Study Reveals Proteins Most Associated With Aging
The finding by Stony Brook University researchers, published in Structure, may be a foundation to better understanding the cellular process and age-related disease
STONY BROOK, N.Y., February 4, 2016 – Certain proteins known to be associated with aging and age-related diseases such as Alzheimer’s disease and cancer are also at a high risk for destabilization caused by oxidation. This finding by a team of researchers at the Laufer Center for Physical and Quantitative Biology at Stony Brook University provides an understanding of how oxidative damage, which is a natural process in aging cells, affects proteins. It could also prove to be a foundation to a better understanding of age-related diseases. The paper, titled “Highly charged proteins: the Achilles’ heel of aging proteomes,” is published in the journal Structure.
By the time people turn 80 years of age, approximately half of the body’s proteins are damaged by oxidation. Oxidation occurs because of random chemical degradations that are associated with converting food to energy in the presence of oxygen. Oxidation in the human body, mediated by free radicals, damages cellular proteins, lipids, DNA, and other cellular structures that contribute to disease processes.
Kenneth Dill, right, and co-authors Adam de Graff, left, and Michael Hazoglou, center, standing beside a computerized display of three proteins: (Left) – A normal protein called ubiquitin that has a balance of charges and thus at low risk for oxidative destabilization; (Center) – The RbAp48 protein, which is part of a complex that modifies histones and is important in memory loss, is at risk because of a high negative charge (red area). (Right) – Telomerase protein is at risk because of high net positive charge (blue area).
The Stony Brook research team, led by senior author Ken A. Dill, PhD, Distinguished Professor of Chemistry and Physics and Director of the Laufer Center of Physical and Quantitative Biology, used physics principles and computer analysis to evaluate protein electrostatics, or charges. They found that short, highly charged proteins are particularly susceptible to large destabilization and that even a single oxidation event within these proteins is sufficient to unfold its normally balled-up, folded structure.
To understand more about Professor Dill’s protein research at the Laufer Center, see this Stony Brook University video.
“Our paper explains the molecular mechanism by which natural chemical processes of aging affect our proteins,” says Dr. Dill. “Our method predicts which proteins are the most at risk of unfolding when they get damaged. We then applied the principle in searching protein databases. Interestingly, we found that the proteins most at-risk for oxidative unfolding included 20 proteins that span a wide-spectrum of functionalities, all of which had been known by researchers previously to be associated with aging.”
The list of proteins includes telomerase proteins, which play a major role in aging of cells and cancer development by the extending of telomeres; and histones, which are DNA-binding proteins known to be relevant for many processes, including memory loss and cancer.
Dr. Dill explained that the mechanism provides a foundation for scientists to better understand how oxidative damage affects proteins in aging cells. The team will continue to use the method to search further databases of proteins to seek additional proteins that may be important to aging and age-related diseases.
The research, he added, could be a first step toward finding other proteins, not currently suspected, that are susceptible to high oxidation, instability and age-related diseases. The proteins could prove to be the key to targeted treatments against certain age-related diseases.
Co-authors on the paper include Adam M.R. de Graff and Michael Hazoglou of the Stony Brook University Department of Physics and Astronomy and the Laufer Center.
About Stony Brook University
Part of the State University of New York system, Stony Brook University encompasses 200 buildings on 1,450 acres. Since welcoming its first incoming class in 1957, the University has grown tremendously, now with more than 25,000 students and 2,500 faculty. Its membership in the prestigious Association of American Universities (AAU) places Stony Brook among the top 62 research institutions in North America. U.S. News & World Report ranks Stony Brook among the top 100 universities in the nation and top 40 public universities, and Kiplinger names it one of the 35 best values in public colleges. One of four University Center campuses in the SUNY system, Stony Brook co-manages Brookhaven National Laboratory, putting it in an elite group of universities that run federal research and development laboratories. A global ranking by U.S. News & World Report places Stony Brook in the top 1 percent of institutions worldwide. It is one of only 10 universities nationwide recognized by the National Science Foundation for combining research with undergraduate education. As the largest single-site employer on Long Island, Stony Brook is a driving force of the regional economy, with an annual economic impact of $4.65 billion, generating nearly 60,000 jobs, and accounts for nearly 4 percent of all economic activity in Nassau and Suffolk counties, and roughly 7.5 percent of total jobs in Suffolk County.
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