Living Longer, Aging Better


by Brenda Patoine

January, 2004

 

Richard J. Hodes, M.D.

Director National Institute on Aging (NIA), National Institutes of Health

Q: Life expectancy for Americans continues to increase. What are the biggest health challenges facing our aging population and how can those challenges best be met?  

RH: Our society is growing notably older. The sheer numbers of people in the U.S. age 65 and older, now about 36 million, are projected to more than double by 2030. In addition, the pro­portion of the population over 65 will expand from about 12 percent to about 20 percent over that same time period. One intriguing projec­tion from the Census Bureau estimates that the number of centenarians will rise during this same time period by over 500 percent (from about 59,000 today to about 400,000 in 2030). 

This dramatic aging of the U.S., and, indeed, the world, presents us with good news on longevity but a number of significant challenges. We know that aging is a leading risk factor for a range of diseases—Alzheimer’s disease, cancer, heart disease, and diabetes, for example. The aging of the population will put millions more at increased risk for disability and death that such diseases can bring. The NIA, its sister institutes at the National Institutes of Health (NIH), and researchers worldwide are working with a sense of urgency to understand the specific genetic, biological, environmental, and social and behavioral factors contributing to these diseases, as well as to gain insights into the processes of aging itself. The doubling of the NIH budget over the past five years has allowed us to intensify these efforts, aimed ultimately at find­ing ways to reduce disease and prevent disability. 

Q: While the population is aging, rates of disability have declined steadily over the past decade. What are the critical factors contributing to this decline?  

RH: Rates of disability among older men and women over the past decade have declined dra­matically, a trend that was recently confirmed in a meta-analysis of several demographic stud­ies of older people. This finding tells us that while risk of disease and disability may increase with age, those risks appear to have been sub­stantially reduced in recent years. The underly­ing message from these studies is an important one: Age is not necessarily synonymous with disease and disability, and a greater proportion of older people can be healthy, vigorous, and productive. 

Age is not necessarily synonymous with disease and disability … older people can be healthy, vigorous, and productive.

 In order to maintain and perhaps even accel­erate the decline in disability rates, it will be critically important to measure and understand the factors behind it. Additional research is needed to try and pinpoint the factors which may have played a part, looking at improve­ments in maternal nutrition and public health early in the last century; better control of infec­tious diseases associated with childhood; signifi­cant increases in education and finances of suc­ceeding generations reaching old age; health-related behavioral changes such as smoking ces­sation; improved control and treatment of such diseases and hypertension and heart disease; development and use of new surgical interven­tions; and the impact of newly developed drugs.

 Q: To what degree is successful aging a result of an individual’s genetic make-up?  

RH: Genes can clearly have a substantial impact on longevity in multiple animal model systems and it appears that genes can have a sig­nificant impact on human aging and longevity as well. Based on comparative studies of identi­cal and fraternal twins, scientists now estimate that lifespan is determined both by environmen­tal and genetic factors, with genes accounting for up to 35 percent of this complex interaction. Determining what interactions of genetic and environmental factors predispose some individu­als and families to exceptional survival or what protects certain individuals against multiple age-related conditions is a major research goal. 

Centenarians, for example, have survived more than 20 years past average life expectancy. Evidence from studies of exceptionally old indi­viduals suggests that centenarians as a group are well protected against disease and disability earlier in life, that the propensity for exception­al longevity runs in families, and that longevity could have a significant genetic component. One recent report on the link between choles­terol and exceptional longevity tied health and longevity to a genetic switch of a single amino acid in a critical protein, which leads to the production of larger than average lipoprotein molecules. These large molecules, according to the scientists, may protect against heart disease, stroke, diabetes, and other diseases that claim the lives of many older people. Such studies are helping to identify protective factors for excep­tional longevity and could ultimately lead to new interventions to prevent age-related diseases and disabilities and extend healthy life span. 

Q: NIA has launched a large-scale initiative to test, in animal models, intervention strategies that may slow the rate of aging, including unproven strategies that are already in substan­tial and growing use by older Americans. Given that this research is ongoing, can you provide some clues about which strategies seem particularly promising?  

RH: There are several areas of research in which interventions to maintain health and prevent frailty look promising, beyond the known lifestyle practices of exercising and quit­ting smoking. One of the more active areas of research is caloric restriction. Since the 1930s, investigators have consistently found that labora­tory animals, including rats, mice and fruit flies, live up to 40 percent longer than usual when fed a diet that has at least 30 percent fewer calo­ries than they would normally consume. The NIA is currently studying the effects of a similar diet in rhesus and squirrel monkeys. Carefully controlled pilot studies of caloric restriction in people are only now getting underway. These studies, collectively known as CALERIE (Comprehensive Assessment of Long-term Effects of Restricted Intake of Energy), will test effects of two to three years of caloric restriction (20-30% reduction) in young and middle-aged people who are not obese. The caloric restric­tion regimen will also be compared with exer­cise that produces weight loss to compare the effects of these different interventions. Based on the results of these short-term studies, we will then consider additional studies to test longer-term effects.

As medical researchers test a variety of inter­ventions for maintaining health and preventing frailty and disease, it is important to remember that some approaches, such as use of currently-available hormones or supplements falling into the category of “anti-aging” remedies, require much further testing to determine their safety and efficacy. 

Q: What are some key areas of aging research to watch in the year ahead? 

RH: Activities in several broad areas of research will be of interest in the coming year: 

Biology of aging—The molecular and cellular changes underlying the aging process constitute a growing area of research. A special focus is the identification of genes that influ­ence how we age, and understanding what those genes do. One recent study, for example in the tiny worm, C. elegans, showed that some 200 genes caused an increase in longevity. Studies of such animal models and humans, including expanding study of the very elderly and centenarians, will help us uncover the biological “secrets” of aging. 

