PORTFOLIO FOR PROGRESS

National Institutes of Health

National Institute

on Aging
The mission of the National Institute on Aging:

“the conduct and support of biomedical, social

and behavioral research, training, health information dissemination, and other programs with

respect to the aging process and the diseases and

other special problems and needs of the aged.”

Research on Aging Act of 1974, 

as amended in 1990 by P.L101-557
National Institute 

on Aging

PORTFOLIO FOR PROGRESS

TABLE OF CONTENTS

2 Message from the Office of the Director

4 The Biology of Aging

· The Genetics of Longevity and Disease

· Environmental Factors and Aging

· Vital Systems and Organs

12 Reducing Disease and Disability

· Reducing Cardiovascular Disease

· A Focus on Independence: 

The Claude D. Pepper Centers

· Enhancing Musculoskeletal Function

· Managing Diabetes

· Treating Cancer

· The Future of Clinically-Focused Research

20 The Aging Mind: Alzheimer’s Disease 

and Normal Aging

· Alzheimer’s Disease Causes and Risk Factors

· Diagnosing Alzheimer’s Disease

· A Framework for Finding Answers

· Treating Alzheimer’s Disease

· Caring for Alzheimer’s Disease Patients 

and Families

· Normal Aging of the Brain

· Information on Alzheimer’s Disease 

and Brain Aging

30 Behavioral and Social Aspects of Aging

· Personality and Social/Behavioral Influences on Health

· From Lab Bench to Bench Press: 

NIA Launches an Exercise Campaign

· Personal Behaviors and Population 

Trends in Health

40 Health Disparities: Research on Minority Aging

44 For More Information
2

The trend toward very advanced age was

remarkable in the 20th century and is

expected to continue unabated until at least the

middle of the new millennium. Only 10 million

people reached age 50 or older in 1900, a time

when the average life expectancy was only 49.

Today, some 76 million of us are age 50 or

more. A newborn can expect to live well into

his or her seventies and very often beyond.

Looking ahead, the first wave of the famous

“baby boom” will turn 65 in 2011, accelerating

an already underway “senior boom.” We are

captivated, too, by the notion that more and

more of us will be centenarians.

This aging of America moves us into a

new phase of our national life, with profound

implications for individuals, families, and society. A portrait of an older America is beginning to emerge, and it is a conflicted one. On

one hand, research finds that we are healthier

and wealthier than ever before. A majority of

us age 65 and older say our health is good or

excellent. Rates of disability and of several

diseases are falling dramatically, despite a

notable increase in the number of older people. Fewer of us live in nursing homes than

did just a decade ago. And the poverty that

used to accompany advancing age has been

greatly reduced. 

On the other hand, however, good health

and well-being with age are far from a universal reality. Studies show that most of us age 70

and older have at least one of seven potentially disabling conditions, such as arthritis,

heart disease, or diabetes. About one-fifth of

people 65 and older — seven million in all —

report some level of disability. At greatest risk

for disease and disability is the age group that

is growing the fastest, people age 85 and

older, nearly half of whom suffer from

Alzheimer’s disease (AD). Family and friends

are often brought into the picture as caregivers, making up a large and informal corps

of support for loved ones who cannot function

well on their own.

Understanding this dichotomy — between

an independent, active later life and one that is

MESSAGE FROM THE OFFICE OF THE DIRECTOR

Older Population by Age

1910 to 2030 (In Millions)

65 to 84

85+

NEVER BEFORE HAVE SO MANY

PEOPLE LIVED FOR SO LONG. 

Source: U.S. Census Bureau

Dr. Richard J. Hodes

Director, NIA
3

characterized by frailty

and dependence — is

what research on aging

is all about. Discovering

what happens in the

many, varied manifestations of aging, even in

different species, will

allow us to develop

insights and interventions that promote health and prevent disease.

The research program pursued by the

National Institute on Aging (NIA), part of the

National Institutes of Health, covers a broad

range of issues and concerns. Aimed at

improving the quality of life for older people

and their families, research is focused in four

general areas — the biology of aging, reducing

disease and disability, AD and cognitive

changes, and the behavioral and social aspects

of aging. Within this framework, scientists and

those supported by Institute grants and contracts explore everything from cell function to

social interaction. Overall, there is an increasing emphasis on the study of gender and racial

and ethnic disparities in health and a concentrated effort to include more minorities in

research and train new minority scientists.

Enormous progress is being made. This

booklet describes some of what we know and

what we have yet to find out about growing

older. Research has already contributed to the

revolution in longevity. What we now seek are

ways to embrace aging, individually and collectively, and make it the best that it can be.

Richard J. Hodes, M.D.

Director, National Institute on Aging

Dr. Judith A. Salerno

Deputy Director, NIA
The Biology

of Aging
Gee, he sure doesn’t look 70.” “Oh, she’s

got to be at least 60.” “You’re how old?”

At one time or another, most of us have

formed some opinion about what it is to look

or feel a certain age. The truth is, of course,

there’s no real standard. One 75 year-old may

be active and healthy, with an almost visible

vitality. Another can project a more stereotypical image of someone in his or her mid 70s,

perhaps with a few wrinkles and a bit slower

in step. 

The basis for much of modern research on

aging is this notion of heterogeneity, or differences, among individuals. That is, people

“age” differently — outwardly, in the appearance of our hair, eyes, and skin, and inside, in

our muscles, bones, heart, brain, and other

vital tissues and organs. It is now clear to scientists that each of us is a product of a complex mix of heredity, environment, and

lifestyle. Understanding the genetic, molecular, and cellular processes common to aging 

as well as how these processes may differ in

individuals will lead to biological and lifestyle

interventions that maintain function and prevent disease. 

The past decade of study has moved us

away from the idea that

any one process or gene

is responsible for how we

age biologically. “There is

no single theory to

explain aging,” says Dr.

Huber Warner, NIA Associate Director, Biology of Aging Program. “It’s

possible that some age-related changes are

genetically programmed while others involve

the effects of less predictable activity, such as

free radical damage to cells or other insults

that seem to occur with age.” 

Research supported and conducted by

the NIA examines many of these fundamental

mechanisms of aging — in genes, in the biochemistry of cells, and in critical organs of the

body. Scientists expect that the next few

years will be particularly prolific for basic

research on aging because of the promise of a

number of new technologies. From the use of

new microarray techniques to measure the

activity of thousands of genes at once to

refinements in developing new animal models

for the study of gene function, “I think the

development of technologies for a new generation of research at the genetic and molecular

level will bring major breakthroughs in the

biological sciences,” says Dr. Warner. 

Scientists at the NIA’s Laboratory of

Genetics, for example, have taken a major

step forward in the use of new microarray

technologies. The laboratory’s work is based

on the thinking that important genes begin

to determine the course of aging at the very

start of life. But these studies have lagged

because many of the genes active in early 

life have not been part of gene libraries 

“

NATIONAL INSTITUTE ON AGING

The Biology

of Aging
previously made available for analysis. Senior

investigators in the laboratory’s Developmental Genomics and Aging Section recently

developed a new method to recover copies of

all the genes “expressed” — turned on and

functioning — in the early stages of development of mouse embryos. They have so far

recovered 15,000 unique genes and have

made a clone set freely available to the

research community worldwide for further

study. “This important tool will help analyze

changes in the expression of many genes during aging and/or during stress,” says Dr. David

Schlessinger, chief of the Laboratory of

Genetics. NIA scientists are working to release

an expanded unique set of 26,000 genes. 

THE GENETICS OF LONGEVITY 

AND DISEASE 

Much of our knowledge about genes and

aging comes from the study of laboratory animals, organisms, and animal and human cells.

While not a perfect imitation of people, animal models like fruit flies, mice, and nematodes (worms) and organisms like yeast,

have short life spans that allow scientists to

pursue two lines of inquiry — how genes

influence aging and how aging, in turn, may

affect genetic stability and the biochemistry

of cells and systems. 

Studies of Caenorhabditis elegans (C.

elegans), a genetically simple roundworm

subject to scientific scrutiny for several years,

and Drosophila melanogaster, a fruit fly,

have been especially productive. For example,

the C.elegans’ age-1

and daf-2 gene products

appear to play a role in

determining longevity.

The daf-2 gene was first

identified because it controls an alternative state

in the worm’s development, called dauer formation. This state occurs during a stress, such

as food scarcity or heat, when the worm

responds by going into hibernation. A protein

produced by the daf-2 gene moves the worm

past this non-aging, dauer state when the

stress is gone. Researchers have shown that

when the daf-2 gene is altered so that the

activity of the protein produced by the gene is

reduced, the life span of the normal, fertile

adult worm doubled. Mutations in some other

daf genes have resulted in an increase in the

worm’s lifespan three or four times beyond its

normal 2-week course. Similar results have

been found in other yeast and fruit fly genes.

In order to gain insights that may prove

valuable in the search for human longevity

and disease-related genes, it is important to

know if the genes found in animal models are

like those found in mammals, including

humans. The longevity genes found in C. 

elegans, for example, have striking similarities to genes found in fruit flies, mice, and

Drosophila melanogaster, a fruit fly

At the top is the mouse

embryo about two-thirds

of the way through its

development. Genes that

are active in the embryo

at this time are shown

as the colored spots on

the NIA 15K microarray.

AT ONE TIME OR ANOTHER, MOST OF US

HAVE FORMED SOME OPINION ABOUT WHAT

IT IS TO LOOK OR FEEL A CERTAIN AGE.

6 NATIONAL INSTITUTE ON AGING
THE BIOLOGY OF AGING 7

humans. Recent studies have shown that

some of these longevity genes appear to affect

the worm’s nutrient-sensing pathway. Scientists believe that a further look into the similarities between the protein produced by the

daf-2 gene and a human insulin receptor may

advance understanding of how human insulin

regulates metabolism and why this regulation

fails in diabetes, and may even affect life span.

Another way scientists look at genetic

influences on aging is to examine cases in

which people exhibit exceptional longevity,

either living to very advanced age or aging prematurely. In one study, NIA-supported scientists looked at 137 sets of brothers and sisters

90 years and older, with at least one sibling 98

and older, seeking to identify genes that may

be linked to their longevity. A preliminary

report from their genomic “scan” suggests that

somewhere among the hundreds of genes in a

region on chromosome 4 there could be a gene

or genes whose subtle modifications influence

aging and can give a person a better chance of

living well beyond the average life expectancy.

It may be, the researchers theorize, that some

genes associated with human longevity could

be involved in helping people avoid certain

age-associated diseases.

Studies of premature aging have identified

a defect in the WRN gene believed to be

responsible for Werner’s

syndrome (WS), a disease in which people at a

young chronological age

develop some characteristics associated with

aging, such as wrinkled

skin, gray hair, cataracts,

diabetes, heart disease,

and osteoporosis. People

with WS mostly die by

age 50. Because of the

apparent acceleration of

aging in WS, scientists at

NIA and at a number of

laboratories supported by

the Institute are delving

into its causes, hoping to

shed light on the disease

and the degenerative processes that occur

with normal aging. At NIA’s Laboratory of Molecular Gerontology, scientists are focusing in

on the high level of genetic instability in WS

cells in an attempt to understand the abnormal nature of biochemical processes that are

associated with this syndrome and develop

during aging. 

An NIA Laboratory of Genetics research

team is studying the condition of premature

ovarian failure (POF), in which a genetic

mutation appears to both produce eyelid

defects in newborns and trigger early onset of

menopause decades later affecting the ability

to bear children in women suffering with POF.

