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Can We Prevent Aging? Tips from the National Institute on Aging

People are living longer. In 1970, the average life Antioxidants expectancy at birth in the United States was Antioxidants protect the body from the harmful 70.8 years; in 2008, it was 78.0 years; and by 2020, effects of by-products known as free radicals, the U.S. Census Bureau projects life expectancy made normally when the body changes oxygen will reach 79.5 years. and food into energy. The discovery of antioxi- Views on aging are also changing. Disease and dants raised hopes that people could slow aging disability were once considered an inevitable part simply by adding them to the diet. So far, studies of growing older, but that is no longer true. While of antioxidant-laden foods and supplements in aging does put us at greater risk for health issues, humans have yielded little support for this many older adults can be healthy and active well conclusion. Further research, including large-scale into their advancing years. epidemiological studies, might clarify whether The National Institute on Aging (NIA), part of dietary antioxidants can help people live longer, the Federal Government’s National Institutes of healthier lives. For now, although the effectiveness Health (NIH), investigates ways to support healthy of dietary antioxidant supplementation remains aging and prevent or delay the onset of age-related controversial, there is positive evidence for the disease and decline. We have already gained health benefits of fruits and vegetables. important insights, and what we learn from ongoing Calorie Restriction, Intermittent and future studies may not only help to increase Fasting, Resveratrol, and Rapamycin longevity, but may also promote what is known as “active life expectancy”—the time in late life free Scientists are discovering that what you eat, how of disability. We already know, for example, that frequently, and how much may have an effect on healthy eating and exercise and physical activity quality and years of life. Of particular interest has help promote healthy aging. Are there other inter- been calorie restriction, a diet that is lower by a ventions that can help? NIA-supported and other specific percent of calories than the normal diet studies are taking a look at the possible benefits but includes all needed nutrients. Research in and risks of a number of approaches, including some animals has shown calorie restriction of up antioxidants, calorie restriction, and hormone to 40 percent fewer calories than normal to have supplements. This tip sheet provides an overview an impressive positive effect on disease, markers of what we know about these interventions and of aging, and, perhaps, life span. the research needed to learn more. Until we have Even though calorie restriction appears to work in a better understanding, it is a good idea to be a variety of species, its effects on longevity are far skeptical of claims that any supplements can solve from universal. It has been found to extend the life your age-related problems. of protozoa (very small, one-celled organisms), #532 www.odmhsas.org 405-522-3810 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Can We Prevent Aging? yeast, fruit flies, some strains of mice, and rats, as were healthier and lived longer than the overweight well as other species. However, several animal mice that did not get resveratrol. In a follow-up models, including wild mice, show no lifespan study, researchers found that, when started at extension by calorie restriction. In some strains middle age, resveratrol slowed age-related deterio- of mice, calorie restriction even appears to shorten ration and functional decline of mice on a standard lifespan. Studies in nonhuman primates have also diet, but did not increase longevity. A recent study had conflicting results. in humans reported that resveratrol may have some similar health benefits to those in animals; however, Calorie restriction studies with humans and other it is still too early to make any definitive conclusions primates, such as monkeys, are ongoing. Some about how resveratrol affects human health and studies in nonhuman primates have shown that aging. More research is needed before scientists calorie restriction reduces the incidence of certain know if there is a proper and safe dose of resveratrol diseases such as cancer. Other studies in primates or if it has any clinical applicability in people. have not yet reached final conclusions. Rapamycin is also being investigated. This Findings of the Comprehensive Assessment compound is used to help suppress the immune of Long-term Effects of Reducing Intake of system in transplant patients so that the body does Energy (CALERIE) pilot study in humans showed not reject the new organ. Rapamycin has been that overweight adults who cut their calorie found to extend median and maximum lifespan consumption by 20 to 30 percent lowered their of mice, even when fed to the animals beginning fasting insulin levels and core body temperature. at early-old age. This finding suggests that an Both of these changes correlate with increased intervention started later in life may still increase longevity in animal models. The lower calorie longevity. Researchers are now looking for rapa- intake also reduced their risk for major causes mycin’s effects on health span of animal models. of mortality such as heart disease and diabetes. Since rapamycin treatment in people is associated CALERIE is currently evaluating a 2-year, 25 percent with