The aim of this sub-study is to determine whether healthy individuals over 90 years of age possess immune cells that are involved in protection from chronic disease. The immune system is well known to produce anti-cancer and other immune cells, called antibodies that can be beneficial to our health. In this study the investigators will evaluate the immune status of the healthy individuals over 90 years of age. The investigators will be focused on studying molecules known to be involved in cholesterol, cancer like those for prostate cancer and breast cancer, inflammatory diseases, and infectious diseases like influenza.

The aim of this sub-study is to determine whether the Wellderly posess neutralizing antibodies targeting antigens involved in chronic disease. The humoral immune system is well known to produce anti-cancer and other antibodies that can be long lived in vivo. In this study we will evaluate the antibody status of the Wellderly with respect to neutralizing (i) molecules known to induce cholesterol like PCSK9, (ii) antibodies against cancer antigens like PMSA (prostate cancer) or Her2 (Breast cancer), (iii) antibodies against inflammatory molecules like TNFa or IL-6, (iv) antibodies that have broad neutralizing activity against infectious diseases like influenza.

INCLUSION CRITERIA

1. Age 90 and over

2. Gender: Male and Female

3. Enrolled in the Healthy Elderly (HEAL) study prior to enrollment in this sub-study

4. Eligible for Blood draw

5. Be reliable, cooperative and willing to comply with all protocol-specified procedures.

6. Able to understand and grant informed consent

7. Be healthy or have mild medical conditions that may be associated with the normal aging process, including:

   • Hypertension, well controlled with no more than 3 medications
   • Osteoporosis or Osteopenia
   • Osteoarthritis
   • Benign Prostatic Hypertrophy
   • Cataracts, Glaucoma or Macular Degeneration
   • Dyslipidemia
   • Hypothyroidism
   • Pre-Diabetes/Impaired Fasting Glucose (fasting blood glucose 100-126 mg/dL, if known)
   • Basal or Squamous Cell Carcinoma

Individuals will be excluded if ANY of the following conditions apply:

EXCLUSION CRITERIA

1. Less than 90 years of age

2. Currently undergoing treatment with any investigational agents or devices within 30 preceding enrollment in this study.

3. Self-reported history or current diagnosis of significant chronic conditions including:

   • Any Cancer (including polycythemia; excluding basal or squamous cell carcinoma
   • Coronary Artery Disease, Myocardial Infarction
   • Stroke or Transient Ischemic Attack (TIA)
   • Deep Vein Thrombosis or Pulmonary Embolism
   • Chronic Renal Disease or Hemodialysis
   • Significant Auto-Immune or Inflammatory conditions such as Rheumatoid Arthritis, Lupus, Crohn's Disease, etc.
   • Alzheimer's or Parkinson's Disease
   • Diabetes (Hemoglobin A1C > 6.5% or fasting glucose > 126 mg/dL or is treated with insulin or oral diabetic medication
   • Aortic or Cerebral Aneurysm

4. Currently taking any of the following medications on a regular basis:

   • Chemotherapeutic agents (ex. Tamoxifen, Doxorubicin, Mitoxantrone, bleomycin
   • Anti-platelet or anticoagulant agents, not including Aspirin (ex. Clopidogrel/Plavix, Dipyridamole/Aggrenox/Persantine, Ticlopidine/Ticlid, Warfarin/Coumadin, Prasugrel, etc.)
   • Cholinesterase inhibitor for Alzheimer's disease (ex. Donzepril/Aricept)
   • Insulin or oral diabetic medication

5. Individual has a significant medical condition which, in the investigator's opinion, may interfere with the individual's optimal participation in the study or would potentially confound interpretation of the individual's phenotype.

Age 90 and over Gender: Male and Female Enrolled in the Healthy Elderly (HEAL) study prior to enrollment in this sub-study