Inhibiting TOR boosts regenerative potential of adult tissuesDecember 07, 2017
Adult stem cells replenish dying cells and regenerate damaged tissues throughout our lifetime. We lose many of those stem cells, along with their regenerative capacity, as we age. Working in flies and mice, researchers at the Buck Institute and elsewhere discovered that TOR, a nutrient sensing pathway which is central to the aging process, drives the loss of adult stem cells. Treating mice with the TOR-inhibitor rapamycin prevented this loss and could reverse age-related loss of stem cells in mouse trachea. The research is published in Cell Stem Cell.
In most of our tissues, adult stem cells hang out in a quiet state - ready to be activated in case of infection or injury. In response to such injury, however, stem cells have to be able to rapidly divide, to generate daughter cells that differentiate into cells that repair the tissue. This division has to be "asymmetric", meaning that only one of the two cells generated during the stem cell division goes on to differentiate, while the other cell remains a stem cell.
Buck professor and senior author Heinrich Jasper, PhD, says previous research showed that TOR needs to be maintained at a low level in order to preserve stem cells in a quiet state and prevent their differentiation. But in this study, researchers discovered that TOR signaling becomes activated in many stem cell types when they are engaged in a regenerative response. Jasper, who is now a staff scientist at Genentech, says this activation is important for rapid tissue repair, but at the same time it also increases the probability that stem cells will differentiate, thus losing their stem cell status. Jasper says this loss - in this case in the fly intestine, mouse muscle and mouse trachea - is particularly prevalent when the tissue is under heavy or chronic pressure to regenerate, which occurs in response to infections or other trauma to the tissue. During aging, Jasper says that repeated or chronic activation of TOR signaling contributes to the gradual loss of stem cells. Accordingly, by performing genetic or pharmacological interventions to limit TOR activity chronically, the researchers were able to prevent or reverse stem cell loss in tracheae and muscle of aging mice.
"It's all about maintaining a balance between stem cell renewal and differentiation," said Jasper. "It's easy to see how a loss of adult stem cells might accrue over a lifetime and accelerate with aging. We are excited to have a means of rescuing stem cells, boosting their ability to maintain healthy tissue."
The work at the Buck Institute, led by postdoctoral fellow Samantha Haller, PhD, began in the intestines of fruit flies and moved to mouse trachea - tissues that share many similarities. Experiments involving mouse muscle were done at Stanford University. At the Buck Institute, mice were put on differing regimens of rapamycin treatment starting at different stages of life. Jasper says rapamycin was able to rescue stem cells even when given to mice starting at 15 months of age - the human equivalent of 50 years of age. "In every case we saw a decline in the number of stem cells, and rapamycin would bring it back." Whether this recovery of tissue stem cell numbers is due to a replenishment of the stem cell pool from more differentiated cells, or due to an increase in "asymmetric" stem cell divisions that allow one stem cell to generate two new ones, remains to be answered, he said.
Jasper says TOR can be regulated by a number of stimuli, and researchers are now attempting to better understand how the activity of this signaling pathway is controlled in stem cells. "Is there a chronic increase in TOR over a lifetime, or is activation stronger in aging animals? What happens downstream of TOR?" Jasper says researchers at the Buck are also testing homologues of rapamycin that are more specifically aimed at TOR Complex 1 - a key complex containing TOR that regulates cell growth and metabolism in all complex organisms.
Other Buck researchers involved in the study include Samantha Haller, Subir Kapuria, Rebeccah R. Riley, Monique N. O'Leary, Katherine H. Schreiber, Julie K. Andersen, Simon Melov and Brian Kennedy. Other collaborators include Thomas A. Rando and Joseph T. Rodgers, Paul Glenn Laboratories for the Biology of Aging, Stanford University, Stanford, CA; Jianwen Que, Department of Medicine, Columbia University, New York, NY; and Jason Rock, Department of Anatomy, USCF School of Medicine, San Francisco, CA.
The work was supported by grants from the National Institutes of Health R01 AG041764, R01 AG047497, R01 DK100342.
About the Buck Institute for Research on Aging
The Buck Institute is the U.S.'s first independent research organization devoted to Geroscience - focused on the connection between normal aging and chronic disease. Based in Novato, California, the Buck is dedicated to extending "healthspan," the healthy years of human life, and does so by utilizing a unique interdisciplinary approach involving laboratories studying the mechanisms of aging and others focused on specific diseases. Buck scientists strive to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimer's and Parkinson's, cancer, cardiovascular disease, macular degeneration, osteoporosis, diabetes and stroke. In their collaborative research, they are supported by the most recent developments in genomics, proteomics, bioinformatics and stem cell technologies. For more information: http://www.thebuck.org.
Buck Institute for Research on Aging
Related Stem Cells Articles:
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
Researchers have developed a new approach for growing and studying cells they hope one day will lead to curing lung diseases such as cystic fibrosis through 'personalized medicine.'
Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists.
DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells.
With age, the chromosomes of our cardiac stem cells compress as they move into a state of safe, semiretirement.
A team of researchers from the Medical University of South Carolina and elsewhere has found a better way to purify liver cells made from induced pluripotent stem cells.
International stem cell scientists, co-led in Canada by Dr. John Dick and in the Netherlands by Dr.
Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St.
In a new Cell Reports paper, a team led by John P.