serious toxicities, its potential for human reduction in caloric intake for feasibility, safety, long-term use is uncertain. Researchers do not and effects on factors influencing longevity know if rapamycin has any effect on human aging and health. or if any potential benefit would outweigh risks. Scientists do not yet know if long-term calorie But, this discovery in mice has led to an exciting restriction is safe, beneficial, or practical for new research direction. humans. However, the study of calorie restriction Scientists are also looking at the effect of inter- offers new insights into the aging process and mittent fasting or reduced meal frequency. In biological mechanisms that could influence animals, like mice, reduced meal frequency healthy aging. This research may also provide appears to have a protective effect on the brain clues about how to prevent or delay diseases that and may also help with heart function and become more prevalent with age and inform the regulation of sugar content in the blood. However, development of treatments for such diseases. here, too, the influence of intermittent fasting on Some studies focus on identifying chemicals that human health and longevity is currently unclear. somehow mimic calorie restriction’s benefits. While research into these types of approaches Resveratrol, a compound found naturally in foods continues, it is important to remember there like grapes and nuts, is of interest. In one study, is already plenty of research supporting the scientists compared two groups of overweight value of a healthy, balanced diet and physical mice on a high-fat diet. One group was given a activity to help delay or prevent age-related high dose of resveratrol together with the high-fat health problems. diet. The overweight mice receiving resveratrol 2 TIPS FROM THE NATIONAL INSTITUTE ON AGING

Hormones A hormone may fit with many types of cells but may not affect all cells in the same way. For example, Hormones are chemical messengers that set in one hormone may stimulate one cell to perform motion different processes to keep our bodies a task, but it might also turn off a different cell. working properly. For example, they are involved Additionally, how a cell responds to a hormone in regulating our metabolism, immune function, may change throughout life. sexual reproduction, and growth. Hormones are made by specialized groups of cells within the Hormone Therapy body’s glands. The glands—such as the pituitary, Levels of some hormones change naturally over the thyroid, adrenals, ovaries, and testes—release lifespan. Some hormones increase with age, like hormones into the body as needed to stimulate, parathyroid hormone that helps regulate the amount regulate, and control the function of other tissues of calcium in the blood and bone. Some tend to and organs involved in biological processes. Most decrease over time, such as testosterone in men hormones are typically found in very low concen- and estrogen in women. When the body fails to trations in the bloodstream. But a hormone’s make enough of a hormone because of a disease concentration will fluctuate depending on the or disorder, a doctor may prescribe hormone body’s activity or time of day. supplements. These come in many forms such as We cannot survive without hormones. As children, pills, shots, topicals (gels, creams, and sprays hormones help us grow up. In our teenage years, applied to the skin), and medicated skin patches. they drive puberty. As we get older, some hormone You may have read magazine articles or seen levels naturally decline. But what does that mean? television programs suggesting that treatment Scientists do not know exactly. with hormones can make people feel young again In order to learn more, NIA is investigating how or can slow or prevent aging. That’s because the administration of hormones to older people finding a “fountain of youth” is a captivating story. affects frailty and function. Many of these studies The truth is that, to date, no research has shown focus on hormones that naturally decline with that hormone therapies add years to life or prevent age, including: age-related frailty. And, while some drugs have real health benefits for people with clinical hormone zz Human growth hormone deficiencies due to a disease or disorder, they also zz Testosterone can cause harmful side effects. That’s why people zz Estrogen and progesterone (as part of who have a diagnosed hormone deficiency should menopausal hormone therapy) still only take hormones prescribed by a doctor and zz Dehydroepiandrosterone (DHEA) under a doctor’s supervision. How Hormones Work In some cases, the U.S. Food and Drug Adminis- A hormone acts upon a cell much like a key tration (FDA) may have approved a hormone unlocking a door. After being released by a gland, (or hormone therapy) for one purpose, but it is a hormone molecule travels through the blood prescribed by physicians for another. This off- until it finds a cell with the right fit. The hormone label use may occur when physicians believe that latches onto a cell via the cell’s receptor. When research, such as clinical studies, demonstrates a this happens a signal is sent into the cell. These drug’s usefulness for another condition. However, signals may instruct the cell to multiply, make consumers should be aware that off-label use of proteins or enzymes, or perform other vital tasks. any drug may not have been tested and verified to Some hormones can even cause a cell to release the same degree as the original use of the drug. other hormones.

