Feb 11, 2026Longevity Gene Activation: SIRT1, AMPK, mTOR, and NRF2 — Compound-by-Compound Evidence MapFour gene networks — SIRT1 (longevity deacetylase), AMPK (energy sensor), mTOR (growth regulator), and NRF2 (antioxidant response) — are the primary longevity targets for supplement intervention. This article maps which compounds activate which genes, the quality of evidence, and where interactions become relevant.
Feb 10, 2026Exercise Mimetics: Can Supplements Replace Movement? AICAR, Resveratrol, and Irisin EvidenceExercise produces benefits through AMPK activation, BDNF upregulation, and irisin release that no supplement fully replicates. Some compounds (resveratrol, AICAR) partially activate overlapping pathways in animals. Human evidence for exercise replacement is weak. This article separates marketing from mechanism.
Feb 6, 2026Berberine and AMPK: Metabolic Health, Blood Sugar, Lipids, and Comparison to MetforminBerberine activates AMPK through mechanisms similar to metformin and shows comparable glucose-lowering effects in head-to-head trials. Lipid-lowering effects are also well-supported. Bioavailability is limited but DHBerberine improves absorption.
Feb 5, 2026Metformin for Longevity: TAME Trial, Off-Label Use in Non-Diabetics, Safety, and ContraindicationsMetformin activates AMPK and has extensive epidemiological longevity data from diabetic populations. The TAME trial will provide the first RCT data for longevity in non-diabetics. Off-label use has meaningful risks including vitamin B12 depletion, GI effects, and contraindications.
Feb 5, 2026mTOR, AMPK, and SIRT1: Longevity Pathway Switches and How Supplements Modulate ThemThree interlocked pathways — mTOR (growth/anabolism), AMPK (energy sensing), and SIRT1 (NAD-dependent deacetylase) — function as master longevity regulators. Supplements like rapamycin, berberine, and NMN modulate them through distinct entry points. Understanding the pathway logic prevents counterproductive stacking.