Everolimus Aging Study

Inclusion Criteria: Adults aged 55-80 years old

• Free of overt chronic disease

• Willing to provide informed consent

• Willing to comply with all study procedures and be available for the duration of thestudy

• Able to use and be contacted by the telephone

• Ability to take oral medication

• Insulin Resistant defined by HOMA-IR greater than or equal to 1.5 or prediabeticdefined as:

• impaired fasting glucose (100-125 mg/dL)

• HbA1c (5.7-6.4 percent)

• glucose 2 hours after a 75 gram oral glucose tolerance test (140-199 mg/dL)

• previous diagnosis of prediabetes in the past year

• Not planning to change diet or physical activity status

• Adequate organ function as indicated by standard laboratory tests: hematology (complete blood count), clinical chemistry and urinalysis

• Females of childbearing potential must have a negative urine pregnancy test beforeDEXA and before the oral glucose tolerance test (OGTT). A female of child-bearingpotential is any woman (regardless of sexual orientation, having undergone a tuballigation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or

• Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,has had menses at any time in the preceding 12 consecutive months)

• Women of childbearing potential in sexual relationships with men must use anacceptable method of contraception from 30 days prior to enrollment until 4 weeksafter completing study visits. Males must agree to avoid impregnation of womenduring and for four weeks after completing study visits through use of an acceptablemethod of contraception.

• Note: Includes, but is not limited to, barrier with additional spermicidal foamor jelly, intrauterine device, hormonal contraception (started at least 30 daysprior to study enrollment), intercourse with men who underwent vasectomy.

Inclusion Criteria: Younger Adults aged 18-35 (No intervention)

• Free overt chronic disease

Exclusion Criteria:

• Pregnancy or breastfeeding

• Heart disease

• Cerebrovascular disease

• Cancer or less than 5 years in remission

• Chronic respiratory disease

• Chronic liver disease

• Diabetes

• Alzheimer's

• Chronic kidney disease

• For those undergoing muscle biopsy: problems with bleeding, on medication thatprolongs bleeding time

• Taking azathioprine (Imuran), cyclosporine (Gengraf, Neoral, Sandimmune),dexamethasone (Decadron, Dexpak), methotrexate (Rheumatrex, Trexall), prednisolone (Orapred, Pediapred, Prelone), prednisone (Sterapred), sirolimus (Rapamune), andtacrolimus (Prograf) or other medications proposed to lower the immune system. Dailyuse of high potency topical corticosteroids used on greater than or equal to 10% ofbody surface area will not be eligible. Nasal sprays or inhaled corticosteroids willbe reviewed on a case-by-case basis.

• Taking strong or moderate CYP3A4 and/or P-glycoprotein (PgP) inhibitors

• Taking strong CYP3A4 activators

• Taking daily NSAIDs with the exception of baby asprin (81 mg)

• Subjects who are not willing to restrict the use of grapefruit, grapefruit juice,and other foods that are known to inhibit cytochrome P450 and PgP activity and mayincrease everolimus exposures and should be avoided during treatment

• Subjects who are not willing to restrict the use of St. John's Wort (Hypericumperforatum) because it may decrease everolimus exposure unpredictably

• Subjects who are not willing to avoid blood donations 8 weeks prior to the firstvisit and 8 weeks after the last visit

• For those undergoing MRI, contraindications with MRI which could include metal onyour body

• Low white-blood cell count (<4,000 cell/µL)

• History of stomatitis or ulcers in the mouth

• Those on glucose lowering drugs

• Participating in intensive exercise training program (high to moderate intensityexercise greater than 150 minutes per week) or planning to start new exerciseprogram during study period

• Tobacco use

• Allergies to lidocaine or everolimus

• Subjects currently enrolled in other clinical trials. Subjects may be eligible aftera washout period that will be reviewed on a case by case basis.

• Individuals with limited English proficiency

• Subjects who are planning to have elective surgery 12 weeks prior to or during theintervention