The condition is an example of a critical

process during aging that had been little

investigated. The laboratory recently isolated

a gene, FOXL2, required both for normal eyelid development and for formation of the full

complement of eggs in the ovaries before

birth. Continuing study of premature ovarian

failure could help tell us how genetic

processes during fetal development can

affect aging later on. “It’s becoming increasingly clear that early events in embryonic and

fetal life are important for what happens

later during aging,” says Dr. Schlessinger.

Having identified the gene and its purpose,

the next phase of research is to look for

underlying mechanisms that cause women

with the mutation to produce fewer eggs and

have an early menopause.

There may be other genetic differences

that affect aging but are not as specifically

damaging as mutations that cause conditions

...and at age 48. like POF. Scientific interest is increasing in

Werner’s syndrome

patient, age 14...

MUCH OF OUR KNOWLEDGE ABOUT GENES

AND AGING COMES FROM THE STUDY OF

LABORATORY ANIMALS, ORGANISMS, AND

ANIMAL AND HUMAN CELLS.
single nucleotide polymorphisms, or SNPs,

slight genetic differences in DNA that can be

widespread in populations. SNPs occur in DNA

in relatively high frequency in people, about

one per every thousand base pairs. The effect

of the differences may be slight, but over

many years, they could contribute to the

development of age-related declines and disease. An important goal of research is to identify these SNPs and determine which have a

significant impact on aging. 

How do the dozens, perhaps hundreds, of

disease and longevity-related genes in

humans exert their influence? One possibility

is genetic control over cell division. Most cells

have a finite life span; that is, after a certain

number of divisions, they enter a state where

they can no longer divide. Their ability to synthesize DNA is blocked and they fail to function appropriately. This “replicative senescence,” as it is called, may help explain some

aspects of the aging process. Several genes

have been identified that seem to control

senescence, some by triggering cell division

and others that counter, or “silence,” it. 

Research into what causes cells to mature

and to lose the capacity to reproduce promises to provide valuable insights about the

causes of disease and disability. Digging even

deeper into replicative senescence, for example, scientists have found cell division is

accompanied by a reduction in the length of

telomeres, the tail-like formations at the end

of chromosomes, which shorten each time a

cell divides. The telomeres protect the chromosomes, but can become so short that the

chromosomes they are attached to can no

longer replicate. One study found that mutant

mice which undergo excessive telomere

shortening in certain cells exhibit graying fur

and fur loss, increased vulnerability to skin

lesions and problems in wound healing. In

addition, these mice were smaller and had a

life span that was only 75 percent of normal.

ENVIRONMENTAL FACTORS AND AGING 

When a gene is expressed, it produces a protein, which may be an enzyme, an antibody, a

hormone, or one of tens of thousands of other

proteins essential to the body. Some of these

are believed to be linked to the aging process

and have sparked a growing body of research

on the molecular aspects of aging. Of particular interest is damage to cellular macromolecules — cell membranes, proteins, and DNA

— and the enzymes that prevent or repair

that damage. 

Prime culprits in this damage are oxygen

free radicals, highly reactive oxygen molecules

that are products of normal metabolism of the

mitochondria, the part of the cell that metabolizes sugars into energy. These free radicals

can readily enter into chemical combinations,

causing oxidative stress that can damage

macromolecules. One defense against free

radicals includes the body’s manufacture of

8 NATIONAL INSTITUTE ON AGING

OF PARTICULAR INTEREST IS DAMAGE TO 

CELLULAR MACROMOLECULES AND THE

ENZYMES THAT PREVENT OR REPAIR IT.
antioxidants, which can neutralize the oxygen

radicals, rendering them harmless. But studies

in animals have not yet demonstrated directly

that use of natural antioxidants, such as vitamin E, can improve health or extend life span. 

There may be other ways to combat

oxidative stress, and scientists are looking in

some new directions. To date, laboratories

have had mixed success in affecting the aging

of animals genetically altered to “overexpress” either superoxide dismutase (SOD), or

SOD and catalase, enzymes that reduce oxidative damage. One recent study in nematodes,

however, not only provides evidence that

oxidative stress is a major risk factor in the

rate of aging, but strongly suggests that aging

might be slowed and life span increased by a

specific drug intervention. In this experiment,

an artificial compound developed in the private sector, EUK-134, which mimics both SOD

and catalase activity, was shown to increase

the life span of nematodes by about 50 percent. EUK-134 also reversed premature aging

in a strain of the worm with elevated oxidative

damage. Perhaps this or similar compounds

eventually could be developed to lessen

oxidative stress in humans and delay or

reduce some age-related diseases. 

Of increasing interest is the effect of

blood sugar — glucose — on health. “I think

we are only just starting to learn the extent to

which glucose metabolism affects the health

and function of cells and tissues,” Dr. Warner

notes. Oxidative stress and cellular deterioration can be promoted by glucose in several

different ways. In one process, glucose molecules, in an activity called non-enzymatic glycosylation or glycation, can bind themselves

to proteins, and, after some molecular

rearrangement, cause the proteins to hook

together, or crosslink. Immune cells called

macrophages can combat glycation. But scientists are discovering that this process is

incomplete and that the crosslinked proteins,

known as advanced glycosylation end products, or AGEs, accumulate with age. Appearing to toughen or stiffen tissues, AGEs are

believed to be involved in several age-associated conditions such as atherosclerosis,

cataracts, and reduced kidney function. The

study of crosslinking is a particular focus of

research on diabetes as well, a disease in

which complications mimic physiologic

changes that can accompany advancing age. 

THE BIOLOGY OF AGING 9

NEW COMPOUNDS MAY BE DEVELOPED TO

LESSEN OXIDATIVE STRESS AND DELAY OR

REDUCE SOME AGE-RELATED DISEASES.
VITAL SYSTEMS AND ORGANS 

One way to directly focus on potential interventions against disease and disability is to

look at the biological changes with age in tissues, vital organs, or particular body systems.

This expanding area of study has uncovered a

number of clues about the state of our heart,

brain, kidneys, and other important systems

with age. An especially active area of research

is the musculoskeletal system — bone, cartilage, and muscle — as scientists look for ways

to prevent frailty caused by diseases such as

osteoporosis, osteoarthritis, or sarcopenia,

the wasting away of muscle with age. 

The biology of bone has been studied with

increasing intensity in recent years, revealing

possible new ways to treat and cure osteoporosis, an often crippling disease of bone

loss and breakage. Ever since the discovery in

the mid-1960s that bone is a dynamic tissue

that constantly remodels, research has concentrated on the dynamics of the bone

renewal process, particularly on the balance

and regulation of bone degradation by cells

called osteoclasts versus bone formation by

other cells known as osteoblasts. 

A major risk factor in osteoporosis is the

loss of estrogen production in women at

menopause and a consequent imbalance

between bone-building cells and bonedestroying cells. After several years of

research, one study team supported by NIA

recently described a new action of estrogen.

Instead of binding to estrogen receptors

inside cells, where genes are housed, the scientists found that estrogen can act more

quickly to attach itself to a receptor at the

outer cell membrane. This new pathway, discovered in a cell culture, is the one that estrogen uses to extend the life of bone-building

cells. The finding has implications for understanding the action of estrogen not only in

bone, but in other tissues, including the heart

and the brain. Further, it suggests that estrogen-mimicking drugs might be designed to

lessen bone-thinning problems by rescuing

bone-building cells from cell death.

Research on stem cells is another promising area of study for cell replacement or

repair of specific tissues. It is hoped that

these cells, which maintain the flexibility to

“differentiate” from multi-potent cells into

cells with specific functions, can be used in

degenerative diseases where loss of cells is

currently irreversible, such as musculoskeletal disorders, Alzheimer’s and Parkinson’s 

disease, stroke, heart attacks, immune system

dysfunction, and diabetes. Several studies

have suggested the potential for stem cell

replacement therapy. 

Recently, NIA-supported scientists examined cells from adult mouse bone marrow. In

one study, the mouse marrow cells, when

injected into the circulatory system of mice,

THE STUDY OF BIOLOGICAL CHANGES WITH

AGE IN TISSUES, ORGANS, AND 

SPECIFIC BODY SYSTEMS MAY LEAD TO NEW

INTERVENTIONS.

10
found their way into the brains of the mice

and within 1 to 6 months became neuronal

cells. A second study showed that adult

mouse bone marrow cells could also develop

into heart cells and vascular structures,

resulting in the substantial replacement of

damaged heart tissue within 2 weeks. 

A great deal of progress is being made in

discovering the secrets of our aging cells and

selves. But many scientists conducting

research in this area sound a note of caution,

as so-called “anti-aging” therapies are introduced into the marketplace. While some of

these products and approaches may be based

on sound theoretical or experimental concepts, many have not been tested adequately

in large numbers of people for their ability to

improve function and to measure potential

side effects. Scientists are seeking, but do not

yet have, despite considerable research, biomarkers, or measurements, of aging that

could gauge the rate of aging or predict

remaining years of life.

Concerned about possible growing use of

these therapies, the NIA developed public

information materials to outline what is known

and what is not yet known about some of the

more widely used hormones, vitamins, and

other supplements marketed as antidotes to

the effects of aging. NIA’s television public

service announcement on the subject, produced in 1999, garnered an Emmy award from

the National Academy of Television Arts and

Sciences, a first for a Federal Government

agency. Its consumer publication, Pills, Patches,

and Shots: Can Hormones Prevent Aging? 

is also widely distributed and may be obtained

from the NIA Information Center or viewed online. See resources at the end of this booklet.

Regeneration of the

infarcted heart in 

mice injected with

hematopoietic stem cells.

Arrows indicate newly

formed myocardium in

the infarcted region of

the ventricular wall (VM

is viable myocardium).

Another study showed

that adult mouse bone

marrow cells could

develop into neuronal

(brain) cells.

MANY SCIENTISTS SOUND A NOTE OF 

CAUTION AS SO-CALLED “ANTI-AGING” 

THERAPIES ARE INTRODUCED INTO THE 

MARKETPLACE.

THE BIOLOGY OF AGING 11
Reducing Disease &

Disability
The paramount goal of research on aging is

to “add life to years,” to use an expression

favored by gerontologists and other experts on

aging. Many of us will live far beyond the standard retirement marker of age 65, and we want

our advanced years to be as active and healthy

as they can be. Clinically-focused research at

NIA looks for specific, practical ways to reduce

disability and to promote independence by

studying the causes, prevention, and treatment

of health problems that occur as we age.

At one time, this interventionist view was

not well understood, says geriatrician Dr. Evan Hadley, NIA Associate

Director, Geriatrics Program. Dr.

Hadley came to the NIA in the late

1970s, just a few years after the Institute’s

founding in 1974. He was among a new generation of physicians specializing in aging

research and he recalls how disease and disability were widely thought to be inevitable

consequences of aging. “I remember that

many people were surprised by early studies

showing that strength in the very old, even in

people who were in their nineties, improved

dramatically after strength training exercises,” he notes. 

Attitudes are only now beginning to

change. “We still see, although perhaps less so,

the old stereotypes that aches and pains and

functional decline are ‘just aging’ and that nothing can be done about them. That’s just not so.

We now have powerful evidence that we can

intervene for the better,” says Dr. Hadley.

