Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (GESTALT)

Background: \- 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. Objective: \- To learn more about biomarkers and their relationship to aging. Eligibility: \- 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. Design: * Participants will be screened with medical history, physical exam, EKG and blood and urine tests. * Participants will have 3-day visits. They will return every 2 years. * All visits include: * Blood and urine collection * Physical performance tests * Health questionnaires * Memory and problem-solving tests * Magnetic Resonance Imaging (MRI) and Computerized Tomography (CT) scans. * Muscle metabolism/ exercise tests * Taste strips * Muscle and/or skin biopsies/ red light therapy * Retinal imaging/ eye tracking * Sleep study * ODD visits also include: * Cytapheresis * Bone marrow aspirate * EVEN visits also include: * Hyperglycemic CLAMP * Lumbar Puncture (LP) * Continuous Glucose Monitor (CGM)

* Since the study of gene expression and epigenetic regulation are essential aims of GESTALT, all participants are required to consent to DNA/RNA testing and storage at all visits. Participants that refuse genetic testing and storage will not be eligible to participate or to continue to participate in the study. The criteria below for each group pertains only to the Screening and Baseline Visits, except where otherwise noted. If any of the conditions develop while the participant is in the study, the participant remains in the study. However, participants that develop severe cognitive problems and are diagnosed by the cognition group with dementia, will no longer be able to participate in the study. INCLUSION CRITERIA for the Healthy Group: * Age greater than or equal to 20 years of age. * Are willing to return every 2 years for study visit procedures. * Agree to genetic (DNA/RNA) sample collection, analysis and storage. * Have good venous access for cytapheresis and are in good health as determined by the Apheresis Health History Questionnaire and are found eligible for apheresis (Apheresis Eligibility form). * Weigh greater than or equal to 110lbs and a body mass index (BMI) \< 30. * Do not have established genetic diseases such as sickle cell, hemochromatosis (iron overload), cystic fibrosis or Ehlers-Danlos syndrome (connective tissue disorder). * Do not have autoimmune diseases such as Hashimoto's thyroiditis, Myasthenia Gravis or Rheumatoid arthritis. * Report that they are able to perform daily self- care without assistance. * Report that they able to walk independently for at least 400 meters without assistance and without developing severe symptoms. * Report they are able to perform normal activities of daily living without shortness of breath (walking or climbing stairs) or other severe symptoms. * Do not have cognitive impairment based on mental status screening tests and evaluations and in the absence of any drug treatment. * Do not have a history of cardiovascular disease or cerebrovascular disease including angina (requiring treatment), myocardial infarction, congestive heart failure, uncontrolled hypertension, pacemaker, stroke, or transient ischemic attacks (TIA). * Do not have a history of diabetes (requiring any medical treatment other than diet and exercise) and their fasting Glucose is \ 10.7 mg/dl (all groups). * Albumin \< 3.1 g/dl (only Healthy group). * Cholesterol, LDL and/or Triglycerides \>1.5x normal (only Healthy group). * Positive Urine Drug Screen (unless taking prescribed medication and at the discretion of the PI) (all groups). * Currently pregnant or a nursing mother (all groups). Furthermore, if the participant is found eligible at Screening and Baseline but fails a urine drug screen (unless taking a prescribed medication and at the discretion of the PI) at any of the subsequent visits, the participant will be asked to return to repeat the test and if positive, will no longer be eligible to participate in the study.