William A. Haseltine, chairman and CEO of Human Genome Sciences Inc. in Rockville, Md., comments, "We're now in the beginning stages of a major revolution of research and understanding of aging, not of the aging process itself, but what to do about it. A major thrust of medical research, especially finding new ways to treat and cure disease, will be directed at the problems of the aging. There's been a major redefinition that aging should not be studied only as a holistic phenomenon; it should be viewed as a series of treatable, and in some cases, preventable diseases."
Jobseekers take note: "I think the most interesting work in aging will not be done by people who call themselves 'aging researchers,'" states Haseltine. "In fact, they are to be avoided. If you want somebody who's going to do great aging research, get someone who understands bone metabolism to work on osteoporosis." The same idea, he continues, applies to research on neurodegeneration: "Get people who work on nerve stem cell biology. For atherosclerosis, hire those who understand lipid metabolism." And to rebuild tissues, in a new area of research that Haseltine terms "regenerative medicine," he urges searching out researchers who are expert in each of the tissues.
The dilemma of where to place the emphasis when discussing aging research is compounded by the stigma of "searching for the fountain of youth" that has plagued the field in the past. "I think [the stigma] has kept the field of biogerontology from standing tall alongside molecular biology and cell biology because it attracted the fringe element earlier in the century and even before that," remarks Perry.
Last fall, a Science paper that described the extension of the life span of Caenorhabditis elegans could arguably be a case in point about this problem. Collaborators from the Buck Institute for Age Research in Novato, Calif. (See story, page 1), the University of Manchester, United Kingdom, Emory University, and Eukarion Inc., a biotech firm in Bedford, Mass., demonstrated that synthetic catalytic scavengers can cross the blood-brain barrier, inactivate toxic oxygen radicals, and thereby increase the normal life span in the nematode worm.1 Despite this discovery, Susan Doctrow, vice president of research at Eukarion and coauthor of the paper, does not consider the worm work strictly aging research per se. Still, says Doctrow, she and her colleagues at Eukarion and collaborating institutions field calls from people asking when they're going to start human trials to extend life span. The paper was even the subject of a Sylvia cartoon late last fall, entitled Bad Girl Chats About Biology. "We all got a kick out of that," remembers Doctrow.
|Reprinted with permission, Nicole Hollander|
Nevertheless, Eukarion is one of almost 30 biotech companies profiled in a recent AAR report (see Web site listed in Resources) entitled, "The Dawn of Gero-Technology: Pioneers in Aging and Regenerative Medicine." Perry describes these firms as U.S. biotech companies doing research that could be applied to diseases and aliments related to the aging process.
What's more, many institutes and researchers don't shrink from using the word "age" in their titles. Dale Bredesen, CEO and president at the Buck Institute, categorizes those interested in the aging process into three general groups:
* "First are those who attempt to address the question: 'What is aging itself?' These are scientists who study the genes of aging, asking what are the best simple models to describe it? Is it programmed or is it by accident?"
* The second group, he says, comprises researchers who address the question of why certain diseases increase so dramatically with age.
* The third group, which he says is synergistic with the other categories, are "the technophiles and basic research developers who bring new tools to the table, who don't see themselves necessarily as researchers in the aging process, but rather as people who are studying the fundamental laws of biology, chemistry, and physics who would like to apply their knowledge and expertise to the aging process."
As in most areas of biomedicine, researchers agree there is a lack of those versed in translational medicine. Christopher M. Clark, director of the Memory Disorders Clinic for the University of Pennsylvania Health System in Philadelphia, agrees that there is a need for researchers who understand what is found at the bench and in animal models and how that applies to patients, but he adds that these students still need a medical degree.
Clark's area of clinical research--neurodegenerative dementia--is dominated by M.D.s with training in neurology. A second, smaller group in the clinic includes biologically based psychiatrists who have an interest in aging and have additional training in geriatric psychology. There certainly are job opportunities, Clark notes, but clinical researchers still need to come up from an educational background from medicine or biology. "Basically they're physicians with one foot in the lab and one foot in the clinic," he explains.
At the Cusp of Change
Perry believes that the prevalence of neuroscience as the dominant field in age-related research over the last 10 to 15 years is at the cusp of change. About half of National Institute on Aging (NIA) grants are given to neuroscience and Alzheimer's research, according to Perry. "I believe that regenerative medicine is going to change that balance to enlarge the amount of academic and scientific interest in such things as stem cells and replacement parts, but neuroscience will still play a large role as long as we're facing the huge and very visible challenge of Alzheimer's."
Marcelle Morrison-Bogorad, the NIA acting deputy director and associate director of the neuroscience and neuropsychology of aging program, states that if she were putting together a research team, she would emphasize the need for its members to have cross-disciplinary knowledge. "Of course you can get this by hiring people on a team with different skills," she relates, "But it is so much more interesting if you can identify individuals with experience in cell biology and genetics, for example, or genetics plus neuroscience, or anatomy plus cell biology, or neuroscience plus biophysics."
Specifically, these disciplines are being brought to bear in a number of areas, such as expanding the life of neurons, as well as protein folding and structure and how these relate to neurodegenerative diseases, says Morrison-Bogorad. Other areas of study include identifying drugs that affect certain pathways, such as those that lead to Alzheimer's disease; developing transgenics, and determining how long-term and short-term memory works.
Rebuild, Replace, Restore
An increasing number of researchers are directing their efforts at harnessing the body's innate potential capacity to restore itself, in part to offset the declines associated with age-related diseases. Haseltine's concept of regenerative medicine is based on the notion that if the body wears out or is injured by trauma or disease, it can rebuild, replace, or restore the affected body part to its normal healthy function.
One branch of this field focuses on the use of human genes, antibodies, and proteins as drugs to stimulate the body or to correct defects without organ replacement. According to Haseltine, treatment could include adding genes to stimulate regrowth of blood vessels or strengthen muscle, or using antibodies to clear hormones that are overproduced in older people. Another branch centers on the use of organs made from one's own tissue and grown outside the body for reimplantation. "We can now do this with bladder, trachea, bone, ligaments, to some extent skin, and we're starting to do it with blood vessels and heart valves. I think within five to ten years we'll be able to do it with kidney function, liver function, and an ever-increasing array of tissues," predicts Haseltine.
A third area is the use of cells and stem cells as medicine to replace in situ tissues that are aged or diseased. And replacing sensory organs and nervous function with artificial parts is yet another area. For instance, he says, there are now titanium ears and new programs to create artificial retinas.
Haseltine summarizes regenerative medicine and its allied fields as "a tremendous growth area, but it will not be defined as traditional aging research has been defined. Aging is not a uniform syndrome, a single inevitable process, but a series of specific treatable diseases."
Karen Young Kreeger (email@example.com) is a contributing editor for The Scientist.
1. S. Melov et al., "Extension of life-span with superoxide dismutase/catalase mimetics," Science, 289:1567-9, 2000.
Alliance for Aging Research
Alzheimer's Disease Forum
Buck Institute for Age Research
Human Genome Sciences
National Institute on Aging