Chronic diseases and conditions like diabetes, cardiovascular disease, osteoporosis,

and arthritis are major causes of frailty and

disability in late life. Risks for disease and disability increase with age and can be made

worse by our own lifestyle choices or by other

behavioral and social factors. Scientists have

come to believe, that, with age, certain

changes in the body or the mind, such as hormonal or other shifts, could play a role in how

we function in later life. While not characterized as disease, these “previously unappreciated” changes, as one NIA scientist calls them,

can also affect cells or body systems in a way

that leads to frailty or disability. 

To investigate these diseases and ageassociated changes, the NIA works closely

with other parts of the National Institutes of

Health, such as the National Cancer Institute

(NCI); the National Heart, Lung, and Blood

Institute; and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Research primarily funded and conducted by

the NIA concentrates on the underlying

causes of age-related disability and developing therapies for maintaining function with

age. Cardiovascular disease, diabetes, and the

maintenance of bone health and muscle function are of particular interest

because of their impact on the daily

lives of older people.

NATIONAL INSTITUTE ON AGING

Reducing Disease &

Disability
REDUCING CARDIOVASCULAR DISEASE 

Cardiovascular disease (CVD) is the main

cause of disability and the leading cause of

death among people 65 and older. While we

know a great deal about CVD and its risk factors, new areas of research are beginning to

shed further light on the link between aging

and the development and course of CVD. 

Scientists at NIA are paying special attention to the relationship between vascular

(blood vessel) aging and cardiac function.

Studies by Dr. Edward Lakatta and investigators at NIA’s intramural Laboratory of Cardiovascular Science (LCS) show that aging is

accompanied by a thickening of the left ventricular muscular wall of the heart, affecting

certain heart functions. Examining the mechanisms behind these changes, Dr. Lakatta,

LCS Chief, and colleagues discovered that the

culprit is vascular stiffness, a condition that

occurs with age as flexible fibers in vascular

tissue are replaced with less elastic collagen

and calcium. This process heightens systolic

blood pressure and pulse pressure and is

associated with thickening of the interior

layer of the blood vessel wall. 

This arterial remodeling, once considered

a “normal” part of aging, is really like a subclinical disease, in Dr. Lakatta’s view, putting

people at increased risk for cardiovascular

disease with advancing age. In one recent epidemiological study, increased pulse pressure,

which is determined to a substantial degree

by large artery stiffness, was the best predictor of the risk of dying. “If vascular aging is a

risk factor for disease, then it is a target for

treatment and prevention,” says Dr. Lakatta.

“We are now turning our attention to ways to

slow vascular aging down.” 

Researchers at NIA and elsewhere are

testing a number of potential exercise and

drug interventions for reducing arterial stiffness, with some success. In one approach,

NIA and scientists at a private laboratory are

looking at the compound ALT-711, a novel

drug that breaks down vascular collagen

bonds in the body. It alters the properties of

the arterial wall by snipping bonds, or

crosslinks, created in the arteries when glucose attaches to collagen. By altering the

properties of the arterial wall, it is believed,

the compound makes it easier for the heart to

eject blood into the blood vessels. In studies

of rhesus monkeys, 6 weeks after receiving

the last treatment, all of the vessel walls

tested were more flexible, and the effect persisted for more than 4 months after final

administration of the drug. Blood flow

through the heart also increased, an improvement that held for 10 months after the last

treatment. Further research, including ongoing studies in people, is underway to confirm

or extend these findings. 

Other research in NIA’s cardiovascular sciences laboratory seeks new ways to prevent

14 NATIONAL INSTITUTE ON AGING

CLINICALLY-FOCUSED RESEARCH 

AT NIA LOOKS FOR SPECIFIC, PRACTICAL

WAYS TO REDUCE DISABILITY AND 

TO PROMOTE INDEPENDENCE.
A Focus on Independence: 

The Claude D. Pepper Centers 

Research at the Claude D. Pepper Older

Americans Independence Centers targets one fear people have most about

growing older—the decline of physical

function and loss of independence.

Created to organize and enhance

research on aging, the Pepper Centers,

as they are called, pursue a range of

studies on aging. They also have a special mission to bring scientists from all

disciplines into aging research and

train the next generation of investigators in the field.

The Centers honor the memory of

former Florida Senator and Congressman Pepper, whose legislative career

was devoted to improving the lives of

older Americans. The Pepper Centers

conduct studies in the basic biomedical sciences, such as biology and

genetics, as well as clinical and applied

research that directly improves the

lives of older people, and offer a unified structure in which scientists from

different disciplines can contribute to

each other’s research. Research from a

number of these Centers is cited

throughout this booklet.

In 2001, the NIA supported nine

Pepper Centers across the U.S., each

with a specific area of emphasis beyond

the basic role in research and training:

University of California at Los Angeles

(UCLA) — Advance the understanding

and practice of comprehensive geriatric

assessment and examine ways to

improve medical and nursing care for

nursing home residents.

Duke University Medical Center,

Durham, NC — Focus on improving the

physical, psychological, and social functioning of older adults disabled by acute

and chronic disease.

Harvard Medical School, Boston, MA

— Develop junior faculty geriatricians

into academic leaders, with a focus on

innovative, multidisciplinary research

and training in aging processes.

University of Maryland, Baltimore —

Emphasis on cardiovascular disease.

Study basic mechanisms and test aggressive approaches in diet, exercise, and

smoking cessation to improve function

with peripheral arterial disease.

Yale University Medical School, New

Haven, CT — Use of a “multi-factorial”

approach, looking at the combination of

factors affecting functional ability and

designing coordinated interventions to

address them. 

University of Texas Medical Branch,

Galveston — Focus on basic mechanisms in cell biology and muscle function, aimed at interventions to maintain

and improve muscle function.

Wake Forest University School of Medicine, Winston-Salem, NC — Use of

behavior-based approaches, such as

physical activity or nutrition, to hold off

declines in physical function from diseases such as knee osteoarthritis.

University of Michigan, Ann Arbor —

Foster collaboration and sponsor multidisciplinary research on cognitive and

physical function, and health and wellbeing of older people looking at both

basic mechanisms and interventions.

Develop innovative projects to translate

research findings into use and practice.

University of Kansas Medical Center,

Kansas City — Emphasis on intervention studies for improving function of

older people recovering from stroke,

integrating this research with study of

the underlying mechanisms of stroke

recovery.

LIFE IS LIKE RIDING A BICYCLE. 

YOU DON'T FALL OFF UNLESS YOU

STOP PEDDLING. — CLAUDE D. PEPPER

REDUCING DISEASE AND DISABILITY 15
coronary artery restenosis. Restenosis is a

gradual narrowing of the arteries that occurs

as a consequence of vascular healing that follows angioplasty, the surgical procedure used

to relieve arterial blockages by widening the

vessels. Restenosis is aggravated by the

implanting of stents, in which tiny metal scaffolds are placed inside the artery at the injury

site to hold the vessel open. Restenosis usually occurs within 6 months of angioplasty and

results from the migration of cells from the

middle of the arterial wall into the inner layer

of the artery, where they multiply and block

normal blood flow. 

Recognizing that cell division is crucial to

the development of restenosis, scientists at

the NIA and in laboratories elsewhere have

begun to test the anti-cancer drug paclitaxel

as a means of preventing the tissue growth

that leads to vessel narrowing. Studies in laboratory animals demonstrate that coronary

stents coated with paclitaxel can significantly

delay restenosis, at lower doses and with less

toxicity than the higher, anti-cancer doses of

the drug. Clinical studies in Europe testing

the approach developed in the NIA laboratory

have been encouraging, and studies in the

U.S. by NIA and extramural partners will begin

soon. In addition, further experiments on the

cellular and molecular events in restenosis

are being conducted in animals as comparative testing of paclitaxel and radiation therapy

for preventing restenosis gets underway. 

As exciting new approaches like these are

developed, important research also is underway to assess how medical practice and the

public use new and even standard treatments.

Unfortunately, prescription therapies on

pharmacists’ shelves today are not always

being used effectively, as some studies on

CVD demonstrate. Only an estimated 25 percent of Americans age 60 and older have their

blood pressure under control, despite considerable evidence that high blood pressure can

lead to heart attack, stroke, heart failure, and

other serious health consequences. 

In one study, a higher blood pressure level

(defined as greater than 140/90mmHg), in

people already being treated, was directly

related to an increased risk of heart attack,

leading the study’s scientists to suggest that

developing new strategies to improve blood

pressure control might prevent an estimated

15 percent of heart attacks among older 

people with hypertension. An investigation

16 NATIONAL INSTITUTE ON AGING

NEW AREAS OF RESEARCH ARE BEGINNING TO

SHED FURTHER LIGHT ON THE LINK BETWEEN

AGING AND THE DEVELOPMENT AND COURSE

OF CARDIOVASCULAR DISEASE.

Paclitaxel-coated stent

reduces restenosis following

balloon angioplasty.
looking at use of warfarin, a drug used to

inhibit blood clotting, showed it, too, was

vastly under-prescribed for older people. The

medication is known to dramatically reduce

the risk of stroke in patients with the heart

rhythm abnormality atrial fibrillation (AF).

Yet, about 38 percent of those with AF and at

least one other additional stroke risk factor,

described by researchers as “ideal” candidates for warfarin, did not receive the drug

when it would have been appropriate. 

ENHANCING MUSCULOSKELETAL

FUNCTION 

It is a portrait that many of us have of aging —

a stooped posture and frail appearance, slow

gait, or more general problems with physical

function, such as difficulty getting up from a

chair. In recent years, dramatic reductions in

the rate of disability have changed this picture

for the better. Despite such progress, however,

age-associated changes in bone and muscle

and diseases common to advancing age still

take a significant toll. Osteoporosis, osteoarthritis, and age-related loss of muscle mass

make it difficult for older people to get around

and, in many cases, to remain independent.

A number of elements make up the effort

to combat what has been called “physical dysfunction.” As in other aspects of biomedical

research, scientists are looking beyond traditional study methods, trying to come up with

better and more reliable ways to conduct

research. Studies of bone and muscle can

involve painful and invasive muscle biopsies,

for example, and scientists are looking at 

better technology and more patient-friendly

ways to measure, where possible, what happens to muscle with age. One approach

involves use of new and sensitive imaging

methods to look at fatty infiltration of skeletal

muscle that occurs with age, a contributor to

metabolic problems and muscle dysfunction.

Scientists are now successfully testing magnetic resonance spectroscopy (MRS) and computerized tomography (CT) as a way to

characterize fatty infiltration of skeletal muscle. The advance is welcome both for the comfort of study participants and for improving

measurement in this area. 

Studies in recent years have shown that

changes in bone composition and quality, a

loss of supporting and protective skeletal

muscle, or a combination of the two can lead

to falls, weakness, frailty, and ultimately fractures. A number of studies, many by

researchers at NIA-supported Claude D. Pepper Older Americans Independence Centers,

examine strategies, from exercise interventions to hormone therapies, for maintaining

and improving physical function with age. For

example, there has been some controversy

about whether older people with osteoarthritis of the knee should increase or decrease

their level of activity to keep frailty at bay.

Research at one Pepper Center demonstrates

that exercise can reduce risk for disability significantly. Among people 60 and older with

REDUCING DISEASE AND DISABILITY 17

IT IS A PORTRAIT MANY OF US HAVE OF

AGING — A STOOPED POSTURE AND FRAIL

APPEARANCE, SLOW GAIT, OR DIFFICULTY 

IN GETTING UP FROM A CHAIR.
osteoarthritis, an 18-month strength training

program reduced the risk of disability by 

40 percent and an aerobic exercise program

cut the risk by 47 percent. 

