Review
Biochemistry & Molecular Biology
Nastaran Daneshgar, Peter S. Rabinovitch, Dao-Fu Dai
Summary: mTOR signaling plays a crucial role in regulating cellular metabolism and aging by controlling key cellular processes such as protein synthesis, autophagy, and mitochondrial function. Dysregulation of mTOR signaling has been associated with various age-related pathologies, including heart failure and age-related cardiac dysfunction.
Review
Biochemistry & Molecular Biology
Alek S. Torres, Marina K. Holz
Summary: mTOR plays a crucial role at the interface between the cell and its environment, directing a wide range of cellular activities in response to nutrients, growth factors, and stress. Recent studies have explored the role of nuclear mTOR in specific cellular programs, shedding light on its function in the nucleus and how these pathways interact with each other. This evolving understanding of nuclear mTOR has led to the proposal of new ideas, hypotheses, and future research directions.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Review
Cell Biology
Yan Zhang, Jinjin Zhang, Shixuan Wang
Summary: Anti-aging is a complex global challenge, and rapamycin can prolong healthy lifespan by inhibiting the mTOR pathway, although current evidence for its effectiveness in lifespan extension is not yet comprehensive. This drug has significant anti-aging effects on multiple organ systems.
AGEING RESEARCH REVIEWS
(2021)
Article
Medicine, Research & Experimental
Alvaro Gonzalez-Dominguez, Raul Montanez, Beatriz Castejon-Vega, Jessica Nunez-Vasco, Debora Lendines-Cordero, Chun Wang, Gabriel Mbalaviele, Jose M. Navarro-Pando, Elisabet Alcocer-Gomez, Mario D. Cordero
Summary: This study showed increased expression of NLRP3 inflammasome components in HGPS skin fibroblasts and lymphoblasts, as well as in hearts and livers of Zmpste24(-/-) mice. Inhibiting the NLRP3 inflammasome with MCC950 improved cellular phenotype, extended lifespan of progeroid animals, and reduced inflammation, suggesting a potential therapeutic approach for HGPS.
EMBO MOLECULAR MEDICINE
(2021)
Review
Immunology
Anne E. O'Shea, Franklin A. Valdera, Daniel Ensley, Todd R. Smolinsky, Jessica L. Cindass, Phillip M. Kemp Bohan, Annelies T. Hickerson, Elizabeth L. Carpenter, Patrick M. McCarthy, Alexandra M. Adams, Timothy J. Vreeland, Guy T. Clifton, George E. Peoples
Summary: Rapamycin inhibits mTOR signaling, exhibiting both immunosuppressive and immunostimulatory effects on innate and adaptive immune responses. The dose and administration schedule play a crucial role in modulating rapamycin's immunologic effects.
CLINICAL IMMUNOLOGY
(2022)
Article
Cell Biology
Diego Quintana-Torres, Alejandra Valle-Cao, Pablo Bousquets-Munoz, Sandra Freitas-Rodriguez, Francisco Rodriguez, Alejandro Lucia, Carlos Lopez-Otin, Alejandro Lopez-Soto, Alicia R. Folgueras
Summary: This study conducted a global plasma proteomic analysis in progeroid mouse models and found several upregulated proteins related to cardiovascular disease, the main cause of death in HGPS patients. The plasma proteome of progeroid mice exhibited an old signature, indicating accelerated aging. Furthermore, specific differences were observed in the circulating proteins between physiological and premature aging, highlighting potential biomarkers and therapeutic targets.
Article
Biochemistry & Molecular Biology
R. Mahalakshmi, J. Priyanga, Dipita Bhakta-Guha, Gunjan Guha
Summary: This study demonstrates that low doses of rapamycin can alleviate aging-associated mitochondrial dyshomeostasis in WRL-68 cells, such as oxidative damage to mitochondrial nucleic acids and proteins, as well as imbalance in mitochondrial density, membrane potential, biogenesis, mitophagy, and overall metabolism.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Multidisciplinary Sciences
Yuexia Wang, Khurts Shilagardi, Trunee Hsu, Kamsi O. Odinammadu, Takamitsu Maruyama, Wei Wu, Chyuan-Sheng Lin, Christopher B. Damoci, Eric D. Spear, Ji-Yeon Shin, Wei Hsu, Susan Michaelis, Howard J. Worman
Summary: Prelamin A, a farnesylated precursor of lamin A, can cause progeria syndrome when accumulated as progerin. Mutations in ZMPSTE24, the processing enzyme of prelamin A, can lead to progeroid disorders. This study generated a mouse model with permanently farnesylated prelamin A and found that these mice have extended lifespan and exhibit skeletal and nuclear defects during physiological aging.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Genetics & Heredity
Noelle J. Batista, Sanket G. Desai, Alexis M. Perez, Alexa Finkelstein, Rachel Radigan, Manrose Singh, Aaron Landman, Brian Drittel, Daniella Abramov, Mina Ahsan, Samantha Cornwell, Dong Zhang
Summary: Hutchinson-Gilford progeria syndrome (HGPS) is a rare, autosomal-dominant, and fatal premature aging syndrome caused by a point mutation in the LMNA gene. The resulting mutant protein, progerin, behaves in a dominant-negative fashion, leading to cellular and molecular changes similar to normal aging cells. However, HGPS manifests in an accelerated manner and primarily affects connective tissues. Epigenetic changes in HGPS have been studied and may play a crucial role in the disease's pathogenesis. Recent treatments for HGPS have shown important effects at a cellular level, improving symptoms and increasing lifespan.
