wang, Binsheng Wang, Nathan S. Gasek, Yueying Zhou, Rachel L. Cohn, Dominique E. Martin, Wulin Zuo, William F. Flynn, Chun Guo, Evan R. Jellison, Taewan Kim, Larissa G. P. Langhi Prata, Allyson K. Palmer, Ming Li, Christina L. Inman, Lauren S. Barber, Iman M. A. Al-Naggar, Yanjiao Zhou, Wenqiang Du, Kshitiz, George A. Kuchel, Alexander Meves, Tamar Tchkonia, James L. Kirkland, Paul Robson, Ming Xu
Summary: This study identifies a small population of p21 high-expressing cells that accumulate in adipose tissue with obesity and shows that intermittent clearance of these cells can prevent and alleviate insulin resistance. Inactivation of the NF-kB pathway within these cells attenuates insulin resistance. Additionally, a drug combination of dasatinib and quercetin can eliminate p21 high-expressing cells in human fat and mitigate insulin resistance.
Article
Cell Biology
Lei Zhang, Jing Zhao, Xiaodong Mu, Sara J. McGowan, Luise Angelini, Ryan D. O'Kelly, Matthew J. Yousefzadeh, Ayumi Sakamoto, Zaira Aversa, Nathan K. LeBrasseur, Yousin Suh, Johnny Huard, Theodore M. Kamenecka, Laura J. Niedernhofer, Paul D. Robbins
Summary: Inhibiting NF-κ B activation with SR12343 shows promising results in reducing cellular senescence markers, improving muscle fiber size, and extending healthy lifespan. The therapeutic effects of SR12343 were observed in different mouse models, suggesting it as a potential treatment for reducing cellular senescence and aging-related diseases.
Article
Multidisciplinary Sciences
Laura Sole, Teresa Lobo-Jarne, Daniel Alvarez-Villanueva, Josune Alonso-Maranon, Yolanda Guillen, Marta Guix, Irene Sangrador, Catalina Rozalen, Anna Vert, Antonio Barbachano, Joan Lop, Marta Salido, Beatriz Bellosillo, Raquel Garcia-Romero, Marta Garrido, Jessica Gonzalez, Maria Martinez-Iniesta, Erika Lopez-Arribillaga, Ramon Salazar, Clara Montagut, Ferran Torres, Mar Iglesias, Toni Celia-Terrassa, Alberto Munoz, Alberto Villanueva, Anna Bigas, Lluis Espinosa
Summary: This study reveals that sub-lethal dose of chemotherapy induces a quiescence-like phenotype and a YAP-dependent fetal-like intestinal stem cell state in wild-type p53 colorectal cancers, which is associated with higher metastatic activity and poor prognosis in patients.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Marina Kolesnichenko, Nadine Mikuda, Uta E. Hoepken, Eva Kaergel, Bora Uyar, Ahmet Bugra Tufan, Maja Milanovic, Wei Sun, Inge Krahn, Kolja Schleich, Linda Hoff, Michael Hinz, Michael Willenbrock, Sabine Jungmann, Altuna Akalin, Soyoung Lee, Ruth Schmidt-Ullrich, Clemens A. Schmitt, Claus Scheidereit
Summary: The study reveals that DNA double-strand breaks elicit two subsequent phases of NF-kappa B activation, with the first phase controlling anti-apoptotic gene expression and the second phase driving expression of senescence-associated genes.
Article
Biochemistry & Molecular Biology
Giovanna M. Bernal, Longtao Wu, David J. Voce, Ralph R. Weichselbaum, Bakhtiar Yamini
Summary: This study found that the p52 subunit increases in the nucleus of cells during senescence, and factors in the conditioned media play a role in promoting p52 nuclear translocation. Additionally, mature p52 can induce cellular senescence. These findings support the observation of increased p52 in aged tissue and suggest that p52 contributes to organismal aging.
CELL AND BIOSCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Qian Li, Yu-Heng Zhao, Cheng Xu, Ye-Lin Liang, Yin Zhao, Qing-Mei He, Jun-Yan Li, Kai-Lin Chen, Han Qiao, Na Liu, Jun Ma, Lei Chen, Ying-Qin Li
Summary: This study reveals that circWDR37 deficiency limits the proliferation, migration, and invasion of senescent NPC cells induced by cisplatin or gemcitabine. Mechanistically, circWDR37 binds and dimerizes PKR, leading to PKR autophosphorylation and activation. Activated PKR phosphorylates IKKβ, releasing RELA from IκBα and activating NF-κB, thus promoting the transcription of CCND1 and senescence-associated secretory phenotype component genes in a circWDR37-dependent manner. Low circWDR37 levels are associated with favorable survival and chemotherapy response in NPC patients treated with gemcitabine or cisplatin induction chemotherapy.
