Department of Cardiology, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, P.R. China.

Moderate consumption of red wine is associated with a reduced risk of coronary heart disease (CHD). This phenomenon is based on data from epidemiological observations known as the French paradox, and has been attributed to CHD-protective phytochemicals, e.g. resveratrol in red wine. Since red wine also contains alcohol, it is conceivable that alcohol interacts with resveratrol to elicit the observed cardioprotective effects.

To determine whether resveratrol has alcohol-independent affects, we compared cardioprotective properties of dealcoholized Chinese red wine with alcohol-containing Chinese red wine having comparable amounts of resveratrol, using a hypercholesterolemic rabbit model and resveratrol as a reference. Animals fed a high cholesterol (1.5%) diet were simultaneously given water containing resveratrol (3 mg/kg/day) or red wine (4 ml/kg/day) containing 3.98 mg/l and 3.23 mg/l resveratrol for regular and dealcoholized red wine, respectively, for a 12-week duration. Total, HDL- and LDL-cholesterol and triglyceride levels in the plasma were measured before and after the cholesterol challenge. Atherosclerotic plaques in the thoracic aorta were evaluated using histochemical methods. Vascular and endothelial functions in the femoral artery were also assessed by ultrasonographic image analysis.

High cholesterol-fed animals showed a significant increase in plasma levels of total, HDL- and LDL-cholesterol, but not triglycerides, compared to those fed a regular diet. Dietary cholesterol-elicited lipid changes were similarly observed in animals concurrently fed dealcoholized red wine, red wine or resveratrol. In contrast, whereas atherosclerotic lesions were clearly evident in specimens prepared from the thoracic aorta of high cholesterol-fed animals, the size, density, and mean area of atherosclerotic plaques, and thickness of the intima layer were significantly reduced in rabbits given dealcoholized red wine, red wine, or resveratrol.

These results were in agreement with data obtained by an ultrasound analysis of endothelial function, which showed a 25% reduction in flow-mediated dilation (FMD) in rabbits fed a high cholesterol diet compared to animals on control diet. This decrease was effectively prevented by the simultaneous exposure to dealcoholized red wine, red wine, or resveratrol. Our study shows that animals given dealcoholized red wine exhibited cardio-active effects comparable to those of animals orally administered resveratrol, and suggests that wine polyphenolics, rather than alcohol present in red wine, suffice in exerting cardioprotective properties. The results also provide support for the notion that resveratrol and phytochemicals in red wine can suppress atherosclerosis without affecting plasma lipid levels.

For over a decade researchers have debated whether red wine produces health benefits because of its alcohol content, or because of other molecules in red wine. Now researchers at Nanjing Medical University in China report on the use of de-alcoholized red wine and cardiovascular health. Animals were fed alcohol, red wine, de-alcoholized red wine and pure research-grade resveratrol, a molecule found in red wine. Animals were then fed a high cholesterol diet and the human equivalent of 210 milligrams of resveratrol, or 280 millilters of red wine or alcohol-free red wine.

The results of the study are surprising. After 12 weeks the animals actually experienced a rise in circulating levels of total cholesterol, LDL cholesterol, and “good” HDL cholesterol regardless of whether they were fed alcohol, red wine, alcohol-free red wine or resveratrol.

However, while cholesterol plaque formed in the arteries (thoracic aorta) of the cholesterol-fed animals, the size, density, and mean area of atherosclerotic plaques were significantly reduced in rabbits given de-alcoholized red wine, red wine, or resveratrol.

Resveratrol prevents cholesterol plaque from forming within artery wall regardless of whether circulating levels of cholesterol are high or low.

Here is the abstract of the study, for your review:

SOURCE:International Journal Molecular Medicine 16:533-540, 2005

PMID: 16766037 [PubMed - indexed for MEDLINE]

Excitement for Resveratrol in combating Alzheimers Disease

PMID: 18254804 [PubMed - indexed for MEDLINE]

PMID: 18046409 [PubMed - indexed for MEDLINE]

Now, more than 70 years later, a large body of research shows that a calorie-restricted diet, coupled with adequate nutrition, extends the lifespans of protozoa, yeast, worms, spiders, flies, and rodents. Research also suggests that calorie-restricted animals, including primates, tend to be more resistant to age-related chronic diseases, and that restricting calories while maintaining sufficient nutrient levels is associated with lower cholesterol, serum glucose, and blood pressure levels.

Still open to debate, though, are the reasons why calorie restriction (CR) boosts longevity in some animals and lower organisms, and the effects of this less-is-more approach to energy consumption in humans. Confirming CR’s effects and pinpointing the mechanism—or mechanisms—through which CR promotes longevity remain scientific goals, and NIA investigators and grantees working in this niche of aging research are actively searching for answers.

“Calorie restriction remained a black box for many years, and only in the past 5 years have we begun to get a handle on the box’s contents,” says Felipe Sierra, Ph.D., director of NIA’s Biology of Aging Program. “NIA is very interested in calorie restriction and is funding a wide variety of research in this area. Our goal is to examine the relationship of CR to healthy aging and disease. We’re not necessarily trying to find ways for people to live very long lives, but to find ways to improve health so they can live better in their later years.”

Deciphering the mechanisms behind CR

Although scientists have been studying CR for years, only recently have they begun to decipher the cellular and molecular mechanisms that may mediate its positive effects. Elucidation of these mechanisms, many believe, offers hope for advancing understanding of aging processes. Ultimately, it also could help scientists identify drug targets or one day develop gene therapies or other interventions to prevent and treat some of the most prevalent aging-related diseases.

“We need to study the mechanisms and the relationships among them so we can learn more about the process of aging. This may help us identify interventions that act like calorie restriction without actually restricting diet,” Sierra says.

Dr. Rafael de Cabo, NIA Laboratory of Experimental Gerontology

A review of recently published CR-related research illustrates the wide range of mechanisms—from expression of genes known as sirtuins to involvement of insulin signaling pathways—that are currently under investigation, notes Rafael de Cabo, Ph.D., head of the Aging, Metabolism, and Nutrition Unit in NIA’s Laboratory of Experimental Gerontology (LEG). His unit’s bench and rodent experiments focus on identifying potentially protective mechanisms invoked by CR and on evaluating the consequences of dietary interventions on lifespan, pathology, and behavioral function. The lab team also works closely with NIA grantees on CR-related studies.

