AMPK (AMP-Activated Protein Kinase)

What it is

AMPK is a heterotrimeric kinase that senses the AMP:ATP ratio. When ATP drops, AMP rises, and AMPK is activated. It then phosphorylates substrates that turn off energy-consuming processes (protein synthesis, lipogenesis) and turn on energy-producing ones (fatty-acid oxidation, mitochondrial biogenesis, autophagy).

Why it matters in aging

AMPK activity declines with age. Reactivation through caloric restriction, exercise, or pharmacological agonists (metformin, AICAR) opposes many hallmarks of aging: it suppresses mTOR, promotes autophagy, improves insulin sensitivity, and increases mitochondrial quality.

Activators

• Metformin (indirect, via complex I inhibition).
• Exercise (direct, via ATP demand).
• Caloric restriction and fasting.
• Berberine (modest data).
• Salicylates / aspirin (in vitro).

Cross-talk

• Inhibits mTORC1 via TSC2 phosphorylation and direct Raptor phosphorylation.
• Activates autophagy via ULK1.
• Activates PGC-1α for mitochondrial biogenesis (where applicable).
• Activates SIRT1 by raising NAD⁺.

Related entries

mTOR, Sirtuins, NAD+ precursors.