The Baltimore Longitudinal Study of Aging (BLSA) is a multidisciplinary observational study of the physiological and psychological aspects of human aging and diseases and conditions that increase with age. Information from the BLSA may help to define strategies to improve quality of life in old age and prevent and delay loss of independence.

The BLSA is the NIA's major clinical research program in human aging that has been conducted in Baltimore since 1958. The study population is a series of healthy volunteers of different ages followed indefinitely with serial evaluations over time. A consortium of scientists collect and analyze data from this study population with the aim of characterizing normal and pathological aging. The goals of the BLSA are: 1) the description of the anatomical, physiological and functional changes that occur over the aging process; 2) the identification of the biological, behavioral and environmental factors that account for these changes; 3) the identification of the biological and physiological pathways that lead to frailty in older persons; 4) the study of factors that predict healthy aging and health-related outcomes across the life-span; 5) the development of hypotheses concerning possible targets for interventions that may positively affect several aspects of the aging process and prevent age-related diseases.

In this context, age-related frailty is viewed as an increased susceptibility to diseases and reduced ability to sustain stress. This condition is often found in older individuals. Frailty affects multiple physiological systems, including those that are important for mobility and cognitive function. The study hypothesizes that frail older persons show decline in multiple physiological systems, while individuals that develop specific diseases show, at least initially, clinical features that suggest selective and localized organ-specific damage. Accordingly, fluctuation and instability in health status are considered characteristics of frailty, and there is a 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 non frail individuals; 2) The early stage of frailty may be detected only by stress tests that challenge the functional reserve and the ability to compensate; 3) Frailty is caused by 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 is based on three basic levels of measure: 1). Measures of mobility and physical function; 2) Measures of the anatomical integrity and functionality of the physiological systems that are important for mobility, including the Central Nervous system, the Peripheral Nervous System, the Musculoskeletal System, the Energy Production and Delivery System and the Sensory System; 3) Measures of the physiological signaling systems important at the whole organism level to maintain the biological homeostasis, including energy production and delivery. These systems include Dietary Intake, Physical Exercise, and Immunity with particular focus on Inflammatory Markers, Autonomic Nervous System, and Oxidative Stress/ Antioxidants. Measures of all these systems are included in the BLSA, in order to study their cross-sectional and longitudinal reciprocal relationships and to understand how changes in these parameters affect aging, age-related diseases and the development of frailty and disability.