Article
Oncology
Bei Liu, Li Cheng, Honghao Gao, Jiale Zhang, Yanxin Dong, Wenda Gao, Shunzong Yuan, Taiqian Gong, Wenrong Huang
Summary: VSIG4 is a transmembrane receptor expressed exclusively in a subset of tissue-resident macrophages, playing a pivotal role in clearing pathogens and maintaining immune homeostasis. It has potential therapeutic effects for immune-mediated inflammatory diseases and cancer, and can serve as a biomarker for macrophage activation-related diseases.
Review
Endocrinology & Metabolism
Zhaohua Cai, Ben He
Summary: This article reviews the latest research progress on adipose tissue aging, focusing on the complex interplay between metabolism, immune system, and sympathetic nervous system during the aging process. The rejuvenation strategies to delay aging and extend lifespan are also discussed.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2023)
Review
Endocrinology & Metabolism
Ann Hertzel, Jeongsik Yong, Xiaoli Chen, David A. Bernlohr
Summary: Immune cells infiltrate adipose tissue and play major roles in regulating fat cell mitochondrial function, affecting gene expression and cell death pathways.
Review
Endocrinology & Metabolism
Sierra A. Nance, Lindsey Muir, Carey Lumeng
Summary: This review provides an updated overview of ATM activation and function, ATM diversity in humans and rodents, and novel ATM functions that contribute to metabolic homeostasis and disease.
MOLECULAR METABOLISM
(2022)
Review
Pharmacology & Pharmacy
Marjorie Reyes-Farias, Julia Fos-Domenech, Dolors Serra, Laura Herrero, David Sanchez-Infantes
Summary: Both obesity and aging are linked to metabolic diseases like type 2 diabetes and cardiovascular disease. Chronic low-grade inflammation of adipose tissue plays a role in the progression of these diseases. Obesity and aging lead to alterations in adipose tissue, triggering a pro-inflammatory phenotype in resident immune cells. They also share characteristics such as a higher visceral fat to subcutaneous fat ratio and a reduced lifespan.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Immunology
Yi-Xiang Zhang, Min-Yi Ou, Zi-Han Yang, Yu Sun, Qing-Feng Li, Shuang-Bai Zhou
Summary: Adipose tissue undergoes various changes during aging, leading to inflammation and dysfunction. These changes include fat depot redistribution, decrease in brown and beige fat, decline in adipose progenitor and stem cell function, accumulation of senescent cells, and dysregulation of immune cells. These contribute to age-related diseases and inflammation in adipose tissue.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Hao Xie, Christoph Heier, Xia Meng, Latifa Bakiri, Isabella Pototschnig, Zhiyuan Tang, Silvia Schauer, Vanessa J. Baumgartner, Gernot F. Grabner, Gernot Schabbauer, Heimo Wolinski, Graham R. Robertson, Gerald Hoefler, Wenwen Zeng, Erwin F. Wagner, Martina Schweiger, Rudolf Zechner
Summary: This study shows that cachexigenic tumors activate type 2 immunity in cachectic white adipose tissue (WAT), leading to an increase in sympathetic activity and induction of WAT browning. The targeting of macrophage-sympathetic neuron cross-talk within adipose tissue could be a promising therapeutic approach for cachexia in cancer patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Ji-Won Noh, Min-Soo Jun, Hee-Kwon Yang, Byung-Cheol Lee
Summary: Berberine has anti-obesity and anti-inflammatory effects by modulating ATM recruitment and activation.
Article
Cell Biology
Jianrui Song, Diana Farris, Paola Ariza, Smriti Moorjani, Mita Varghese, Muriel Blin, Judy Chen, Daniel Tyrrell, Min Zhang, Kanakadurga Singer, Morgan Salmon, Daniel R. Goldstein
Summary: This study reveals that aging enhances atherosclerosis through the increased inflammation of visceral fat. The transplantation of aged fat onto the carotid artery of mice resulted in larger atherosclerotic plaques with increased macrophage numbers. Inflammatory factors secreted by adipose tissue macrophages, including TNF alpha, CXCL2, and CCL2, were found to contribute to the enhancement of atherosclerosis in aging fat transplants.