Recently, for example, a research team including de Cabo and David Sinclair, Ph.D., of Harvard Medical School, discovered in mice that two sirtuin genes, SIRT3 and SIRT4, influence the stability of mitochondria, structures within cells that convert nutrients into energy-yielding molecules and play a role in cell survival. They observed that a gene called NAMPT is activated in calorically restricted cells, resulting in accumulation of NAD+ molecules, which are needed for many metabolic processes. This accumulation, in turn, causes enzymes created by the SIRT3 and SIRT4 genes in the mitochondria to increase, slowing the cell’s aging process.

The findings (PDF, 1.1M), reported September 21, 2007, in Cell, provide clues to cell survival in mammals following the stress brought on by CR, and have potential implications for longevity and aging-associated diseases such as cancer, diabetes, and neurodegenerative diseases such as Alzheimer’s disease.

With each bit of knowledge gained, de Cabo says, investigators are edging closer to understanding at the most basic level why CR may protect against disease and increase longevity. Complementing these efforts, NIA investigators and grantees are searching for mimetics—compounds that mimic the protective cellular effects that appear to occur with restricted energy intake. For example, resveratrol—a natural compound found in grapes, red wine, and nuts—has been shown to improve health and survival in overweight, aged mice. Similar research is now underway in monkeys in a recently launched, 2-year controlled trial at NIA.

Studies in nonhuman primates ongoing

While NIA investigators and grantees continue to probe the mechanisms behind CR, for the past two decades NIA LEG researchers and colleagues at the University of Wisconsin have been studying CR’s effects on mortality, morbidity, and function in nonhuman primates.

NIA’s Intramural Primate Aging Study, begun in 1987, currently includes 80 healthy rhesus monkeys that ranged in age from 1 to 23 years when they entered the study, as well as a smaller group of squirrel monkeys. The experimental CR and control groups are fed the same mix of nutrient-rich foods, but the CR group is given 30 percent fewer calories than the age- and weight-matched controls.

Dr. Julie A. Mattison, NIA Primate Aging Study

“Monkey studies are incredibly valuable because they’re the closest we can come to human studies,” says Julie Mattison, Ph.D., facility head of NIA’s nonhuman primate program. “Rhesus monkeys are a great model for studying calorie restriction and the mechanisms of aging because they age at a rate about three times that of humans, are genetically close to humans, and get many of the age-related diseases seen in humans.”

Thus far, the physiological effects of CR seen in these primate studies are generally comparable to those seen in rodent studies. For example, compared with free-feeding monkeys, the CR monkeys have lower body weight, less abdominal fat, lower fasting glucose levels, increased insulin sensitivity, lower systolic blood pressure, lower levels of serum triglycerides, and higher HDL levels—all markers associated with reduced risk of age-associated diseases. The CR monkeys also show improved immune response and less severe response to induced inflammation.

Although it is not yet known if CR extends the lifespan of nonhuman primates, the findings emerging from these studies are encouraging, showing that calorie-restricted monkeys have a lower incidence and less severe effects of age-related diseases, particularly cardiovascular disease and diabetes. Recently launched studies also are examining the effects of CR on the monkeys’ behavior, motor skills, learning and memory, macular degeneration, reproductive health, hearing, and osteoarthritis.

“As the monkeys approach older age, we’ll learn more about the long-term effects of CR and possible mechanisms that regulate these effects,” Mattison says.

Human trial begins

Recently, NIA extended its CR research one step further when the Institute awarded funding for the first randomized, controlled trial to assess the effects of CR in humans—the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) study. Before the CALERIE pilot studies began, all well-controlled investigations into CR’s effects had been in lower organisms and animals other than humans.

Studying this dietary practice in humans is different from studying it in animals, points out Sergei Romashkan, M.D., Ph.D, chief of the Clinical Trials Branch in NIA’s Geriatrics and Clinical Gerontology Program. “Unlike animals kept in a lab, humans can choose to eat when and what they want,” Romashkan says. “The CALERIE study will help us to understand the adaptive physiologic and metabolic changes that have been observed in animal studies and to learn whether humans can sustain a nutrient-rich, calorie-restricted diet over time. It also will help us to learn about the safety of calorie restriction.”

CALERIE began in 2002 with pilot studies at three sites: Pennington Biomedical Research Center in Baton Rouge, Tufts University in Boston, and Washington University in St. Louis. This small-scale research compared the outcomes of varying levels of CR, exercise regimens designed to produce an energy deficit equivalent to that seen with CR, and a healthy lifestyle control intervention. Each of the pilot studies involved 48 volunteers.

The pilot studies showed that after 1 year, depending on the protocol, volunteers in the CR or exercise arms had lower fasting glucose, total cholesterol, core body temperature, body weight, and visceral fat. The CR and exercise groups also had increased expression of genes encoding proteins involved in mitochondrial function and reduced DNA damage.

The full-scale, 5-year CALERIE study, launched in early 2007, involves 250 healthy volunteers ages 25 to 45, who are assigned to either a CR intervention or a control group. During a 2-year period, participants in the intervention group will reduce their baseline calorie consumption by 25 percent, while the control group members will continue their usual diets.

The researchers will measure a range of outcomes, from insulin and glucose metabolism to oxidative cellular and DNA damage, muscle strength, and cognition. They will also amass a repository of blood, urine, and tissue samples that will be available to investigators studying oxidative damage in cells and molecular mechanisms associated with CR.

“The CALERIE study will let us look at the feasibility of such a diet and whether sustained calorie restriction in healthy men and women results in the same adaptive changes that occur in rodents subjected to CR and how CR may affect markers of diseases associated with aging,” Romashkan says. Because the study timeframe is 2 years, the analyses will not show whether CR can extend human lifespan, he notes.

Whether they are studying the cellular and molecular mechanisms behind CR’s effects or assessing the impact of CR on the health and longevity of lower organisms, animals, or humans, many scientists believe that progress is being made. “This field is extremely exciting, and many of us are coming to the same conclusions about the pathways that are being activated,” says NIA’s de Cabo. “In the next 5 to 10 years, we may make important strides toward designing compounds to emulate CR’s effects.”

National Institute on Aging | http://www.nia.nih.gov

Views on aging are also changing. It no longer necessarily means physical decline and illness—in the last two decades, the rate of disability among older people has declined dramatically.

The National Institute on Aging (NIA), part of the Federal Government’s National Institutes of Health (NIH), investigates ways to support healthy aging and prevent or delay the onset of diseases that disproportionately affect us as we age. These studies not only may increase what is known as “active life expectancy”—the time of advancing years free of disability—but also may promote longevity. NIA’s research includes hormone and dietary approaches, including calorie restriction.

