Document text
Principal Investigator: ELEANOR Marie SIMONSICK
Organization: NATIONAL INSTITUTE ON AGING
Fiscal Year: 2024
Award: $8,568,920
Funding agency: National Institute on Aging
The Baltimore Longitudinal Study of Aging (BLSA), the major research program on human aging supported by the Intramural Research Program of the NIA, was established in 1958 and conducted at the Gerontology Research Center through 2003. Beginning in 2003 a new research unit was established at Harbor Hospital (Baltimore). The study continues to represent a consortium of scientists who work collaboratively to characterize normal, exceptional and pathological aging. The current team of researchers directing the BLSA has implemented major changes in its design and assessment technology. The primary scientific goals remain consistent with the original BLSA legacy to: 1) identify age-associated differences among individuals that are not explained by diseases and 2) characterize factors that affect transitions from normal to pathological aging. New measures have and continue to be implemented aimed at gaining a better understanding of the effect of age and diseases on the process that leads to mobility disability, cognitive impairment, dementia and poor quality of life in many older adults. Using an integrative and multidisciplinary approach, the study aims to identify and delineate the compensatory mechanisms that occur at multiple levels (cells, tissues, organs, whole body, society) that allow many older persons to maintain a high level of mobility and cognitive performance in the absence or in spite of multiple pathological processes.
The study population consists of a cohort of volunteers followed for life over multiple follow-up visits. Many participants have been enrolled in the study for over 20 years, and some for as long as 60 years. The study conducted a targeted enrollment of individuals 80 years and older who are extremely well-functioning and have exceptional health. This component of the BLSA has been named "The IDEAL (Insight into the Determinants of Exceptional Aging and Longevity) Study". Current enrollment now targets healthy individuals under age 60.
Historically, the BLSA has been the gold-standard reference for aging-related changes in multiple systems. Important findings in cardiovascular function over the life course, factors affecting risk of prostate cancer, age-associated decline in cognitive function, glucose metabolism, muscle strength and bone integrity continue to be published in the present day. Some research goals will be pursued by conducting, in parallel, ancillary studies limited to defined subsets of participants and designed to address pre-formulated hypotheses with the objective of providing information more directly applicable to clinical medicine.
The structure of the current BLSA design is based on four levels of measurement:
1. The reference outcome measures are physical and cognitive function. All other measures, directly or indirectly, are aimed at understanding the mechanisms by which old age is associated with high risk of developing mobility disability and impaired cognitive function. Accordingly, the BLSA collects an extensive set of measures on many different aspects of physical and cognitive function;
2. The intermediate level includes measures of anatomical integrity and functionality of the physiological systems important for mobility: central nervous system, peripheral nervous system, muscle, bone and joints, delivery of substances important for energy production, sensory systems that provide feedback from the environment;
3. The third level includes the physiological systems important for maintaining a stable biological homeostasis and include measures of immune function, hormones, oxidative stress/antioxidants, autonomic nervous system, nutritional intake, and physical activity.
4. The fourth level of measurement has recently emerged and reflects substantial technological advances in the assessment of several "hallmarks" of aging including but not limited to metabolomics, proteomics, DNA methylation and genomics and capitalizes on the substantial cache of biological specimens collected and stored over several decades.
The overarching hypothesis is that dysfunction of the systems that maintain biological homeostasis is the primary cause of age-associated decline in physical function and development of frailty. Considerable resources have been dedicated to restructuring, documentation and cleaning the data collected over the last 64 years. This project is already in an advanced stage of development and producing important results concerning clinical features for the diagnosis and prognosis of prostate cancer, secular trends in WBC, body weight, muscular strength and their relationship with mortality over the last half of the century and genetic traits associated with accelerated decline in physical function. An essential part of this plan is the inventory, classification and quality control of the entire collection of biological specimens (urine, blood, serum, plasma, red blood cells, etc) collected in BLSA participants during the entire course of the study. In addition, a wide genome scan (Illumina 550K) has been performed in over 1450 participants with available DNA.
Using the rich collection of phenotypes collected over many years and the Illumina genotypes, the BLSA has contributed data to several genetic consortia examining the contribution of genetic variability to different human phenotypes, such as blood pressure, circulating lipids, uric acid, pro-inflammatory markers and many others. In addition, we are starting new work on gene-environment interactions.
An important sub-project consists of a newly recruited cohort of exceptionally healthy older persons (IDEAL), examining the cross-sectional characteristics of this group compared to the general population, and measuring several physiological parameters that may be directly or indirectly connected with physical and cognitive function. From this prospective, the future plan for the BLSA is to become a permanent laboratory of physiology that studies the different physiological changes that occur over the aging process, with the final aim of understanding their inter-relationships and describing the mechanisms by which they contribute to maintenance of homeostatic equilibrium.
Since many BLSA participants who become sick and disabled were often unable to come to the Baltimore clinic for a traditional visit in the clinic creating a severe ascertainment bias informative censoring) in the study of age-related outcome the BLSA has retained a "home visit" project aimed at collecting information from individuals that are no longer able to come to the Clinical Research Unit for their traditional visit. This portion of the project is described in another report.
In May 2020, an interim survey was developed and administered over the phone or sent by mail to collect data related to COVID-19 exposure and symptoms and impact of the pandemic and its consequences on daily life, feelings of isolation, health-related behaviors, social interaction, personal finances and the like. In January 2021, a follow-up to the May 2020 COVID-19 survey was developed and administered to all persons enrolled the BLSA to tract their experience with COVID-19 including vaccination status.