Article
Dermatology
A. J. Duran-Romero, J. C. Hernandez-Rodriguez, J. Ortiz-Alvarez, J. J. Dominguez-Cruz, M. T. Monserrat-Garcia, J. Conejo-Mir Sanchez, J. Bernabeu-Wittel
Summary: Oral sirolimus shows good efficacy and safety in treating high-flow vascular malformations, with most patients experiencing partial relief and tolerating the treatment well. It can be a useful option for long-term stabilization of patients with high-flow vascular malformations.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lucia Lisi, Michela Pizzoferrato, Gabriella Maria Pia Ciotti, Maria Martire, Pierluigi Navarra
Summary: Initially used as immunosuppressants in therapy, selective inhibitors of mTORC1 have now been approved for the treatment of solid tumors. Non-selective mTOR inhibitors are being developed in preclinical and clinical studies in oncology to overcome limitations of selective inhibitors, such as tumor resistance. In this study, we compared the effects of a non-selective mTOR inhibitor, sapanisertib, with rapamycin in glioblastoma cell lines and microglia, and found overlapping and diverging effects, especially in the activation of tumor-associated microglia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Aigli G. Vakrakou, Anastasia Alexaki, Maria-Evgenia Brinia, Maria Anagnostouli, Leonidas Stefanis, Panos Stathopoulos
Summary: This article summarizes the evidence on the role of mammalian targets of rapamycin (mTOR) complex pathways in multiple sclerosis (MS), including autophagy, inflammasome activation, immune responses, and neuronal toxicity. There is robust evidence that mTOR inhibitors, such as rapamycin, improve the clinical course of MS animal models. New research highlights the effects of mTOR on T cells and myeloid cells, providing insight into MS pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Anastasia V. Poznyak, Vasily N. Sukhorukov, Alexander Zhuravlev, Nikolay A. Orekhov, Vladislav Kalmykov, Alexander N. Orekhov
Summary: Atherosclerosis has been a leading cause of death in developed countries for over a decade. The treatment and prevention of this disease are crucial, but there are still gaps in our understanding of its pathogenesis. The mTOR signaling pathway, although well-studied, continues to reveal new details. Therapeutic strategies associated with rapamycin have shown promise in other diseases, suggesting potential effectiveness in atherosclerosis as well.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Wayne A. Cabral, Urraca L. Tavarez, Indeevar Beeram, Diana Yeritsyan, Yoseph D. Boku, Michael A. Eckhaus, Ara Nazarian, Michael R. Erdos, Francis S. Collins
Summary: Hutchinson-Gilford progeria syndrome (HGPS) is a rare accelerated aging disorder characterized by cardiovascular disease and premature death, mostly caused by a single nucleotide mutation in the LMNA gene. A study using mice models carrying two copies of the BAC showed a more complete replication of HGPS phenotypic features in various tissues, and genetic reduction of mTOR extended the lifespan of these mice significantly, suggesting a potential treatment for HGPS through pharmacologic inhibition of the mTOR pathway.
Article
Cell Biology
Yantenew G. Gete, Luke W. Koblan, Xiaojing Mao, Mason Trappio, Bhushan Mahadik, John P. Fisher, David R. Liu, Kan Cao
Summary: HGPS is a rare genetic disorder caused by a mutation in the LMNA gene, leading to the production of toxic progerin protein that affects angiogenesis. Using iPSC-EC models, it was found that HGPS cells exhibit endothelial dysfunction and deficits in microvascular network formation.