3 Can We Prevent Aging?

Some Dangers of Hormone Therapy and other medications. NIA does not recommend “Anti-Aging” Supplements taking any supplement touted as an “anti-aging” remedy because there is no proof of effectiveness Higher concentrations of hormones in your body and the health risks of short- and long-term use are not necessarily better. And, a decrease in are largely unknown. hormone concentration with age is not necessarily a bad thing. The body maintains a delicate balance Human Growth Hormone between how much hormone it produces and how Growth hormone is important for normal growth much it needs to function properly. Natural and development, as well as for maintaining hormone production fluctuates throughout the tissues and organs. It is made by the pituitary day. That means that the amount of hormone in gland, a pea-sized structure located at the base of your blood when you wake up may be different the brain. 2, 12, or 20 hours later. Research supports supplemental use of human If you take hormone supplements, especially growth hormone (hGH) injections in certain without medical supervision, you can adversely circumstances. For instance, hGH injections affect this tightly controlled, regulated system. can help children who do not produce enough Replacement or supplemental hormones cannot growth hormone. Sometimes hGH injections replicate your body’s natural variation. Because may be prescribed for young adults whose obesity hormonal balance is so intricate, too much of a is the result of having had their pituitary gland hormone in your system may actually cause the surgically removed. These uses are different from opposite of the intended effect. For example, taking hGH as an “anti-aging” strategy. As with taking a hormone supplement can cause your other hormones, growth hormone levels often own hormone regulation to stop working. Or, decline with age, but this decrease is not neces- your body may process the supplements differ- sarily bad. At least one epidemiological study ently than the naturally produced hormone, suggests that people who have high levels of causing an alternate, undesired effect. It is also naturally produced growth hormone are more possible that a supplement could amplify negative apt to die at younger ages than those with lower side effects of the hormone naturally produced by levels of the hormone. Researchers have also the body. At this point, scientists do not know all studied animals with genetic disorders that the consequences. suppress growth hormone production and Some hormone-like products are sold over the secretion. They found that reduced growth counter without a prescription. Using them can be hormone secretion actually promotes longevity dangerous. Products that are marketed as dietary in the tested species. supplements are not approved or regulated by the Although there is no conclusive evidence that FDA. That is, companies making dietary supplements hGH can prevent aging or halt age-related physical do not need to provide any proof that their products decline, some clinics market hGH for that purpose, are safe and effective before selling them. There is and some people spend a great deal of money on no guarantee that the “recommended” dosage is such supplements. Shots can cost more than safe, that the same amount of active ingredients is $15,000 a year. These shots are only available by in every bottle, or that the substance is what the prescription and should be administered by a company claims. What you bought over the doctor. But, because of the unknown risks—and counter may not have been thoroughly studied, the evidence suggests that side effects strongly and potential negative side effects may not be overcome any possible benefits—it is hard to understood or defined. In addition, these over- find a doctor who will prescribe hGH shots. the-counter products may interfere with your 4 Tips from the National Institute on AginG

Over-the-counter dietary supplements, known as evidence that this condition, also known as human growth hormone releasers, are currently andropause or viropause, exists. The likelihood being marketed as low-cost alternatives to hGH that an aging man will experience a major shutdown shots. But claims of their anti-aging effects, like all of testosterone production similar to a woman’s those regarding hGH, are unsubstantiated. menopause is very remote. In fact, many of the changes that take place in older men often are Research is starting to paint a fuller picture of the incorrectly attributed to decreasing testosterone effects of hGH, but there is still much to learn. For levels. For instance, some men experiencing erectile instance, study findings indicate that injections of difficulty (impotence) may be tempted to blame it hGH can increase muscle mass; however, it seems on lowered testosterone, but many