5 Surprising Longevity Drugs – Comprehensive Summary
1. Study Background & Methodology
* The Cohort: The study analyzed data from the UK Biobank, involving 501,169 participants aged 37 to 73, followed over a period of approximately 14 years [00:03:42].
* Prescription Data: Researchers examined nearly 56 million prescriptions issued to roughly 222,000 patients [00:03:58].
* Control Pairing: To determine the effect of a drug, patients taking a specific medication were paired with "control" subjects of similar age, sex, and health status (e.g., matching two diabetic males) who did not take the drug [00:06:46].
* Endpoint: The study used mortality (death) as the primary hard endpoint, as it is the most objective and difficult to manipulate in medical research [00:01:27].
2. Key Risk Factors for Mortality
* Smoking: The highest risk factor, with a Hazard Ratio (HR) of 2.0 (doubling the risk of death) [00:04:42].
* Cancer: HR of 1.88 [00:05:00].
* Age: HR of 1.72 [00:06:05].
* Diabetes: HR of 1.65 [00:05:22].
* Sex: Being male carried an HR of 1.64 [00:05:56].
3. The Most Correlated Drugs with Longevity (The "Winners")
* SGLT2 Inhibitors (Flozins): The top performer with a 36% reduction in mortality risk (HR 0.64). These drugs cause the body to excrete glucose through urine independently of insulin. They also act as a "weak ketosis," increasing ketones and LDL cholesterol while protecting blood vessels [00:15:50], [00:23:03].
* PDE5 Inhibitors (e.g., Viagra/Sildenafil, Cialis/Tadalafil): * Tadalafil (Cialis): Showed up to a 28% reduction in mortality risk at a 10mg dose (HR 0.72) [00:19:51].
* Sildenafil (Viagra): Showed a 15% reduction at a 50mg dose (HR 0.85) [00:20:19].
* Mechanism: These drugs stabilize Nitric Oxide (NO) levels, maintaining healthy arteries and preventing cardiovascular incidents [00:18:21].
* Estrogens (Hormone Replacement Therapy): Women taking estrogens saw a 24% reduction in mortality risk (HR 0.76). Positive results were seen across various forms, including oral, transdermal, and vaginal [00:13:50].
* Naproxen: A non-steroidal anti-inflammatory drug (NSAID) that showed a 10-11% reduction in mortality risk. Unlike Ibuprofen (2-hour half-life), Naproxen stays in the body for 17 hours, effectively blocking COX enzymes and reducing blood clotting (thromboxane) [00:17:36], [00:25:26].
* Atorvastatin (Statins): While statins as a group had a minimal effect (3% reduction), Atorvastatin specifically showed a 13% reduction at 20mg. However, higher doses (80mg) actually increased the risk of death [00:16:31].
4. Surprising "Losers" or Neutral Drugs
* Metformin: Long considered a longevity staple, it showed no significant effect on lifespan in this specific cohort (HR 1.01) [00:11:22].
* ACE Inhibitors: Despite being common for blood pressure, they correlated with an 11% increase in mortality risk [00:10:36].
* Morfine & Opioids: Correlated with a 400%+ increase in mortality risk (HR ~5.5), likely due to the terminal conditions (cancer, post-surgery) for which they are prescribed [00:08:16].
* Paracetamol: Correlated with a 48% increase in mortality risk (HR 1.48) [00:08:50].
5. Critical Insights
* Correlation vs. Causation: Most drugs (92% of the 169 significant ones) showed a negative correlation with lifespan, largely because people who need medication are generally in poorer health [00:07:42].
* Flozin Paradox: SGLT2 inhibitors protect the heart and extend life significantly even though they increase LDL cholesterol, challenging the traditional view that lowering cholesterol is the only path to heart health [00:23:13].
* The Role of Nitric Oxide: PDE5 inhibitors are highlighted as "longevity drugs" of the future because they restore physiological arterial regulation [00:19:35].