Results from NIA-sponsored studies and others are likely to improve our understanding of the benefits and risks of hormone supplements, calorie restriction, and other interventions to promote healthy aging. This tip sheet provides an overview of what we know about hormone supplements and calorie restriction and the research needed to learn more. Until we have a better understanding, it is a good idea to be skeptical of claims that hormone or other supplements can solve your age-related problems. Instead, focus on what is known to help promote healthy aging: healthy eating and physical activity.

What Is a Hormone?

The word “hormone” comes from the Greek word, hormo, meaning to set in motion. Hormones are chemical messengers that set in motion different processes to keep our bodies working properly. For example, they are involved in our metabolism, immune function, sexual reproduction, and growth. Hormones are made by specialized groups of cells within the body’s glands. The glands—such as the pituitary, thyroid, adrenals, ovaries, and testes—release hormones into the body as needed to stimulate, regulate, and control the function of other various tissues and organs involved in biological processes.

We cannot survive without hormones. As children, hormones help us “grow up.” In teenagers, they drive puberty. As we get older, some of our hormone levels naturally decline. But what does that mean? Scientists do not know exactly. In order to know more, NIA investigates how replenishing hormones in older people affects frailty and function. Many of these studies focus on hormones that decline with age, including:

• Growth hormone
• Melatonin
• Dehydroepiandrosterone (DHEA)
• Testosterone
• Estrogen and progesterone (as part of menopausal hormone therapy)

How Hormones Work

Most hormones are typically found in very low concentrations in the bloodstream. But a hormone’s concentration will fluctuate depending on the body’s activity. Like a key that unlocks a door, a hormone molecule is released by a gland and travels through the blood until it finds a cell with the right fit, a “receptor.” The hormone latches onto a cell’s receptor and a signal is sent into the cell. These signals may instruct the cell to multiply, make proteins or enzymes, or perform other vital tasks. Some hormones can even cause a cell to release other hormones.

One hormone may fit with many types of cells but may not affect all cells in the same way. For example, one hormone may stimulate one cell to perform a task but it might also turn off a different cell. Additionally, how a cell responds to a hormone may change throughout life.

Hormone Supplements

Levels of some hormones change naturally over the lifespan. Some hormones increase with age, like parathyroid hormone that helps regulate the amount of calcium in the blood and bone. Some tend to decrease over time, such as testosterone in men and estrogen in women. When the body fails to make enough of a hormone because of a disease or disorder, a doctor may prescribe hormone supplements. As opposed to hormones produced naturally by the body, hormone supplements come in many forms such as pills, shots, topical (rub-on) gels, and medicated skin patches.

You may have read magazine articles or seen television segments suggesting that hormone supplements can make people feel young again or can slow or prevent aging. That’s because finding a “fountain of youth” is an attractive story that captivates us all. The truth is no research to date has shown that hormone supplements add years to life or prevent age-related frailty. And, while some supplements have real health benefits for people with clinical hormone deficiencies due to a disease or disorder, they also can cause harmful side effects. That’s why people who have a diagnosed hormone deficiency should still only take hormone supplements under a doctor’s supervision.

In some cases, the U.S. Food and Drug Administration (FDA) may have approved a hormone supplement for one purpose, but it is prescribed by physicians for another. This “off-label” use may occur when physicians believe that research, such as clinical studies done on other groups of people, demonstrates a supplement’s usefulness for another condition. While this is the normal process for evaluating drugs already approved by the FDA, consumers should be aware that a particular off-label use of a drug may not have been tested and verified to the same degree as the original use of the drug.

Dangers of Hormone Supplements

Higher concentrations of hormones in your body are not necessarily better. The body maintains a delicate balance between how much hormone it produces and how much it needs to function properly. Natural hormone production fluctuates throughout the day. That means that the amount of hormone in your blood when you wake up may be different 2, 12, or 20 hours later.

If you take hormone supplements, especially without medical supervision, you can adversely affect this tightly controlled, regulated system. Hormone supplements cannot replicate your body’s natural variation. Because hormonal balance is so intricate, too much of a hormone in your system may actually cause the opposite of your intended effect. For example, taking a hormone supplement can cause your own hormone regulation to stop working. Or, your body may process the supplements differently than the naturally produced hormone, causing an alternate, undesired effect. It is also possible that a supplement could amplify negative side effects of the hormone naturally produced by the body. Scientists may not know the consequences.

Some hormone-like products are sold over-the-counter without a prescription. Self-medicating with them can be dangerous. Products that are marketed as dietary supplements are not regulated by the FDA. This means that companies making dietary supplements do not need to get FDA approval or provide any proof that their products are safe and effective before selling them. There is no guarantee that the “recommended” dosage is safe, that there is the same amount of active ingredients in every bottle, or that the substance is what the company claims. Because there are no standards, the hormone-like dietary supplements sold over-the-counter may not have been thoroughly studied and potential negative side effects may not be understood or defined. In addition, these over-the-counter products may interfere with your other medications. NIA does not recommend taking any supplement touted as an “anti-aging” remedy because there is no proof of effectiveness and the health risks of short and long-term use are unknown.

Human Growth Hormone

Human growth hormone (hGH) is important for normal growth and development, as well as for maintaining tissues and organs. It is made by the pituitary gland, a pea-sized structure located at the base of the brain.

Research supports supplemental use of hGH injections in certain circumstances. For instance, hGH injections can improve the growth of children who do not produce enough hGH. Sometimes hGH injections may be prescribed for young adults whose obesity is the result of having had their pituitary gland surgically removed. These uses are different from taking hGH as an anti-aging strategy. As with other hormones, hGH levels often decline with age, but this decrease is not necessarily bad. At least one epidemiological study suggests that people who have high levels of hGH are more apt to die at younger ages than those with lower levels of the hormone. Researchers have also studied animals with genetic disorders that suppress growth hormone production and secretion and found reduced growth hormone secretion may actually promote longevity in those species that have been tested.

Although there is no conclusive evidence that hGH can prevent aging or halt age-related physical decline, some clinics market hGH for that purpose and some people spend a great deal of money on such supplements. Shots can cost more than $15,000 a year. These shots are only available by prescription and should be administered by a doctor. But, because of the unknown risks, it is hard to find a doctor who will prescribe hGH shots. Over-the-counter dietary supplements, known as human growth hormone releasers, are currently being marketed as low-cost alternatives to hGH shots. But claims of their anti-aging effects, like all those regarding hGH, are unsubstantiated.