Terms: <65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><> 65 years><Acceleration><Active Follow-up><Address><Affect><Age><Aged 65 and Over><Aging><Amentia><Anatomic Sites><Anatomic structures><Anatomy><Ancillary Study><Antioxidants><Autonomic nervous system><Autoregulation><Baltimore><Biological><Blood><Blood Plasma><Blood Pressure><Blood Reticuloendothelial System><Blood Serum><Blood erythrocyte><Body Tissues><Body Weight><CNS Nervous System><COVID-19><COVID-19 exposure><CV-19><Cardiovascular Physiology><Cell Body><Cells><Cellular Immune Function><Central Nervous System><Characteristics><Classification><Clinic><Clinical><Clinical Medical Sciences><Clinical Medicine><Clinical Research><Clinical Study><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Cohort Studies><Collection><Concurrent Studies><Coronavirus Infectious Disease 2019><DNA><DNA Methylation><Data><Decline in mobility><Decrease in mobility><Decreased mobility><Dedications><Dementia><Deoxyribonucleic Acid><Development><Diagnosis><Diminished mobility><Disease><Disorder><Disturbance in cognition><Documentation><Dysfunction><Elderly><Endocrine Gland Secretion><Enrollment><Environment><Equilibrium><Equipment and supply inventories><Erythrocytes><Erythrocytic><Feedback><Feeling><Functional disorder><Future><Gene x Environment Interaction><General Population><General Public><Genetic><Genome Scan><Genomics><Genotype><Gerontology><Goals><GxE interaction><Health><Health Status><Health behavior><Home visitation><Homeostasis><Hormones><Hospitals><House Call><Human><Impaired cognition><Individual><Intake><Intramural Program><Intramural Research Program><Inventory><Investigators><Joints><Laboratories><Length of Life><Level of Health><Life><Life Cycle><Life Cycle Stages><Lipids><Longevity><Longitudinal Studies><Maintenance><Malignant Tumor of the Prostate><Malignant neoplasm of prostate><Malignant prostatic tumor><Marrow erythrocyte><Measurement><Measures><Mobility decline><Mobility disability><Mobility impairment><Modern Man><Muscle><Muscle Tissue><Names><Neuraxis><Nutritional><Older Population><Organ><Outcome><Outcome Measure><Oxidative Stress><Participant><Pathologic Processes><Pathological Processes><Peripheral Nervous System><Personal Financing><Persons><Phenotype><Phone><Physical Function><Physical activity><Physiologic><Physiological><Physiological Homeostasis><Physiology><Physiopathology><Plasma><Plasma Serum><Process><Production><Prognosis><Prostate CA><Prostate Cancer><Prostate malignancy><Prostatic Cancer><Proteomics><Publishing><QOL><Quality Control><Quality of life><Red Blood Cells><Red Cell><Reduced mobility><Reduction in mobility><Reference Standards><Reporting><Research><Research Personnel><Research Resources><Research Specimen><Researchers><Resources><Reticuloendothelial System, Serum, Plasma><SARS-CoV-2 exposure><SARS-CoV2 exposure><Scientist><Serum><Severe acute respiratory syndrome coronavirus 2 exposure><Social Interaction><Societies><Specimen><Structure><Survey Instrument><Surveys><Symptoms><System><Systematics><Technology><Technology Assessment><Telephone><Therapeutic Hormone><Time><Tissues><Trioxopurine><Uric Acid><Urine><Vaccination><Visit><Work><aberrant aging><abnormal aging><above age 65><active followup><advanced age><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age associated><age associated decline><age associated difference><age associated effects><age based difference><age correlated><age dependent><age dependent decline><age dependent difference><age dependent variation><age difference><age effect><age linked><age of 65 years onward><age related><age related decline><age related difference><age related effects><age related variation><age specific><age specific difference><aged 65 and greater><aged 65+><aged ≥65><ages><aging associated><aging effect><aging process><aging related><balance><balance function><biologic><blood corpuscles><bone><cardiovascular function><cognitive dysfunction><cognitive function><cognitive loss><cognitive performance><cohort><coronavirus disease 2019><coronavirus disease 2019 exposure><coronavirus disease-19><coronavirus infectious disease-19><data cleaning><data cleansing><decline with age><design><designing><developmental><differ by age><difference across age><difference in age><disabled><dysfunctional age related change><dysfunctional aging><enroll><environment effect on gene><experience><exposure to COVID-19><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><exposure to coronavirus disease 2019><feelings><follow up><follow-up><followed up><followup><frailty><functional status><gene environment interaction><genome-wide scan><genomewide scan><geriatric><gerontologic><glucose metabolism><hallmarks of aging><health level><health related behavior><high risk><home visit><human old age (65+)><immune function><impact of age><impaired aging><improved><inflammation marker><inflammatory marker><influence of age><insight><interdisciplinary approach><life course><life span><lifespan><long-term study><longitudinal outcome studies><longterm study><maladaptive aging><measurable outcome><metabolism measurement><metabolomics><metabonomics><mortality><multidisciplinary approach><muscle strength><muscular><name><named><naming><nutritious><old age><older adult><older adulthood><older groups><older individuals><older person><outcome measurement><over 65 years><pandemic effect><pandemic impact><pandemic outcome><pandemic repercussions><pathological age related changes><pathological aging><pathophysiology><personal finances><pillars of aging><programs><prospective><prostate cancer risk><recruit><senior citizen><sensory system><study population><trait><trend><variation by age><volunteer><whole-genome scan><≥65 years>