AMPK α1

AMP-Activated Protein Kinase · Energy Sensor

AMPK is your cells' low-battery sensor. When energy runs low – during fasting or exercise – AMPK switches the cell into repair and recycling mode instead of growth mode. This is the main reason exercise is good for longevity. It's also exactly how metformin works: it triggers AMPK artificially, mimicking the benefits of caloric restriction.

Size

559 amino acids

Complexes

αβγ heterotrimer

Key pathway

AMPK / mTOR axis

Controls

Autophagy · Mitochondria

View in AlphaFold Database

Why AMPK is Central to Longevity

AMPK acts as the master switch between two cellular modes: growth (anabolism) and maintenance (catabolism). When energy is scarce – detected via a rising AMP:ATP ratio – AMPK flips the cell into conservation mode: blocking mTOR-driven growth, triggering autophagy to recycle damaged components, and boosting mitochondrial biogenesis for more efficient energy production.

Metformin, the world's most prescribed diabetes drug and a leading candidate in longevity trials (TAME trial), works primarily through AMPK activation. Berberine, a plant compound, activates AMPK through an almost identical mechanism. The convergence of two independently discovered longevity interventions on the same protein validates AMPK as a genuine longevity target.

The structure shown here was predicted by Google DeepMind's AlphaFold 2 model. Colors indicate prediction confidence (pLDDT score): blue regions are predicted with very high accuracy; orange regions represent flexible or disordered segments where confidence is lower.

Interventions Targeting AMPK

Sorted by evidence grade

B+

Metformin

Inhibits mitochondrial complex I, raises AMP:ATP, activates AMPK

B+

Berberine

Similar mechanism to metformin – AMPK activation

B+

Zone 2 Cardio

Aerobic exercise is the strongest physiological AMPK activator

B+

Caloric Restriction

Nutrient scarcity directly activates AMPK via AMP:ATP ratio

B+

Time-Restricted Eating

Fasting periods activate AMPK, promoting autophagy

About this structure

This 3D model was generated by AlphaFold 2, developed by Google DeepMind and EMBL-EBI. The structure represents the full-length human AMPK α1 catalytic subunit (UniProt Q13131). AlphaFold predictions may differ from experimentally determined structures, particularly in disordered regions. Structure data is provided under CC BY 4.0. alphafold.ebi.ac.uk