Research is starting to paint a fuller picture of the effects of hGH supplements, but there is still much to learn. For instance, study findings indicate that supplemental hGH can increase muscle mass; however, it seems to have little impact on muscle strength or function. Questions about potential side effects, such as diabetes, joint pain, and fluid build-up leading to high blood pressure or heart failure remain unanswered, too. A recent report that children who were treated with pituitary growth hormone have an increased risk of cancer created a heightened concern about the dangers of hGH injections. Whether or not older people treated with hGH for extended periods have an increased risk of cancer is unknown. To date, only small, short-term studies have looked specifically at hGH as an anti-aging therapy for older people. Before supporting the use of hGH as an anti-aging therapy, the potential benefits and risks should be assessed through additional research.

Melatonin

Melatonin is a hormone involved with our daily sleep/wake cycle. It is made by the pineal gland located in the brain. Despite some claims to the contrary, melatonin production and release does not necessarily decrease with age. Instead, a number of factors, including light exposure and use of some common medications can affect melatonin secretion in people of any age.

As with other hormones, melatonin is marketed as a dietary supplement. Consumers should look with caution at claims about melatonin supplements’ effects.

One claim for melatonin supplements is that they are an anti-aging remedy, but research on the anti-aging effects has been very limited and focused on animals, not humans. There are also claims that melatonin helps with sleep. Research findings have shown that melatonin supplements, in amounts ranging from 0.1 to 0.5 milligrams, can improve sleep in some cases; however, if taken at the wrong time, melatonin can actually disrupt the sleep/wake cycle. And, melatonin’s benefits as an antioxidant have been touted. Antioxidants protect the body from the harmful effects of by-products, known as free radicals, made when the body changes oxygen and food into energy. Early test-tube studies suggested that, in large doses, melatonin might be an effective antioxidant. More research is needed to know if using melatonin supplements as an antioxidant will decrease the amount of antioxidants cells produce naturally.

Side effects of melatonin supplements may include confusion, drowsiness, and headache. Animal studies suggest that melatonin may cause some blood vessels to constrict, a condition that could be dangerous for people with high blood pressure or other cardiovascular problems.

The usual dose of melatonin sold without a prescription in stores is 3 milligrams. This dose is much larger than the 0.1 to 0.5 milligrams of melatonin researchers used to study its effects on sleep. People who take these supplements may have a 10- to 40-times higher blood concentration of melatonin than normal. Long-term effects of such high concentrations of melatonin on the body are still unknown. Use caution when considering taking these supplements until researchers learn more.

DHEA

Dehydroepiandrosterone, or DHEA, is made from cholesterol by the adrenal glands, which sit on top of each kidney. It is converted by the body into two other important hormones: testosterone and estrogen.

For most people, DHEA production peaks in the mid-20s and then gradually declines with age. The effects of this decline including its role in the aging process are unclear. Even so, some proponents claim that over-the-counter DHEA supplements can improve energy and strength and boost immunity. Claims are also made that supplements increase muscle and decrease fat. To date, there is no conclusive scientific evidence that DHEA supplements have any of these benefits.

The conversion of naturally produced DHEA into a different amount of estrogen and testosterone is highly individualized. There is no way to predict whose body will make more and whose will make less of these hormones. Having an excess of testosterone and estrogen in your body can be risky.

Scientists do not yet know the effects of long-term use (over 1 year) of DHEA supplements. Early indications are that these supplements, even when taken briefly, may have several detrimental effects on the body, including liver damage. But the picture is not clear. Two short-term studies showed that taking DHEA supplements has no harmful effects on blood, prostate, or liver function. However, these studies were too small to lead to conclusions about the safety or efficacy of DHEA supplementation.

Researchers are working to find more definite answers about DHEA’s effects on aging, muscles, and the immune system. In the meantime, if you are thinking about taking DHEA supplements, be aware that the effects are not fully known and might turn out to cause more harm than good.

Testosterone

Most people know testosterone as the hormone that transforms a boy into a man and is somehow associated with sex drive. That may be why some men are concerned about a possible decrease in testosterone production as they age.

Testosterone is a vital sex hormone that plays an important role in puberty. In men, testosterone not only regulates sex drive (libido), it also helps regulate bone mass, fat distribution, muscle mass and strength, and the production of red blood cells and sperm. But testosterone isn’t exclusively a male hormone—women produce small amounts, as well. In men, testosterone is produced in the testes, the reproductive glands that also produce sperm. The amount of testosterone produced in the testes is regulated by the hypothalamus and the pituitary gland.

As men age, their testes often produce somewhat less testosterone, especially when compared to years of peak testosterone production during adolescence and early adulthood. Normal testosterone production ranges widely, and it is unclear what amount of decline or how low a level of testosterone will cause adverse effects.

In recent years, the popular press has reported frequently about male menopause, a condition supposedly caused by diminishing testosterone levels in aging men. There is scant scientific evidence that this condition, also known as andropause or viropause, exists. And the like-lihood that an aging man will experience a major shutdown of testosterone production similar to a woman’s menopause is very remote. In fact, many of the changes that take place in older men often are incorrectly attributed to decreasing testosterone levels. For instance, some men experiencing erectile difficulty (impotence) may be tempted to blame it on lowered testosterone, when in many cases erectile problems are due to circulatory problems.

In certain cases, such as in men whose bodies make very little or no testosterone, testosterone supplementation may offer benefits. FDA-approved testosterone supplements come in different forms, including patches, injections, and topical gels. Men whose testes have been damaged or whose pituitary glands have been harmed or destroyed by trauma, infections, or tumors may be prescribed testosterone. Supplements can also help men with exceptionally low testosterone levels maintain strong muscles and bones and increase their sex drive. It is unclear if men who are at the lower end of the normal range for testosterone production would benefit from supplementation.

More research is needed to learn what effects testosterone replacement may have in healthy older men without these extreme deficiencies. NIA is investigating the role of testosterone therapy in delaying or preventing frailty and helping with other age-related health issues. Results from preliminary studies involving small groups of men have been inconclusive. Specifically, it remains unclear to what degree testosterone supplements can help men maintain strong muscles and sturdy bones, sustain robust sexual activity, or sharpen memory.

There are also concerns about the long-term harmful effects that supplemental testosterone might have on the aging body. Some epidemiologic studies suggest that higher natural levels of testosterone are not associated with a higher incidence of prostate cancer—the second leading cause of cancer death among men. However, scientists do not know if taking supplemental testosterone increases men’s risk for developing prostate cancer or promoting the growth of an existing tumor. There is also concern about a potential increased risk for stroke based on studies that suggest that testosterone supplementation might trigger excessive red blood cell production, which thickens the blood.