New approaches may also be in order on

hormones and osteoporosis. A study by investigators at another Pepper Center on estrogen

replacement therapy (ERT) for osteoporosis

has discovered that low-dose estrogen

reduces bone breakdown in older women.

Women age 65 and older took three different

dosages of estrogen, and researchers measured changes in their bone over 6 months.

Low-dose estrogen — at less than half of the

dosage commonly used in ERT — surprisingly

reduced bone breakdown as effectively as the

highest dose, the researchers found. Importantly, side effects were significantly less frequent. The study suggests that low-dose

estrogen could offer women the benefits of

less bone breakdown while avoiding problematic side effects.

MANAGING DIABETES 

Type 2 diabetes mellitus, the most common

form of the disease, starts to develop in adults

over age 40. It is caused by inability of beta

cells in the pancreas to compensate for

increasing insulin demands, resulting in

raised blood sugar levels. A new generation 

of diabetes treatments, compounds that act

on the pancreatic beta cells to secrete and

produce more insulin and prevent the progressive rise in blood glucose, is under intensive study. Scientists at NIA’s Laboratory of

Clinical Investigation, with researchers in the

private sector, have turned their attention to

a substance called exendin-4, a compound

derived from the saliva of the Gila monster

lizard. It has many of the same properties of

GLP-1, a peptide of the gut that has already

been shown to stimulate beta cells to produce

more insulin. The biologic activity of GLP-1 is

short, however, and its effects quickly wear

off. Tests in rats and mice show exendin-4 to

be long-lived and more potent. Preliminary

studies in small numbers of people with and

without diabetes have demonstrated that

exendin-4 can induce insulin secretion and

normalize blood sugar. In the near future, an

exendin-like drug might possibly become an

effective treatment for type 2 diabetes. 

Scientists are also looking at new ways to

possibly intervene against diabetes before it

NATIONAL INSTITUTE ON AGING

Normal bone (left); 

Osteoporotic bone (right).

Reproduced from J Bone Miner Res 1986;

1:16-21 with permision of the American

Society for Bone and Mineral Research.

A NEW GENERATION OF DIABETES 

TREATMENTS IS UNDER INTENSIVE STUDY.
develops. One focus is insulin resistance, a

metabolic condition thought to precede the

development of type 2 disease in older adults.

In insulin resistance, levels of insulin and of

blood glucose are abnormally high, although

not quite meeting the standards of diagnosis

for diabetes. Obesity and sedentary lifestyle

are the most serious risk factors for insulin

resistance and researchers are now zeroing in

on the possibility that changes in fat metabolism, particularly elevated levels of free fatty

acids as the body breaks down fat, may interfere with normal glucose metabolism and contribute to insulin resistance. Studies of certain

drugs and physical activity are promising in

altering fat metabolism and interfering with

the development of insulin resistance. These

studies suggest that correcting age-related

changes in fat metabolism may be important

for proper treatment of older diabetics. 

TREATING CANCER

Cancer is the second leading cause of death 

in older people, yet some population-based data

demonstrate a systematic bias against older

patients resulting in their failure to receive

potentially life-extending therapy. For example,

in a recent study, half of people over age 65 with

node-positive colon cancer were not treated

with 5-fluorouracil-based adjuvant therapy

despite the fact that such therapy reduces cancer mortality by more than one-third. 

Older women with breast cancer may also

find that their age has an impact on their cancer trajectory, prognosis, and treatment. NIA

researchers, in conjunction with the NCI,

recently concluded an analysis indicating that

older women who had other health problems

when they were first diagnosed with breast

tumors received less aggressive cancer treatment and pretreatment assessments than

women who were younger and healthier. NIA

and NCI are collaborating on a variety of

research initiatives to expand research on the

major cancers common to seniors. Older people are entitled to receive the benefits of therapeutic advances and should actively seek

advice from more than one physician in making

critical decisions.

THE FUTURE OF CLINICALLY-FOCUSED

RESEARCH

These disease and process-specific studies

are not the only way that NIA addresses issues

of aging and health. Research can only be as

successful as the talent and dedication of scientists engaged in such studies. An important

mission of the Institute is development of a

corps of scientists interested in and specially

trained to conduct studies of aging and agerelated issues. NIA actively sponsors fellowship and training programs for junior and

senior scientists at its laboratories in Baltimore, MD, and in research facilities at universities and other institutions across the U.S.

One major effort was the establishment a

decade ago and continued support for the

Claude D. Pepper Older Americans Independence Centers. 

REDUCING DISEASE AND DISABILITY

AN IMPORTANT MISSION OF NIA IS THE

DEVELOPMENT OF A CORPS OF SCIENTISTS

INTERESTED IN AND TRAINED TO STUDY

AGING.
Alzheimer’s Disease

& Normal Aging

Alzheimer’s Disease

& Normal Aging

The

Aging 

Mind
Dr. Marcelle Morrison-Bogorad vividly

remembers her first encounter with

the human side of Alzheimer’s disease (AD), 

the devastating deterioration of the brain

that robs its victims of memory and, ultimately, identity. Dr. Morrison-Bogorad had

trained in molecular biology, but soon found

herself focusing on study of the development

of the brain and, later, on brain aging and AD.

Her work on AD brought her in contact with

representatives from the local and national

Alzheimer’s Association,

where Dr. Morrison-Bogorad advised the groups on

technical issues and

helped the organization in

explaining scientific research to the families

and friends of AD patients and to the public. 

Leaving the shelter of the laboratory to

meet her first AD patient was a shock, Dr. Morrison-Bogorad recalls. “I was thunderstruck.

Here was this great, hulking man, and his wife

had to talk to him

and help him as if he

were an infant. The

blank look in his

eyes was the most

memorable, and disturbing.” Her Scottish accent thickens

and the look in her own eyes intensifies: “You

only have to meet and talk with AD patients and

their families to understand how much we need

to stop it.” 

Today, Dr. Morrison-Bogorad is NIA

Associate Director, Neuroscience and Neuropsychology of Aging Program, where she and

her colleagues in the neurosciences program

oversee hundreds of grants in support of universities and other institutions studying both

the diseased and the normal aging mind. The

program works in concert with neuroscience

researchers at the NIA’s in-house Intramural

Research Program. In that program, led by

Dr. Mark Mattson at the Laboratory of Neurosciences in Baltimore, MD, and Dr. John Hardy

at the Laboratory of Neurogenetics in

Bethesda, MD, scientists are tackling a number of innovative approaches to AD and neurodegenerative diseases. 

In addition, NIA collaborates with other

parts of the National Institutes of Health

involved in neurological research, including

the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Mental Health (NIMH), and the

National Institute of Nursing Research (NINR).

These Federal activities provide a base for and

stimulate research by the private sector as

well, in which groups such as the Alzheimer’s

Association, and pharmaceutical, biotechnology, and other companies are also active in the

search for effective treatments for AD.

There is an increasing urgency to these

efforts. It is estimated that up to 4 million

NATIONAL INSTITUTE ON AGING

ALZHEIMER’S DISEASE DEVELOPS AS A RESULT

OF A COMPLEX CASCADE OF EVENTS.

Alzheimer’s Disease

& Normal Aging

The

Aging 

Mind
people currently may have AD. And the

prevalence of the disease — the number of

people with AD at any one time — doubles

every 5 years beyond age 65. It is expected

that the number of people with AD will

increase with the rapid growth in the older

population. The cost to society of caring 

for AD patients is believed to be as much as

$100 billion per year in direct and indirect

costs. The human toll on AD patients and the

informal network of family and friends in

charge of their care is inestimable. 

For some time, scientists have understood that AD develops as a result of a complex cascade of events taking place over a

period of time inside the brain and influenced

by both genetic and non-genetic factors.

Today’s research digs deeper into these

events, to determine their sequence and pinpoint the various risk factors that may play a

role. There is a new focus, too, on the study of

normal changes in the brain and in cognitive

function with age, which may help to further

differentiate between the simple forgetfulness that we associate with aging and more

serious diseases like AD. The pace and

progress of research against AD have quickened in the past couple of years. “I believe we

are gaining ground, but a lot more needs to be

done,” says Dr. Morrison-Bogorad.

Neuroscience research at the NIA is organized into broad and overlapping areas. The

focus on AD looks at causes and risk factors,

diagnosis, treatment, and caregiving. Expanded

efforts to understand healthy brain aging also

could provide insights for maintaining cognitive

function and protecting against dementia. 

ALZHEIMER’S DISEASE CAUSES 

AND RISK FACTORS 

New understanding from the study of causes

and risk factors is beginning to draw the

roadmap for how we might prevent AD or at

least delay its onset. Basic work is expanding

our knowledge of AD genetics. There have

been major breakthroughs in identifying

genetic mutations responsible for early onset

AD and genetic influences that may be risk

factors for late onset AD. Mutations of genes

on three separate chromosomes that can

cause early onset AD have been discovered

and scientists are on the trail of additional

genetic risk factors for late onset forms of the

disease beyond the known risk factor gene

APOE ∑4. New technologies will allow scientists to home in on more genes more quickly

to learn even more about the molecular

processes underlying the disease. This

research may lead one day to treatment

strategies tailored to an individual’s unique

genetic profile. 

22 NATIONAL INSTITUTE ON AGING

THE STUDY OF CAUSES AND RISK FACTORS 

IS BEGINNING TO DRAW A ROADMAP FOR

HOW WE MIGHT PREVENT ALZHEIMER’S 

DISEASE OR AT LEAST DELAY ITS ONSET.
Amyloid plaques and neurofibrillary tangles are the hallmarks of the disease in the

brains of AD patients. New insights into the

etiology of the disease explain their formation

and role. The knowledge from early studies

that a protein, the amyloid precursor protein,

is mutated in some early onset AD has led to a

research focus on amyloid. Recently, scientists

zeroed in on the identity of enzymes called

secretases, which it is now believed “clip” the

amyloid precursor protein to produce a beta

amyloid peptide that forms the plaques. Supported by both the public and private sector,

this research is leading to development of a

new generation of secretase-inhibiting drugs,

some of which are now being tested. 

An intensified area of study looks at tau, 

a protein that forms the tangles involved in

AD. A new “transgenic” mouse with human tau

mutations that cause another form of dementia may help scientists to understand better

why tangles form and the role they play in 

the death of neurons (brain cells) and the

development of dementia. One group of

researchers has taken the mouse model a step

further, engineering one with both plaques

and tangles in brain regions that are characteristic of human AD, a breakthrough likely to

yield important clues about the relationship

between amyloid and tau.

Several factors are suspected to put us at

risk of AD or protect against it. Aging is the

major risk factor, followed by being a blood

relative of someone with AD. Head injury is

also linked with increased risk. What else in

our health and environment, including factors

that we can possibly control, can affect the

development and course of AD? Under current study are the role of diet, education, and

exercise and physical activity, among a variety of potential influences. Studies in groups

of people and in animals, for example, have

suggested a few ways in which plaque development might be influenced. 

One study in mice looked at the relationship between cholesterol and levels in the

brain of the beta amyloid peptide, known to

predispose people to the formation of amyloid

plaques. Mice were fed both high and low

THE AGING MIND

MANY OF US HAVE WONDERED WHETHER

SIGNS OF FORGETFULNESS ARE NORMAL 

OR THE START OF A MORE SERIOUS MEMORY

OR COGNITIVE PROBLEM.
cholesterol diets for 7 weeks. At the end of

the study, the mice on high cholesterol diets

had more cholesterol in their blood and

brains, and beta amyloid peptide levels and

plaques were also increased. This study is the

first demonstration in a transgenic mouse

that high blood cholesterol levels markedly

increased amyloid “burden” in the brain. 

