[Senate Hearing 107-768] [From the U.S. Government Publishing Office] S. Hrg. 107-768 HEALTHY AGING AND NUTRITION: THE SCIENCE OF LIVING LONGER ======================================================================= FIELD HEARING before the SPECIAL COMMITTEE ON AGING UNITED STATES SENATE ONE HUNDRED SEVENTH CONGRESS SECOND SESSION __________ BATON ROUGE, LA __________ AUGUST 15, 2002 __________ Serial No. 107-32 Printed for the use of the Special Committee on Aging U.S. GOVERNMENT PRINTING OFFICE 82-918 WASHINGTON : 2002 ____________________________________________________________________________ For Sale by the Superintendent of Documents, U.S. Government Printing Office Internet: bookstore.gpo.gov Phone: toll free (866) 512-1800; (202) 512-1800 Fax: (202) 512-2250 Mail: Stop SSOP, Washington, DC 20402-0001 SPECIAL COMMITTEE ON AGING JOHN B. BREAUX, Louisiana, Chairman HARRY REID, Nevada LARRY CRAIG, Idaho, Ranking Member HERB KOHL, Wisconsin CONRAD BURNS, Montana JAMES M. JEFFORDS, Vermont RICHARD SHELBY, Alabama RUSSELL D. FEINGOLD, Wisconsin RICK SANTORUM, Pennsylvania RON WYDEN, Oregon SUSAN COLLINS, Maine BLANCHE L. LINCOLN, Arkansas MIKE ENZI, Wyoming EVAN BAYH, Indiana TIM HUTCHINSON, Arkansas THOMAS R. CARPER, Delaware JOHN ENSIGN, Nevada DEBBIE STABENOW, Michigan CHUCK HAGEL, Nebraska JEAN CARNAHAN, Missouri GORDON SMITH, Oregon Michelle Easton, Staff Director Lupe Wissel, Ranking Member Staff Director (ii) C O N T E N T S ---------- Page Opening Statement of Senator John Breaux......................... 1 Panel of Witnesses William H. Patrick, Jr., Ph.D., Boyd Professor of Oceanography and Coastal Sciences, Wetland Biogeochemistry Institute, Louisiana State University, Baton Rouge, LA.................... 3 Robert N. Butler, M.D., President and Chief Executive Officer, International Longevity Center-USA, New York, NY............... 8 Pamela Starke-Reed, Ph.D., Deputy Director, National Institutes of Health, Division of Nutrition Research Coordination, Bethesda, MD................................................... 16 Claude Bouchard, Ph.D., Executive Director, Pennington Biomedical Research Center, Baton Rouge, LA............................... 30 Appendix Informational pamplets from International Longevity Center....... 49 Prescription for Longevity................................... 49 Is there an Anti-Aging Medicine.............................. 76 Biomakers of Aging From Primitive Organisms to Man........... 138 Achieving and Maintaining Cognitive Vitality with Aging...... 166 Maintaining Healty Lifestyles a Lifetime of Choices.......... 192 (iii) HEALTHY AGING & NUTRITION: THE SCIENCE OF LIVING LONGER ---------- THURSDAY, AUGUST 15, 2002 U.S. Senate, Special Committee on Aging, Baton Rouge, LA The committee met, pursuant to notice, at 10 a.m., at the Pennington Biomedical Center, Administration Building Auditorium, Baton Rouge, LA, Honorable John Breaux (chairman of the committee) presiding. OPENING STATEMENT OF SENATOR JOHN BREAUX, CHAIRMAN The Chairman. Our Senate Aging Committee will please come to order, and good morning everyone. Thank you all for being with us and in attendance. We want to thank everyone at the Pennington Center for their cooperation in helping us with this Senate Aging Committee hearing today here at the Pennington Center, and thank all of our good friends at LSU for their good, strong support, and we certainly appreciate your allowing us to be here and with your colleagues at the university as well. We are very delighted. I serve as Chairman of the Senate Aging Committee in Washington, and this hearing really is to allow some of our witnesses to talk about some of the good things that are happening in the area of aging and also to talk about some of the research that is going on and will continue to be going on in this particular area. I want to particularly thank two of our guests who have traveled from Washington and also New York to be with us today. Dr. Pamela Starke-Reed who is with the National Institutes of Health, thank you very much for being with us, and my good friend, Dr. Robert Butler, who has worked with our Aging Committee in so many areas. He is President and CEO of the International Longevity Center in New York City. We thank both of them for traveling to be with us. Today's hearing I would point out is not science fiction. Our distinguished guests will be discussing some of the current, cutting-edge research which ultimately may add a significant number of years to the human life span. While this topic is indeed very interesting, it's also very exciting, it should be stated also that the increase in life span that we all hope for in long term is not quite yet available. Last September our Special Committee on Aging held investigative hearings to expose fraudulent health care claims being made by people who are nothing more than con men who are trying to sell dietary supplements which they would offer as the key to longevity. Claims that diseases can be cured and the aging process stopped in its tracks by simply taking a little pill have always been well received by people who are looking for that type of cure. Fortunately as we know, when something sounds too good to be true, it generally is too good to be true and is probably false. As of today there is still no scientific evidence that simply dietary supplements alone will slow the aging process or increase longevity. However, we can keep our fingers crossed and we can hope that the work being done by Dr. Butler, at the National Institutes of Health and the Pennington Biomedical Research Center will be very helpful and very useful and produce results in the near future. The Pennington Biomedical Research Center was recently recognized by the NIH as an outstanding research center by being awarded over $12 million in grant funds to study the possible benefits of long-term reduction of calories on aging. For many years now, scientists have known that animals on a high-quality, nutrient-rich, low calorie diet live significantly longer and healthier lives. This phenomenon has been demonstrated in worms, monkeys and just about everything in between. Pennington has been chosen along with two other outstanding research institutions to determine if this effect will occur in humans as well. During the next 2 years, human subjects will be placed on a calorie restricted diet and their risk of heart disease, hypertension, diabetes and other medical problems will be closely monitored. Now, I know many in our audience here in Louisiana must be thinking how are people in Louisiana going to go on a low- calorie diet with all of the temptations that we have in our area. It is not very likely most would think. However, if the diet research proves to have the same beneficial effects in humans that it does in animals, additional research will be conducted to determine how this works at the molecular level. Here is where we start hoping for that miracle pill again. If researchers can determine how caloric restriction works, it is possible that they would be able to duplicate it synthetically. Remember, however, that this is not a reality yet. If by the end of the year you see a supplement claiming that it contains all the herbs necessary to duplicate caloric restrictions, run the other way. It is probably not true. I look forward to learning more about this incredibly interesting topic from our panelists, and again I want to thank the Pennington Biomedical Research Center and all of the associates at the university for cooperating in this effort. I truly believe that the Pennington Biomedical Research Center can be one of the world's leading institutions in this effort. As Chairman of the Senate Aging Committee, I want to do everything in my power to see that that wish becomes a reality. The panel of witnesses, as I mentioned, that we have here today are truly distinguished experts that I am very excited to hear from. Their testimony will be made part of our Congressional Record. First we want to hear from Dr. William Patrick. Dr. Patrick will discuss how nutrition and physical activity has positively impacted his life as he has grown older. He is still an active research