The bottom line: Although some older men who use testosterone therapy may report feeling more energetic or younger, there is no scientific proof that testosterone therapy in healthy men will help them age better. Until more scientifically rigorous studies are conducted, it is not known if the possible benefits of testosterone therapy outweigh any of its potential risks. NIA continues to conduct research to gather more evidence about the effects of testosterone supplements in aging men.

Hormones in Women

Estrogen and progesterone are two hormones that play an important part in women’s menstrual cycle and pregnancy. Estrogen also helps maintain bone strength and might prevent heart disease and protect memory before menopause. Both estrogen and progesterone are produced naturally by the ovaries. However, after menopause, the ovaries stop making these hormones. For more than 60 years, millions of women have used estrogen supplements to control for menopausal symptoms, especially hot flashes and vaginal dryness. Women also take it to prevent or treat osteoporosis—loss of bone strength—that often happens after menopause. The use of estrogen (by women whose uterus has been removed) or estrogen with progesterone or a progestin, a synthetic form of progesterone (by women with a uterus), to treat the symptoms of menopause is called menopausal hormone therapy (MHT), formerly known as hormone replacement therapy (HRT).

There is a rich research base investigating estrogen. Many large, reliable long-term studies of estrogen and its effects on the body have been conducted. Yet, much remains unknown. In fact, the history of estrogen research demonstrates why it is important to examine both the benefits and risks of a hormone before it becomes widely used. Here’s what scientists know:

• Endometrial problems—While estrogen helps some women with symptom management during and after menopause, it can raise the risk of certain problems. Estrogen may cause a thickening of the lining of the uterus (endometrium) and a slightly increased risk of endometrial cancer. To lessen these risks, doctors now prescribe progestin to women with a uterus to protect the lining.
• Heart disease—The role of estrogen in heart disease is complex. Early studies suggested MHT could lower postmenopausal women’s risk for heart disease—the number one killer of women in the United States. But results from the Women’s Health Initiative (WHI), a study of MHT by the NIH, suggest that using estrogen with or without a progestin after menopause does not protect women from heart disease and may even increase their risk.In 2002, WHI scientists reported that using estrogen plus progestin actually elevates some postmenopausal women’s chance of developing heart disease, stroke, blood clots, and breast cancer, but women also experienced fewer hip fractures and cases of colorectal cancer. In 2004, WHI scientists published another report, this time on postmenopausal women who used estrogen alone, which had some similar findings: women had an increased risk of stroke and blood clots, but fewer hip fractures. Then, in 2007, a closer analysis of the WHI results indicated that younger women, ages 50 to 59 at the start of the trial, who used estrogen alone had significantly less plaque in their coronary arteries than women not using estrogen. Increased plaque in coronary arteries is a risk factor for heart attacks. Scientists also determined that the risk of heart attack might not be increased in women who started MHT less than 10 years after menopause, but that there is increasing risk in women who begin MHT more than 10 years after menopause.
• Dementia—Some studies suggest that estrogen may protect against Alzheimer’s disease. However, this has not yet been proven. In 2003, researchers in a sub-study of the WHI, called the WHI Memory Study (WHIMS), reported that women age 65 and older who take a combination of estrogen and progestin were at twice the risk for developing dementia than women who do not take any hormones. In 2004, these WHIMS scientists reported that using estrogen alone could also increase the risk of developing dementia in women age 65 and older compared to women not taking any hormones.

For all the research findings, there are still many unknowns about the risks of MHT. For instance, scientists have not yet determined if risks differ between women who have menopausal symptoms and those who don’t. Also, because women in their early 50’s were only a small part of the WHI, scientists do not yet know if certain risks are applicable to younger women who use estrogen to control symptoms during the menopausal transition.

You may also have heard about a relatively new approach to hormone therapy for women—bioidentical hormones. These are man-made hormones (from plants such as soy or yams) that have the same chemical structure as hormones produced by the human body. The term “bioidentical hormones” is now also being applied to the practice of compounding or combining hormones such as estrogen and progesterone, theoretically based on a woman’s individual hormonal needs. Large clinical trials of these compound hormones have not been done, and many bioidentical hormones that are available without a prescription are not regulated or approved for safety and efficacy by the FDA. FDA-regulated bioidentical hormones, such as estradiol and progesterone, are available by prescription for women considering MHT.

For middle age and older women, the decision to take hormones is far more complex and difficult than ever before. Questions about menopausal hormone therapy remain: Would using a different estrogen and/or progestin or different dose change the risks? Would the results be different if the hormones were given as a patch or cream, rather than a pill? Would taking the progestin less often be as effective and safe? Does starting menopausal hormone therapy around the time of menopause compared to years later change the risks? Can we predict which women will benefit or be harmed by using menopausal hormone therapy? As these and other questions are addressed by research, women should re-review the pros and cons of menopausal hormone therapy with their doctors, assess the personal risks and benefits, and then make an informed decision about whether or not this therapy is for them.

NIA has additional free information on menopausal hormone therapy. Call 1-800-222-2225 (toll-free) or visit the NIA website at www.nia.nih.gov/HealthInformation.

Calorie Restriction, Intermittent Fasting, and Resveratrol

Scientists are discovering that what you eat, how frequently, and how much may have an effect on quality and years of life. Of particular interest has been calorie restriction, a diet comprised by generally 25 to 40 percent fewer calories than normal but including all needed nutrients. Research in animals has shown calorie restriction to have an impressive effect on disease and markers of aging. It has been found to extend the life of protozoa (very small, one-celled organisms), yeast, fruit flies, mice, and rats. Recent calorie restriction studies with humans and other primates, such as monkeys, are on-going. However, early findings of the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) study, show that adults who cut their calorie consumption by 25 percent lowered their fasting insulin levels and core body temperature, both of which correlate with increased longevity in animal models. In other studies with non-human primates, researchers have found that calorie restriction reduced incidence of heart disease and cancer.

Scientists do not know if long-term calorie restriction is safe for humans. It is unclear whether or not a calorie-restricted diet will ever be recommended for people. However, studying calorie restriction may offer new insights into the aging process and biological mechanisms that could influence healthy aging. This research may also provide clues about how to prevent or delay diseases that become more prevalent with age.

Other ongoing studies focus on identifying chemicals that mimic calorie restriction’s benefits. Resveratrol, found naturally in very small amounts in grapes and nuts, is one of the compounds being studied. Scientists compared two groups of overweight mice on a high fat diet. One group was given a high dose of resveratrol. The overweight mice receiving resveratrol were healthier and lived longer than the other overweight group. In a follow-up study, scientists found that, when started at middle age, resveratrol slowed age-related health problems in mice on a standard diet but did not increase longevity. More research is needed before scientists know if resveratrol is safe for people or even if it has the same effects as it has in mice.