In people, epidemiological research on the

possible cholesterol-AD connection has

shown that those taking cholesterol-lowering

drugs called statins appear to have a lower

risk of AD than those untreated. These studies are sparking increased interest in the role

that blood lipids such as cholesterol might

play in AD and are turning researchers’ attention to the possibility that cholesterol-lowering drugs could reduce the risk for dementia.

Experiments by Dr. Mattson and scientists at NIA’s Laboratory of Neurosciences

provide the first evidence in laboratory animals that calorie restriction can increase the

resistance of neurons to stresses associated

with disease and aging. How calorie restriction produces these effects is yet unknown,

but recent findings suggest that a low calorie

diet stimulates the production of neurotrophic factors, proteins that promote the

survival and growth of neurons. “Eventually,

we may find a way to mimic the benefits of

caloric restriction to reduce neuronal damage

and have an effect on neurodegenerative disorders in humans,” says Dr. Mattson.

The neurosciences laboratory also is 

focusing on neural stem cells, a type of cell

that can divide repeatedly and then form new

neurons. Such stem cells are present in the

brains of adult rodents and humans, and it is

believed that they provide a cellular “reservoir,” as researchers describe it, that can be

tapped to replace lost or damaged neurons.

An exciting and rapidly advancing area of

research, studies of neural stem cells suggest

that they can be mobilized by calorie restriction. NIA-funded researchers have also found

in mice that “intellectual activity” may stimulate stem cells to produce more neurons, in

experiments comparing mice in a normal laboratory environment with those in an

enriched environment of toys and other

objects. These studies, notes Dr. Mattson,

suggest that the production of new neurons

might be modified by diet or activities that

stimulate the brain intellectually. 

24 NATIONAL INSTITUTE ON AGING

An enriched environment

stimulates stem cells in

the brain to produce

more neurons. (Control

sample, left, and enriched

sample, right.)

RESEARCHERS BELIEVE THAT NEURAL STEM

CELLS PROVIDE A CELLULAR “RESERVOIR”

THAT CAN BE TAPPED TO REPLACE LOST 

OR DAMAGED NEURONS.
THE AGING MIND 25

DIAGNOSING ALZHEIMER’S DISEASE

At one time or another, many of us have wondered—for ourselves or a loved one—whether

signs of forgetfulness are normal or the start of

a more serious memory or cognitive problem.

One way scientists are tackling this question is

by studying the difference between normal

cognitive aging and early signs of AD. This particularly active area of research involves the

imaging of brain structure and function and

testing for a variety of cognitive abilities in

order to identify as early as possible people at

highest risk for AD. These diagnostic tools

could be used to help clinicians and patients

evaluate symptoms, and they will be useful for

determining who should participate in clinical

trials. Down the road, as therapies are developed and we are better able to intervene early

in the disease process, early diagnosis will be

critical for targeting specific treatments to

people most at risk. 

Scientists are especially interested in trying to identify people who might have Mild

Cognitive Impairment (MCI). In MCI, people

have demonstrable memory impairment but do

not meet the established criteria for a diagnosis of AD. Eighty percent of people diagnosed

with MCI in one study developed AD within 

8 years. Imaging studies of people with MCI

found that the smaller the hippocampus (a

particular brain region associated with learning

and memory) at the beginning of the study and

the more rapidly the hippocampus shrinks

with age, the more likely people were to

develop AD within a few years when compared

with people of similar age and health status. 

To expand and expedite the search

for causes and for treatments of

AD, the NIA maintains and supports a nationwide infrastructure

for research and assistance. This

includes:

Alzheimer’s Disease Centers

(ADCs). Located at major medical

institutions around the country, the

29 ADCs clinically evaluate and conduct research of AD patients and

their families. Specifically, the Centers systematically collect and analyze longitudinal data on people

with and without dementia; work to

translate research advances into

clinical practice; educate and train

professionals in research, evaluation, and treatment of AD; and participate in clinical trials. Satellite

centers strengthen the network,

many recruiting minority participants to the Centers program. 

The National Alzheimer’s

Coordinating Center (NACC). The

center was established to collect

and begin to standardize data collection from all the ADCs. The

“strength in numbers” provided by

this endeavor will enable researchers to conduct studies that would

not be possible with the smaller

number of participants in individual centers. The data will allow scientists to characterize earlier,

preclinical stages of the disease

and rarer forms of AD as well as

possible genetic and ethnic differences. Currently, the NACC holds

data from approximately 40,000

research participants evaluated at

the ADCs since 1984.

Alzheimer’s Disease Cooperative Study (ADCS). This consortium of some 31 academic medical

centers, including most of the

ADCs, conducts cooperative clinical trials on drugs to manage and

treat the cognitive and behavioral

symptoms of AD. It is designed to

help speed up the movement of

drug testing from epidemiological

and laboratory research to the

clinic, examining both currently

available compounds and newly

designed drugs for AD. 

Drug Discovery Initiatives. NIA

employs a number of ways to encourage the development and testing of new compounds to manage or

prevent AD. The Institute funds

small as well as regular research

grants, small business innovation

research grants, small business

technology transfer grants, and

contracts in this effort. 

National Cell Repository. This is

a growing repository of blood samples collected from AD patients and

their families, an effort that facilitates the study of genetic defects

associated with the disease. In addition, all of the ADCs maintain their

own brain banks and banks of biological samples and have developed

an extensive network of tissue sharing with other investigators.

Alzheimer’s Disease Education

and Referral Center (ADEAR). This

information center is a central

source for information on all aspects of AD. Information on how to

contact ADEAR is at the end of this

booklet.

A Framework for Finding Answers 
New studies also suggest that it may be

important to try to identify people at risk of

AD, even before MCI develops. This work indicates that older people with MCI already have

dramatic decreases in the number of neurons

and a reduction in the volume of part of the

brain’s entorhinal cortex, which plays a crucial role in memory processing and which is

one of the areas first affected in AD. These

brain changes were associated with very early

cognitive changes and suggest that damage to

the brain in AD may start to occur long before

the disease is diagnosed. 

TREATING ALZHEIMER’S DISEASE

A decade ago, just a handful of medications

for AD were being tested. Today, human clinical trials involve dozens of compounds. Under

scrutiny are such well-known drugs as nonsteroidal anti-inflammatory drugs (NSAIDS)

for their possible effectiveness against cognitive decline and AD and wholly new molecules

designed to interrupt underlying mechanisms

of the disease. These studies target three

main treatment goals: prevent AD altogether

or slow its development; maintain cognitive

function in the short-term; and manage the

difficult behavioral problems, such as agitation, aggression, wandering, and sleep disorders, associated with the disease. 

In 2001, the NIA supported some 21 pilot

and full-scale clinical trials for AD. Some of

these studies are prevention trials to see if a

particular treatment slows or prevents the

onset of cognitive decline or diagnosed AD.

Currently available compounds being tested

include NSAIDs and aspirin, antioxidants such

as vitamin E, combined folate/B6/B12 supplementation, and ginkgo biloba, which is being

tested in a trial supported mainly by the NIH’s

National Center for Complementary and

Alternative Medicine. In addition, estrogen

replacement therapy is being evaluated to see

if it might prevent AD in women with a family

history of the disease. 

As a result of greater understanding of

the genetic, molecular, and cellular factors

involved in AD, the design and testing of new

therapeutic approaches is gaining momentum

as well. Secretase-inhibiting drugs are a focus

in the private sector and both public and privately funded researchers have stepped up

efforts to further study and test a new vaccine

against AD, which may protect against the formation of amyloid plaques altogether. The

NIA has issued a request for new research

applications to conduct further vaccinerelated basic research. These studies, in animal models, should help to further understand

the mechanisms and long-term effects of vaccines against AD. One pharmaceutical company is in the very early stages of testing a

vaccine in humans. 

26 NATIONAL INSTITUTE ON AGING

A DECADE AGO, JUST A HANDFUL OF 

MEDICATIONS FOR AD WERE BEING TESTED.

TODAY, HUMAN CLINICAL TRIALS INVOLVE 

DOZENS OF COMPOUNDS.
CARING FOR ALZHEIMER’S DISEASE

PATIENTS AND FAMILIES

Beyond the patient, AD takes a considerable

toll on families, caregivers, and friends. The

memory loss and altered emotions and behaviors associated with the disease are an almost

impossible burden, posing an enormous physical and emotional challenge for caregivers. One

recent survey indicates that caring for someone with dementia, compared with attending

to someone with other types of illnesses,

involves significantly more time spent on caregiving tasks, greater employment complications, caregiver strain, mental and physical

health problems (including lowered resistance

to disease) and family conflict, as well as less

time for leisure and other family members. 

Research on caregiving and long-term care

examines ways to alleviate or prevent some of

these problems. The effectiveness of support

groups, behavioral skills training programs,

family-based interventions, computer-based

information and communications services is

now being tested. Data are now being reviewed

from a number of sites in the NIA- and NINRsupported REACH (Resources to Enhance

Family Caregiver Health) initiative, which

should provide important clues about what

works—and what doesn’t—to support families

of patients with AD. Studies so far suggest that

information and problem solving needs of

caregivers change with time as the disease progresses and issues change. “The study of caregiving, with its mix of physical, emotional, and

social and cultural factors, is an especially challenging one for research,” notes Dr. MorrisonBogorad. The Institute works closely with the

Alzheimer’s Association and other groups to

share research findings on caregiving and

other aspects of AD and aging.

27

THE EMOTIONS AND BEHAVIORS ASSOCIATED

WITH ALZHEIMER’S DISEASE POSE AN 

ENORMOUS PHYSICAL AND EMOTIONAL

CHALLENGE FOR CAREGIVERS.
NORMAL AGING OF THE BRAIN

Scientists are also intensifying their focus on

normal aging of the brain. Research to date

indicates that overall structural integrity, in

many regions, appears largely to be preserved

as we grow older. Contrary to what was once

thought, there is no general neuron loss with

age and there are parts of the brain, such as

the hippocampus, where new neurons are

formed well into old age. But there is increasing evidence that cellular and molecular

changes take place in the brain over time.

And many changes in brain-related functions

have been measured in older adults, such as

non-dementia memory loss and cognitive

declines; “tip-of-the-tongue” problems; impairments in vision, hearing, and taste; and changes

in sleep rhythms and sleep quality. 

The risk for cognitive impairment, for

example, is known to increase with age. Complex cognitive behaviors of attention, language, learning, and memory become

vulnerable to insults. This can result in

declines in performance of everyday tasks

such as driving or managing finances, causing

frustration and concern among older people

and often leading to isolation from loved ones

and society. At their worst, problems at first

viewed as normal changes with age can

become severe enough to be classified as MCI

and, ultimately, as AD.

To understand these changes, scientists

are pursuing several avenues of study. Studies

of learning, for example, reveal that older animals and people can learn new information

well, but acquire it more slowly than younger

adults. In some studies, old rabbits need

many more tries to learn a new response than

their younger counterparts. Analysis of brain

cells from these animals shows that while the

nerve cells from the older animals do still

function, the cells actually have to rest longer

between episodes of communication with one

another. Further study indicates that this

change is due to an impaired ability of the

older nerve cells to control how much calcium

enters the cell. Age-related problems in learning improve when the excess entry of calcium

into the cell is blocked.

