Scientists have long known that a class of proteins called sirtuins promotes fitness and longevity in most organisms ranging from single-celled yeast to mammals. At the cellular level, sirtuins protect genome integrity, enhance resistance to adverse stresses, and antagonize senescence. However, the underlying molecular mechanisms have remained poorly understood.
The team, led by senior author Shelley Berger, Ph.D., Hilary Koprowski Professor at The Wistar Institute, demonstrated for the first time a molecular target for a member of this class, Sir2, in regulation of aging in yeast cells. Sir2 removes an acetyl group attached to a specific site (lysine at position 16 or K16) on histone H4—histones are proteins that package and organize the long strands of DNA within the nucleus and also are central regulators in turning genes on and off.
The study reveals that removal of this acetyl group by Sir2 near the chromosome ends—the telomeres—is important for yeast cells to maintain the ability to replicate. Researchers found that Sir2 levels decline as cells age, and there is a concomitant accumulation of the acetylation mark along with disrupted histone organization at telomeres.
Deacetylation of H4K16 by Sir2 and consequent telomere stability play a major role in maintaining long lifespan in yeast. Since sirtuins deacetylate many different proteins, these results clarify a key role of Sir2 protein in control of lifespan.
“Some modifications on histones, like this acetylation on histone H4 lysine 16, are persistent and are maintained through generations of cell divisions. This DNA-independent inheritance is called epigenetics,” Berger says. “Characteristic epigenetic features have been discovered for various developmental processes in recent years. Understanding epigenetic changes associated with aging is a hugely exciting direction in aging research. It will provide insights and ideas not only for new therapies to regulate cells that have lost control of proliferation, such as ‘immortal’ cells found in cancers, but also for new strategies to maintain health and fitness.”
“We plan to continue to search for new targets of Sir2 and other aging regulators,” says lead author Weiwei Dang, Ph.D., a postdoctoral scientist working with Berger. “We are designing unbiased screens for other aging targets and mechanisms in chromatin. Using yeast as our aging model enables us to do many discovery screens that are impossible with other, more complex organisms. Yet it is remarkable that many of these chromatin mechanisms associated with yeast could turn out to be relevant even for aging human cells.”
Along with senior author Berger and lead author Dang, other authors include: research assistants Rocco Perry and Jean A. Dorsey, from Wistar; graduate student Kristan K. Steffen, Assistant Professor Matt Kaeberlein, Ph.D., and Assistant Professor Brian K. Kennedy, Ph.D., from the University of Washington, Seattle; Assistant Professor F. Brad Johnson, M.D., Ph.D., from the University of Pennsylvania; and Investigator Ali Shilatifard, Ph.D., from the Stowers Institute. This work was funded by the National Institutes of Health and an AFAR Julie Martin Mid-Career Award in Aging Research.
The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. Discoveries at Wistar led to the creation of the rubella vaccine that eradicated the disease in the United States, human rabies vaccines used worldwide, and a rotavirus vaccine approved in 2006. Today, Wistar is home to preeminent research programs studying skin cancer, lung cancer, and brain tumors. Wistar Institute Vaccine Center scientists are creating new vaccines against pandemic influenza, HIV, and other diseases threatening global health. The Institute works actively to transfer its inventions to the commercial sector to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today’s Discoveries — Tomorrow’s Cures.
Susan Finkelstein | Newswise Science News
Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society
127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
18.01.2017 | Materials Sciences
18.01.2017 | Information Technology
18.01.2017 | Ecology, The Environment and Conservation