scientist and is currently the No. 2 ranked tennis player in the State in his age group and was a member of the silver medal winning basketball team at the most recent senior games. He is a person who I have a great deal of admiration for. My goal in life is to win the national 100 and over tennis championship by being the only entry. [Laughter.] But perhaps if research proves effective, there will be many more entrants at that time. So first we will hear from Dr. Patrick. Dr. Patrick, we are glad to have you with us. STATEMENT OF WILLIAM H. PATRICK, JR., PH.D., BOYD PROFESSOR OF OCEANOGRAPHY AND COASTAL SCIENCES, WETLAND BIOGEOCHEMISTRY INSTITUTE, LOUISIANA STATE UNIVERSITY, BATON ROUGE, LA Dr. Patrick. Thank you, Senator Breaux, ladies and gentleman. I am a Boyd Professor of Oceanography and Coastal Sciences here at Louisiana State University. I have been asked by the Pennington Center to discuss some of the aspects of healthy aging from a layman's point of view. I am not a professional in this area, and so I am sort of here as a guest. I was probably asked to speak to this committee because I am the senior active member of the whole LSU system in terms of years of service. There is no one left in the system who was here when I was appointed an assistant professor on July 1, 1953. Although my wife, Ruth, over here does not like for me to tell my age, I am 76 years old, so I have established longevity credentials here. Another possible reason I was asked to speak to you is because I am still carrying on a full program of scientific research and teaching. I plan to use my time today to discuss what I think are some of the important aspects of healthy aging, and try to illustrate them with my own experience. Of course, one of the most important requirements for healthy aging is to have good genes. A MacArthur Foundation study showed that about one third of the aging process is controlled by genetics. I was fortunate to have chosen good parents. This leaves two thirds of the aging process due to other factors, all of which are under the control of the individual. These other factors that contribute to healthy aging, according to the MacArthur Foundation report, are good nutrition, regular exercise, stimulating mental activities, and a sense of community. Good nutrition is an ever-present concern in my family since I have been married for a long time to Dr. Ruth Patrick, a specialist in human nutrition and the recently retired Chief of the Pennington Nutrition Education Program. Of course, I do not faithfully follow good nutrition practices all the time, but I am certainly aware of it when I do not. In addition to a good balance of nutrients in the diet, effective weight control is also important, and although I owe my adequate weight largely to my genetic makeup, I once had to limit my food intake to bring my weight down to a favorable level. There is no doubt that regular exercise contributes greatly to both the physical and mental aspects of healthy aging. Early in my scientific career I used extensive field work to supplement sports to maintain a healthy body, and I still do considerable field work in many parts of the world as the attached photographs taken from a coastal swamp last July shows. I do not know if you can--if you had it close up, you could see the sweat and mud on this photograph here. This appeared in a German scientific publication as part of a cooperative project with a German research institute. In recent decades, I have still supplemented field work with sports to maintain body vigor. As the Senator mentioned, I play singles tennis and last year was No. 2 in the State Senior Olympics in my age bracket. This year I was one year older and new people were coming in, so I fell to three, but I do not know where I will be next year. I also play basketball, and because I have some good teammates, last year our team won our age bracket's National Senior Olympics silver medal. Responding to medical needs is an absolutely essential part of healthy aging, and we all appreciate Senator Breaux's efforts in this direction. Taking advantage of the high-quality medical support available in this country will add both time and quality to an aging person's life. My life would certainly not have its current quality without the benefits of hernia surgery, cataract surgery, retina reattachment, arthroscopic knee surgery, dental implants and small doses of blood pressure-lowering and cholesterol-lowering medications. Engaging in mentally stimulating activities is probably the most important component of my quest for healthy aging. All of us who want to extend their careers beyond ages 65 or 70 owe a debt of gratitude to one of Senator Breaux's earlier colleagues, Claude Pepper of Florida, who championed legislation that eliminated a mandatory retirement age. Even at this stage of my career at age 76, I am the principal investigator of five outside-funded research projects, ranging from basic scientific environmental chemistry studies supported by the National Science Foundation to applied studies of the effect of sea level rise on coastal Louisiana ecosystems. This fall I will be teaching a new course that I developed on the effect of global climate change on the stability of coastal wetlands. Over a quarter century ago I established the Wetland Biogeochemistry Institute at LSU where my colleagues and I are largely funded by grant and contract funds and which has produced over 600 scientific papers and reports covering work done largely in Louisiana but also in many other states and quite a few foreign countries. I still have the same enthusiasm for research that I did a half century ago. In fact, there have been two periods when I felt under considerable pressure to succeed, the first when I started out and was trying to establish myself as a research scientist, and now when I feel the pressure to justify my staying on beyond the normal retirement age. The MacArthur study found that a sense of community or belonging is important in maintaining a healthy outlook into old age. An active person is involved in a number of communities, and my interaction with several communities brings a great deal of satisfaction. Without doubt the most important is my family consisting of my wife, four children and their spouses and twelve grandchildren. To celebrate her recent retirement, my wife sponsored all 22 of us for a week at Vail, CO, this summer, which did catch me up considerably with community involvement. In conclusion, I would like to reiterate that the recipe for healthy aging is to build onto a favorable genetic heritage with good nutrition, effective exercise, good medical care, stimulating mental activities, and a sense of community. Thank you. [The prepared statement of Mr. Patrick follows:] [GRAPHICS NOT AVAILABLE IN TIFF FORMAT] The Chairman. Thank you very much, Dr. Patrick. That was well stated, and we are delighted to have that in the record. Next we are going to hear, as I indicated earlier, from Dr. Robert Butler who is the President and Chief Executive Officer of the International Longevity Center in the USA, and he is a very special friend of the Special Committee on Aging. Dr. Butler, glad to have you. STATEMENT OF ROBERT N. BUTLER, M.D., PRESIDENT AND CHIEF EXECUTIVE OFFICER, INTERNATIONAL LONGEVITY CENTER-USA, NEW YORK, NY Dr. Butler. Thank you very much, Senator Breaux. It is a privilege to be here in Louisiana and to say good morning to everyone, and thank you for this opportunity to speak to the science associated with healthy aging and nutrition. In the last century, as you know, we gained an extraordinary 30 additional years of life, and not only added life but fortunately increased quality of life. There were declining disability rates. My new friend on my right I think is a wonderful illustration of that. I would like to submit for the record my comprehensive statement but to speak just briefly from it and to say that the International Longevity Center in New York--we do have centers also in Paris, London, Tokyo and Santo Domingo--is interested in helping individuals and societies prepare for this extraordinary increase in longevity and population aging