Healthy older people can have attention

deficits as well, particularly when they have to

divide their attention among two or more

things. In one study of visual attention and

reaction time, it took older adults more time

to focus on a particular item, such as a specific letter, than younger people. The older

adults were less able to ignore competing but

irrelevant information, such as other letters in

their field of view. 

28 NATIONAL INSTITUTE ON AGING

STUDIES OF LEARNING REVEAL THAT 

OLDER ANIMALS AND PEOPLE CAN LEARN

NEW INFORMATION WELL, BUT ACQUIRE IT

MORE SLOWLY THAN YOUNGER ADULTS.
The use of neuroimaging technologies is

an exciting development in research on brain

changes and function. It allows scientists to

look deep inside the brain during performance

of cognitive tasks. In several studies, older

adults show activation of more brain regions in

the frontal cortex of the brain than younger

adults during performance of a short-term

memory task. The different pattern of brain

activity between older and younger adults

doing the same task may have a number of

explanations, researchers say. Perhaps the

older brain needs to “recruit” more areas in

order to successfully accomplish a cognitive

task. It also may be that the older brain

engages in different strategies to do a task,

strategies that stem from years of experience.

Scientists believe that use of imaging in these

types of psychological and neurological

research will reveal much more about the

direct relationship between brain changes and

our ability to perform cognitive tasks. Such

research will lead to development of effective

ways to help maintain brain function.

Results up to now from such human and

animal research have been promising, but

much more needs to be discovered. Toward

that end, the Institute is part of a new

“Healthy Brain Project” initiative, bringing

together NIA, NINDS, and NIMH to learn more

about the cognitive and emotional health of

older adults. Researchers hope that the effort

can accelerate the pace of scientific advances

in the study of cognition and emotion and

their effects on well-being as we age.

INFORMATION ON ALZHEIMER’S

DISEASE AND BRAIN AGING 

For the latest information on AD, the NIA

operates the Alzheimer’s Disease Education 

& Referral (ADEAR) Center, a service devoted

to providing information on memory and

dementia, specifically AD. The Center, mandated by Congress, serves health professionals, patients and their families, the media,

and the public. It provides general publications on AD and annually prepares a Progress

Report on Alzheimer’s Disease, describing

research efforts on dementia and AD supported and conducted across the National

Institutes of Health. ADEAR also offers referrals to NIA-funded Alzheimer’s Disease Centers across the U.S. that specialize in research

and patient diagnosis. It can conduct custom

searches from the Combined Health Information Database (CHID) and provide training

and resource materials for physicians, nurses,

and other health care workers. Contact information for the ADEAR Center and the NIA’s

general aging Information Center appears at

the end of this booklet.

THE AGING MIND 29

THE OVERALL STRUCTURAL INTEGRITY OF THE

BRAIN APPEARS TO BE PRESERVED, BUT THERE

IS EVIDENCE THAT CELLULAR AND MOLECULAR

CHANGES TAKE PLACE OVER TIME.
Behavioral 

& Social

Aspects of Aging
Personal behavior and lifestyle choices —

whether or not we smoke, or exercise, or

take prescribed medicines, even our individual

personalities — make a major difference in

health and well-being in later life. Society’s decisions about such things as access to health care

or pension and retirement policy, also significantly impact how we age. As the power of

these influences, along with the effects of education and wealth, are more evident, behavioral

and social research has become an energized

area of study. From large national surveys of

population trends to research delving into how

individuals approach their own aging, behavioral and social research provides intriguing and

useful insights into ourselves and the world

around us. Armed with such knowledge, scientists seek to inform social policy and develop

interventions for improved health. 

The interplay among health, behavior, and

socioeconomic factors is a particular focus of

NIA’s nationwide Health and Retirement Study

(HRS). In the mid-1980s, Dr. Richard Suzman,

now NIA Associate Director, Behavioral and

Social Research Program, joined by a small

group of other leading

experts in health and economics, began to realize

that research on retirement and on health essentially treated these two

aspects of aging as if they

had nothing to do with each other. Dr. Suzman

and his colleagues thought of retirement as a

process well beyond simply collecting a pension or Social Security. “It was very clear to us

that more needed to be known about the

dynamics preceding and during retirement,

especially the interrelationships of health, disability, economics, work, and family,” he says.

After much discussion and careful design,

in 1992, the HRS, one of the largest and most

innovative surveys ever conducted in the U.S.

on health and retirement, began interviewing

participants. Today, the study is conducted by

the University of Michigan’s Institute for

Social Research, which every 2 years surveys

about 20,000 Americans age 51 and older

about work, health status, disability, pensions

and retirement, family relationships, community activities, and other selected aspects of

aging.

Scientists are now mining the rich fields

of data provided by the HRS. The study has

helped define the relationship between health

and wealth, suggesting that, throughout life,

the dynamic appears to cut both ways —

wealth influences health, but poor health also

affects the accumulation or loss of wealth in

later years. Surprisingly, the HRS findings

indicate that a significant percentage of older

people support their adult children financially

and in other ways, such as caring for grandchildren, challenging the common view of a

dependent elderly population. The HRS also

NATIONAL INSTITUTE ON AGING

Behavioral 

& Social

Aspects of Aging
hints that employers and pension planners

might want to rethink the transition into

retirement: about half of people nearing

retirement say they would prefer to phase out

of the workplace, rather than to quit “cold

turkey,” as is often the case today. 

Over the next few years, the HRS is

expected to address a number of significant

questions. How well, for instance, are the socalled “baby boomers” prepared for retirement? How will changes in Social Security,

Medicare, and Medicaid affect older Americans and their families? What impact will the

high rate of divorce in recent years have on

pensions and, equally important, on caregiving in later life? “I believe the HRS can play a

central role in telling the story of the aging

baby boom,” says Dr. Suzman. He points out

that some other developed countries are now

using the HRS as a model for studies of their

aging populations as well.

The NIA plays a leading role in funding a

variety of major demographic studies and in

assuring that national surveys related to

aging, health, and retirement are technically

sound and useful to the public and policymakers. In 1994, NIA established its Centers

on the Demography of Aging at research institutions around the country to improve the

quality and relevance of demographic

research on health, economics, and population aging. In 2001, NIA supported 11 such

centers, each characterized by its own focus

or specialization. 

In the mid-1980’s, NIA helped found the

Federal Interagency Forum on Aging-Related

Statistics. The Forum works closely with the

Bureau of the Census, the National Center for

Health Statistics, and other Federal statistical

agencies on the quality, collection, and confidentiality of data on older people from government-supported studies. 

In July 2000, the Forum published its first

status report on aging in America, Older

Americans 2000: Key Indicators of WellBeing. Based on a review of more than a

dozen national data sets, it found that while

there is good news about gains in health and

wealth among older people, a large proportion

of the older population, including many racial

and ethnic minorities, still face disability,

chronic health problems, and economic

stress. 

NIA’s support of behavioral, psychological,

and social research casts a very wide net, as it

examines everything from personality to populations. This research looks at the spectrum

of possible influences on longevity, health,

and behavior, including potential biological

and genetic factors that may play a role. A few

areas of growing interest are highlighted here

— the role that personality and attitudes

might play in late-life health, including cognition, and how public health might be

improved with greater understanding of individual health behaviors and of the changing

patterns of health and mortality. 

BEHAVIORAL AND SOCIAL RESEARCH PROVIDES

INTRIGUING AND USEFUL INSIGHTS INTO

OURSELVES AND THE WORLD AROUND US.

32
BEHAVIORAL AND SOCIAL ASPECTS OF AGING 33

PERSONALITY AND SOCIAL/

BEHAVIORAL INFLUENCES ON HEALTH 

On the most individual level, can personality

and outlook affect your risk of disease or

death? Studies of personality suggest that it

can. Led by Dr. Paul T. Costa, Jr., chief of the

NIA’s Laboratory of Personality and Cognition,

NIA’s researchers have developed a model to

provide a way to characterize personality,

examine its effects, and measure possible personality-specific interventions against disease

and disability. This Five-Factor Model is a

comprehensive characterization of five key

dimensions — neuroticism, extraversion,

openness, agreeableness, and conscientiousness. For example, new data from the FiveFactor Model questionnaire identify several

dimensions of personality associated with

success or failure to achieve adequate compliance with a drug regimen. In a specific case,

studies are now underway to measure personality traits that are linked to complying

with anti-retroviral therapies for HIV/AIDS.

“By identifying individuals whose questionnaire responses show they are prone to experience stress and have poor self-discipline, we

can target these patients for special interventions,” says Dr. Costa. 

It is also important to obtain information

on personality from older people unable to

respond to questionnaires, such as those with

dementia. New tools developed by scientists at

the NIA’s laboratory open a window for scientists to assess the previously unmeasured

impact of dementing disorders on personality.

This “observer-rating” form of the Five-Factor

Model questionnaire has been used in a number of studies in the U.S. and Europe to look at

patients with Alzheimer’s disease (AD), Parkinson’s disease, and traumatic brain injury. Information from caregivers and family members

shows that patients with these diseases

undergo significant changes in personality. In

AD, for example, personality changes reflect

diminished capacity for organization, punctuality, dependability, goal-setting, and planning.

Ongoing studies will attempt to determine the

ordering of these personality changes, whether

they occur before the disease becomes evident

Style of Defense

Vertical Axis: Neuroticism (N) / Horizontal Axis: Openness (O)

80

70

60

30 40 50 60 70

30

20

40

20 80

High

Neuroticism

Low

Neuroticism

High

Openness

Low

Openness

Style of Well-Being

Vertical Axis: Neuroticism (N) / Horizontal Axis: Extraversion (E)

80

High

Neuroticism

Low

Neuroticism

High

Extroversion

Low

Extroversion

70

60

30 40 50 60 70

30

20

40

20 80

N+EGloomy Pessimists

These people face a dark and dreary life.

There is little that cheers them, and much

that causes anguish and distress. Especially under stressful circumstances,

they may succumb to periods of

clinical depression, and even

when they are functioning

normally, they often find life

to be hard and joyless.

N+E+

Overly Emotional

These people experience both positive and

negative emotions fully, and may swing

rapidly from one mood to another. Their

interpersonal interactions may be tumultuous, because they are so easily carried away by their feelings. They

may show features of the histrionic personality disorder, but

they may also feel that their

lives are full of excitement.

N-ELow-keyed

Neither good news nor bad

has much effect on these people;

they maintain a stoic indifference

to events that would frighten or

delight others. Their interpersonal relationships may suffer because people find

them to be “cold fish.” Their emotional

experience of life is bland.

N-E+

Upbeat Optimists

These people are usually cheerful, because they are not unduly

troubled by problems, and have a

keen appreciation for life’s pleasures.

When faced with frustration or disappointment, they may become angry or sad, but

they quickly put these feelings behind

them. They prefer to concentrate on the

future, which they view with eager anticipation. They enjoy life.

N+OMaladaptive

These individuals tend to use primitive

and ineffective defenses such as repression, denial, and reaction formation. They

prefer not to think about disturbing

ideas, and may refuse to acknowledge possible dangers (such as a

serious illness). They lack insight

into the distressing affects they

experience, and because they

cannot verbalize their feelings, they may be considered alexithymic.

N+O+

Hypersensitive

Hypersensitive individuals seem undefended. They are alert to danger, and

vividly imagine possible misfortunes. They

may be prone to nightmares. Because

they think in unusual and creative

ways, they may sometimes be troubled by odd and eccentric ideas.

