Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (GESTALT)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02339012|
Recruitment Status : Recruiting
First Posted : January 15, 2015
Last Update Posted : August 20, 2020
- Biomarkers are substances in people s blood and tissues. They help researchers understand diseases and signs of aging. Scientists want to do more research on biomarkers to find ways to improve quality of life in old age.
- To learn more about biomarkers and their relationship to aging.
- Adults at least 20 years old who weigh at least 110 pounds and have a body mass index below 30. They must agree that their genetic samples can be collected, studied, and stored.
- Participants will be screened with medical history, physical exam, and blood and urine tests. They will have heart tests and nurse will assess their veins. They will fill out a questionnaire.
- Participants will have a 2-day baseline visit. Then they will return every 2 years for up to 10 years. These follow-up visits will repeat the baseline visit:
- Repeat of screening procedures.
- Physical performance tests like balance and walking tests.
- Leg and grip strength tests.
- Health and mental state questions.
- Memory and problem solving tests.
- Cytapheresis. Blood will be removed through a needle in the vein of one arm and run through a machine. The blood will be returned through a needle in a vein of the other arm.
- Visits may also include:
- Magnetic resonance imaging scans. Participants will lie on a table that slides in and out of a machine that takes pictures.
- Diabetes test. After fasting, participants will drink a sweet drink and give blood.
- Breathing and walking tests.
- Wearing a device that record physical activity.
- Scan of the abdomen and the right leg.
- A small amount of muscle tissue and/or skin removed.
|Condition or disease|
Under the assumption that aging is caused by dysfunction of specific biological mechanisms, it is reasonable to hypothesize that slowing aging should delay the onset of chronic diseases that typically affect older persons and improve their longevity and quality of life. Indeed, there is emerging evidence that factors associated with premature mortality are also involved in multiple pathologic conditions typical of aging. Scientists have suggested that these factors are genetic in nature and involve variations in the genetic code sequence. Contrary to this view, genetic approaches to study of aging have had limited success and it has been argued that the study of aging and longevity requires a more comprehensive analysis that includes non-genetic biomarkers such as epigenetic, gene expression and protein biomarkers. This is because these nongenetic biomarkers reflect the interaction between genetic variation and environmental/behavioral factors. A major limitation in this approach to date is that most studies of epigenetic, gene expression and protein biomarkers rely on blood specimens, which may not recapitulate the biology of other tissues. In addition, although all cell types from the same person have exactly the same genetic code; information on epigenetic modifications, RNAm, and protein expression likely differ across cell types and at different points in time. Thus, global measures of these biomarkers in specific cell types can be affected by percentages of these cell types in the blood, and it is well known that such percentages change with aging and chronic diseases.
To overcome the limitations described above, we plan to use cytapheresis to collect large number of PBMCs in a group of healthy individuals dispersed over a wide age-range. The collection of large number of PBMCs is essential to obtain enough cells for each cell type to support measurements of the biomarkers of interest. The information collected will be used to identify biomarkers that change with aging in individuals who are initially healthy, independent of changes in specific PBMCs cell types. We will also develop a statistical model that can be used by other studies of biomarkers to adjust their analysis for PBMCs cell type composition without having to perform complex and expensive measures, such as flow cytometry. The data collected in PBMCs will be compared to similar biomarker data obtained from muscle/fat and skin biopsies to understand to what extent biomarkers measured in the blood recapitulate similar changes that occur in different human tissues. Finally, once methodological limitations of measuring biomarkers in the blood have been addressed, we plan to assess the relationship of biomarkers assessed in specific circulating cell types, in the whole blood, bone marrow aspirate and in muscle/fat and skin biopsies to physiological measures that typically change with aging, including measures of body composition (anthropometrics, CT scan and MRI), energetics (spirometry at rest and during different degrees of exercise intensity), homeostatic equilibrium (hormones and inflammatory markers), neurological function (neurocognitive testing, brain MRI, nerve conduction studies). At the first follow-up, Year 2 (and every four years after it) we will focus on in depth characterization of phenotypes that are relevant for aging. This strategy reduces the burden to participants but still allows delineating trajectories of essential variables and relate them longitudinally. The final goal is to develop new hypotheses about the biological nature of the aging process and how aging is associated with decline of physical and cognitive function.
|Study Type :||Observational|
|Estimated Enrollment :||300 participants|
|Official Title:||The Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (GESTALT)|
|Actual Study Start Date :||April 1, 2015|
|Estimated Primary Completion Date :||December 31, 2099|
|Estimated Study Completion Date :||December 31, 2099|
- Development of state-of-the-art expression/methylation/protein PBMC atlas in aging [ Time Frame: longitudinal ]measurement of epigenetic, gene expression, and protein biomarkers
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02339012
|Contact: Linda M Zukley, Ph.D.||(410) firstname.lastname@example.org|
|Contact: Luigi Ferrucci, M.D.||(410) email@example.com|
|United States, Maryland|
|National Institute of Aging, Clinical Research Unit||Recruiting|
|Baltimore, Maryland, United States, 21224|
|Contact: NIA Studies Recruitment 410-350-3941 firstname.lastname@example.org|
|Principal Investigator:||Luigi Ferrucci, M.D.||National Institute on Aging (NIA)|