Acarbose Anti-aging Effects in Geriatric Subjects (Substudy B & C)

Acarbose as a Safe Effective Modulator of Aging Deficits in Geriatric Subjects

This study addresses a "lifespan approach to healthy development and aging" with direct relevance to humans by testing the anti-aging effects of acarbose in humans. It is a pilot study to: i) better estimate power for a larger trial, ii) establish the safety and potential beneficial effects of acarbose in non-diabetic elderly humans, and iii) determine whether the effects of acarbose on the microbiome likely play a role in its enhancement of longevity and/or healthy aging. These are essential initial steps for translating acarbose into an anti-aging human therapy.

Treatment with acarbose, an α-glucosidase inhibitor, extends median lifespan by 22% in male mice. Acarbose is FDA-approved for use in humans and has been extensively employed for the management of diabetics; there have been few associated side effects reported. Acarbose is considered a very safe treatment. Thus, the investigators hypothesize that acarbose treatment could be used in elderly humans to elicit improvement in systems known to be negatively affected by aging. Since the outcomes of acarbose treatment may be differentially affected by age, it is imperative to test the drug directly in older subjects for its safety and efficacy. Towards this end, the investigators propose to perform a small pilot study assessing the effects of acarbose in ten elderly subjects, aged 75-95 years old. Briefly, a cohort of non-diabetics will be recruited; subjects will be in generally good health with all chronic diseases (hypertension, coronary artery disease, etc.) clinically stable. Trial participants will be studied before drug initiation (pre-treatment), during 3 months of acarbose (blood draws at 1 month and 3 months of treatment), and following termination of the drug (1 and 3 months post treatment) such that each subject will serve as his own control. Gut microbiome composition will be assessed.

Inclusion Criteria:

• age 70-95
• participants will be in good health with all chronic diseases (hypertension, coronary artery disease, etc.) clinically stable.
• participants must have adequate cognitive function to be able to give informed consent. This will be established by enrolling participants with CLOX 1 scores of ≥10.

Exclusion Criteria:

• unstable ischemic heart disease
• clinically significant pulmonary disease
• history of immunodeficiency or receiving immunosuppressive therapy
• history of a coagulopathy or receiving a medical condition requiring anticoagulation
• an estimated glomerular filtration rate of <30ml/min
• uncontrolled hypercholesteremia >350mg/dl;
• uncontrolled hypertriglyceridemia >500mg/dl
• diabetes
• history of skin ulcers or poor wound healing
• smoking
• liver disease treatment with drugs known to affect cytochrome P450 3A (diltiazem, erythromycin)