N-OHyposensitive

These individuals rarely experience strong negative effect, and

when they do, they downplay its

importance. They do not dwell on threats

or losses, turning instead to concrete

action to solve the problem or simply to

distract themselves. They put their faith

in higher powers. 

N-O+

Adaptive

Adaptive individuals are keenly

aware of conflict, stress, and threat,

but use these to stimulate creative

adaptions. They grapple intellectually

with their own intrapsychic problems, and

they can react to life stress as a source of

humor or artistic inspiration.

Reprinted with permission. Copyright 1998 by Psychological Assessment Resources, Inc., Odessa, FL.

Personality styles are defined by combinations of factors. 

Two of 10 combinations are illustrated here.
34 NATIONAL INSTITUTE ON AGING

or whether they follow memory changes. 

Scientists are also hoping to determine if personality changes might be an early marker for

the start of special interventions or treatment

for dementia. 

It may be that how we look at life can

affect how we age. A study of 1,002 disabled

women age 65 and older participating in the

NIA-sponsored Women’s Health and Aging

Study found that “emotional vitality,” that is, a

sense of personal mastery, being happy, and

having low anxiety and depression, is linked

with reduced risk of further disability and

even death. Recent findings from the Nun

Study, a longitudinal survey of older Catholic

Sisters, found a strong relationship between

positive emotions expressed in early life writings and reduced risk of death in their 80s and

90s. In the study, handwritten biographies

written by 180 nuns in their 20s were evaluated for positive emotional content and then

were related to survival. This growing body of

research suggests that we might press beyond

looking at depression and other aspects of

emotional dysfunction to study the role that

positive emotions may play in health and

longevity.

Researchers are also looking at how social

and behavioral factors might affect cognition.

According to a number of studies, cognitive

ability — the process of thinking, learning, and

remembering — can decline with age. This is

of concern because cognitive skills are critically important in allowing older people to

maintain their vitality and independence. 

Social and behavioral influences on cognition may be considerable, according to current research. In one study, older adults were

exposed, without being directly aware of it, to

both positive and negative stereotypes about

aging. Researchers created scenarios using

words such as “wise” or “senile,” for example,

and then tested participants immediately on

a variety of measures. On both cognitive tests

and physiological measurements, older adults

exposed to negative stereotypes about aging

performed poorly when compared with those

exposed to positive stereotypes. Researchers

are now looking at ways to further test the 

COGNITIVE SKILLS ARE CRITICALLY 

IMPORTANT IN ALLOWING OLDER PEOPLE 

TO MAINTAIN THEIR VITALITY AND 

INDEPENDENCE.
BEHAVIORAL AND SOCIAL ASPECTS OF AGING 35

“

From bench to bedside.” It’s an

expression that health scientists and educators use in talking

about how to take what is discovered at the laboratory workbench

and make it a part of everyday medical practice. 

As a practical matter, research

should make its way into the public

health consciousness, and NIA scientists and public information and

health education experts constantly

look for opportunities

to communicate scientific results in the

most effective way to

the world outside the

Institute’s corridors.

“Improving public

health is really the

bottom line for research,” says Jane

Shure, director of the NIA’s Office of

Communications and Public Liaison.

“Sharing what we have learned, with

clinicians and with the public, is an

important part of that effort.” 

The Institute’s national education campaign on exercise, notes

Ms. Shure, is a model case in point.

In 1998, the NIA, with astronaut and

Senator John Glenn, and other Federal agency partners, launched a

national education campaign for

keeping fit after 50. The centerpiece

of the campaign was publication of

the important new book, Exercise:

A Guide from the National Institute on Aging. By 2000, the enormously popular and award-winning

publication had been made into a

video version featuring exercise

expert Margaret Richard. The print

Guide is distributed free in single

copies and the video is offered at

cost. Some 370,000 booklets have

been sent out and the video is

quickly catching up. In 2001, the

NIA published a Spanish language

version of the exercise Guide. Other

organizations have translated it into

Japanese and French. 

Why exercise? In 1996, when the

idea of the project was raised, two

key developments had taken place.

First, research on exercise and its

benefits for aging populations had

reached a critical mass. Scientists

were convinced that exercise could

make a difference, and they had data

on what specific exercises would

work best. Second, NIA’s public information staff noticed increased interest in healthy aging from the media

and the general public, with a distinct

focus on exercise. But in telling the

press and the public about the benefits of exercise, it was difficult to follow up on the next logical questions:

What type of exercises should people 50 and older do? How should

they get started? 

So, in September 1996, the NIA

gathered an important panel of outside experts and its own scientific

From Lab Bench to Bench Press:

NIA Launches an Exercise Campaign
study’s findings that link negative age stereotypes to measureable health risk. They also

suggest that the reverse may be true — positive self-images of aging might be employed to

improve health, including cognitive performance. Maintaining close social relationships as

we age may also relate to cognition. Studies

are beginning to indicate that these relationships may help protect against declines in

cognitive and physical function as well as positively affect longevity. 

As scientists continue to examine what

may threaten cognitive function in later life,

NIA supports testing of potential of interventions to maintain it. The ACTIVE (Advanced

Cognitive Training for Independent and Vital

Elderly) initiative is an ongoing multi-site

study in which more than 2,800 older adults

receive training in skills related to memory,

reasoning, and speed-of-processing. Participants will be tested over time to see if the

training helps to maintain function or postpone cognitive decline.

BECAUSE OF THEIR PROVEN BENEFITS 

ON HEALTH, WELL-BEING, AND LONGEVITY, 

PHYSICAL ACTIVITY AND EXERCISE ARE 

A MAJOR FOCUS OF STUDY.

staff to answer these questions. It

was agreed that the time was right

to proceed with developing an

exercise program that would fill

the need for this information. The

Guide was completed and printed

in 1998, after a major scientific literature analysis, extensive writing

and editing, and reviews and revisions incorporating the comments

of more than 40 reviewers representing a broad expertise in health,

aging, and exercise. 

The NIA works intensively to get

the exercise book into the hands

and living rooms of middle-age and

older people. Through public service announcements, participation 

in meetings of health and fitness

educators and instructors, liaison

with the medical community, and

other marketing efforts, the Institute continues to shine the spotlight on exercise as one of the most

effective interventions known for

healthy aging. 

The Guide and video, as well as

NIA’s general publications on aging,

are distributed by the NIA Information Center. Contact information for

the Information Center is located at

the end of this booklet. 

Exercise Campaign

Continued from previous page

36 NATIONAL INSTITUTE ON AGING
PERSONAL BEHAVIORS AND

POPULATION TRENDS IN HEALTH

Behavioral medicine deals with how people

develop and maintain behaviors affecting

health and illness. It examines the choices we

make, almost daily, in lifestyle practices, managing ourselves medically, and, when we have

to, coping with chronic disease or disability. 

Because of their proven positive benefits

on health, well-being, and longevity, physical

activity and exercise are a major focus of

study. An alarming 75 percent of older Americans do not engage in at least 30 minutes of

physical activity a day, as national health

guidelines suggest, and public health officials

and advocates are in search of ways to turn

that sedentary trend around. A key question

for research: Once a couch potato always a

couch potato? The answer is no, according to

new studies in this area. Health behaviors can

change at any age.

In one test, researchers used a behaviorally based approach at an existing community program. Participants explored their

reasons for not exercising and then drew up

personal plans for increasing physical activity.

Personal attention and telephone calls from

staff, plus an informational meeting, were

found to help motivate the participants to

achieve their goals. One year later, physical

activity in the group had increased by an average of 487 calories per week with exercises of

moderate intensity, the equivalent of adding

five brisk 1-mile walks per week. After 2 years,

the exercisers were still burning an average of

445 more calories a week compared with levels before the start of the program. 

Even disabled people can turn their activity levels around. A clinical trial involving more

than 200 sedentary, disabled older people,

ages 60 through 94, tested a home-based

strength training program. The program

started out with a home visit in which exercisers viewed a motivational tape on the benefits

of exercise and potential obstacles to exercise,

they set goals and received exercise instruction on how to use elastic bands for strength

training. A second, reinforcing home visit 

3 weeks later was followed up by an average of

7-8 phone calls between the exercise group

and health professionals over the 26 weeks of

the study. At the end of 6 months, a high proportion of the older people — some 78 percent — stuck with the exercise program. In

this group, function greatly improved and

37

A KEY QUESTION FOR RESEARCH: ONCE A

COUCH POTATO ALWAYS A COUCH POTATO?

THE ANSWER IS NO, ACCORDING TO NEW

STUDIES ABOUT PHYSICAL ACTIVITY.
overall disability declined by about 18 percent.

This study is one of several conducted at the

NIA-supported Edward R. Roybal Centers for

Research on Applied Gerontology. The Centers are designed to move promising social

and behavioral research findings in a number

of areas — exercise, computer skills, driving

ability, caregiving, nursing home care — out of

the laboratory and into programs that can help

improve the lives of older people and their

families.

One way older people may also be able to

exert more control over their own health is

through improved communication with physicians and other clinicians. Research by scientists supported by NIA, as well as the

pharmaceutical industry, is trying to open 

a window into what happens in the doctor’s

office when it comes to discussing medications.

One recent study of communications about

over-the-counter (OTC) medications followed

414 patients of 27 doctors. Some 58 percent of

the patients in the survey said they discussed

the use of these types of medications with

their physicians. Doctors asked about OTC

use in only 37 percent of the patients’ visits.

Researchers suggest that more might be done

on both sides to encourage discussions about

OTC medications so that patients can become

more active partners in the management of

their medicines.

Along these lines, the NIA has published

two award-winning guides, one for patients

and the other for clinicians. The companion

publications, Talking with Your Doctor and

Working With Your Older Patient, have

been widely distributed, and they are among

the most requested of NIA’s public information materials. Both publications can be

viewed on NIA’s website. Printed copies of

Talking with Your Doctor are also available

from NIA’s Information Center. See the back

of this booklet for contact information.

As research continues to explore the role

that individual capabilities and attitudes play

in health and age, it is critical to understand

population issues as well. Each of us is part 

of a larger world of public and social institutions — the health care system, Federal,

state, and local government, and other private and public agencies — that can have a

direct affect on aging, health, and retirement.

38 NATIONAL INSTITUTE ON AGING

OLDER PEOPLE MAY BE ABLE TO EXERT 

MORE CONTROL OVER THEIR OWN HEALTH

THROUGH IMPROVED COMMUNICATIONS

WITH PHYSICIANS AND OTHER CLINICIANS.
As the population ages, the ability to characterize demographic trends and understand

what is behind them will become increasingly

important. A number of studies are underway

that should help inform policymakers and

others in addressing the aging of society. 

A most basic question, of course, is how

long will we live. As biologists and geneticists

search for the molecular and cellular secrets

of aging, population studies by NIA-supported

demographers provide new and compelling

evidence that median life span in industrialized countries is increasing, and at an accelerated rate. A recent examination of Swedish

national demographic data from 1861 through

1999, provides the longest available series of

reliable information on extreme old age in the

world. The data show that the maximum age

at death during the time studied rose from

101 to 108. Before 1969, the pace of the

increase was .44 years per decade; it accelerated to 1.1 years per decade after 1969.

According to researchers, reductions in death

rates at older ages are responsible for the

increase in life span in Sweden and in other

industrialized countries over the last few

years. These trends, they say, seem likely to

continue and may gradually extend the limits

of human longevity even further.