Article
Immunology
Yu Xiao, Jiaqi Liang, Kenneth W. Witwer, Ying Zhang, Qian Wang, Hang Yin
Summary: In our study, we discovered that extracellular vesicles (EVs) play a crucial role in aging, as they can induce chronic inflammation by activating immune cells. We found that EVs derived from senescent cells contain miR-30b-5p, which downregulates SIRT1 and enhances pro-inflammatory cytokine production. Additionally, we observed increased levels of miR-30b-5p in both the aging animal model and EVs harvested from tissues. EVs carrying pro-inflammatory signals can alter immune cell activity in the aging microenvironment, leading to an increase in inflammation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ruoxi W. Wang, Sonia Vigano, Uri Ben-David, Angelika Amon, Stefano Santaguida
Summary: The study suggests that non-cell-autonomous mechanisms in aneuploid cells predominantly mediate their clearance by NK cells, with NF-kappa B signaling upregulation playing a central role in triggering the immune response. While NF-kappa B upregulation correlates with the degree of aneuploidy in cancer cell lines, it is not sufficient to trigger NK cell-mediated clearance, indicating that additional mechanisms may be at play during cancer evolution to counteract NF-kappa B-mediated immunogenicity.
Article
Fisheries
Yuan Song, Ryuji Okazaki, Yasuhiro Yoshida
Summary: The study revealed that mice exposed to radiation at a young age exhibited increased expression and phosphorylation of certain molecules in splenocytes, along with a NF-kappa B-related immune response and elevated levels of senescence marker proteins like CDKs and IL-6. This suggests that radiation-induced cellular senescence in the spleen involves DNA damage-related stress responses, potentially contributing to aging.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Da-Yeon Lee, Su-Jeong Lee, Prabha Chandrasekaran, Gopal Lamichhane, Jennifer F. O'Connell, Josephine M. Egan, Yoo Kim
Summary: This study investigated the effects of dietary curcumin (CUR) as an antioxidant on hepatic cellular senescence in aged mice. The results showed that CUR supplementation downregulated senescence-associated hepatic gene expressions, enhanced antioxidant properties, suppressed MAPK signaling cascades, and inhibited proinflammatory cytokines and SASPs expression, suggesting that CUR may be a nutritional strategy to prevent hepatic cellular senescence.
Article
Orthopedics
H. Chen, J. Qin, H. Shi, Q. Li, S. Zhou, L. Chen
Summary: The study shows that ROF inhibits the expression of inflammatory factors and chondrocyte senescence, improves the progression of OA through the Nrf2/NF-κB axis, and has potential as a therapeutic agent for OA.
OSTEOARTHRITIS AND CARTILAGE
(2022)
Article
Cell Biology
Kelvin Yin, Daniel Patten, Sarah Gough, Susana de Barros Goncalves, Adelyne Chan, Ioana Olan, Liam Cassidy, Marta Poblocka, Haoran Zhu, Aaron Lun, Martijn Schuijs, Andrew Young, Celia Martinez-Jimenez, Timotheus Y. F. Halim, Shishir Shetty, Masashi Narita, Matthew Hoare
Summary: Senescence is a stress-responsive tumor suppressor mechanism associated with the expression of the senescence-associated secretory phenotype (SASP). Through SASP, senescent cells trigger their own immune-mediated elimination, which is prevented by the endothelium. This study demonstrates that SASP induces endothelial cell NF-kappa B activity and that this activity regulates immune cell recruitment and senescence surveillance. Furthermore, oncogenic hepatocyte senescence also influences endothelial NF-kappa B activity in vivo.
GENES & DEVELOPMENT
(2022)
Article
Chemistry, Medicinal
Yizhou Xu, Xiaofang Hu, Jiale Cai, Yunlun Li, Ying Zou, Yihan Wang, Changnan Xie, Shuyi Xu, Yanqing Wang, Yuli Zheng, Djibril Adam Mahamat, Yuantao Xu, Xianghai Wang, Xican Li, Aijun Liu, Dongfeng Chen, Lixin Zhu, Jiasong Guo
Summary: This study aimed to investigate the effects of Atractylenolide-III (AT-III) on osteoarthritis and its underlying mechanisms. The results showed that AT-III can alleviate the severity of osteoarthritis and chondrocyte senescence through the NF-kappa B pathway. Therefore, AT-III may be a potential drug for osteoarthritis treatment.