Article
Biochemistry & Molecular Biology
Oh-Jun Kwon, Ji-Won Noh, Byung-Cheol Lee
Summary: The study demonstrates that Coptidis Rhizoma has therapeutic effects on obesity-induced inflammation by inhibiting macrophage-mediated inflammation in adipose tissue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Maria Carmen Carceller, Maria Isabel Guillen, Maria Luisa Gil, Maria Jose Alcaraz
Summary: The study investigated the anti-inflammatory effects of mouse-derived adipose tissue stem cell secretome on mouse-derived peritoneal macrophages stimulated with LPS, showing a reduction in inflammatory response and modulation of macrophage activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Cheoljun Choi, Abhirup Saha, Seungchan An, Yoon Keun Cho, Heeseong Kim, Minsoo Noh, Yun-Hee Lee
Summary: This study found that during obesity, increased expression of Cx43 in macrophages promotes inflammatory responses in adipose tissue. Knocking out Cx43 in macrophages can reduce inflammatory responses in adipose tissue and improve glucose tolerance.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Zhaohua Cai, Yijie Huang, Ben He
Summary: Obesity is a global epidemic associated with chronic low-grade inflammation. Macrophages play a crucial role in obesity-associated inflammation. Recent research has provided insights into the diverse roles of adipose tissue macrophages (ATMs) in obesity and comorbidities. This review summarizes the characterization of different subpopulations of ATMs in obesity, the extensive crosstalk between adipocytes and ATMs, and the extended crosstalk within adipose tissue between perivascular mesenchymal cells and ATMs.
Article
Biochemistry & Molecular Biology
Ji-Won Noh, Hee-Kwon Yang, Min-Soo Jun, Byung-Cheol Lee
Summary: This study evaluated the effects of puerarin on obesity and metabolic complications, and investigated the underlying immunological mechanisms. The results showed that puerarin has potential anti-obesity effects by reducing adipocyte size, fat accumulation, and regulating lipid metabolism.
Article
Physiology
Camila Manrique-Acevedo, Jaume Padilla, Huma Naz, Makenzie L. Woodford, Thaysa Ghiarone, Annayya R. Aroor, Jack L. Hulse, Francisco J. Cabral-Amador, Vanesa Martinez-Diaz, Chetan P. Hans, Adam Whaley-Connell, Luis A. Martinez-Lemus, Guido Lastra
Summary: This study demonstrates the critical role of MR activation in myeloid cells in the pathogenesis of vascular dysfunction in females, associated with pro-inflammatory macrophage polarization in adipose tissue compartments. The findings have potential clinical implications for the prevention and management of cardiovascular disease in women who are at a higher risk for poor outcomes.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Oncology
Fangyi Gu, Mark K. Farrugia, William D. Duncan, Yingdong Feng, Alan D. Hutson, Nicolas F. Schlecht, Elizabeth A. Repasky, Marina P. Antoch, Austin Miller, Alexis Platek, Mary E. Platek, Austin J. Iovoli, Anurag K. Singh
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2020)
Article
Oncology
Lioubov Korotchkina, Denis Kazyulkin, Pavel G. Komarov, Alex Polinsky, Ekaterina L. Andrianova, Sangeeta Joshi, Mahima Gupta, Slavoljub Vujcic, Eugene Kononov, Ilia Toshkov, Yuan Tian, Peter Krasnov, Mikhail Chernov, Jean Veith, Marina P. Antoch, Shiloh Middlemiss, Klaartje Somers, Richard B. Lock, Murray D. Norris, Michelle J. Henderson, Michelle Haber, Olga B. Chernova, Andrei Gudkov
Article
Cell Biology
Mikolaj Ogrodnik, Shane A. Evans, Edward Fielder, Stella Victorelli, Patrick Kruger, Hanna Salmonowicz, Bettina M. Weigand, Ayush D. Patel, Tamar Pirtskhalava, Christine L. Inman, Kurt O. Johnson, Stephanie L. Dickinson, Azucena Rocha, Marissa J. Schafer, Yi Zhu, David B. Allison, Thomas von Zglinicki, Nathan K. LeBrasseur, Tamar Tchkonia, Nicola Neretti, Joao F. Passos, James L. Kirkland, Diana Jurk
Summary: Clearing senescent cells, either through drug treatment or senolytic cocktail, has been shown to improve cognitive function, providing proof-of-concept for senolytic interventions as a potential therapeutic avenue for alleviating age-associated cognitive impairment.
Article
Urology & Nephrology
Hajrunisa Cubro, Karl A. Nath, Sonja Suvakov, Oscar Garcia-Valencia, Santosh Parashuram, Wendy M. White, Tracey L. Weissgerber, Meryl C. Nath, Natasa M. Milic, Fernando Sontag, Livius D'Uscio, Yi Zhu, James L. Kirkland, Tamar Tchkonia, Mariam P. Alexander, Reade A. Quinton, Zvonimir S. Katusic, Joseph P. Grande, Vesna D. Garovic
Summary: In the IL-10-/-sPE murine model, aortic contractions to phenylephrine were significantly augmented compared to wild type normotensive mice, indicating impaired endothelium-dependent and to a lesser extent, endothelium-independent relaxation. The results highlight the role of IL-10 deficiency in dysregulation of the cyclooxygenase pathway and vascular dysfunction in the IL-10-/-sPE murine model of preeclampsia, suggesting a possible contribution of nitric oxide dysregulation.
