Life Extension Magazine October 2001
The Buck Institute For Age Research
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Back in the mid-1970's, a humanitarian and multi-millionaire did something that had a rather unusual result. Beryl H. Buck left behind a fortune-now valued at nearly $1 billion- for the benefit of her community. In order to properly manage her generous contribution, which multiplied rapidly thereafter, a Foundation was later set up. Among other projects, the Foundation helped to build and support an institute for the purpose of conducting research aimed at understanding the biology of aging and extending the healthy human life span.
Beryl Buck's foresight has resulted in the establishment of a world-class research facility where scientists are aggressively researching the causes of age-related diseases using multi-disciplinary approaches. The following article reveals what has been going on at the Buck Institute for Age Research located in Marin County, California.
by Melissa Block, M.Ed.
The Buck Institute For Age Research is a non-profit, totally independent research center, not affected by political or economic interests. Because of this, the scientists working there are free to do the work they believe is in the best interest of life extension, and are not beholden to large pharmaceutical companies, medical associations, HMOs, politicians or any of the other parties who tend to stifle groundbreaking research.
The Institute’s headquarters have been called “a magnificent blend of art, architecture and science,” and are considered a Marin County landmark. They were designed by famed architect I.M. Pei, with the intent to create the ideal environment for the use of cutting-edge methods and for the collaboration of scientists in various areas of aging research. Phase I of construction includes 185,000 square feet, including a 238-seat auditorium, administrative offices, three libraries, faculty offices and laboratories. When completed, the complex will measure a total of 355,000 square feet. On the 488-acre property, which includes 128 units of housing for entry-level researchers and visiting scholars, 238 acres are dedicated to permanent agricultural use and 70 acres will be open public space. In such an environment, where brilliant scientists are able to spend one hundred percent of their efforts on research, and where they have complete access to state-of-the-art equipment and research methods, great things are bound to be discovered.
As a freestanding research center, The Buck Institute collaborates on projects with universities, biotechnology firms and other public and private research organizations. In fact, researchers from The Buck Institute collaborated with scientists from Eukarion, Inc. to lengthen the life span of nematode worms with synthetic catalytic scavengers (SCSs). Buck Institute research teams have also collaborated with the University of California, San Diego (UCSD), the University of California, San Francisco (UCSF) and Smith-Kettlewell Eye Institute.
The Buck Institute’s mission is to find ways to stave off or altogether prevent the degenerative diseases of aging, effectively defusing the upcoming health care crisis expected as the world’s population ages. By identifying very early diagnostic markers in people who will eventually develop these diseases, Buck Institute scientists hope to create therapies that will delay the disease’s onset for 5, 10, even 50 years. These innovative scientists seek to understand the nature of the aging process—and the disease processes that often accompany aging—at the cellular and molecular levels. In other words, The Buck Institute’s quest is to locate the exact triggers of age-associated disease, and to turn those triggers off or delay them from being turned on. What makes The Buck Institute truly extraordinary is its research staff. Culled from top universities and research centers in the U.S. and abroad, these dedicated scientists have come together in an unprecedented joint effort to hold back the tide of age-related disease. Unique research is ongoing in each of the Institute’s laboratories, and there is a constant exchange of information between researchers in various disciplines that enriches the pursuit of each individual team of scientists. Interns and junior research fellows are an integral part of the facility’s staff; senior staff members appreciate the importance of bringing in and mentoring young scientists. Senior staffers also recognize the need for their own continuing education as research methods become more and more technologically advanced.
Present research on age-related neurological disorders
Gerontologist Julie Andersen, Ph.D., studies Parkinson’s disease, a hereditary neurodegenerative disease that strikes one out of every 100 Americans over the age of 65. Parkinson’s causes progressive stiffness, tremor and loss of control over body movements, and is caused by the destruction of dopamine-producing cells in a part of the brain called the substantia nigra. Dr. Andersen is studying the role of free radicals in the progression of Parkinson’s disease; more specifically, whether the age-related decrease in cells’ ability to make the antioxidant glutathione is partly responsible for the disease’s progression.
Dale E. Bredesen, M.D., the founding president and CEO of The Buck Institute, is a neuroscientist of the highest caliber. He has belonged to the neurology faculty at UCLA and worked as a professor and director of the Burnham Institute’s Program on Aging and Cancer in San Diego, California. In his laboratory, a dozen researchers are working towards a complete picture of the molecular and cellular mechanisms that cause the death of nerve and brain cells in diseases such as Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease). Once those mechanisms are understood, the Bredesen lab will use this knowledge to develop techniques for early identification and treatment of these diseases, extending healthy years of life for people predisposed to them.
In an issue of the journal Nature Medicine [Nat Med 2000 Apr;6(4):397-404], Dr. Bredesen and Dr. Edward Koo of UCSD reported on their Alzheimer’s research. In the brains of Alzheimer’s patients, an abundance of a sticky deposit known as beta-amyloid is thought to be the main cause of nerve cell degeneration. Drs. Bredesen and Koo report that another substance, which they named the C31 peptide, appears to contribute to the progressive brain cell damage and death characteristic of Alzheimer’s disease as well. This research could have significant effects on drug development for Alzheimer’s, which until recently has focused on affecting the formation of beta-amyloid plaques alone. Further research could lead to better targeted drug therapies for slowing the progression of this disease.
Chemist Lisa Ellerby, Ph.D., is one of the founding faculty members of The Buck Institute. Dr. Ellerby and her research team seek to understand why the cells of the nervous system die off in people with inherited, age-dependent neurodegenerative diseases, including Huntington’s chorea (which causes progressive loss of motor control and dementia), Kennedy’s disease (a disease of muscle atrophy that only affects males) and Machado-Joseph disease (a Parkinson’s-like disorder that strikes mostly people of Portugese descent). Specifically, she is studying how changes in the structure of a neurotransmitter molecule affect the activity of enzymes that spur cell death. Her goal is to identify which of these enzymes are involved in neurodegenerative disease.
Vivian Y.H. Hook, Ph.D., holds a joint faculty position as Adjunct Professor of Neurosciences and Medicine at UCSD. She also directs a pre- and postdoctoral training program in the neurosciences at both UCSD and The Buck Institute. She has received several grants from government and private sources to further her research. Her research focus is the role of enzymes called proteases—and of specialized molecules that inhibit their activity—in the development of Alzheimer’s, Huntington’s and other neurodegenerative diseases.
Her research into proteases could have a more general application for age-related problems, as well. Proteases regulate the production of neuropeptides, which, in turn, regulate stress responses, pain, blood pressure and weight gain. Dr. Hook hopes to manipulate proteases with drugs in ways that will relieve pain, downregulate stress reactions and blood pressure, and control the tendency towards obesity often seen in aging people.