cases of erectile to have little impact on muscle strength or function. problems are due to circulatory problems. Questions about potential side effects, such as diabetes, joint pain, and fluid buildup leading to For men whose bodies make very little or no high blood pressure or heart failure, remain testosterone, testosterone replacement may offer unanswered, too. A report that children who were benefits. FDA-approved testosterone drugs come treated with pituitary growth hormone have an in different forms, including patches, injections, increased risk of cancer created a heightened and topical gels. Men whose testes (the repro- concern about the dangers of hGH injections. ductive glands that make testosterone and sperm) Whether or not older people treated with hGH have been damaged or whose pituitary glands have for extended periods have an increased risk of been harmed or destroyed by trauma, infections, cancer is unknown. To date, only small, short- or tumors may also be prescribed testosterone. term studies have looked specifically at hGH Treatment with testosterone drugs can help men as an “anti-aging” therapy for older people. with exceptionally low testosterone levels maintain Additional research is necessary to assess the strong muscles and bones and increase their sex potential risks and benefits of hGH. drive. It is unclear if men who are at the lower end Testosterone of the normal range for testosterone production would benefit from treatment. Testosterone is a vital sex hormone that plays an More research is needed to learn what effects important role in puberty. In men, testosterone testosterone drug therapy may have in healthy not only regulates sex drive (libido), it also helps older men without these extreme deficiencies. regulate bone mass, fat distribution, muscle mass NIA is investigating the role of testosterone therapy and strength, and the production of red blood cells in delaying or preventing frailty and helping with and sperm. Testosterone isn’t exclusively a male other age-related health issues. Results from hormone—women produce small amounts as well. preliminary studies involving small groups of men As men age, they often produce somewhat less are inconclusive. Specifically, it remains unclear to testosterone, especially compared to years of peak what degree testosterone supplements can help testosterone production during adolescence and men maintain strong muscles and sturdy bones, early adulthood. Normal testosterone production sustain robust sexual activity, or sharpen memory. ranges widely, and it is unclear what amount of There are also concerns about the long-term, decline or how low a level of testosterone will harmful effects that testosterone drugs might have cause adverse effects. on the aging body. Most epidemiological studies In recent years, the popular press has increasingly suggest that higher natural levels of testosterone reported about “male menopause,” a condition are not associated with a higher incidence of supposedly caused by diminishing testosterone prostate cancer—the second leading cause of levels in aging men. There is very little scientific cancer death among men. However, scientists do 5 Can We Prevent Aging? not know if taking testosterone drugs increases of estrogen research demonstrates why it is men’s risk for developing prostate cancer or important to examine both the benefits and risks promoting the growth of an existing tumor. There of any hormone therapy before it becomes widely is also uncertainty about effects of testosterone used. Here’s what scientists know: treatment on the cardiovascular system in older zz Endometrial problems—While estrogen men, especially men with mobility limitations and helps some women with symptom management other diseases. Future studies will address this issue during and after menopause, it can raise the risk of to ensure that older men receiving testosterone certain problems. Estrogen may cause a thickening treatment are not exposed to unnecessary risks. of the lining of the uterus (endometrium) and The bottom line: there is no scientific proof that increase the risk of endometrial cancer. To lessen testosterone treatment in healthy men will help these risks, doctors now prescribe progesterone them age better. Until more scientifically rigorous or a progestin, in combination with estrogen, to studies are conducted, it is not known if the women with a uterus, to protect the lining. possible benefits of testosterone therapy outweigh zz Heart disease—The role of estrogen in heart any of its potential risks. NIA continues to conduct disease is complex. Early studies suggested MHT research to gather more evidence about the effects could lower postmenopausal women’s risk for of testosterone treatment in aging men. heart disease—the number one killer of women Hormones in Women in the United