Longevity science has accelerated dramatically over the past decade. We now understand several of the core molecular pathways that drive biological ageing - and we have compounds that appear to modulate them. This guide covers the longevity supplement stack that targets multiple ageing mechanisms simultaneously, based on the current best human evidence.
The Key Longevity Pathways
Four pathways are most consistently implicated in biological ageing: mTOR (promotes growth when active, accelerates ageing with chronic overactivation), AMPK (energy sensor - activated by caloric restriction and exercise, promotes longevity), Sirtuins (NAD+-dependent enzymes that regulate gene expression and cellular repair), and NF-κB (master inflammatory transcription factor - chronic activation drives inflammaging).
The Stack
Berberine (500mg 3x daily with meals)
Activates AMPK - mimicking the metabolic effects of caloric restriction. Improves insulin sensitivity, reduces blood glucose, and has direct evidence for extending lifespan in animal models. In humans, consistent evidence for improved metabolic markers across 2+ year trials.
Resveratrol (150 - 500mg trans-resveratrol daily)
Activates SIRT1 - the primary longevity sirtuin. Also inhibits NF-κB inflammation and upregulates Nrf2 (endogenous antioxidant defense). Best taken with piperine or in highly bioavailable form.
CoQ10 Ubiquinone (200 - 300mg daily)
Supports mitochondrial function at the electron transport chain level. Declining CoQ10 is one of the most consistent markers of biological ageing. The Q-SYMBIO trial showed dramatic cardiovascular outcomes with supplementation.
Omega-3 EPA+DHA (2 - 3g daily)
Reduces chronic low-grade inflammation (inflammaging) - a primary driver of age-related disease across virtually every organ system. EPA is particularly potent against NF-κB-driven inflammatory gene expression.
Synergistic Effects
Berberine + resveratrol have additive effects on AMPK/SIRT1 signalling - both activate the pathways through different mechanisms, and the combination produces greater effect than either alone. CoQ10 and omega-3 together address the two major cellular stressors: energy depletion and oxidative/inflammatory damage.