Related Stem Cells Reading:
Stem Cell Therapy: A Rising Tide: How Stem Cells Are Disrupting Medicine and Transforming Lives
by Neil H Riordan (Author)
Stem cells are the repair cells of your body. When there aren’t enough of them, or they aren’t working properly, chronic diseases can manifest and persist. From industry leaders, sport stars, and Hollywood icons to thousands of everyday, ordinary people, stem cell therapy has helped when standard medicine failed. Many of them had lost hope. These are their stories.
Neil H Riordan, author of MSC: Clinical Evidence Leading Medicine’s Next Frontier, the definitive textbook on clinical stem cell therapy, brings you an easy-to-read book about how and why stem cells work,... View Details
Stem Cells: An Insider's Guide
by Paul Knoepfler (Author)
Stem Cells: An Insider's Guide is an exciting new book that takes readers inside the world of stem cells guided by international stem cell expert, Dr. Paul Knoepfler. Stem cells are catalyzing a revolution in medicine. The book also tackles the exciting and hotly debated area of stem cell treatments that are capturing the public's imagination. In the future they may also transform how we age and reproduce. However, there are serious risks and ethical challenges, too. The author's goal with this insider's guide is to give readers the information needed to distinguish between the... View Details
The Stem Cell Revolution
by Mark Berman MD (Author), Elliot Lander MD (Contributor)
The book describes the journey into the growing arena of clinical stem cell therapy by highlighting not only the road that brought a team of physicians together but also real stories from a number of their patients that were given their health back through the magic of stem cell therapy. Your fat is loaded with stem cells that can be used now to treat and reverse a large number of inflammatory and degenerative conditions. Most people have no idea that these magical cells actually exist right within our bodies. They think that they must wait until Big Pharma or a university PhD manufactures... View Details
Stem Cells For Dummies
by Lawrence S.B. Goldstein (Author), Meg Schneider (Author)
The first authoritative yet accessible guide to this controversial topic
Stem Cell Research For Dummies offers a balanced, plain-English look at this politically charged topic, cutting away the hype and presenting the facts clearly for you, free from debate. It explains what stem cells are and what they do, the legalities of harvesting them and using them in research, the latest research findings from the U.S. and abroad, and the prospects for medical stem cell therapies in the short and long term.Explains the differences between adult stem cells and embryonic/umbilical... View Details
Stem Cells Are Everywhere
by Irv Weissman MD (Author)
An engaging introduction to stem cells for young scientists
How do you heal when you cut your skin or break a bone? How does your body keep making new blood or brain cells, or even second teeth? How does a plant keep growing larger? The answers lie in stem cells, which are found in every growing plant and animal. Keeping the subject simple enough for young readers, a pioneer of stem cell research explains cells, tissues, normal growth, what can go wrong, and how to fix it. View Details
Stem Cells: A Very Short Introduction
by Jonathan Slack (Author)
Embryonic stem cells have been hot-button topics in recent years, generating intense public interest as well as much confusion and misinformation. In this Very Short Introduction, leading authority Jonathan Slack offers a clear and informative overview of stem cells--what they are, what scientists do with them, what stem cell therapies are available today, and how they might be used in the future. Slack explains the difference between embryonic stem cells, which exist only in laboratory cultures, and tissue-specific stem cells, which exist in our bodies, and he discusses how... View Details
Stem Cells: A Short Course
by Rob Burgess (Author)
Stem Cells: A Short Course is a comprehensive text for students delving into the rapidly evolving discipline of stem cell research. Comprised of eight chapters, the text addresses all of the major facets and disciplines related to stem cell biology and research. A brief history of stem cell research serves as an introduction, followed by coverage of stem cell fundamentals; chapters then explore embryonic and fetal amniotic stem cells, adult stem cells, nuclear reprogramming, and cancer stem cells. The book concludes with chapters on stem cell applications, including the role of stem... View Details
The Stem Cell Secret: How to Activate and Regerate Your Stem Cells Naturally and Affordably
Stem Cells live in every cell in your entire body and are designed to repair and rejuvenate your organs and tissues. Our Stem Cells become less effective in healing over time and at times can become overwhelmed with disease. This book shows how to use nutrition, supplements and life style tips to activate your Stem Cells and allow them to heal your body. View Details
Essentials of Stem Cell Biology, Third Edition
by Robert Lanza (Editor), Anthony Atala (Editor)
First developed as an accessible abridgement of the successful Handbook of Stem Cells, Essentials of Stem Cell Biology serves the needs of the evolving population of scientists, researchers, practitioners, and students embracing the latest advances in stem cells. Representing the combined effort of 7 editors and more than 200 scholars and scientists whose pioneering work has defined our understanding of stem cells, this book combines the prerequisites for a general understanding of adult and embryonic stem cells with a presentation by the world's experts of the latest... View Details
The Science of Stem Cells
by Jonathan M. W. Slack (Author)
Introduces all of the essential cell biology and developmental biology background for the study of stem cells
This book gives you all the important information you need to become a stem cell scientist. It covers the characterization of cells, genetic techniques for modifying cells and organisms, tissue culture technology, transplantation immunology, properties of pluripotent and tissue specific stem cells and, in particular, the relevant aspects of mammalian developmental biology. It dispels many misconceptions about stem cells—especially that they can be miracle... View Details