but to do so in positive and productive ways. Therefore, we do focus upon healthy and productive aging. We are particularly interested in maintaining and extending and promoting good health habits, advancing biomedical research and in combating unsubstantiated claims with respect to so-called anti-aging medicine. I was much impressed to see the Pennington Biomedical Research Center receive such a wonderful grant in support for its studies of nutrition and aging, and that contrasts in my mind so much from the claims unsubstantiated by the anti-aging industry which can be so misleading because it is not based upon scientific validation and well-established measurements. This does become serious from my earlier experience in establishing the National Institute on Aging, we found that some of those who made such unsubstantiated claims actually reduced the amount of support that Congress in its wisdom wanted to give us because Members thought an awful lot of it was foolishness. Now, the concept of caloric restriction goes back 70 years to a remarkable Cornell scientist named Clive McKay who gave undernutrition, not malnutrition, to rodents and found that by reducing their intake by some 30 percent he was able to extend their lives by about 30 percent. There have been now many studies on many different species to demonstrate this. Since the 1980's the National Institute on Aging has been supporting studies within the laboratories of NIH in Poolseville, MD, and at the University of Wisconsin-Madison on squirrel and rhesus monkeys, and the results at the moment suggest that the animals appear to be younger and that certain biological findings seem to be distinctive, lower blood levels of insulin, lower body temperature and the slower decline of a particular hormone called dehydroepiandrosterone, or DHEA for short. Now, it does not seem possible, as already suggested this morning, especially with the wonderful cuisine in this great State, that people will reduce their caloric intake by 30 or 40 percent. But as already mentioned, if we can secure the underlying mechanism, why it is that caloric restriction has its effect, we might be able to create mimetics, that means agents that would mimick the effects of caloric restriction, you will be hearing some of the work being done here and also some of the work of Susan Roberts at Tufts University that will give us further understanding of the underlying mechanism of caloric restriction. Now, it is very important to carry out the best of science as I have described, and I think a very good example of that was the recent, surprising perhaps and certainly in many ways painful findings of the Women's Health Initiative at the National Institutes of Health. For a long time we had depended upon the Boston Nurses Study for information related to the appropriateness of hormone replacement therapy. In retrospect it appears that the health habits of the nurses in that study helped contribute to a misunderstanding and over hopefulness with respect to the concept that hormone replacement therapy would be preventative of heart disease. Having definitive randomized clinical trials and the best scientific methodology has unfortunately demonstrated that such hormone replacement therapy not only does not reduce heart disease but may even be a risk. Similar things have happened that have led to the evolution of so-called anti-aging medicine. A very respectable scientist, Daniel Rudman, at the University of Wisconsin-Milwaukee, for example, after only a 6-month study found results or increasing muscle mass, decreasing fat and greater elasticity of the skin using human growth hormone. So it is not unreasonable to think this worthy of investigation, and indeed it is. But unfortunately such investigations have not yet been completed, and yet this hormone is being widely touted and used in so- called anti-aging medicine. Now, just a matter of weeks ago a study appeared in The Lancet magazine by Swerdlow and others identifying individuals who had been treated with human growth hormone between 1959 and 1985 for ``dwarfism'' and finding that they had an increased incidence of overall cancer mortality and a greater incidence specifically of colorectal cancer and of Hodgkins disease. A warning sign, I think. It is not definitive yet. The point is that we have to undertake critical studies when it comes to dietary supplements, hormones, herbals or any other putative agent said to reduce, reverse or stop aging. We do not have such information at this time. Now, some of it has been deeply wedded to the development of geriatric medicine; that is, the proper, humane, effective, holistic care of older persons. So it is distressing to me to see the term ``anti-aging'' medicine because aging in many respects can be viewed as a normative process, and we need to differentiate age-related diseases which are the proper purview of those of us who are deeply interested in developing full scale better treatment of older people. In closing let me also tell you briefly about certain workshops which we hold, modified NIH-type consensus workshops. We bring together some of the finest scientists in the country to address a particularly critical topic, and we put them to work for 4 days. We ask them to meet the four following charges: What do we really know about this particular topic such as anti-aging medicine? Where we do not know, what is the research agenda that should be developed to help us answer the unanswered questions? Third, what can we responsibly tell the public? Finally, are there implications of a policy character for business, government or foundations? So I would like to present to you, Senator Breaux, some of the workshop results, one on the biomarkers of aging which are means we do not yet possess to accurately evaluate alleged anti-aging agents, one on maintaining healthy lifestyles and a few others which I think would be of use to the country. We do make them available on our own website, and they are also available in print versions. Let me conclude by saying it is an honor and pleasure to be here, and I hope that the kind of research being done by Pennington and by others supported by the great National Institutes of Health can help us to lead an increasing high quality as well as a longer life. Thank you very much. [The prepared statement of Dr. Butler follows:] [GRAPHICS NOT AVAILABLE IN TIFF FORMAT] The Chairman. Thank you very much, Dr. Butler, for a very concise and very informative statement, and thank you for your participation. Next as I indicated, we will hear from Dr. Pamela Starke-Reed. She is the Deputy Director of the National Institutes of Health, Division of Nutrition Research Coordination. Before that she was the Program Director of the Biology of Aging Program at the National Institute of Aging. We are delighted to have you with us. STATEMENT OF PAMELA STARKE-REED, PH.D., DEPUTY DIRECTOR, NATIONAL INSTITUTES OF HEALTH, DIVISION OF NUTRITION RESEARCH COORDINATION, BETHESDA, MD Dr. Starke-Reed. Thank you. Thank you for the opportunity to appear before you today representing the National Institutes of Health, Division of Nutrition Research Coordination. I would also like to thank you for the challenge of having me summarize nutrition and aging research across the Federal Government in 5 to 7 minutes. The Chairman. There is flexibility. Dr. Starke-Reed. So, therefore, this testimony will include a brief overview of the Federal Government's efforts in this area. Today, approximately 13 percent of Americans are over 65. By the year 2030, the number of individuals age 65 and older will likely double--reaching 70.3 million or 20 percent of the total population. Of great concern is the explosive increase in numbers anticipated among those most at risk of disease and disability--people age 85 and older. Their ranks are expected to grow from 4.3 million in 2000 to at least 19.4 million in 2050. With a rapidly aging population, it is critically important to identify ways to maximize the span of good health and thereby improve the quality of life of older people. Nutritional factors hold great promise for realizing this goal. The Federal research