What is aging? That’s the question the National Institutes of Health (NIH) sought to answer in 1958 when it launched the Baltimore Longitudinal Study of Aging (BLSA)—now the world’s longest-running study of human aging.

Some 3,200 men and women have played a critical role in advancing our understanding of what it means to get older. And these particular volunteers made a lifelong commitment to participate in the research. In over six decades of work, BLSA researchers say they are certain of just two things: Aging is not synonymous with disease. And we all age differently.

A number of disorders that typically occur in old age, such as diabetes, hypertension and dementia, are not normal aging, but rather a result of disease processes. And, no single, chronological timetable of human aging exists. We all age differently. Researchers say that in fact, “in terms of change and development, there are more differences among older people than among younger people. Genetics, lifestyle and disease processes affect the rate of aging between and within all individuals.

The scope of the aging question has evolved over the years. In the beginning, the BLSA focused on the physical and cognitive changes of normal, disease-free aging. Later, researchers began addressing the interrelationship between disease and age-related changes and their combined effect on physical and cognitive function. Today, scientists have added “exceptional aging” to their repertoire, targeting those rare individuals who go through most of their life, some well into their eighties and beyond, with no health problems. As scientists focus in on what influences aging, they hope to develop disease prevention strategies and promote healthy aging.

The most comprehensive and longest running longitudinal examination of human aging in the world started with a conversation in 1958 between Nathan Shock, Ph.D., chief of the Gerontology Branch at the NIH, and William W. Peter, M.D., a retired U.S. Public Health Service officer and missionary doctor. Wholly dedicated to medicine, Peter wanted to make a final contribution to the art by donating his body to science. But Shock thought aging research was ready for a new direction.

Rather than study the donated bodies of the deceased to learn about aging, Shock wanted to study normal aging or how people aged while they were still living, and he wanted to do it by repeatedly evaluating the same people over time. According to the National Institute on Aging (NIA), which was established as part of NIH in 1974, “He hypothesized that important concepts pertinent to aging could only be understood by looking at healthy, independently living people at regular intervals over a number of years.”

At the time it was a radical concept. Peter volunteered to be the first participant. And so Shock, Peter and a new study coordinator, Arthur Norris, outlined the new study’s parameters—the three decided the BLSA would “observe and document the physical, mental and emotional effects of the aging process in healthy, active people.”

Women were not part of the study until 1978, when scientists decided to try to better understand the influence of sex on aging. This was especially important because at the time, women lived 8 to 9 years longer than men. According to the NIA, many of the original female participants were wives or widows of male volunteers. A handful of participants have been in the study for over 50 years. One participant has made 42 visits to the BLSA testing facility.

The NIA’s Intramural Research Program in Baltimore today works with more than 1,300 male and female BLSA participants ranging in age from their twenties to 100s. The volunteers come to the BLSA every 1 to 4 years, depending on their age, for a comprehensive health, cognitive and functional evaluation that takes nearly 3 days to complete. The regularly scheduled assessments help scientists observe changes over years of life.

The BLSA today continues to pursue the following objectives:

Describe longitudinal physical and cognitive changes that define aging.

Identify genetic, physical, behavioral and environmental factors that affect the rate of change in these traits.

Understand the interrelationship between aging and chronic disease and other conditions and their independent and joint impact on age-related decline.

The study of gerontology in Baltimore began in 1940 when The Macy Foundation provided a grant to establish a Gerontology Unit at the Baltimore City Hospital. The unit was a partnership between the NIH, which provided research staff support, and the City of Baltimore, which provided lab space and access to patients. The NIH took over full financial support the following year.

In 1962, Congress appropriated $1 million for a new facility for aging research. The city of Baltimore transferred just shy of 5 acres to the Federal Government “exclusively for purposes of scientific research and other related activities in the field of Gerontology.” And in 1968, the $7.5 million, four-story Gerontology Research Center building was dedicated.