Reducing disease and disability—The etiology of specific diseases is becoming better understood, leading to success in developing and testing therapies and interventions for several conditions associated with aging, includ­ing Alzheimer’s disease, diabetes, heart disease, arthritis, and frailty. We expect the coming year to bring further progress. In Alzheimer’s disease, basic research on the genetic and biological aspects of the disease continues to provide exciting insights, and some 24 clinical trials are now underway. Findings from these studies will be reported over the next few years. 

Social and behavioral aspects of health— Personal behavior, lifestyle choices, economic circumstances, and racial and ethnic factors clearly play a role in health and well-being with advancing age. Major national surveys, such as the Health and Retirement Study of people 50 and older, are helping us to understand important issues such as the relationship between health and wealth, economic and other support among generations in a family, and how middle-aged adults are preparing for retirement. Other research is providing new and useful insights into how individuals deal on a personal level with their own aging. One recent study, for example, suggested that negative attitudes by individuals about their own aging can influence longevity. Also, the effort to understand health disparities among various groups is gaining momentum, with the recent establishment of NIH-supported centers to help focus this research. 

 
Claudia Kawas, M.D.

Professor of Neurology Institute for Brain Aging and Dementia, University of California, Irvine

Q: You are leading an ongoing research study on people in their 90s to try to better understand the critical factors that separate those who remain healthy and independent from those who don’t. What are the goals of the research?

CK: My study is looking at about 1,400 people over age 90 who filled out questionnaires and health information in 1981 and up to three more times over the last two decades. Some of the questions had to do with diet, exercise, and certain medications, like estrogen. What I am trying to do now is take the information they prospectively gave in 1981 and look at the things that mattered, both in terms of longevity—just making it to 90—and in terms of making it to 90 in good shape versus not such good shape.

I’m trying to better understand the clinical and pathologic features of cognitive loss in this age group, because it doesn’t look the same as the garden-variety Alzheimer’s disease we see in 70-year-olds, at least to my eyes. It might be that different things cause dementia at different ages, maybe vascular or other pathologies, or things having to do with cell death. We’re trying to look at all these questions. We’ve also collected fami­ly history information and are trying to start a DNA bank to look at genes related to longevity.

Q: Recognizing that you have so far examined only about half of the participants, what have you found so far?

CK: Many people made it to 90 in better shape than others. It’s kind of remarkable to see how well some of them have done; they look much younger than their age. If I had to gener­alize just from seeing them right now, it’s clear that people do better if they stay active both physically and mentally. And it’s clear that people seem to do better if they get out of their houses and interact with other individuals, even if that interaction is not particularly sophisticated— you don’t necessarily have to go take French classes.

When you see something like this, however, you have to ask, is it because they’re doing well that they can get out of their home and have all this contact, or is it because they have all this contact that they do better? Hopefully, by having available data from as far back as 1981, we might have a chance at getting a handle on that.

Q: How big a role do genetics play in healthy aging?

CK: Genetics are a key to longevity, and in fact a key to everything. That’s different from saying genetics determine everything however. People who live into their 90s are more likely to have siblings who live into their 90s and are more likely to have children who live into their 90s. I’m personally interested, and always have been, in a lot of the nongenetic things, because we’re not ready to change our genes—at least not right now—but we can change our lifestyles. Even in Alzheimer’s disease, which has a strong genetic component, if one identical twin gets Alzheimer’s at any particular age, the other twin has only about a 50 percent chance of develop­ing the disease. So you know it’s not the genes, because they share the same genes. In some cases, where both twins have developed Alzheimer’s, they’ve done so 14 years apart. If I could make Alzheimer’s disease develop 14 years later in everybody who is going to get it, the public health impact would be unbeliev­able. So, there’s reason to believe it’s something that’s in the environment that could potentially be manipulated. That’s why we’re looking at diet, medication use, activities, things like that.

Q: What have we learned so far about diet and Alzheimer’s risk?

CK: From my study it’s clearly too early. We’ve seen some interesting things from work that I did with the Baltimore Longitudinal Study of Aging, as well as from other studies that have looked at diet in various ways. The antioxidant vitamins are very intriguing in a lot of ways, but I think one of the most interesting things that has surfaced is folate, which is a B vitamin. I think folate is going to be the next thing that gets a lot of attention. We presented an abstract at the 2003 American Academy of Neurology meeting showing that folate reduced the risk of Alzheimer’s disease. Right now folate is being used in a clinical trial for Alzheimer’s patients, along with other B vitamins, to lower homocys­teine, which has been associated as a risk factor for Alzheimer’s as well as for vascular dementia. There’s an association; does that mean lowering it will help? In cardiovascular disease it’s not clear that it does help, at least not yet, and we don’t know whether it will in Alzheimer’s or other dementias. But whether it’s working through homocysteine and vascular mecha­nisms or working in some other way, folate is still a very intriguing possibility.

Everybody wants us to say that one thing causes Alzheimer’s or one thing can prevent it. I actually think a lot of these dietary things that surface are really markers for a healthy diet. I don’t think it’s that you necessarily consumed more vitamin C or more folate than the next person. But if you had a diet that was high in those nutrients, overall you had a better diet, and better diets are associated with a lot of good things. We’ve increased life expectancy in this century by over 27 years and a lot of that has to do with diet. Having a diet that is nutrient-rich is the most important part, and in particular one rich in vegetables and fruits. You’re not just getting vitamin C when you eat an orange; you’re getting a ton of other vitamins as well, and all together they probably end up being important.

So the advice is: do what your mother told you to do; eat all those healthy vegetables and fruits…

So the advice is: Do what your mother told you to do; eat all those healthy vegetables and fruits. All the things your Mom told you were good for you, I think she was right.