PHYTOTHERAPY RESEARCH
(2023)
Editorial Material
Biochemistry & Molecular Biology
Eran Segal, Feng Zhang, Xihong Lin, Gary King, Ophir Shalem, Smadar Shilo, William E. Allen, Faisal Alquaddoomi, Han Altae-Tran, Simon Anders, Ran Balicer, Tal Bauman, Ximena Bonilla, Gisel Booman, Andrew T. Chan, Ori Cohen, Silvano Coletti, Natalie Davidson, Yuval Dor, David A. Drew, Olivier Elemento, Georgina Evans, Phil Ewels, Joshua Gale, Amir Gavrieli, Benjamin Geiger, Yonatan H. Grad, Casey S. Greene, Iman Hajirasouliha, Roman Jerala, Andre Kahles, Olli Kallioniemi, Ayya Keshet, Ljupco Kocarev, Gregory Landua, Tomer Meir, Aline Muller, Long H. Nguyen, Matej Oresic, Svetlana Ovchinnikova, Hedi Peterson, Jana Prodanova, Jay Rajagopal, Gunnar Ratsch, Hagai Rossman, Johan Rung, Andrea Sboner, Alexandros Sigaras, Tim Spector, Ron Steinherz, Irene Stevens, Jaak Vilo, Paul Wilmes
Correction
Biochemistry & Molecular Biology
Eran Segal, Feng Zhang, Xihong Lin, Gary King, Ophir Shalem, Smadar Shilo, William E. Allen, Faisal Alquaddoomi, Han Altae-Tran, Simon Anders, Ran Balicer, Tal Bauman, Ximena Bonilla, Gisel Booman, Andrew T. Chan, Ori Cohen, Silvano Coletti, Natalie Davidson, Yuval Dor, David A. Drew, Olivier Elemento, Georgina Evans, Phil Ewels, Joshua Gale, Amir Gavrieli, Benjamin Geiger, Yonatan H. Grad, Casey S. Greene, Iman Hajirasouliha, Roman Jerala, Andre Kahles, Olli Kallioniemi, Ayya Keshet, Ljupco Kocarev, Gregory Landua, Tomer Meir, Aline Muller, Long H. Nguyen, Matej Oresic, Svetlana Ovchinnikova, Hedi Peterson, Jana Prodanova, Jay Rajagopal, Gunnar Raetsch, Hagai Rossman, Johan Rung, Andrea Sboner, Alexandros Sigaras, Tim Spector, Ron Steinherz, Irene Stevens, Jaak Vilo, Paul Wilmes
Article
Biochemistry & Molecular Biology
Hagai Rossman, Smadar Shilo, Tomer Meir, Malka Gorfine, Uri Shalit, Eran Segal
Summary: This study analyzed data from the Israeli Ministry of Health to investigate the real-life impact of a national vaccination campaign on the dynamics of the COVID-19 pandemic. The findings revealed a significant and early decrease in COVID-19 cases and hospitalizations in individuals aged 60 years and older who were prioritized for vaccination, indicating the effectiveness of the vaccine rollout in reducing the spread of the virus.
Article
Multidisciplinary Sciences
Hagai Rossman, Tomer Meir, Jonathan Somer, Smadar Shilo, Rom Gutman, Asaf Ben Arie, Eran Segal, Uri Shalit, Malka Gorfine
Summary: The study reveals that in Israel, during periods of moderate or high hospital load due to severely ill COVID-19 patients, the in-hospital mortality rates significantly increased, independent of patient characteristics.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Thomas Vogl, Shelley Klompus, Sigal Leviatan, Iris N. Kalka, Adina Weinberger, Cisca Wijmenga, Jingyuan Fu, Alexandra Zhernakova, Rinse K. Weersma, Eran Segal
Summary: The study profiled serum antibody responses of 997 healthy individuals against 244,000 rationally selected peptide antigens, finding individual-specific and shared antibody responses against microbiota associated with age and gender. The antibody epitope repertoires were shown to be more longitudinally stable than gut microbiome species abundances, suggesting their potential as an immunologic fingerprint.
Editorial Material
Microbiology
Hagai Rossman, Eran Segal
NATURE MICROBIOLOGY
(2022)
Article
Medicine, Research & Experimental
Yoong Wearn Lim, Adam S. Adler, David S. Johnson
Summary: This study utilized deep learning methods to investigate antibody sequences, encoding antibody images and training neural network models for classification, and further generating synthetic antibodies using generative adversarial network models. The results demonstrate that deep learning methods can offer insights into antibody engineering, optimization, and discovery by mining and learning patterns in antibody sequences.