The NIA was established on the recommendation of the White House Conference on Aging. Robert N. Butler, M.D. was appointed the NIA’s first director in 1976. He left the post in 1982 to head the first geriatrics department in the United States—Mt. Sinai Geriatrics.

Mount Sinai’s pioneering work in geriatric medicine began in 1909 when Ignatz Leo Nascher, M.D., coined the term “geriatrics” in his first paper on geriatric medicine. He suggested the new term as “an addition to our vocabulary, to cover the same field in old age that is covered by the term pediatrics in childhood, to emphasize the necessity of considering senility and its diseases apart from maturity and to assign it a separate place in medicine.” At the time Nascher was practicing medicine, only 4 percent of the U.S. population was over the age of 65. The average life expectancy was 45 years. Nascher also wrote the first American textbook on geriatric medicine in 1914.

Just a year after celebrating its 25th anniversary, the BLSA, in 1984, published “Normal Human Aging,” an overview of the first 20 years of research findings about the natural course of human aging.

Defining “normal aging” is not as easy as it sounds. In fact, the NIA says it is quite complex and involves asking “how to identify the true effects of aging and how to separate factors such as disease, socioeconomic disadvantage, or lack of educational opportunity from the underlying biological or other mechanisms common to human aging.”

In its research, the BLSA has found that while most people do age differently, there are certain common changes experienced by nearly everyone. Discovering along the way that normal aging is not synonymous with disease—though they’re not mutually exclusive either—led scientists to the question, “What is the relationship between aging and disease?”

“BLSA’s longitudinal design supports the pursuit of links between aging and disease,” the NIA reports. “Scientists can look back at information collected from participants over time, including data from years before a diagnosis, and attempt to identify the changes that precede and perhaps predict clinical symptoms, the so-called precursors of disease. They can determine what distinguishes two seemingly healthy people: one who will go on to develop a certain health problem, the other who will not.”

Since 1958, the BLSA has helped to explain relationships between aging and disease in heart health, testing for prostate cancer, and aging and cognitive health. “Discoveries from the BLSA have helped to transform the way we conceptualize aging. Understanding why some people are resistant to disease and functional decline and identifying ways to stay healthy are the challenges for the future. With the help of study participants, the BLSA will address these questions. The answers may set in motion new ways to live healthier and longer than ever before.”

By incorporating the study of disease into their understanding of normal aging, BLSA scientists have been able to:

  • Quantify areas of natural, age-related decline and compare these declines with changes related to disease.
  • Build knowledge of the relationship between health risk factors and aging.
  • Track trends for behaviors that promote health or risk for disease.

The BLSA is still accepting new participants in their 60’s, although currently there is a wait list for volunteers older than that. The BLSA is working to recruit a new generation of participants in their 20’s, 30’s and 40’s who are interested in being part of the study for many years to come.

According to the NIA, to enroll in the BLSA, a person must:

  • Be at least 20 years old.
  • Be in good health.
  • Have no difficulties or need for help in performing self-care or instrumental activities of daily living (grooming, dressing, etc.).
  • Be able to walk independently for at least 400 meters without using assistive devices or experiencing any symptoms.
  • Have no shortness of breath while performing normal activities of daily living, such as walking or climbing stairs.
  • Have no substantial cognitive impairment based on mental status screening tests.
  • Show no evidence of compromised immune function.
  • Weigh less than 300 pounds and/or have a BMI of less than 40.
  • Have no history of:
  • Diabetes
  • Kidney or liver disease
  • Heart attack or heart failure
  • Angina
  • Stroke
  • Active cancer
  • Cardiovascular disease
  • Metabolic disease
  • Severe hormonal dysfunction
  • Neurological disease
  • Established genetic diseases
  • Birth defects
  • Severe gastrointestinal disease
  • Muscle-skeletal conditions due to disease or trauma
  • Severe psychiatric conditions
  • Any medical condition that requires continuous use for long-term treatment with antibiotics, corticosteroids, immunosuppressants, H2 blockers, or pain medications
  • Severe sensory deficits (e.g., legally blind)
  • Any condition that precludes neuropsychological testing or providing informed consent.