efforts in this area of nutrition recognize the need to combine physical activity and diet. I have included some examples of these in the written testimony such as the diabetes prevention program, and the details are in the writeup. Dr. Butler has already discussed with you some of the background of caloric restriction, so I am not going to repeat that here. But what I would like to talk about is what NIA has been doing, the National Institute on Aging, has been doing recently. In an effort to further elucidate the role of caloric restriction in extending healthy lifespan in humans, in March 1999, the National Institute on Aging and the National Institute of Diabetes, Digestive and Kidney Disease cosponsored a meeting of the Caloric Restriction Implications Advisory Group. In October 2000, based on the scientific recommendations from this group, the NIA and the NIDDK issued research solicitations for exploratory studies of sustained caloric restriction in non-obese persons. Three sites were awarded a research grant: Tufts University in Boston, Washington University at St. Louis and Pennington Biomedical Research Center right here. Collectively, the three projects are known as CALERIE, which stand for Comprehensive Assessment of Long- Term Effects of Reducing Intake of Energy. Government needs to always confuse us with cute little sayings. Briefly, CALERIE projects involve exploratory, controlled human intervention studies on the effects of caloric restriction interventions on physiology, body composition and risk factors for age-related disease in non-obese persons. The primary goals of the project are to gain knowledge about the effects in humans of sustained caloric restriction on physiology, metabolism, body composition, risk factors for age-related pathologies, progression of age-related changes and the potential adverse effects and to gain knowledge of similarities, differences and interactions between the effects of caloric restriction and physical activity on previous outcomes when employed in interventions to prevent weight gain. The endpoints of CALERIE studies including energy intake and expenditure, physical activity, body composition, endocrine responses, insulin glucose metabolism, cardiovascular function, bone density, immune function, quality of life, and the potential adverse effects of caloric restriction. The study populations of CALERIE projects are non-obese adults with a likely age range of 25 to 60 years. Expected duration of the CALERIE project is 7 years, and it is about to begin the Phase I, or the pilot portion, of the study which is expected to last two years, and I believe you will be hearing a lot more about this from Dr. Bouchard. Another area of very critical research which the NIA is very interested in right now is the use of dietary supplements. The use of dietary supplements has increased dramatically as the knowledge has increased about the role of nutrient and other bioactive components of food in our health. Although much of the information about the diet and health connection that has driven this trend is related to the reduction of chronic disease in adults, there is belief in the prophylactic use of these substances has been extended to consumers throughout the life span. Dietary supplements encompass a wide range of products. They include vitamins, minerals, amino acid, herbs and other botanicals. They also include dietary substances used to supplement the diet by increasing the total dietary intake. The amount of scientific data available on the safety and efficacy of dietary supplements varies enormously ranging from folklore to fact. For some supplements recommended levels for the elderly have been established through extensive research and published, but for others, serious negative health consequences can occur. Findings from the CDC's third National Health and Nutrition Examination Survey suggests that 40 percent of the Americans use dietary supplements, and approximately 56 percent of middle-aged and older adults consume at least one supplement on a regular basis. The problems surrounding the use of dietary supplements include adverse events, interactions with prescription drugs and/or over-the-counter medications, interactions with medical conditions, contamination of the preparations, mislabeling and high cost. Of particular concern for the elderly is the issue of interactions of dietary supplements and prescription medication because the elderly take more prescription drugs than any other age group. For example, the effects of anticoagulant medications commonly taken by the elderly may be adversely affected by coenzyme Q10, gingko biloba, garlic, ginseng, glucosamine and St. John's Wort. Another major issue is the high cost of many dietary supplements. The elderly are often living on modest fixed incomes, and paying for unnecessary or potentially harmful supplements may present an economic hardship. But on the other hand, there are significant benefits associated with the use of certain vitamin and mineral supplements. I have given examples of these in the written testimony, but I would like to mention one. There is increasing clinical evidence that the B vitamins such as folic acid, B6 and B12 play a role in preventing blood vessel disease and maintaining normal cognitive function. Some exciting recent work has examined the role of folic acid supplementation in protecting the brain's aging and possibly preventing Alzheimer's disease, Parkinson's disease and other neurodegenerative disorders. In a new study, investigators fed genetically engineered mice to develop the plaques that we normally see in Alzheimer's brains. They fed them a diet that included normal amounts of folate, and a second group was fed a diet deficient in this vitamin. The investigators found a decreased number of neurons in one region of the hippo-campus in mice fed the deficient diet. In transgenic mice fed the deficient diet, nerve cells of hippo-campus exhibited damage to their DNA. Such damage was not seen in the mice fed adequate amounts of folate. In another experiment the investigators looked at the effect of a different area of the brain with folate sufficient in folic and deficient diets. Basically what they found was the same thing. In the area of the substantial nigra, which is the area affected during Parkinson's disease, they saw that the folic acid sufficient animals did not show the same damage that the folic acid deficient animals showed. In the subsequent experiments in cell culture, they have suggested that the folic acid deficiency may compromise a neuron's ability to repair its DNA successfully. Based on this research, consuming adequate amounts of folate either in the diet or by supplementation could be beneficial to an aging brain and could help protect it against Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases. However, it should be noted that currently available data, although suggestive, do not establish the role of folic acid in susceptibility to neurodegenerative diseases. Definitive determination of whether folic acid plays a role in Alzheimer's disease or Parkinson's disease will require a completion of controlled clinical trials. In order to further investigate the role of supplements in preventing or delaying age-associated diseases, the NIA, in accommodation with the NIH Office of Dietary Supplements, will convene a 2-day conference in January 2003 to present current data and research about dietary supplement use in the elderly in both the United States and in the international populations. The goals of this conference are to develop a focused research program in this area. Mr. Chairman and Members of the Committee, I thank you again for inviting me to review aging and nutrition issues and to highlight some exciting research that is ongoing. I would be happy to answer any questions. [The prepared statement of Dr. Starke-Reed follows:] [GRAPHICS NOT AVAILABLE IN TIFF FORMAT] The Chairman. Thank you very much Dr. Starke-Reed for that testimony. It was interesting that while she was talking about all the supplements I was holding my Centrum Silver and my Calcitrate that I was trying to take while she was