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What is Normal Aging? Lessons from the BLSA

The Baltimore Longitudinal Study of Aging (BLSA) looks for answers to the question, "What is normal aging?" This may seem like a simple question, but for scientists, it gets to the heart of something quite complex: 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.

The study of normal aging has helped change our understanding of what it means to grow older. Although, for the most part, people age differently, scientists have identified certain common changes experienced by nearly everyone.

What Are the Links Between Aging and Disease?

To study normal aging, BLSA scientists originally attempted to cut out all diseases from their research. They found, as predicted, that "normal" aging is not synonymous with disease. But they also found that the two were probably not independent either. Answers to "What is normal aging?" 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. 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.

Below are a few examples of relationships between aging and disease the BLSA has helped explain.

Aging and Heart Health

The BLSA is changing our understanding of cardiovascular disease. Scientists looking at the aging heart found that age-related changes in the arteries, like arterial stiffening, do increase the risk for cardiovascular diseases. They also found that cardiovascular diseases, in turn, accelerate arterial aging. Given this correlation, scientists realized that they could not study the normal aging heart without considering heart disease. And, by studying the two together, they would be better equipped to identify strategies to prevent or slow arterial aging before cardiovascular disease occurred.

Testing for Prostate Cancer

The discovery of the relationship between prostate-specific antigen levels, or PSA levels, and prostate cancer illustrates the value of this "retrospective." While the medical community knew that the PSA enzyme tended to be elevated among men with prostate cancer, definitive information about the rate of this change in precancerous men was unknown. In 1991, BLSA researchers analyzed blood samples collected over a period of years from 54 men in the study (18 already diagnosed with prostate cancer), to see how the PSA levels changed over time. This small early study revealed there was a rapid rise in PSA levels about 5 years before the prostate cancer was diagnosed. Furthermore, scientists determined that examining the ratio of free PSA (not attached to a protein) to total PSA helps reduce incorrect diagnosis and that the percentage of free PSA in the blood can predict the aggressiveness of prostate cancer a decade before diagnosis.

Aging and Cognitive Health

BLSA measurements of cognition — the ability to think, learn, and remember — began in 1960. Scientists were then looking for natural changes with age. In 1985, the focus shifted to distinguishing normal cognitive decline from decline associated with dementias like Alzheimer's disease (AD). BLSA's longitudinal data has been used by scientists to create a history map for the time preceding a participant's diagnosis of AD. These maps showed when participants experienced an accelerated decline in memory, verbal intelligence, and executive function (the ability to use past experiences to carry out cognitive actions like correctly categorizing animals, fruits, and vegetables or identifying and recalling important details). In 2008, BLSA scientists reported that almost everyone experienced a steady rate of natural decline in their cognitive abilities. However, the rate of decline among people who went onto develop AD varied over time. Memory decline, for example, increased (compared to normal) approximately 7 years before the AD diagnosis and then accelerated a second time, 2 to 3 years before diagnosis.

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.

Read about healthy aging.