Aspirin (low-dose) — The Classic Anti-Inflammatory and Anti-Platelet Agent
Low-dose aspirin is a widely used nonsteroidal anti-inflammatory drug (NSAID) primarily known for its cardiovascular protective effects. In the context of longevity, it is studied for its potential to reduce systemic inflammation, prevent atherothrombotic events, and lower the risk of certain cancers, particularly colorectal cancer.
Mechanism of Action
Aspirin irreversibly inhibits cyclooxygenase (COX) enzymes, primarily COX-1 at low doses, by acetylating a serine residue in the active site. This inhibition blocks the conversion of arachidonic acid to thromboxane A2 (TXA2) in platelets, thereby reducing platelet aggregation and thrombosis risk. At slightly higher doses, it also inhibits COX-2, reducing the synthesis of pro-inflammatory prostaglandins. Additionally, aspirin may activate AMP-activated protein kinase (AMPK) and modulate the NF-κB pathway, contributing to its broader anti-inflammatory and potential anti-neoplastic effects.
Human Trial Evidence
Extensive human trials, including the ASPREE (Aspirin in Reducing Events in the Elderly) trial, have evaluated low-dose aspirin for primary prevention in older adults. While historically recommended for cardiovascular disease prevention, recent large-scale trials have shown that the bleeding risks often outweigh the benefits for primary prevention in healthy older adults. However, it remains a cornerstone for secondary prevention of cardiovascular events and has demonstrated efficacy in reducing the long-term incidence of colorectal cancer.
Dosing Protocol
75–100 mg/day (commonly 81 mg in the US) is the standard low-dose regimen. It is typically taken orally, once daily, with food to minimize gastrointestinal irritation. Enteric-coated formulations are often used, though their superiority in preventing GI bleeding is debated.
Safety & Contraindications
The primary adverse effect is an increased risk of gastrointestinal bleeding and, less commonly, hemorrhagic stroke. It is contraindicated in individuals with active peptic ulcer disease, bleeding disorders, or a history of severe aspirin allergy. Concomitant use with other NSAIDs, anticoagulants, or antiplatelet agents significantly increases bleeding risk.