testifying. I might reconsider perhaps the benefits of that. [Laughter.] Thank you very much. Next we will hear from our own Dr. Claude Bouchard, of course, who is the Executive Director of Pennington Biomedical Research Center, and who will tell us and the Committee for the record about some of the work that you are doing right here in Louisiana. Mr. Bouchard. Before I do that, let me give you a copy of my slides so that you will not have to do any body contortions. The Chairman. I will move. Thank you. STATEMENT OF CLAUDE BOUCHARD, PH.D., EXECUTIVE DIRECTOR, PENNINGTON BIOMEDICAL RESEARCH CENTER, BATON ROUGE, LA Mr. Bouchard. Thank you, Mr. Chairman. We at the Pennington Center, a campus of the Louisiana State University System, are particularly honored to welcome you today. We are pleased to have been selected by the Senate Special Committee on Aging as the site for the hearing on the science associated with healthy aging and nutrition. By the year 2020, there will be an estimated 10 million Americans above the age of 85. This reflects a steady increase in life expectancy. Forty-five percent of people above the age of 85 need some assistance with one or more basic activities of daily living. Today the common life expectancy for males and females is 76 years, and it will be almost 80 years by 2020. Healthy aging depends on a multitude of factors. They are genetic defects having a strong impact on the risk of disease often causing premature death. For instance, the carriers of a severe deficiency in the low-density lipoprotein receptor gene, if untreated, will die around 30 to 35 years of age. However, not all genetic differences exert such a strong impact on health. Most of the time these genetic differences are subtle and cause only a predisposition to the risk of disease or untimely death. We also know that such subtle differences play a significant role in longevity. Twin studies have produced convincing results in this regard, and the fact that old age nonagenarians and centenarians aggregate in families is also evidence for a role of human genetic variation in longevity. Although biological inheritance is of great importance, the environment in which a person lives, particularly his or her lifestyle within that environment, exerts strong effects as well. For example, someone may have a predisposition to become diabetic but because he or she has a prudent diet, a physically active lifestyle and a healthy body weight, the disease may never manifest itself. A similar line of reasoning applies to hypertension, heart disease, osteoporosis and some types of cancer. Aging is associated with the loss of physical and/or mental attributes. The central question is whether healthy nutritional habits can prevent the decline in functions commonly seen with aging. The loss of skeletal muscle mass and strength and bone mass is associated with low energy and protein intake. Vitamin D intake also seems to play a role. Decreases in skeletal muscle and bone mineral mass are associated with frailty and increased risks of falls and fractures. This is significant since almost one quarter of people 65 years of age and older are considered to be physically frail. After 85, one person in two falls into this category. One of the strongest hypotheses regarding the decline in cognitive function is that oxidative stress is a risk factor. This is supported by studies indicating that levels of intake of antioxidants such as vitamin E, vitamin C, folate, iron and other nutrients are correlated with higher cognitive performance and apparent prevention of cognitive decline with age. The Recommended Dietary Allowances for the elderly have typically suggested a decrease in total energy intake compared to young and middle-aged adults. However, because of metabolic differences commonly associated with age, supplements of calcium, vitamin D, vitamin B12, and others are recommended. Hence, the paradox. Even though the prevalence of obesity tends to decline after 65 years, its frequency remains high. This is an important issue since obesity is a risk factor for several common chronic diseases, several of which are quite prevalent in the elderly population. We would like to emphasize that there are significant interactions and synergy between nutrition and levels of physical activity. Physically active people typically consume more food but are more frequently normal weight than sedentary people. The extra food consumed provides a safety buffer against nutritional deficiency. Nutrition can also interact with medication, and this is potentially of greater significance in the elderly than in young and middle-aged adults. A word about the Pennington Center. The mission of the Pennington Center is to promote healthier lives through research and education in nutrition and preventive medicine. The Center was established through Doc Pennington's gift of $125 million to Louisiana State University. With the new buildings currently under construction, the Center will enjoy the use of about 500,000 square feet of research space by mid next year. Today the Center has 70 faculty scientists and employs 400 staff and support personnel, and its current expansion program will allow for the doubling of these human resources to about 1,000. The Center began operating in 1989. Since then more than 200 clinical research projects have been completed and hundreds of basic research projects have been performed. I would like to highlight a few of these clinical research projects that have important implications for nutrition and healthy aging. The first one is the Dietary Approaches to Stop Hypertension, the so-called DASH Study. DASH was a multicenter investigation of the effects of dietary patterns on blood pressure in adults with high normal to borderline hypertension. Drs. George Bray and David Harsha and other Pennington Center colleagues played a leadership role in this clinical trial. A total of 459 volunteers were randomized to one of three diets: typical American diet controlled on this site, fruit and vegetable diet, and fruit, vegetable plus low-fat diet. Results demonstrated reduction in blood pressure of those of the fruit and vegetable and low-fat diet in both the systolic and the diastolic pressure. For those with borderline hypertension, the reduction was 11 millimeters of mercury for systolic and more than 5 millimeters of mercury for diastolic. The DASH Diet parallels the dietary recommendations of the American Heart Association, the U.S. Department of Agriculture, the U.S. Department of Health and Human Services, and the National Cancer Institute and other health organizations, and these findings were applicable to both men and women, ethnic groups, normal tensive and hypertensive and younger and older adults as well. The Diabetes Prevention Program. The Diabetes Prevention Program is a multicenter NIH-funded clinical trial designed to determine whether the onset of diabetes can be delayed or totally prevented in high-risk individuals. This trial involves 27 centers around the United States. Professors George Bray and Donna Ryan are the leading investigators at the Pennington Center. The first part of the trial finished in April 2001 when it became clear that one of the treatment arms was much more effective than the others. Among the 3,200 individuals in this study, those randomly assigned to the intensive lifestyle program of diet, exercise and behavioral strategies had a 58 percent reduction in their rate of developing diabetes compared to individuals in the placebo group. A third group receiving the anti-diabetic drug metformin had an intermediate rate of conversion to diabetes. These are the data, 58 percent versus 31 percent. The effectiveness of the lifestyle intervention in reducing the risk of diabetes was demonstrated in men and women, in all ethnic groups and in older and younger Americans. Regular physical activity translates into important health benefits as shown on this slide which applies to the risk of premature death here. It is also known that physical working capacity, an indicator of fitness, decreases with age. A low physical working capacity can easily compromise personal autonomy. For