Effect of mTOR Inhibition & Other Metabolism Modulating Interventions on the Elderly [SubStudy Rapa & cMRI to Evaluate Cardiac Function]

The ability to mount an effective immune response declines with age, leaving the elderly increasingly susceptible to infectious diseases and cancer. Rapamycin, an FDA approved drug to prevent transplant rejection, increases the lifespan and healthspan of mice and ameliorates age-related declines in immune responsiveness, cancer survival, and cognition in laboratory animals. Investigators are conducting a translational trial to test whether rapamycin also improves life functions in humans focusing on elderly persons (aged 70-95).

Substudy E will evaluate the Rapamycin and Cardiac Function.

The main study has completed and results are reported (NCT02874924)

Purpose of Sub-study E - Rapamycin and cMRI to evaluate cardiac function:

The over-arching hypothesis is that RAPA treatment will effect simultaneous improvement in parameters known to be negatively impacted by aging. For example, systemic inflammation is higher in older individuals and contributes to the development of age-related pathologies affecting both the heart and the vasculature. In particular, evidence indicates that aging-associated alterations in inflammatory and pro-fibrotic pathways are critically involved in the etiology of age-related declines. The study team hypothesize that mTOR antagonism with RAPA will improve detrimental age-related pathologies affecting the heart in elderly humans.

Eligibility Criteria:
Inclusion Criteria:

* 70-95 years of age.
* Subjects will be in good general health with all chronic diseases (hypertension, coronary artery disease, etc.) clinically stable. Selected subjects will be in good health (Per the World Health Organization good health will be defined as complete physical, mental, and social well-being and not merely the absence of disease or infirmity.
* For our purposes all diseases or infirmities will be clinically stable whether managed by medications or not.
* All ethnicities will be included.
* For cardiac and brain imaging by MRI, a pre-MRI screening questionnaire will be used to assess MRI safety and neurological health.

Exclusion Criteria:

* Diabetes, (with A1c ≥6.5 or if treated with medication affecting glucose homeostasis History of skin ulcers or poor wound healing,
* Smoking,
* Liver disease,
* Coumadin anti-coagulation,
* Treatment with drugs known to affect cytochrome P450 3A (diltiazem, erythromycin, etc) due to its role in RAPA metabolism,
* Treatment (\>30days of therapy or long term) with a systemic immunosuppressant (prednisone, etc.) within the last year,
* History of recent (within 6 months) Myocardial Infarction or active Coronary Disease,
* Patients with history of recent (within 6 months) intestinal disorders,
* Exclusion criteria for MRI scan: known claustrophobia, metal implants in soft tissue of the body including pacemakers, aneurysm clips, ferrous metal fragments not anchored to bone (bullets, BBs, shrapnel, metal shavings), implanted medication pumps, and oral-facial metal appliances that are permanently secured but may result in low image quality. Participants may also be excluded for history of severe head trauma, brain injury, brain surgery, inflammation of the brain, or history of seizures.
* Female (Studies with mTOR antagonists show that there are often substantial differences in responses by sex, sometimes favoring females, other times males. Our initial pilot study was done in males for this reason and shows trends toward improved cardiac parameters. We will study males in Substudy E, an extension of our prior trial, to generate statistically significant results while obviating potential confounding by differing pharmacodynamics sex effects. Statistically significant results will be used to support larger trials in both sexes.)
* Positive COVID19 test.