Article
Cell Biology
Meghan K. Driscoll, Wolfgang Losert, Ken Jacobson, Maryna Kapustina
Article
Multidisciplinary Sciences
Xiaoyu Sun, Meghan K. Driscoll, Can Guven, Satarupa Das, Carole A. Parent, John T. Fourkas, Wolfgang Losert
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2015)
Review
Cell Biology
Meghan K. Driscoll, Gaudenz Danuser
TRENDS IN CELL BIOLOGY
(2015)
Article
Engineering, Biomedical
Desu Chen, Sumona Sarkar, Julian Candia, Stephen J. Florczyk, Subhadip Bodhak, Meghan K. Driscoll, Carl G. Simon, Joy P. Dunkers, Wolfgang Losert
Article
Cell Biology
Erik S. Welf, Meghan K. Driscoll, Kevin M. Dean, Claudia Schaefer, Jun Chu, Michael W. Davidson, Michael Z. Lin, Gaudenz Danuser, Reto Fiolka
DEVELOPMENTAL CELL
(2016)
Article
Chemistry, Multidisciplinary
Meghan K. Driscoll, Xiaoyu Sun, Can Guven, John T. Fourkas, Wolfgang Losert
Article
Multidisciplinary Sciences
Chenlu Wang, Sagar Chowdhury, Meghan Driscoll, Carole A. Parent, S. K. Gupta, Wolfgang Losert
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2014)
Article
Multidisciplinary Sciences
Oliver Nagel, Can Guven, Matthias Theves, Meghan Driscoll, Wolfgang Losert, Carsten Beta
Article
Biochemical Research Methods
Julian Candia, Ryan Maunu, Meghan Driscoll, Angelique Biancotto, Pradeep Dagur, J. Philip McCoy, H. Nida Sen, Lai Wei, Amos Maritan, Kan Cao, Robert B. Nussenblatt, Jayanth R. Banavar, Wolfgang Losert
PLOS COMPUTATIONAL BIOLOGY
(2013)
Article
Multidisciplinary Sciences
Joerg Renkawitz, Aglaja Kopf, Julian Stopp, Ingrid de Vries, Meghan K. Driscoll, Jack Merrin, Robert Hauschild, Erik S. Welf, Gaudenz Danuser, Reto Fiolka, Michael Sixt
Article
Biochemical Research Methods
Meghan K. Driscoll, Erik S. Welf, Andrew R. Jamieson, Kevin M. Dean, Tadamoto Isogai, Reto Fiolka, Gaudenz Danuser
Article
Biochemical Research Methods
Tonmoy Chakraborty, Meghan K. Driscoll, Elise Jeffery, Malea M. Murphy, Philippe Roudot, Bo-Jui Chang, Saumya Vora, Wen Mai Wong, Cara D. Nielson, Hua Zhang, Vladimir Zhemkov, Chitkale Hiremath, Estanislao Daniel De la Cruz, Yating Yi, Ilya Bezprozvanny, Hu Zhao, Raju Tomer, Rainer Heintzmann, Julian P. Meeks, Denise K. Marciano, Sean J. Morrison, Gaudenz Danuser, Kevin M. Dean, Reto Fiolka
Article
Cell Biology
Meghan K. Driscoll, Assaf Zaritsky
Summary: Cell imaging has entered the 'Big Data' era, with new technologies leading to an explosion in high content, dynamic, and multidimensional imaging data. Data science plays a crucial role in processing, analyzing, and mining these vast amounts of data in the field of cell imaging.
JOURNAL OF CELL SCIENCE
(2021)
Article
Multidisciplinary Sciences
Andrew D. Weems, Erik S. Welf, Meghan K. Driscoll, Felix Y. Zhou, Hanieh Mazloom-Farsibaf, Bo-Jui Chang, Vasanth S. Murali, Gabriel M. Gihana, Byron G. Weiss, Joseph Chi, Divya Rajendran, Kevin M. Dean, Reto Fiolka, Gaudenz Danuser
Summary: Most human cells require anchorage for survival, and loss of cell-substrate adhesion can result in anoikis, a form of programmed cell death. Blebbing, the formation of small hemispherical plasma membrane protrusions, triggers the formation of signalling hubs that confer anoikis resistance by recruiting septin proteins as scaffolds for mutant NRAS and effectors. These signalling hubs activate pro-survival pathways, such as ERK and PI3K. Inhibition of blebs or septins in detached cells causes mislocalization of NRAS, reduced MAPK and PI3K activity, and cell death. Therefore, blebs play a crucial role in providing robust anoikis resistance.