instance, the capacity to work at a rate equivalent to three to four times the level of energy expended at rest is typically seen as the minimal compatible with physical autonomy. Three to four times would be on the ``Y'' axis, the number of times that one can expend energy over the resting value. So when we reach above that level here, the personal autonomy is compromised. In a multicenter trial designed to investigate the genetic and molecular basis of the response to regular exercise, about 800 individuals from 200 families of African-American and Caucasian ancestries were recruited and exercised regularly in the laboratory at four clinical centers for 5 months. Considerable individual differences were observed in the progress made under the influence of this physical activity program with some gaining a lot of increased tolerance to exercise by maximum oxygen update measurement. In others, none at all. However, these high responders aggregated in some families, and these others were in other families showing that there is an inherited propensity to benefit from the regular physical activity program. Thus, there is an inherited capacity to adapt to changes in environmental conditions such as those associated with regular physical activity or with dietary modifications as was shown in another study. Therefore, we would like to suggest that any research effort designed to define the optimal nutrient and energy intake associated with successful and health aging be undertaken from the comprehensive perspective, one that incorporates physical activity, medication, smoking status, socioeconomic circumstances, family history, as well as biological individuality as defined by the genes. Herbal Supplements and aging research at the Pennington Center. Many herbal supplements are touted to retard the aging process. Many of these herbal supplements attempt to raise the blood levels of substances to the levels associated with youth. There is no scientific evidence that this approach will retard aging, will increase longevity or improve the quality of life. The Pennington Center is addressing herbal supplements from a more scientific perspective. The focus of such research is on safety and efficacy. For instance, Drs. Frank Greenway and Steve Smith and their collaborators have been evaluating caffeine and ephedrine in overweight subjects. People taking caffeine and ephedrine lose an average of 7 percent of their body weight, but this is a loss which is totally composed of fat with no loss of muscle tissue. Currently, studies are in progress to study the effect of herbal caffeine and ephedrine on physical strength and endurance. If both strength and endurance were improved in addition to the loss of fat and a protection from muscle loss, then it will be desirable to extend these studies to elderly people. Caloric restriction. Caloric restriction prolongs life in several species. However, it is not established whether caloric restriction will extend life in humans. Caloric restriction results in loss of weight and tissues and lowers the rate of metabolism. One hypothesis is that caloric restriction lessens the oxidative damage of vital tissues by reducing energy flux and metabolism. Based on these various lines of evidence as was mentioned before, NIA requested application for studies on the role of caloric restrictions in humans, and the Pennington Center was one of the three centers selected nationally. Professor Eric Ravussin is the leading investigator on this research grant that benefits from the collaboration of Professors Andy Deutsch, Don Williamson, Steve Smith, Jim DeLany and other Pennington scientists. They will investigate whether the expected decline in metabolic rate that accompanies caloric restriction will be associated with reduced oxidated stress in tissues and risk factors for age-related metabolic diseases, including cardiovascular and type 2 diabetes. In addition, they will verify whether combining physical activity and caloric restriction to produce the same caloric deficit alters the changes caused by caloric restriction alone. Finally, the expression of genes involved in energy metabolism and oxidative stress that are known to be associated with longevity in lower organisms will also be assessed. One of the most accepted theories of aging is an increased release of free radicals, which are unstable molecules that wreak havoc on many substances including DNA. The end result is that individual cells may exhibit increased failure to inactivate free radicals and impair ability to repair DNA damage. One approach to slowing the aging process is to supply the body with ammunition against free radicals in the form of nutritional antioxidants. Numerous studies in other species indicate an increase in longevity is correlated with an organism's ability to effectively cope with free radical damage to DNA. The Pennington Center has one of the most active laboratories for measuring DNA damage in aging tissues, and Professor Andy Deutsch and his collaborators have devised technologies to measure specific DNA alterations that may be a consequence of the aging process, and they will be using it in the caloric restriction study. Finally, a word about our project on physical and cognitive capacity in non-agenarians. A multicenter study led by Professor Michael Jazwinski from Louisiana State University Health Science Center in New Orleans is investigating the role that metabolic factors play in the aging process. To this end, a population of Louisiana non-agenarians is being assembled. In the context of that study, scientists from the Pennington Center, Professor Ravussin and colleagues, are making a major contribution. They will be measuring resting metabolic rate, total energy expenditure, parameters of oxidative stress, blood protein profile and dietary habits in these non-agenarians. This study will generate a new hypothesis about mechanisms, metabolic pathways and other indicators of the aging process, and these are some of the participants in this particular project. We would like to take the opportunity provided to us today, Mr. Senator, to formulate a few recommendations for the Senate Special Committee on Aging. First, measures should be taken at all levels of government to ensure that elderly people have access to adequate nutrition. This is of particular relevance since the decrease in appetite typically seen in the elderly can easily result in nutritional deficiencies. Second, measures should be taken to ensure that elderly people have the opportunity to be physically active on a regular basis. This is also of importance as the level of fitness is probably the single most important determinant of autonomy in the elderly. Third, education programs targeting the elderly should be developed to communicate information on nutritional habits, physical activity and proper use of medication. Finally, we would like to recommend the establishment of a national center on nutrition and healthy aging. Its mission would be to improve the health of America's aging population through a focus on research but also on education. This mission would be achieved by: developing basic research programs to determine the molecular and cellular determinants of the adaptation to various dietary regimes and classes of nutrients including herbal and other dietary supplements in the elderly; clinical research programs designed to investigate the impact of various dietary practices and physical activity regimes on physical functions and cognitive abilities in older people, including potential interactions with medication and smoking; behavioral research programs to identify the optimal conditions to induce favorable behavioral changes in the elderly with the goal of reducing morbidity, the risk of premature death, and with the goal of retaining physical and cognitive abilities; integrated research programs to define the interactions among factors such as nutrition, physical activity, medication and genetic individuality; and finally, education and behavioral changes designed to apply the knowledge developed in the four proceeding programs to the elderly population. Thank you very much. [The