ACE inhibitor (lisinopril) — The RAAS Modulator
Lisinopril is a widely prescribed angiotensin-converting enzyme (ACE) inhibitor primarily used to treat hypertension and heart failure. In longevity medicine, it is of interest for its potential to modulate the renin-angiotensin system, which may preserve physical function, mitigate sarcopenia, and extend healthspan as observed in preclinical models.
Mechanism of Action
Lisinopril is a competitive inhibitor of angiotensin-converting enzyme (ACE), preventing the conversion of angiotensin I to the potent vasoconstrictor angiotensin II. This inhibition downregulates the renin-angiotensin-aldosterone system (RAAS), reducing blood pressure and sympathetic activity. In the context of longevity, RAAS inhibition is thought to reduce oxidative stress, lower inflammation, and improve mitochondrial function. Downstream effects may include modulation of IGF-1 levels and enhanced insulin sensitivity, which are implicated in preserving muscle mass and metabolic health during aging.
Human Trial Evidence
Lisinopril is widely used in humans for cardiovascular indications, where it improves survival in heart failure and post-myocardial infarction. In the context of aging, observational studies and small trials suggest ACE inhibitors may preserve muscle mass and physical function in older adults, potentially mitigating sarcopenia. However, there are no published human trials explicitly evaluating lisinopril for lifespan extension in healthy individuals.
Dosing Protocol
10–40 mg/day is the standard clinical range for hypertension and heart failure, taken orally once daily. Lower starting doses (2.5–5 mg) are used in elderly patients or those with renal impairment. Dose-finding specifically for longevity or sarcopenia in healthy humans is unestablished. Prescription required.
Safety & Contraindications
Common adverse effects include a persistent dry cough, hypotension, dizziness, and hyperkalemia. It is contraindicated in pregnancy due to fetal toxicity and in patients with a history of angioedema. Caution is advised when combined with potassium-sparing diuretics or NSAIDs due to the risk of hyperkalemia and renal impairment. Prescription required.