Scientists are also studying the effect of intermittent fasting or reduced meal frequency. In animal models, like mice, reduced meal frequency appears to have a protective effect on the brain and may also help with heart function and regulating sugar in the blood. However, the influence of intermittent fasting on human health and longevity is currently unclear.

While research into calorie restriction and intermittent fasting continues, there is already plenty of research supporting the value of a healthy, balanced diet and physical activity to help delay or prevent age-related health problems.

Many Questions, Seeking Answers

NIA supports research that seeks to tell us more about aging and the risks and benefits of potential interventions such as hormone therapies, supplements, and calorie restriction. One goal is to determine whether DHEA, melatonin, and other hormonal supplements improve the health of older people, have no effect, or are harmful. Researchers are also trying to determine if calorie restriction is safe for humans and if there are any compounds that could replicate in humans the benefits of calorie restriction seen in animals.

These studies will take some time. Research on supplements and calorie restriction is ongoing and a great deal of basic animal and clinical research is yet to be done. Don’t be surprised if these studies open the door to more questions as well as answers. Research is an incremental process; results can move knowledge forward, but can also take you back to basics.

Until more is known about DHEA, melatonin, hGH, and resveratrol, consumers should view these types of supplements with a good deal of caution and doubt. Despite what advertisements and media, like television and magazines, may claim, there are no specific therapies proven to “prevent” aging. Some harmful side effects already have been discovered and additional research may uncover others.

People with genuine deficiencies of hormones should consult with their doctors about supplements. Talk to your doctor if you are interested in any form of hormone supplementation or “anti-aging” approaches beyond healthy diet and physical activity. Meanwhile, people who choose to take any hormone supplement without a doctor’s supervision should be aware that these supplements appear to have few clear-cut benefits for healthy individuals and no proven influence on the aging process.

For more information on health and aging, contact:

National Institute on Aging Information Center
P.O. Box 8057
Gaithersburg, MD 20898-8057
800-222-2225 (toll-free)
800-222-4225 (TTY/toll-free)
www.nia.nih.gov
www.nia.nih.gov/Espanol

Director’s Overview

There are currently 35 million Americans over the age of 65. Of these, more than four million are over 85, and some 65,000 have attained their hundredth birthday. By 2030, the number of individuals age 65 and older will likely double, reaching 70.3 million and comprising a larger proportion of the entire population, rising from 13 percent today to 20 percent in 2030, and the number of the “oldest old” — people age 85 and older — is expected to grow from 4.3 million in 2000 to at least 19.4 million by 2050. 1

As life expectancy increases, we are challenged to find ways to keep the additional years of life free of disease and disability. Today, more than half of all Americans over age 65 show evidence of osteoarthritis in at least one joint.2 Over half of Americans older than 50 have osteoporosis or low bone mass.3 Cardiovascular disease, cancer, and diabetes remain common among older Americans, and as many as 4.5 million Americans suffer from Alzheimer’s disease (AD).4 For many, modern medicine and new insights into lifestyle and other environmental influences are allowing people to remain healthy and socially and emotionally vital into very advanced ages; however, NIA supported research continues to address the needs of the growing number of people who will live longer.

The National Institute on Aging (NIA) leads a national scientific effort to understand the nature of aging and to extend the healthy, active years of life for all Americans. NIA achieves its mission through a robust extramural research program composed of the four research areas as described in the Budget Justification section plus a vibrant intramural research program.

NIA’s research programs cover a wide range of topics critical to understanding aging and its interaction with the initiation and progression of disease and disability. For example, NIA research has identified lifestyle factors and health behaviors that directly influence physical and mental fitness and risk of disease in aging populations. NIA-supported scientists develop and refine recommendations for people of all ages regarding optimal diet, dietary supplement use, exercise, and safety to increase their likelihood of enjoying a physically and mentally healthy old age. Other researchers work to find better ways to enhance the physical, mental, and interpersonal capabilities of older people and to expand opportunities for them to achieve personal goals and contribute to society in meaningful ways. Still others explore the molecular, cellular, and genetic changes that take place in the body as we age, with the ultimate goal of developing new prevention strategies and novel therapeutic approaches to eliminate or delay the debilitating physical, cognitive, and psychological changes that can occur.

As the research on aging advances, NIA will focus more effort on the translation of basic research findings into clinical studies and trials. The institute supports large multidisciplinary programs in translational research, including:

• Edward R. Roybal Centers for Research on Applied Gerontology, designed to advance promising social and behavioral basic research findings from the laboratory and into programs, practices, and policies to improve the lives of older people and enhance the capacity of the nation to adapt to the societal shifts that come with an aging population.
• Claude D. Pepper Older American Independence Centers (OAIC), established to increase scientific knowledge for the development of innovative and cost-effective ways to maintain and restore independence.
• The Alzheimer’s Disease Translational Initiative, a major effort to encourage more researchers to move from basic research on Alzheimer’s disease and associated disorders into translational research and drug testing in clinical trials. Components of this initiative include program announcements on drug discovery and preclinical development and a program of toxicology services for academic and small business investigators who believe they have promising compounds for the treatment or prevention of Alzheimer’s disease but lack the resources to perform the required toxicology studies.

Additional translational research efforts include:

• Recent findings which have shown that overweight, aged male mice whose high-calorie diet was supplemented with the natural compound resveratrol had better health and longer survival than their counterparts who did not receive it. NIA plans to test the effects of dietary supplementation with resveratrol in non-human primates, an important step to inform the consideration of human clinical trials.
• Several studies which suggest that physical exercise may prevent physical disability, including impaired mobility, in healthy and frail older adults. To develop definitive evidence, NIA and grantee researchers have developed the LIFE (Lifestyle Interventions and Independence in Elders) study, a clinical trial testing the effects of a physical activity program vs. a health education program among older Americans. A successful pilot study (LIFE-P) completed in 2005 showed both feasibility and positive preliminary data, permitting design and consideration of this large-scale clinical trial.
• A large body of research in animal models which indicates that substantially reducing caloric intake while maintaining optimal nutrition results in significant increase in life span. NIA-supported Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) will help to determine if these beneficial effects extend to humans. Results from pilot studies demonstrated that overweight people who cut their calories by 25 percent for six months have reduced fasting insulin levels and core body temperature, two markers that may be associated with increased longevity in humans. A longer-term study will begin in January 2007.

