* 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 \<126 mg/dL.
* Do not have active (any activity in the last 10 years) cancer, except for locally limited squamous and basal cell cancer.
* Do not have clinically significant hormonal dysfunction (Self-reported or laboratory values out of range. Mild hypothyroidism in participants over 60 is not considered exclusion).
* Do not have a history of neurological diseases or birth defects (other than minor anatomical abnormalities, which do not affect physical and/or cognitive function).
* Do not have a history of kidney or liver disease (associated with reduced kidney or liver function).
* Do not have a history of severe gastrointestinal (G.I.) diseases, with symptoms or requiring chronic treatment such as gastroesophageal reflux disease (GERD), Crohn s disease or ulcerative colitis.
* Do not have a history of severe pulmonary disease such as chronic obstructive pulmonary disease (COPD) or asthma requiring continuous medication use.
* Do not have muscle-skeletal conditions due to diseases or traumas (that cause pathological weakness and/or chronic pain).
* Do not have a history of severe psychiatric conditions associated with behavioral problems or requiring absolute and continuous need for medical treatment.
* Do not have any medical condition that requires absolute and continuous need for long term treatment with antibiotics, corticosteroids, immunosuppressors, H2 blockers and/or proton pump inhibitors, or pain medications.
* Do not have a medical condition that requires the use of chronic anticoagulant medication such as Coumadin, heparin, or antiplatelet agents other than low dose aspirin.
* Do not have important sensory deficits (legally blind and/or any condition that precludes the participant from being tested with standard neuropsychological tests or providing informed consent).
* Are able to read and speak English.
* Are able to understand the study risks and procedures, and consent to participate in the study.
* Not currently pregnant or a nursing mother.
* Do not currently smoke and have not smoked in the past 3 months.
* Veins are adequate for cytapheresis.
* No current illness that as judged by the study physician substantially increases the risks associated with cytapheresis (active infections, allergies, etc.).
* No history of allergy to acid- citrate- dextrose (ACD) anticoagulant.
* No history of an active bleeding disorder such as hemophilia or Von Willebrand disease.
* No history of seizures within the last 3 months.
* No history of Lyme disease, unless six weeks' post treatment and no new symptoms, of Chagas disease, Babesiosis, or Leishmanias.
* Are not claustrophobic and are eligible to perform 3TMRI as per the MRI eligibility form.
* Do not have hip or knee replacements or other medical conditions that prevent 3TMRI research scans from being performed.
INCLUSION CRITERIA for the Non-Healthy-or-Frail and Frail groups:
* Age \>= 20 years of age in the NHF group.
* Age \>= 50 years of age in the F group.
* 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 blood sampling.
* Weigh \>= 110lbs and a body mass index (BMI) \<= 35.
* 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 important sensory deficits (legally blind and/or any condition that precludes the participant from being tested with standard neuropsychological tests or providing informed consent).
* Are able to read and speak English.
* Are able to understand the study risks and procedures, and consent to participate in the study.
* Not currently pregnant or a nursing mother.
* No current acute medical condition.
* No history of an active bleeding disorder such as hemophilia or Von Willebrand disease.
* No history of seizures within the last 3 months.
* Are not claustrophobic and are eligible to perform 3TMRI as per the MRI eligibility form.
* Do not have other medical conditions that prevent 3TMRI research scans from being performed.
* Frail participants meet the A and B criteria as reported.
* Not-Healthy-or-Frail participants will not be eligible for the Healthy group because of medical or functional problems and also do not meet the criteria for the Frail Group.
Participant Exclusion Criteria:
These criteria pertain to the Screening and Baseline Visits. If conditions considered as exclusion criteria for study entry develop any time after the Baseline evaluation, the participant remains in the study.
Exclusion Criteria:
* HIV virus infection (all groups).
* Hepatitis B or C (all groups).
* Active syphilis, gonorrhea or TB requiring treatment (all groups).
* WBC \<3,000 or \> 12,000/k/microL (only Healthy group).
* Platelets \< 100,000 or \>600,000 k/ microL (only Healthy group).
* Hemoglobin \< 11.0 gm/dL in women and \< 12.0 gm/dL in men (only Healthy group).
* GFR \<50 mL/min/1.73 m\^2 (only Healthy group)
* GFR \<= to 30 (only non-Healthy-or-Frail group or Frail group)
* Bilirubin \> 1.5 mg/dl (unless higher levels can be ascribed to Gilbert's disease (only Healthy group).
* ALT, AST, or alkaline phosphatase twice the normal serum concentration (only Healthy group).
* Corrected calcium \< 8.5 or \> 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.
