This is a study assessing the feasibility of performing an anti-aging intervention which is a combination of an exercise regimen, spermidine supplementation, and either rapamycin or lamivudine.

Inclusion Criteria:

• Patients 65-80 years old
• Current or former smokers
• BMI 25-32
• No cancer requiring active therapy within the last 2 years
• No autoimmune disease requiring disease modifying agents
• No patients with CKD stage 3/4 or ESRD
• No class 3 or 4 heart failure

Exclusion Criteria:

• Patients may not have cancer requiring active therapy within the last 2 years
• Patients may not have autoimmune disease requiring disease modifying agents
• Patients may not be receiving immune modifying biologic therapies
• Patients may not have chronic kidney disease stage 3/4 or end stage renal disease
• Patients may not have a known history of metabolic dysfunction-associated steatohepatitis
• Patients may not have a known chronic viral infection such as HIV or active Hepatitis B or C, or a known history of genital HSV. Patients who have spontaneously or through treatment cleared hepatitis B or C are candidates for the trial. If Hepatitis B core ab is positive must document a negative PCR.
• Patients may not have class 3 or 4 heart failure, or have experienced a myocardial infarction or cerebrovascular event in the past 6 months
• Patients may not have uncontrolled diabetes mellitus
• Patients may not have a history of clinically significant interstitial lung disease (ILD).
• Patients may not have clinically significant active wound healing due to recent injury or surgery
• Patients may not have signs or symptoms of clinically significant acute infectious illness on screening laboratory testing or physical examination.
• Patients may not have evidence of active or latent tuberculosis
• Patients may not have nephrotic range proteinuria on screening labs
• Patients may not have received a live virus within one month of study initiation.
• Patients cannot have uncontrolled hypertension (persistent systolic >160; diastolic >100)
• Patients with an inherited primary immunodeficiency
• Patients may not have a history of, or current evidence of, clinically significant chronic liver disease
• Patients may not be receiving any chronic immunosuppressive therapy.
• Patients may not be receiving medications that could increase rapamycin blood concentrations, such as strong inhibitors and inducers of CYP3A4 and/or P-gp (ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, or clarithromycin; rifampin or rifabutin), bromocriptine, cimetidine, cisapride, clotrimazole, danazol, diltiazem, fluconazole, protease inhibitors, metoclopramide, nicardipine, troleandomycin, verapamil. Furthermore, these medications may not be used during the study if patient is assigned to the rapamycin cohort.
• Patients may not be receiving medications that could decrease rapamycin blood concentrations, such as: carbamazepine, phenobarbital, phenytoin, rifapentine, St. John's Wort. Furthermore, these medications may not be used during the study if patient is assigned to the rapamycin cohort.
• Patients may not be receiving medications known to cause angioedema with concomitant use of rapamycin, such as angiotensin-converting enzyme (ACE) inhibitors. Furthermore, these medications may not be used during the study if patient is assigned to the rapamycin cohort.

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Immediately following publication. No end date.

Researchers who provide a methodologically sound proposal. To achieve aims in the approved proposal. Proposals should be directed to thomas.marron@mssm.edu. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website (Link to be determined).