NIA’s Intramural Research Program is very active in the translation of basic research findings to clinical studies. One of its primary resources, the Advanced Studies in Translational Research on Aging (ASTRA) unit, is a state-of-the-art facility located at Baltimore’s Harbor Hospital. ASTRA, opened in January 2003, is equipped with a fully functional 10-bed acute care inpatient unit, an outpatient examination and treatment unit, and other resources vital to the conduct of translational research. Recently, the Baltimore Longitudinal Study of Aging, which has been the gold-standard reference for all epidemiological studies on aging, was moved to the ASTRA unit where NIA plans to launch a number of ancillary studies that are more likely to provide information that can be directly applied to clinical medicine.

Overall Budget Policy

Investigator-initiated research projects and new investigator research and career development are the Institute’s highest priorities. In order to maximize the number of competing research project grants that can be made, NIA has a cap on the amount that can be awarded to individual program project awards and is following the NIH policy in providing no inflationary increases for non-competing or competing grants. In addition, the NIA has targeted a portion of the funds available for competing research project grants to support high priority projects outside of the payline, including awards to new investigators and first-time renewals. The Institute also seeks to maintain a balance between solicitations issued to the extramural community in areas that need stimulation and funding made available to support investigator-initiated projects.

Narrative by Program

Biology of Aging Program:
Understanding Aging Processes, Health, and Longevity

Investigators supported by NIA’s Biology of Aging Program (BAP) seek to better understand the basic biochemical, genetic, and physiological mechanisms that underlie the process of aging and age-related changes in humans and in animal models. BAP supports research on age-related changes in structure and function, from the molecular and cellular level to entire organisms, as well as the ways in which these changes are related to diseases and conditions common to aging. This program supports integrated research on genetics and other aspects of aging-related changes in multiple model systems, including both mammals and non-mammalian organisms (e.g. flies, worms, and yeast).

Budget Policy: The 2008 budget estimate for the Biology of Aging Program is $175,672,000, an increase of $72,000 or 0.04 percent from the FY 2007 Continuing Resolution of $175,600,000. Program objectives for FY 2008 include plans to:

• Continue the search for interventions that extend the lifespan. The recent finding that resveratrol could affect the health and survival of mammals exemplifies the promise of this research. An important component in this area is the Intervention Testing Program, which supports the testing of compounds with the potential to extend the lifespan and delay disease and dysfunction in a mouse model. Plans are to renew this promising initiative in FY 2007 for funding in FY 2008.
• Continue to search for genes and biological pathways that influence longevity and aging. NIA’s primary mechanism for this endeavor is the Longevity Associated Gene initiative, which to date has identified over one hundred new longevity-associated genes, along with many conserved biological processes and pathways that regulate longevity in a host of divergent species, including humans.
• Increase our understanding of the aging immune system. A new initiative on “Membrane Associated Signaling Defects in Immune Cells with Aging” seeks to shed light on the cellular processes that may lead to impaired immune function in older people.
• Understand the role of nuclear receptors in aging. Research supported under two complementary program announcements will focus on the biologic mechanisms that underlie the activity of nuclear receptors, which are molecules that play key roles in various physiologic and pathophysiologic processes, including those involved in aging and in age-related diseases.
• Continue the highly successful Nathan Shock Centers of Excellence in Basic Biology of Aging. These centers enhance the ability of institutions with well-developed research programs in basic research on aging to use state-of-the-art research resources to provide the strongest environment for the conduct of research on aging.

Behavioral and Social Research Program:
Understanding and Addressing the Behavioral, Emotional, and Social Dynamics of Aging

NIA Behavioral and Social Research Program (BSR) supports social and behavioral research to better understand the processes of aging at both the individual and societal level. Research areas include the behavioral, emotional, and social changes individuals undergo throughout the adult lifespan; interrelationships between older people and social institutions; and the societal impact of the changing age composition of the population. BSR also supports research training, development of research resources, and a knowledge base for the development of interventions to maximize active life and health expectancy.

Budget Policy: The 2008 budget estimate for the Behavioral and Social Research Program is $168,850,000, an increase of $70,000 or 0.04 percent from the FY 2007 Continuing Resolution of $168,780,000. Program plans for FY 2008 are to:

• Initiate a new wave of the National Long-Term Care Survey (NLTCS) and continue other major demographic studies. The NLTCS is a longitudinal survey to study changes in the health and functional status of older Americans and track health expenditures; Medicare services used; and the availability of personal, family, and community resources for caregiving. It is considered one of the most useful resources for analyzing national disability trends. Other important ongoing studies include the Health and Retirement Survey and collaborations with the Census Bureau and the Federal Forum on Aging.
• Support research initiatives to address financial challenges faced by American elders. Funding for two major initiatives in this area will run through FY 2008. One initiative, “Developing Integrated Economic Models of Health Retirement,” will stimulate development of comprehensive econometric models of retirement from the labor force. The other focuses on the neuroeconomics of aging and supports research to examine the social, emotional, cognitive, motivational processes and neurobiological mechanisms of decision-making behavior in older people.
• Support research on ways in which data from ongoing clinical trials and other studies can be used to plan and prepare for future natural and man-made disasters. Three coordinated research solicitations focused on behavioral and social aspects of disasters were released in 2006 to stimulate research on the consequences of natural and man-made disasters and their effects on the health of vulnerable groups, with the ultimate goal of preventing and/or mitigating harmful consequences.

Neuroscience and Neuropsychology of Aging:
Understanding, Preventing, and Treating Cognitive Decline and Disability

NIA’s Neuroscience and Neuropsychology of Aging (NNA) Program supports a broad spectrum of research and training aimed at better understanding age-related normal and pathological changes in the structure and function of the nervous system and how such changes affect behavior. The basic mission is to expand knowledge on the aging nervous system to allow improvement in the quality of life of older people. This includes basic and clinical studies of the nervous system, clinical trials of treatments and preventive interventions for neurological disease, and epidemiological research to identify risk factors and to establish prevalence and incidence estimates of pathologic conditions. Additionally, it supports research relevant to those geriatric problems arising from psychiatric and neurologic disorders associated with aging.