Review
Biochemistry & Molecular Biology
Arno R. Bourgonje, Thomas Vogl, Eran Segal, Rinse K. Weersma
Summary: The adequate functioning of the intestinal barrier is crucial for protecting against pathogens and tolerating microbiota and self-antigens. Inflammatory bowel diseases (IBDs) are characterized by a disrupted intestinal barrier integrity, resulting in an abnormal immune response. Recent innovative antibody profiling technologies have the potential to provide a comprehensive understanding of humoral immunity and its applications in disease diagnosis, therapy, and prevention in IBD.
TRENDS IN MOLECULAR MEDICINE
(2022)
Article
Multidisciplinary Sciences
Sigal Leviatan, Saar Shoer, Daphna Rothschild, Maria Gorodetski, Eran Segal
Summary: This study produces a new human gut microbiome reference set of 3,594 species genomes, including 310 previously undescribed species, which serves as a valuable resource for further research.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Yochai Edlitz, Eran Segal
Summary: The study analyzed data from 44,709 UK Biobank participants to develop two different predictive models for T2D onset risk, one using non-laboratory data and one incorporating laboratory tests. These models accurately predict T2D risk, aiding medical decision-makers in assessing populations at elevated risk for T2D to improve medical strategies.
Article
Microbiology
Rena A. Mizrahi, Wendy Y. Lin, Ashley Gras, Ariel R. Niedecken, Ellen K. Wagner, Sheila M. Keating, Nikita Ikon, Vishal A. Manickam, Michael A. Asensio, Jackson Leong, Angelica Medina-Cucurella, Emily Benzie, Kyle P. Carter, Yao Chiang, Robert C. Edgar, Renee Leong, Yoong Wearn Lim, Jan Fredrik Simons, Matthew J. Spindler, Kacy Stadtmiller, Nicholas Wayham, Dirk Buscher, Jose Vicente Terencio, Clara Di Germanio, Steven M. Chamow, Charles Olson, Paula A. Pino, Jun-Gyu Park, Amberlee Hicks, Chengjin Ye, Andreu Garcia-Vilanova, Luis Martinez-Sobrido, Jordi B. Torrelles, David S. Johnson, Adam S. Adler
Summary: This study successfully generated a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 using microfluidics, flow sorting, and a targeted integration cell line. The drug was manufactured consistently at the clinical scale and offers a new approach to treating infectious diseases by targeting multiple epitopes of the virus.
Article
Multidisciplinary Sciences
Thomas Vogl, Iris N. Kalka, Shelley Klompus, Sigal Leviatan, Adina Weinberger, Eran Segal
Summary: This study reveals distinct antibody responses against gut microbiota in patients with severe ME/CFS compared to healthy controls. Machine learning algorithms utilizing these differences provide improved molecular diagnostics for ME/CFS, indicating the involvement of the microbiota-immune axis in its pathogenesis.
Article
Cell Biology
Ayya Keshet, Smadar Shilo, Anastasia Godneva, Yeela Talmor-Barkan, Yaron Aviv, Eran Segal, Hagai Rossman
Summary: Despite the increasing prevalence of diabetes, its diagnosis still relies on blood tests. Continuous glucose monitoring (CGM) devices provide a potential tool to better understand glucose control and variability in individuals with and without diabetes. This study presents CGMap, the characterization of CGM data collected from over 7,000 non-diabetic individuals, aged 40-70 years, between 2019 and 2022. The study provides reference values for key CGM-derived clinical measures and explores the relationship between CGM-derived measures and diabetes-related clinical parameters, revealing novel research directions for understanding the influence of glucose levels on various aspects of human health.
Article
Endocrinology & Metabolism
Ayya Keshet, Lee Reicher, Noam Bar, Eran Segal
Summary: The authors review the current and emerging wearable and digital devices that can provide information about specific metabolic outcomes, and discuss their potential for tailoring preventive and therapeutic strategies against cardiometabolic disease.
Article
Biochemistry & Molecular Biology
Liron Zahavi, Amit Lavon, Lee Reicher, Saar Shoer, Anastasia Godneva, Sigal Leviatan, Michal Rein, Omer Weissbrod, Adina Weinberger, Eran Segal
Summary: This study developed a framework for metagenome-wide association studies (MWAS) to systematically detect bacterial SNPs and associate them with host phenotypes. The researchers discovered 1,358 statistically significant associations between a bacterial SNP and host body mass index (BMI), most of which were independent of diet, medications or physical exercise. Seventeen associations replicated in a geographically independent cohort. The study highlights the importance of considering nucleotide-level diversity in microbiome studies and reveals bacterial SNPs associated with BMI.