States. But results from the NIH Women’s Health Initiative (WHI) suggest that Estrogen and progesterone are two hormones using estrogen with or without a progestin after that play an important part in women’s menstrual menopause does not protect women from heart cycle and pregnancy. Estrogen also helps maintain disease and may even increase their risk. bone strength and may reduce the risk of heart disease and memory problems before menopause. In 2002, WHI scientists reported that using Both estrogen and progesterone are produced estrogen plus progestin actually elevates some naturally by the ovaries. However, after menopause, postmenopausal women’s chance of developing the ovaries make much less of these hormones. heart disease, stroke, blood clots, and breast cancer, For more than 60 years, millions of women have but women also experienced fewer hip fractures used estrogen to relieve their menopausal symptoms, and cases of colorectal cancer. In 2004, WHI especially hot flashes and vaginal dryness. Some scientists published another report, this time on women may also be prescribed estrogen to prevent postmenopausal women who used estrogen alone, or treat osteoporosis—loss of bone strength—that which had some similar findings: women had an often happens after menopause. The use of estrogen increased risk of stroke and blood clots, but fewer (by a woman whose uterus has been removed) or hip fractures. Then, in 2007, a closer analysis of estrogen with progesterone or a progestin, a the WHI results indicated that younger women, synthetic form of progesterone (by a woman with ages 50 to 59 at the start of the trial, who used a uterus), to treat the symptoms of menopause is estrogen alone, had significantly less calcified called menopausal hormone therapy (MHT), plaque in their coronary arteries than women not formerly known as hormone replacement using estrogen. Increased plaque in coronary therapy (HRT). arteries is a risk factor for heart attacks. Scientists also noted that the risk of heart attack increased There is a rich research base investigating estrogen. in women who started MHT more than 10 years Many large, reliable long-term studies of estrogen after menopause (especially if these women had and its effects on the body have been conducted. menopausal symptoms). There was no evidence of Yet, much remains unknown. In fact, the history

6 TIPS FROM THE NATIONAL INSTITUTE ON AGING increased risk of heart attack in women who began hormones have not been done, and many bioiden- MHT within 10 years of going through menopause. tical hormones that are available without a prescription are not regulated or approved for zz Dementia—Some observational studies have safety and efficacy by the FDA. FDA-regulated suggested that estrogen may protect against bioidentical hormones, such as estradiol and Alzheimer’s disease. However, testing in clinical progesterone, are available by prescription for trials in older, postmenopausal women has women considering MHT. challenged that view. In 2003, researchers leading the WHI Memory Study (WHIMS), a substudy of For middle-age and older women, the decision to the WHI, reported that women age 65 and older take hormones is far more complex and difficult who took one kind of estrogen combined with than ever before. Questions about MHT remain. progestin were at twice the risk for developing Would using a different estrogen and/or progestin dementia compared to women who did not take or different dose change the risks? Would the any hormones. In 2004, WHIMS scientists reported results be different if the hormones were given as that using the same kind of estrogen alone also a patch or cream, rather than a pill? Would taking increased the risk of developing dementia in women progestin less often be as effective and safe? Does age 65 and older compared to women not taking starting MHT around the time of menopause, any hormones. What possibly accounts for the compared to years later, change the risks? Can we different findings between the observational and predict which women will benefit or be harmed by clinical studies? One central issue may be timing. using MHT? As these and other questions are The women in the WHIMS trial started treatment addressed by research, women should continue to a decade or more after menopause. In observational review the pros and cons of MHT with their studies that reported estrogen’s positive effects on doctors. They should assess the benefits as well cognition, the majority of women began treatment as personal risks to make an informed decision soon after menopause. This has led researchers to about whether or not this therapy is right for wonder if it may be advantageous to begin treatment them. NIA has additional free information on earlier, at a time closer to menopause. Additionally, menopausal hormone therapy in the tip sheet