February 21, 2011
Studying Aging, and Fearing Budget Cuts
By MILT FREUDENHEIM

Dr. Richard J. Hodes presides over the nation’s prime source of grants for studies of aging at a worrisome time for researchers. Just when the cohort of elderly Americans is surging, many scientists fear that government budget cuts may hamper a broad array of research efforts on Alzheimer’s and other diseases of aging — not to mention the eye-catching recent progress on reversing age-related decline in genetically altered mice.

Dr. Hodes, 67, has been the director of the National Institute on Aging at the National Institutes of Health for 17 years. Although its budget has grown to $1.1 billion on his watch, his agency would get only $20 million more under President Obama’s 2012 budget proposal. (Other agencies within the N.I.H. spend about $2 billion combined on age-related research.)

A low-key laboratory scientist himself, he dresses the part, often coming to work without a tie and in short sleeves. Former colleagues describe him as a model citizen who works long hours and practices what he preaches, eating a careful diet and lifting weights three times a week.

Born in New York on Dec. 31, 1943, just ahead of the baby boom, he graduated from Yale and Harvard Medical School, and then spent most of his professional life as a researcher at the National Cancer Institute. Indeed, he held onto his lab there after being named director of the National Institute on Aging in 1993. He leads a group that is experimenting with telomeres, the tips of chromosomes in cells, hoping to understand aging and cancer.

Geriatric scientists say there has been tremendous growth in recent years in understanding the biology of aging, and they credit Dr. Hodes with supporting a broad range of studies that include lifestyle and psychological issues, starting from the premise that there are no magic solutions in the offing.

In the following excerpts from a telephone interview and follow-up exchanges by e-mail, Dr. Hodes discusses some of the latest important developments in aging research.

Q. What is the latest in aging research?

A. The challenging question has to do with the aging process itself. The research includes some exciting discoveries showing that genetic mutations in species that range from yeast to worms to flies to mice can extend longevity. But the ultimate question, of relevance to humans, remains unanswered.

Recently there was a report about reversing the aging process in laboratory mice. The study, supported in part by N.I.H., involved telomeres — structures on the ends of chromosomes that shorten with age, causing disrupted function of the chromosomes. In mice, if you knock out the gene that encodes for an enzyme that regulates telomere length and function, these mice over time have decreased function and life expectancy.

Scientists used a genetic manipulation to turn the enzyme called telomerase back on in these mice. This restored telomere function and reversed many of the signs of aging. This study gained serious attention by suggesting an intervention that might be feasible using restoration of telomerase activity and telomere function.

Q. What is the latest on diet and exercise?

A. The evidence that lifestyle makes a difference is abundant in many areas. One of the best examples was in a diabetes prevention study supported by the aging and diabetes institutes. Researchers compared strategies for reducing diabetes in individuals who were at high risk for developing the disease. One group was provided the best information about good treatment; a second took metformin, a drug that lowers blood sugar; and a third “lifestyle” group followed an exercise and diet regimen.

Age was a variable. In younger adults, both the lifestyle and drug treatments were effective. For those aged 60 and older, the drug had no effect, but the lifestyle intervention reduced new cases of diabetes by 71 percent. In 2009, a follow-up study showed the older group had maintained some of the weight loss and activity along with some of the benefits in glucose metabolism. The study is continuing.

Q. And exercise research specific to aging?

A. The epidemiology is certainly awfully strong and suggestive that physical activity and exercise correlate with a lower risk of death, heart disease and disability. However, it will be important to test these correlations in clinical trials, to make sure we know what is really cause and effect.

We have a major clinical trial now in progress that compares one group that gets only information about a healthy lifestyle with a group of similar individuals on a very strict exercise regimen. We will know by the end of this study, in about three years, whether this specific exercise intervention kept people from being disabled — a huge step, beginning from the strong epidemiologic studies and some other short-term studies to determine whether we have an intervention that will prevent disability long term.

The study will also determine whether the exercise affects cognitive change, whether physical activity can preserve cognitive function with age, and whether it might affect Alzheimer’s and dementia.

Studies in mice are quite fascinating. Exercise in their cages actually improves their ability to generate new brain cells. What we don’t know is whether we have an exercise intervention that will actually make a difference in cognitive function over many years.

Q. What are the latest high points in Alzheimer’s research?

A. We feel a real responsibility to pay attention to the right balance of basic discovery in the laboratory — genetic and molecular findings — while at the same time making sure we can translate those findings into new approaches that can make a difference.

One example is the Alzheimer’s Disease Neuroimaging Initiative, an extraordinarily successful example of public-private partnership with other N.I.H. institutes; the F.D.A.; foundations; and more than 20 pharmaceutical, biotechnology and medical imaging companies.

The companies are running dozens of clinical prevention and treatment trials. N.I.H. is supporting 37 clinical trials to determine whether we can make a difference in the slowing or preventing of Alzheimer’s disease. This initiative is intended to look at individuals who have either normal cognition or mild cognitive impairment — that is an early stage of cognitive decline — or have diagnosable Alzheimer’s disease.

We are trying to understand what biomarkers, such as brain images or tests on blood or cerebrospinal fluid, are predictive of whether an individual is or is not going to undergo a decline in cognitive function. In the last year or two, basic science has produced very exciting genetic studies of several new risk factors for Alzheimer’s, variations of genes associated with a greater risk, although not certainty, of developing Alzheimer’s disease.

Q. So is there an example with preliminary results of promise in trials with people?

A. I would love to be able to tell you about positive results in preventing or slowing progression of Alzheimer’s. There are none documented and reported. There are some small preliminary studies.

Q. What are your concerns about the pressures to cut spending on research?

A. It is of great concern that at a time when biomedical research is needed to address conditions that affect the well-being of an increasingly older population, resource constraints are limiting our ability to capitalize on the many very promising and exciting research opportunities. And the potential long-term impact on the scientific work force is of great concern. If we lose many of our current scientists, this will be a significant loss. Even more profoundly, if we discourage young people from entering as a new generation of scientists, that will be difficult to reverse.

Q. Finally, what have we learned about driving safely later in life?

A. It was found that the ability to perceive and evaluate what is within a driver’s field of view is a powerful predictor of driving accidents in the future.

Using a computer program, researchers found that driving performance could be improved by training people in reasoning, speed of processing and memory, which drivers use instinctively as they decide which stimuli may be relevant. The training was actually associated with a decrease in accidents.

Motor vehicle departments in California, Florida and Maryland are using and testing the program to help make decisions about issuing driving licenses. Further, insurance companies like State Farm, Allstate and the Hartford are testing this training approach.

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