The Baltimore Longitudinal Study of Aging (BLSA) is a major clinical research program in human aging conducted in Baltimore by the National Institute on Aging, National Institutes of Health (NIA, NIH). The events that started the BLSA have become almost a legend in the research field of aging. In 1958, Dr. William W. Peter, an officer of the U.S. Public Health Service, decided to bequeath his body to science. An inquiry to NIH yielded the suggestion that he consult Dr. Nathan Shock, who at that time was leading a group of NIH scientists interested in understanding “the biological factors that produce what we perceive as aging” and “the mechanisms that produce impaired performance with age.” Dr. Shock had become convinced of the need to study community-dwelling people over time, that is, “longitudinally.” Thus, when Dr. Peter placed a phone call to Dr. Shock to find out how he could arrange to donate his cadaver for scientific study, Dr. Shock replied, “Let’s have it when you are still alive!” The two scientists met and the BLSA came into existence. Over the subsequent near half-century, the scientific knowledge generated from the BLSA has become so vast that the study is universally considered the most comprehensive study on aging in human subjects ever attempted.
The BLSA study population consists of a series of healthy volunteers of different ages followed indefinitely with serial evaluations over time. A consortium of scientists collects and analyzes data from this study population with the aim of characterizing normal and pathological aging. Thus, the BLSA can be envisioned as a series of nested longitudinal and cross-sectional studies oriented toward (1) describing the anatomical, physiological, and functional changes that occur over the aging process, independent of diseases; (2) identifying the biological, behavioral, and environmental factors that account for these changes; (3) studying factors that predict healthy aging; and (4) developing hypotheses concerning possible targets for interventions that may positively affect several aspects of the aging process and prevent age-related pathology.
In just under 50 years of operation, and with approximately 3,000 participants enrolled and more than 800 manuscripts published in peer-reviewed journals, the BLSA has generated most of the current knowledge of the aging process in humans. Perhaps the BLSA’s most important contribution involves disentangling the effect of disease and illness from the aging process and the development of the notion that aging is distinct from disease. Accordingly, most of the initial BLSA analyses were dedicated to describing changes in physiology and behaviors that are caused by aging per se, independent of disease. The BLSA portfolio includes original discoveries in the physiology and pathophysiology of the cardiovascular system, diabetes, diet and energy metabolism, age-associated modification of and risk factors for changes in cognition and personality, early predictors of prostate cancer, specific patterns of decline in sensory function, age-associated changes in body composition, decline in kidney function, secular trends in physical activity, and dietary intake. These domains represent a small sample of the wealth of information that the BLSA has provided.
In 2002, the BLSA underwent a major change in its design and objectives. Over the previous decade, the fields of genetics and molecular biology have made tremendous steps forward in the understanding of cell biology. Some of the traditional questions concerning the aging process had to be revisited and, to some extent, even reformulated. For example, the plausibility of a clear distinction between aging and disease had come under question. Thus, building on previous experience, the BLSA in 2002 entered into a new stage where its focus was on mechanisms that, over the aging process, lead to the condition of “frailty” conceptualized as increased susceptibility to disease and reduced ability to sustain stress. Additionally, frailty is believed to involve multiple physiological systems, including those important for mobility and cognitive function. It is hypothesized that over time, frail older persons show parallel, accelerated declines in anatomical integrity and function in multiple physiological systems, while individuals that develop specific diseases show, at least initially, clinical features that suggest selective and localized organ or physiological system damage. In accordance with this view, frailty is considered to contribute to fluctuation and instability of health status, high risk of multiple negative health-related outcomes and exhaustion of functional reserve. It is also hypothesized that (1) the destabilizing impact of acute medical events or traumas in older individuals is higher in frail than in nonfrail individuals; (2) early stages of frailty may be detected only by tests that challenge functional reserve and compensatory ability; and (3) frailty stems from dysfunction of some core mechanism that maintains integrity and function at a cellular level.
The paradigm used in the BLSA to study age-related frailty covers three basic levels of measurement: (1) mobility and physical function and cognitive capacity; (2) anatomical integrity and functionality of the physiological systems important for mobility, including the central nervous system, the peripheral nervous system, the muscular-skeletal system, the energy production and delivery system, and the sensory system; (3) physiological signaling systems important at the whole organism level for maintaining biological homeostasis, including energy production and delivery. These features include dietary intake, physical exercise, and immunology, with particular focus on inflammatory markers, autonomic nervous system, and oxidative stress/antioxidants. All of these measures are included in the BLSA core, in order to study their concurrent and longitudinal relationships and understand how changes in these parameters affect aging, age-related diseases and the development of frailty, loss of physiological reserve, and functional decline.
Baltimore Longitudinal Study of Aging, http://www.grc.nia.nih.gov/branches/blsa/blsa.htm