KIDNEY INTERNATIONAL
(2021)
Article
Multidisciplinary Sciences
Matthew J. Yousefzadeh, Rafael R. Flores, Yi Zhu, Zoe C. Schmiechen, Robert W. Brooks, Christy E. Trussoni, Yuxiang Cui, Luise Angelini, Kyoo-A Lee, Sara J. McGowan, Adam L. Burrack, Dong Wang, Qing Dong, Aiping Lu, Tokio Sano, Ryan D. O'Kelly, Collin A. McGuckian, Jonathan I. Kato, Michael P. Bank, Erin A. Wade, Smitha P. S. Pillai, Jenna Klug, Warren C. Ladiges, Christin E. Burd, Sara E. Lewis, Nicholas F. LaRusso, Nam V. Vo, Yinsheng Wang, Eric E. Kelley, Johnny Huard, Ingunn M. Stromnes, Paul D. Robbins, Laura J. Niedernhofer
Summary: Researchers found that aged immune system could lead to attrition and senescence of specific immune cell populations, driving systemic ageing.
Article
Geriatrics & Gerontology
Brandon P. Verdoorn, Tamara K. Evans, Gregory J. Hanson, Yi Zhu, Larissa G. P. Langhi Prata, Robert J. Pignolo, Elizabeth J. Atkinson, Erin O. Wissler-Gerdes, George A. Kuchel, Joan B. Mannick, Stephen B. Kritchevsky, Sundeep Khosla, Stacey A. Rizza, Jeremy D. Walston, Nicolas Musi, Lewis A. Lipsitz, Douglas P. Kiel, Raymond Yung, Nathan K. LeBrasseur, Ravinder J. Singh, Teresa McCarthy, Michael A. Puskarich, Laura J. Niedernhofer, Paul D. Robbins, Matthew Sorenson, Tamara Tchkonia, James L. Kirkland
Summary: Senescent cells (SnCs), which are metabolically active and resistant to apoptosis, increase with age and chronic diseases, making individuals more susceptible to SARS-CoV-2 complications. Senolytic agents, like Fisetin, selectively target and eliminate SnCs, showing promise in delaying or preventing multiple disorders. Clinical trials are underway to investigate the impact of senolytics on decreasing SARS-CoV-2 progression and morbidity in older adults, with logistical challenges considered for conducting trials in long-term care settings.
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
(2021)
Article
Multidisciplinary Sciences
Christina D. Camell, Matthew J. Yousefzadeh, Yi Zhu, Larissa G. P. Langhi Prata, Matthew A. Huggins, Mark Pierson, Lei Zhang, Ryan D. O'Kelly, Tamar Pirtskhalava, Pengcheng Xun, Keisuke Ejima, Ailing Xue, Utkarsh Tripathi, Jair Machado Espindola-Netto, Nino Giorgadze, Elizabeth J. Atkinson, Christina L. Inman, Kurt O. Johnson, Stephanie H. Cholensky, Timothy W. Carlson, Nathan K. LeBrasseur, Sundeep Khosla, M. Gerard O'Sullivan, David B. Allison, Stephen C. Jameson, Alexander Meves, Ming Li, Y. S. Prakash, Sergio E. Chiarella, Sara E. Hamilton, Tamara Tchkonia, Laura J. Niedernhofer, James L. Kirkland, Paul D. Robbins
Summary: The research demonstrates that cellular senescence plays a critical role in pathogen infections, with aging mice experiencing increased senescence and inflammation after exposure to pathogens. Targeting cellular senescence can significantly reduce mortality and inflammatory markers.
Article
Cell Biology
Natalia Fedtsova, Elena A. Komarova, Kellee F. Greene, Liliya R. Novototskaya, Ivan Molodtsov, Craig M. Brackett, Evguenia Strom, Anatoli S. Gleiberman, Alexander N. Shakhov, Andrei V. Gudkov
Summary: The success of bone marrow transplantation depends on p53-mediated protection of critical cells in the bone marrow stroma, as it drives the apoptotic death of hematopoietic cells and protects stromal cells essential for functionality. This study reveals a dual positive role of p53 in BMT by comparing the structural changes in the bone marrow stroma of mice with different p53 statuses.
CELL DEATH & DISEASE
(2021)
Article
Medicine, General & Internal
Sonja Suvakov, Ranine Ghamrawi, Hajrunisa Cubro, Haitao Tu, Wendy M. White, Yvonne S. Butler Tobah, Natasa M. Milic, Joseph P. Grande, Julie M. Cunningham, Fouad T. Chebib, Larissa G. P. Langhi Prata, Yi Zhu, Tamara Tchkonia, James L. Kirkland, Karl A. Nath, Aleksandar Milosavljevic, Vesna D. Garovic
Summary: Preeclamptic women experience accelerated epigenetic ageing and higher levels of senescence-related factors. Treatment with dasatinib rescues angiogenic potential of mesenchymal stem cells from preeclamptic pregnancies, promoting angiogenesis.