it appears that progesterone and progestins Hormones and Menopause. (progesterone-like compounds) differ in their DHEA impact on brain health. Dehydroepiandrosterone, or DHEA, is made from Despite research thus far, there are still many cholesterol by the adrenal glands, which sit on unknowns about the risks and benefits of MHT. top of each kidney. It is converted by the body For instance, because women in their early 50’s into two other important hormones: testosterone were only a small part of the WHI, scientists do and estrogen. not yet know if certain risks are applicable to younger women who use estrogen to relieve their For most people, DHEA production peaks in the symptoms during the menopausal transition. mid-20’s and then gradually declines with age. The effects of this decline, including its role in You may also have heard about another approach the aging process, are unclear. Even so, some to hormone therapy for women—“bioidentical proponents claim that over-the-counter DHEA hormones.” These are hormones derived from supplements can improve energy and strength plants, such as soy or yams, that have identical and boost immunity. Claims are also made that chemical structures to hormones produced by the supplements increase muscle and decrease fat. human body. The term “bioidentical hormones” is To date, there is no conclusive scientific evidence now also being applied to the use of compounded that DHEA supplements have any of these benefits. hormones. Large clinical trials of these compounded

7 Can We Prevent Aging?

The conversion of naturally produced DHEA animal and clinical research remains to be done. into estrogen and testosterone is highly individu- And, because research is an incremental process, alized. There is no way to predict who will make results can move knowledge forward, but it can more or less of these hormones. Having an excess also take scientists back to basics. Although one of testosterone or estrogen in your body could goal of NIA research is to determine whether be risky. these interventions improve the health of older people, have no effect, or are harmful, don’t be Scientists do not yet know the effects of long-term surprised if the results of these studies open the (defined as over 1 year) use of DHEA supplements. door to more questions. Early indications are that these supplements, even when taken briefly, may have detrimental effects Until more is known about antioxidants, resveratrol, on the body, including liver damage. But the and hormone supplements, consumers should picture is not clear. Two short-term studies showed view these types of supplements with a good deal that taking DHEA supplements has no harmful of caution and doubt. Despite what advertisements effects on blood, prostate, or liver function. on television, the Internet, and magazines may However, these studies were too small to lead to claim, there are no specific therapies proven to broader conclusions about the safety or efficacy prevent aging. Some harmful side effects already of DHEA supplementation. have been discovered; additional research may uncover others. Researchers are working to find more definite answers about DHEA’s effects on aging, muscles, People with genuine deficiencies in specific and the immune system. In the meantime, if you hormones should consult their doctors about are thinking about taking DHEA supplements, be appropriate treatments. Talk with your doctor aware that the effects are not fully known and if you are interested in any form of hormone might turn out to cause more harm than good. therapy or “anti-aging” approaches beyond a Many Questions, Seeking Answers healthy diet and physical activity. Meanwhile, people who choose to take any hormone supplement NIA supports research that seeks to learn more without a doctor’s supervision should be aware that about aging and the risks and benefits of potential these supplements appear to have few clear-cut interventions such as antioxidants, calorie benefits for healthy individuals and no proven restriction, hormone therapies, and supplements. influence on the aging process. These studies take time. A great deal of basic

For more information on health and aging, contact: National Institute on Aging Information Center P.O. Box 8057, Gaithersburg, MD 20898-8057 1-800-222-2225 (toll-free) • 1-800-222-4225 (TTY/toll-free) www.nia.nih.gov • www.nia.nih.gov/espanol To order free publications (in English or Spanish) or sign up for regular email alerts, go to: www.nia.nih.gov/health Visit www.nihseniorhealth.gov, a senior-friendly website from the National Institute on Aging and the National Library of Medicine. This website has health and wellness information for older adults. Special features make it simple to use. For example, you can click on a button to make the type larger.

JULY 2010 UPDAted February 2012