prepared statement of Mr. Bouchard follows:] [GRAPHICS NOT AVAILABLE IN TIFF FORMAT] The Chairman. Dr. Bouchard, thank you very much, and I would like to thank all of our Panel Members for some excellent information and suggestions, and information that I think will be very valuable to our Committee. Let me just start with a couple of questions. I do not know, maybe Dr. Butler, if you go into any bookstore in America, I mean, probably the largest section of publications are books on diet and longevity now, and you can find diets that advocate more fat, some that advocate less fat, some advocating high protein, some low protein. I believe the average person in this country becomes very confused about what is proper and what is healthy. If you add onto those books which many are very, very legitimate, all of the scam artists out there, we had hearings on food additives that are being sold that really do very little. One of our biggest witnesses who was running a multimillion-dollar--well, actually over a hundred million- dollar--business came before our Committee and took the fifth amendment. He had been in prison before, and he was absolutely a total scam artist. Well, people are spending hundreds of millions of dollars and not really knowing where to go, what is right, what is wrong, what is good and what is bad. Any suggestions for the average American out there that wants to do what is right with regard to this? Dr. Butler. I do think we in science have the responsibility to be clearer to the public that science is an evolutionary process. It is so disappointing and discouraging and confusing when they hear one thing one day and one thing the next. But it is not because of anything other than the fact that the progress of knowledge develops in that way. I think you have heard a very good demonstration of that both from Dr. Starke-Reed and from Dr. Bouchard in terms of how science progresses. That is No. 1. No. 2, I think Dr. Patrick has been a beautiful example of the very simple fact that probably would be the single major thing one would hope to get out of these proliferation of various books that you referred to, and that is the very simple common sense message of physical activity and small portions of food. The cholesterol hypothesis, the role of certain fats and transacids in the creation of coronary heart disease is very well established through the wonderful work of the National Institutes of Health. Also, it is important to have a balanced diet in terms of fat and protein and vegetables and carbohydrates, particularly complex carbohydrates. But just not--the one thing mom was probably wrong about was clean up your plate and have a second helping. If we could just have small portions and physically remain active, that would be the single, simple message in a one-page book if we could get somebody to write it and get everybody to believe it. The Chairman. When scientists talk about the caloric restrictions, are we talking about just what, eating less, eating smarter, or what are we talking about when we are talking about the value of caloric restriction? Dr. Butler. Well, the original studies of Clive McKay really was an appropriate nutrient diet known at that time for rodents which were in 1935 and 1936, and it was not intended to be anything other than a modest diet as it were. Remarkably these animals live longer. Now there have been studies on spiders and all sorts of animals that demonstrate this truism. I think the message for the public is that, as I have already said, a modest diet and physical activity. It is energy in, energy out that is so impressive and so important. If we can find what the underlying mechanism is, whether it is the reduction of free radical damage or whatever the mechanism is that counts for the fact that we have this increase, by the way, of a vigorous, healthy life in these animals and delay of disease. It is not just living longer. It is living longer better. If we can find out what that is that is responsible and put that on the market, then we have a fully effective agent. The Chairman. Dr. Starke-Reed, do you have a comment on this about what are we talking about? I mean, is it just eating less, or is it eating smarter? I mean, what are the findings that we would be recommending at this time to the American public of what NIH knows about this? Dr. Starke-Reed. Well, I agree with what Dr. Butler said. I think if we go back to some of the early caloric restriction studies in rodents in particular where they altered the definitions of the diets or the composition of the diets, they were all nutritionally sound, but they altered it to where it was a little bit higher in protein or a little bit higher in carbohydrates or sugar. What they found from changing these diets in these various ways was that it really did not matter. If you were nutritionally sound, you had adequate nutrient and vitamin intake and you had lower calories, total calories, they all had positive effects. Adding physical activity is absolutely essential. I must mention, because we look at the problem today facing us, the tremendous obesity problem that we are looking at right now, and we are looking at children, very young children, developing type 2 diabetes, and we know that we are not being a very active population. Look at developing countries now. As they become more westernized, they are having a tremendous increase in their obesity problem as well. These things are not going to lead to healthy aging, so having activity, increasing activity, as well as having smart eating as we say, eating the appropriate things, having a nutritionally balanced diet but lowering the calories is what is going to be probably the best recommendation of all. The Chairman. I mean, and we are talking about the obesity problem in this country which obviously leads, as you say, to all types of very serious health problems. I mean, can you evaluate whether it is mostly because Americans just eat too much or we eat the wrong things? I mean, is it more we just eat too much of whatever we eat, or, you know, are we just eating the wrong type of foods containing harmful and fattening things? Does anybody want to comment? Dr. Butler. I would say both. Dr. Starke-Reed. Well, I would like to say that I do not think there is a definitive study, and as scientists, one would like to base answers on a definitive study. However, I really have to bring into this the physical activity because what is very clear that not only are we changing our dietary habits into very quick, fast, not the most healthy foods being put in front of us, but we are not doing activity the way we used to do it. We are a very, very sedentary population. The Chairman. Can either of you in the time left comment on the valuation between getting the nutrients that we need to live longer, better lives out of the natural foods we eat versus store up on the pills that are supposed to be providing us supplements and the various vitamins that some would probably try and sell you? ``You do not really need to eat food. Just come to our general nutrition store and buy everything in the aisles and take all the pills every day and you do not need to eat.'' I mean, are they valuable but they cannot obviously replace the normal intake? I guess I am talking about food supplements here. I mean, what are their value in general; how important are they; I mean, how much can they be utilized to reduce your caloric intake, or am I only going to eat a very little bit of actual food for breakfast, lunch and dinner, and I am going to supplement it with bottles full of vitamins, so I am going to come out OK? I mean, what is the correlation between the actual, normal regular food we eat and the utilization of supplements to help reach a balanced diet? Dr. Butler. Well, I do think there are supplements that have been demonstrated to be value. For example, folic acid which is now added to cereals and breads has been extremely useful in reducing spina bifida in newborns, and folic acid may also play a role in terms of an agent called homocystine in the body which is related to coronary heart disease. So I do think--and one of the wonderful