Editorial Material
Medicine, General & Internal
Utkarsh Tripathi, Selim Chaib, Erin O. Wissler Gerdes, Kelly A. Hogan, Yi Zhu
Article
Medicine, General & Internal
Yi Zhu, Larissa G. P. Langhi Prata, Erin O. Wissler Gerdes, Jair Machado Espindola Netto, Tamar Pirtskhalava, Nino Giorgadze, Utkarsh Tripathi, Christina L. Inman, Kurt O. Johnson, Ailing Xue, Allyson K. Palmer, Tingjun Chen, Kalli Schaefer, Jamie N. Justice, Anoop M. Nambiar, Nicolas Musi, Stephen B. Kritchevsky, Jun Chen, Sundeep Khosla, Diana Jurk, Marissa J. Schafer, Tamar Tchkonia, James L. Kirkland
Summary: This study demonstrates that targeting senescent cells can increase a-Klotho levels in mice and humans, suggesting a potential therapeutic avenue for enhancing a-Klotho. Removing senescent cells can restore a-Klotho expression, offering a translational feasible strategy for developing orally-active small molecule interventions. Urinary a-Klotho may also serve as a useful biomarker for monitoring senolytic clinical trials.
Article
Multidisciplinary Sciences
Xu Zhang, Vesselina M. Pearsall, Chase M. Carver, Elizabeth J. Atkinson, Benjamin D. S. Clarkson, Ethan M. Grund, Michelle Baez-Faria, Kevin D. Pavelko, Jennifer M. Kachergus, Thomas A. White, Renee K. Johnson, Courtney S. Malo, Alan M. Gonzalez-Suarez, Katayoun Ayasoufi, Kurt O. Johnson, Zachariah P. Tritz, Cori E. Fain, Roman H. Khadka, Mikolaj Ogrodnik, Diana Jurk, Yi Zhu, Tamara Tchkonia, Alexander Revzin, James L. Kirkland, Aaron J. Johnson, Charles L. Howe, E. Aubrey Thompson, Nathan K. LeBrasseur, Marissa J. Schafer
Summary: The authors discovered that proinflammatory senescent myeloid cells may recruit peripheral immune cells in the aged mouse brain. Their findings suggest that senescent cell clearance could be a strategy to counter aged brain inflammation and cognitive decline. This study reveals the identities of senescent cells in the aged brain and how they exert adverse influence.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Ksenia A. Novototskaya-Vlasova, Nickolay S. Neznanov, Ivan Molodtsov, Brandon M. Hall, Mairead Commane, Anatoli S. Gleiberman, Jayne Murray, Michelle Haber, Murray D. Norris, Katerina I. Leonova, Andrei V. Gudkov
Summary: Activation of endogenous retrotransposons in cancer cells contributes to tumor genomic instability. Inhibition of retrotranspositions with nucleoside reverse transcriptase inhibitor stavudine (STV) extended progression-free survival in mouse cancer models following initial complete response to chemotherapy. Moreover, STV reduced the frequency of drug-resistant cells and reversed drug resistance by inhibiting NF-KB activity and reducing the constitutive activity of interferon type I and NF-KB pathways.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
Joshua N. Farr, Dominik Saul, Madison L. Doolittle, Japneet Kaur, Jennifer L. Rowsey, Stephanie J. Vos, Mitchell N. Froemming, Anthony B. Lagnado, Yi Zhu, Megan Weivoda, Yuji Ikeno, Robert J. Pignolo, Laura J. Niedernhofer, Paul D. Robbins, Diana Jurk, Joao F. Passos, Nathan K. LeBrasseur, Tamara Tchkonia, James L. Kirkland, David G. Monroe, Sundeep Khosla
Summary: Clearing senescent cells can prevent age-related pathologies, including bone loss. Local senolysis of senescent osteocytes prevents age-related bone loss in the spine, while systemic senolysis prevents bone loss in both the spine and femur, improving bone formation and reducing osteoclast and marrow adipocyte numbers. Transplanting senescent cells induces bone loss and senescence in distant host osteocytes.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Medicine, Research & Experimental
Lei Zhang, Louise E. Pitcher, Matthew J. Yousefzadeh, Laura J. Niedernhofer, Paul D. Robbins, Yi Zhu
Summary: Cellular senescence is a key factor in aging and age-related diseases, and targeting senescent cells has shown promise in preventing tissue damage and promoting tissue repair and regeneration.
JOURNAL OF CLINICAL INVESTIGATION
(2022)