Budget Policy: The 2008 budget estimate for Neuroscience and Neuropsychology of Aging Program is $413,131,000, an increase of $171,000 or 0.04 percent from the FY 2007 Continuing Resolution of $412,960,000. Program plans for FY 2008 are to:

• Continue to support high-quality research on Alzheimer’s disease (AD). Alzheimer’s disease is a major public health issue for the United States because of its enormous impact on individuals, families, the health care system, and society as a whole. NIA supports a robust portfolio that encompasses all areas of AD research, from the disease’s molecular underpinnings to cutting-edge diagnostic and treatment modalities. NIA will continue a comprehensive drug development program and pilot trials initiative plus a cooperative agreement with the University of California, San Diego to conduct several new clinical trials of interventions to treat AD through the Alzheimer’s Disease Cooperative Study. (See the “program portrait.”)
• Support research on maintenance of cognitive and emotional health into older age. NIA joined with the National Institute of Mental Health and the National Institute on Neurological Disorders and Stroke to launch the Cognitive and Emotional Health Project, which is designed to assess the state of longitudinal and epidemiological research on demographic, social, and biologic determinants of cognitive and emotional health in aging adults and the pathways by which cognitive and emotional health may reciprocally influence each other. A “Cognitive Health Summit” planned for Spring 2007 will inform future research in this area.
• Develop new tools, resources, and training opportunities to accelerate the pace of discovery in neuroscience research through participation in the NIH Blueprint for Neuroscience Research. NIA is one of fifteen NIH Institutes that participate in the Blueprint, designed to enhance collaboration through coordinated initiatives. The first Blueprint initiatives began in FY 2005. The priority in FY 2007 is neurodegeneration with neurodevelopment the priority in FY 2008.
• Continue research on neurological diseases and conditions other than AD that occur in older Americans, including Parkinson’s disease, frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). This research is an important component of NIA’s portfolio. NIA-supported researchers recently identified a misfolded protein that is common to FTD and ALS, which provides important insights about the mechanisms of both diseases.

Geriatrics and Clinical Gerontology Program:
Reducing Disease and Disability Among Older People

As we age, our risk for many other types of disease and/or disability increases dramatically. NIA’s Geriatrics and Clinical Gerontology (GCG) Program supports research on health, disease, and disability in the aged (other than neurodegeneration, which is the focus of the NNA Program). Areas of focus include age-related physical changes and their relationship to health outcomes, the maintenance of health and the development of disease, and specific age-related risk factors for disease. The program also plans and administers clinical trials.

Budget Policy: The 2008 budget estimate for the Geriatrics and Clinical Gerontology Program is $135,148,000, an increase of $55,000 or 0.04 percent from the FY 2007 Continuing Resolution of $135,093,000. Program objectives for FY 2008 include plans to:

• Initiate studies of venous and arterial thrombosis in the elderly. Advanced age is associated with a dramatic increase in venous and arterial thrombosis (the development of dangerous blood clots in the veins and arteries). However, the biologic mechanisms for this increased risk are poorly understood. A new initiative will explore the biological mechanisms, epidemiology, pathophysiology, and clinical aspects (diagnosis, treatment, and prevention) of this common condition.
• Continue clinical trials of the efficacy and safety of testosterone in older men for a variety of conditions. Two trials are targeted to begin in mid-2007 — one for men over 65 and one for younger men. The trials are expected to run for approximately six years. Participants will include men who are experiencing clinical symptoms related to low testosterone levels. Although these are treatment studies, the results may inform future prevention trials.
• Continue research on anemia in the elderly. Anemia is common among older people; however, over half the cases of anemia in older adults occur without a clearly identifiable cause. An ongoing program supports research to better understand the epidemiology, pathophysiology, and clinical aspects of anemia in the elderly. Findings from this research may prove critical to the development of clinical trials.

Intramural Research at NIA

NIA’s Intramural Research Program (IRP) includes the scientific disciplines of biochemistry, cell and molecular biology, structural biology, genetics, immunology, neurogenetics, behavioral sciences (psychology, cognition, and psychophysiology), epidemiology, statistics, and clinical research and the medical disciplines of neurobiology, immunology, endocrinology, cardiology, rheumatology, hematology, oncology, and gerontology. The program seeks to understand the changes associated with healthy aging and to define the criteria for evaluating when a change becomes pathologic. Studies focus on both common age-related diseases (e.g., Alzheimer’s disease, Parkinson’s disease, stroke, atherosclerosis, osteoarthritis, diabetes, cancer) and the determinants of healthy aging.

In 2008, NIA’s IRP will celebrate the 50th anniversary of the Baltimore Longitudinal Study of Aging, America’s longest-running scientific study of human aging. More than 1,400 men and women, ranging in age from the 20s to the 90s, have been study volunteers. Since its inception in 1958, the BLSA has generated numerous findings to elucidate the normal course of aging and disentangle the effects of disease from the normal aging process.

Budget Policy: The 2008 budget estimate for NIA’s Intramural Research Program is $101,370,000, a decrease of $710,000 or 0.7 percent from the FY 2007 Continuing Resolution of $102,080,000. Program objectives for FY 2008 include plans to:

• Determine the effectiveness of already available therapeutic agents for prevention in models of heart disease. Animal studies suggest that the compound fenoterol, widely used for treatment of pulmonary disease, may be effective in the treatment of congestive heart failure. Other studies in animal models have shown that the drug erythropoietin, used to treat certain types of anemia, has a protective effect on the heart if administered shortly after a heart attack. NIA’s IRP is conducting preclinical testing of both agents with the goal of moving them into human clinical trials in future years.
• Continue to study the effects of obesity and sarcopenia on health outcomes. The Health, Aging, and Body Composition (Health ABC) Study is an ongoing study of body composition and weight-related health conditions. Clinical examinations will end in 2007, at which time NIA plans to initiate five years of focused event follow-up for physical and cognitive function, selected disease endpoints (fracture, heart disease, cancer, and stroke), cause-of-death assessment, and maintenance of the biorepository.
• Continue to study the driving factors behind persistent black-white health disparities in overall longevity, cardiovascular disease, and cerebrovascular disease. NIA is in the midst of data collection for its ground-breaking Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study. HANDLS is a community-based, epidemiological study for evaluating health disparities in socioeconomically diverse African American and white populations in Baltimore, Maryland.

Research Management Support

NIA RMS activities provide administrative, budgetary, logistical, and scientific support in the review, award, and monitoring of research grants, training awards and research and development contracts. RMS functions also encompass strategic planning, coordination, and evaluation of the Institute’s programs, regulatory compliance, international coordination, and liaison with other Federal agencies, Congress, and the public. The Institute currently oversees more than 1,840 research project grants and centers, as well as more than 500 full-time training positions and 100 research and support contracts.

Budget Policy: The 2008 budget estimate for NIA’s Research Management and Support is $39,194,000, an increase of $388,000 or 1.0 percent over the FY 2007 Continuing Resolution of $38,806,000. Additional funds will be used to partially offset the costs associated with pay raises and other mandatory increases.

5 Hebert, op. cit.

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