While we are living longer, we are also living better. Researchers were surprised by

recent studies finding that, at the same time

longevity was increasing in the U.S., disability

rates among older Americans were declining.

Since these analyses of data from the National

Long-Term Care Survey were first presented

in the early 1990s, the reduction in the rate of

disability has accelerated, suggesting that

older people in the U.S. are functioning better

than they have in more than a decade. This is

true even for the most vulnerable among us,

people age 85 and older. In fact, the most

recent findings from this research suggest

that the reduction in disability may even be

keeping older people out of nursing homes.

From 1992 through 1999, the study showed a

22 percent drop — some 200,000 people — in

the number of people in nursing homes, a

finding that has broad implications for how

society might address a possible increase in

the need for long-term or nursing home care

as the baby boom ages. “The challenge now,”

says Dr. Suzman, “is to find ways to maintain

or even improve the trends in disability amid

a steep rise in the number and proportion of

older people.” 

BEHAVIORAL AND SOCIAL ASPECTS OF AGING 39

A NUMBER OF STUDIES ARE UNDERWAY 

THAT SHOULD HELP INFORM POLICYMAKERS

AND OTHERS IN ADDRESSING THE AGING 

OF SOCIETY.
Health 

Disparities

A New Focus on

Minority Aging
The racial and ethnic makeup of the U.S. is

changing, and the older population is no

exception. It will become significantly more

diverse in the coming years, a shift that has

potentially broad implications for an aging society and for aging research. And while the health

of racial and ethnic minority groups has

improved steadily in recent years, disturbing

disparities persist among racial and ethnic

groups.

Demographic projections show that the

older population will look dramatically different over the next few decades. This increasing diversity comes amid growing recognition

of differences in health status and life

expectancy among racial and ethnic groups.

In 1997, for example, average

life expectancy at age 65 was

16.1 years for African Americans and 17.8 years for nonHispanic whites. In general,

surveys indicate, African American, American

Indian, and Hispanic ethnic and racial groups

are disadvantaged relative to whites on most

indicators of health and disease, while Asian

Americans appear to be as healthy, if not

healthier. There are important differences

among ethnic subgroups as well.

Studies so far on racial and ethnic differences in health suggest that a complex assortment of factors may be at work. Disease risk,

diagnosis, progression of disease, response to

treatment, caregiving, and overall quality of

life are all affected by a number of important

variables, including race, ethnicity, gender,

socioeconomic status, age, education, occupation, country of origin, and perhaps other lifetime and lifestyle differences. “Understanding

these relationships will require a thoughtful

program of research,” says 

Dr. J. Taylor Harden, NIA Assistant to the

Director for Special Populations.

A major effort is already underway. In

1994, NIA established its Resource Centers on

Minority Aging Research (RCMARs) to study

health status, health practices, and interventions for improving the health of older minorities. The RCMARs also are charged with

training and recruiting minority scientists into

the field of aging research. In addition to the

RCMARs, NIA also supports and conducts a

wide range of related research. These studies

have looked at menopause, osteoarthritis,

cardiovascular disease, cognitive function and

Alzheimer’s disease (AD), diabetes, demographic and social factors, and physical frailty. 

Some important insights are beginning to

emerge. One major effort, the Study of

Women’s Health Across the Nation (SWAN),

follows the natural history of menopause in a

large multi-racial and ethnic sample of women,

age 40 through 55. Initial baseline findings

from the study show that the reporting of specific menopausal symptoms, from hot flashes

and night sweats to forgetfulness, varied 

NATIONAL INSTITUTE ON AGING

A New Focus on

Minority Aging

Health 

Disparities
significantly among racial, ethnic, and socioeconomic groups and by lifestyle. Scientists

point out that research in this area may ultimately be able to help provide guidance to clinicians in assessing symptoms by increasing

their sensitivity to racial and ethnic differences

in reporting menopause symptoms.

One area of increased attention is AD.

Some studies have shown that Hispanic and

African Americans may have a higher overall

risk of AD than do whites. Other reports are

mixed. NIA is most interested in examining the

diagnostic tests for AD to evaluate whether a

diagnosis of AD is affected by racial, ethnic,

cultural, or educational factors. These tests,

which measure abilities in language, memory,

and cognitive function, may be more difficult

in general for people from some cultures and

ethnic groups than others, in ways that are not

related to a diagnosis of dementia. NIA is

working with the research community to

improve the validity and reliability of AD diagnostic testing across different groups. 

In the coming years, the Institute seeks to

do more. The NIA Strategic Plan to Address

Health Disparities in Aging: Fiscal Years

2000-2005, provides guidance, calling for

three major areas of focus: 1) research to

advance understanding of health disparities in

age-related disease, with the goal of developing new and improved approaches for detecting, diagnosing, preventing, delaying, or

treating disease; 2) development of a research

infrastructure to train researchers and support institutions conducting health disparities

research; and 3) using public information, outreach, and education to increase public awareness of health disparities and transfer what

has been learned to health professionals.

Several new initiatives are planned.

Among them is an innovative effort by scientists at NIA’s Intramural Research Program to

rethink how studies are conducted in minority communities and how minorities and

socioeconomically disadvantaged groups can

be included in health and aging research. This

new paradigm, or model, of research on

minority aging includes development of a

Medical Research Vehicle (MRV) for conducting age-related studies in the community. The

47-foot customized semi-trailer includes 3

working areas: an examination room with a

42 NATIONAL INSTITUTE ON AGING

WHILE THE HEALTH OF RACIAL AND ETHNIC

MINORITY GROUPS HAS IMPROVED STEADILY,

DISTURBING DISPARITIES PERSIST AMONG

RACIAL AND ETHNIC GROUPS.
blood donor station; a cardiovascular fitness

and muscle strength testing area; and a bone

density/body composition and vascular studies testing area. The state-of-the-art vehicle is

often used in conjunction with a community

center or other facility, where administrative

activities of the study and other research,

such as cognitive and neuropsychological

testing, can be done. 

The MRV has been used in the pilot phase

of the newly initiated Healthy Aging in Nationally Diverse Longitudinal Samples (HANDLS)

study. The study’s major goal is to help understand the role of socioeconomic status in the

development of age-associated disease and

disability. This research will place special

emphasis on cardiovascular disease, cerebrovascular disease, age-associated changes in

cognition, strength and physical functioning,

and body composition, as well as other areas

in which health disparities have been identified. Recruitment strategies will be examined

to identify the most culturally appropriate,

cost-effective and efficient approaches for

participation of minorities and medically

underserved populations and will specifically

look at the effectiveness of the MRV for these

studies. “We hope that the recruitment strategy, if successful, could serve as a model for

development in other studies that require an

ethnically and socioeconomically diverse

group of participants,” says Dr. Michele Evans,

Deputy Scientific Director of the Intramural

Research Program and Principal Investigator

of the HANDLS study. 

HEALTH DISPARITIES 43

STUDIES ON RACIAL AND ETHNIC 

DIFFERENCES IN HEALTH SUGGEST THAT 

A COMPLEX ASSORTMENT OF FACTORS 

MAY BE AT WORK.

Older Population by Origin

2000 (Actual)

Non-Hispanic White (84%)

Non-Hispanic Black (8%)

Hispanic (6%)

Non-Hispanic Asian/ 

Pacific Islander (2%)

Non-Hispanic American 

Indian/ Alaska Native (<1%)

Non-Hispanic White (64%)

Non-Hispanic Black (12%)

Hispanic (16%)

Non-Hispanic Asian/ 

Pacific Islander (7%)

Non-Hispanic American 

Indian/ Alaska Native (<1%)

2050 (Projected)

Source: U.S. Census Bureau
44 NATIONAL INSTITUTE ON AGING

PUBLICATIONS

NIA offers a wide variety of free publications.

Age Pages are short fact sheets on many different topics. Public information also includes

booklets about exercise, menopause, antiaging therapies, and doctor-patient communication, as well as resource directories for

women’s health and aging services. You can

order publications from the NIA Information

Center, by calling toll free or by writing:

NIA Information Center

P.O. Box 8057

Gaithersburg MD 20898-8057

Toll free telephone: 1-800-222-2225

Toll free TTY: 1-800-222-4225

WEBSITE

The NIA website offers information to the

public, health professionals, and researchers

about the institute and its programs. Most of

the NIA’s publications are available online.

Researchers can find out more about grant

and training opportunities as well. You can

visit the NIA website at:

http://www.nia.nih.gov

ALZHEIMER’S DISEASE (AD)

The NIA’s Alzheimer’s Disease Education and

Referral (ADEAR) Center can send you publications about AD symptoms, diagnosis, and

treatment. Information specialists also can

provide referrals to supportive services and

organizations, as well as referrals to research

facilities or the nationwide network of NIAfunded Alzheimer’s Disease Centers. The

ADEAR website has publications, a calendar

of events, and a bibliographic database as well

as a list of Federally-funded clinical trials on

AD. You can contact ADEAR online, by calling

toll free, or by writing:

ADEAR Center

P.O. Box 8250

Silver Spring, MD 20907-8250

Toll free telephone: 1-800-438-4380

Website: www.alzheimers.org

E-mail: adear@alzheimers.org

MEDIA INQUIRIES

Resources for the media are available through

the NIA’s Office of Communications and Public Liaison (OCPL). 

Office of Communications & Public Liaison

National Institute on Aging

Building 31, Room 5C27

31 Center Drive

MSC 2292

Bethesda, MD 20892-2292

Telephone: 301-496-1752

For More Information
ACKNOWLEDGEMENTS

Writer

Vicky Cahan, Office of Communications and 

Public Liaison, National Institute on Aging

Design

Maggie Soldano, Levine & Associates, Inc., 

Washington, D.C.

Photography

Cover, page 1, 3, 4, 6, 8, 10, 12, 14, 15, 

18–20, 23, 26–29, 30, 32, 34, 36– 40 —

Getty Images, Inc.

Page 1, 6, 26 — Kay Churnush

Page 2, 3, 5, 13, 21, 31, 35, 41 — 

(portraiture) Tina Williams Photography

Page 6 — Courtesy of Dr. Minoru Ko, 

Laboratory of Genetics, National Institute 

on Aging

Page 7 — Courtesy of William and Wilkens

Publishing Co. 

Page 9, 22 — Max Hirshfeld

Page 11 — Courtesy of Dr. Piero Anversa, 

New York Medical College, Valhalla, NY

Page 12, 18 — Reproduced from 

J Bone Miner Res, 1986; 1:16-21 with 

permission of the American Society for Bone

and Mineral Research

Page 16 — Courtesy of Dr. Jeffrey Froehlich,

Laboratory of Cardiovascular Sciences, 

National Institute on Aging

Page 17, 42 — Dynamic Graphics

Page 24 — Courtesy of Dr. Fred H. Gage, 

The Salk Institute for Biological Studies, 

San Diego, CA

Page 25 — Courtesy of Dr. Ronald Killiany, 

Boston University School of Medicine, 

MA and Dr. Marilyn Albert, Harvard Medical

School and Massachusetts General Hospital,

Boston, MA

Page 33 — Reprinted with permission. Copyright

1998 by Psychological Assessment Resources, Inc.,

Odessa, FL.

All other photos from the Office of Communications and Public Liaison, National Institute 

on Aging.
U.S. Department of Health and

Human Services

National Institutes of Health

National Institute on Aging

http://www.nia.nih.gov

NIH Publication No. 02-4995

October 2001