things about the Pennington Center it seems to me is we have got to dramatically increase the amount of teaching to medical students about nutrition throughout the whole country so that they could give better advice. Certainly, the recent studies by the National Institute on Aging seem to be pointing to the importance of vitamin E as a preventative with respect to cognitive dysfunction and possibly Alheizmer's disease. So I think some of these ``pills'' are extremely useful, but as already implied or stated directly by Dr. Starke-Reed, it is so important that this become a consequence of actual science. For instance, if you take too much vitamin E or selenium, which may have their value, you can also wind up with internal bleeding so that there has to be--I guess Aristotle had it right in terms of moderation and common sense. But certainly the degree in which we can get more and more specific so it is not just a smaller amount of food but the right type of added nutrients, it would make a tremendous difference in the quality of life. But back to Dr. Starke-Reed's point too, only one State in the United States now has required daily physical activity, and that is the State of Illinois. I wish I could say that Louisiana and every one of our 50 States had physical activity for our children. But with computers and with television and with computer games, the chance of kids remaining physically active gets totally denied and left out of the equation of their daily round of activities. The Chairman. Well, that is really very, very helpful, I think, and very interesting. I was wanting to follow up on Dr. Bouchard's concepts for a national center of nutrition and healthy aging. I know, Dr. Butler, you were the person who really got the geriatric department started at Mount Sinai Hospital. Out of about 125 medical schools in this country, there are only three that have geriatric departments to teach doctors about specifically aging problems which is an absolutely incredible statement, and you started the one at Mount Sinai, but there are only three. With the vastly growing segment of our population, as Dr. Starke-Reed pointed out, people 85 and older, and 77 million baby boomers getting ready to move into this category of elderly, there will be a lot more people living a lot longer. Yet it seems that we are in a society that is not really focused in on the particular problem of geriatrics and aging and how we can hopefully get people to live longer and also better lives. Dr. Bouchard, you know, it kind of sounds like to me the concept of a national center on nutrition and healthy aging, just do it right here at the Pennington Center. [Applause.] Dr. Jenkins is nodding. Mr. Bouchard. I think this is an excellent suggestion. [Laughter.] The Chairman. I am throwing these softball questions. Mr. Bouchard. For many reasons, we have the current epidemic of obesity. But we also have now a wave of older citizens millions reaching 85 years and above, where about 50 percent are frail and are losing their autonomy. Nutrition is a part of the latter. Physical activity is also a very strong part of it. The Pennington center has a reputation for working on both, integrating them into research together with the fundamental sciences. The goal is to understand the contribution the general mix with trying to of genetic individuality and the physiology and biochemistry. Such a center with a focus on nutrition would be important because we talk about nutrition and disease and aging, and growth or children for that matter, in terms of vitamins, macronutrients, carbohydrates, lipids and proteins. But that is just scratching the surface. There are thousands of molecules in food that we know nothing about yet, literally thousands. Some of them have been identified but we do not know their properties. So a center like the one proposed here would remove progressively the mystery surrounding these molecules. In addition to discovering and isolating them, we would test them in cell systems, in animal models, in engineered animals and then eventually in people to see if they have favorable or unfavorable effects when present in large quantities or in deficient levels. The Chairman. Dr. Starke-Reed, with the NIH, which is our premier government institute on health, how would a center interact with what you all are doing there or what Dr. Butler is doing at his center? Is that something that is compatible? Dr. Starke-Reed. I think most of the institutes within NIH have research centers which are dedicated to those specific problems and efforts. So that would fall very much in line with the way NIA does some of those. Can I---- The Chairman. Dr. Patrick, I do not really have any--do you have another comment, Dr. Starke-Reed? I am sorry. Dr. Starke-Reed. The one thing that I was going to add to that is I think this is already something which has been in the minds of some of the staff at the NIA, having a specific research center, and that is because when you hear something new that has come out which is potentially beneficial for aging, it is nice to be able to take it to a place and compare it to a model system or in an organism or animal but with the same hands that have looked at the other things that we know are either good or not good for the aging process. It is very difficult to compare studies when they are done, even if done within a lab, using different species or different strains depending on whether it is one that is particularly good in aging or bad in aging, and then looking at the outcome. It is very difficult to evaluate whether this product really is having the effect on the aging process desire. Having a center where aging studies are already set up, given you confidence in the results that are generated you trust the reactions that you see in a particular organisms tested there, whether they are good or they are bad. It is very easy to compare it that way. The Chairman. I thank you for that. I hope that while you are here--I am sure you have done this before--but have a chance to visit the facilities here and Dr. Butler to see what they are doing. Mr. Patrick, really I am just so happy to have you here. I mean, and the reason we asked you, not only are you a doctor with great credentials in a different field, it is just to show when you practice this type of good, healthy type of living skills really that it does produce positive results, and, I mean, we have had so many people testify before the Aging Committee who are getting up in age, much older than you are. I mean, I had someone who was 92 years old who was actually still working in construction, and he actually worked out in the field. My question was how could he possibly continue to do that type of work in the field. He said, ``It is much easier than when I was 40.'' He said, ``When I was 40, I was out there with a shovel digging.'' He said, ``Now I am sitting in this machinery that is air conditioned, and I am just pulling back.'' He said, ``It is a lot easier than when I was 40 years old.'' He is 92. So, I mean, you are a good example of that, and we are very pleased that you are here. I want to thank all of our panelists. I think it has been very, very helpful to these people and helpful to the Senate Aging Committee. We are very dedicated to try and help bring about good, honest, solid, scientific research about this issue of aging and to try and separate the legitimate from the illegitimate. There is so much information that is just bogus, and so many people spend an unlimited amount of money trying to look for something that is a miracle, and it is very important that we eat healthy and understand the difference between what is good and what is right and what works as opposed to what does not. I think the Pennington Center is--I am very glad that NIH has saw fit to help with the grant here, and I know that Dr. Bouchard and everybody associated with it is going to do very, very good work. So we thank all of you for being with us, and that will conclude our Senate Aging Committee hearing. Thank you. [Whereupon, at 11:24 a.m., the committee was adjourned.] A P P E N D I X ---------- [GRAPHICS NOT AVAILABLE IN TIFF FORMAT]