Klotho

Anti-Aging Hormone · Type I transmembrane protein

Klotho is one of the most powerful anti-aging proteins known. Animals engineered to lack it age dramatically fast and die young; animals with extra Klotho live 20–30% longer. It circulates in your blood and protects against almost every age-related disease – heart, kidney, brain. Tragically, blood levels drop sharply with age. Exercise is the best-known way to raise them.

Size

1,012 amino acids

Complexes

Membrane-bound + shed

Key pathway

FGF23 / Klotho axis

Controls

Phosphate · Oxidative stress

View in AlphaFold Database

Why Klotho is Central to Longevity

The discovery of Klotho came from a mouse experiment gone right by accident: mice with a disrupted Klotho gene developed a syndrome closely resembling human aging – osteoporosis, arteriosclerosis, skin atrophy, and early death. Conversely, mice overexpressing Klotho lived up to 30% longer with measurably better cognition and organ function.

Klotho acts both as a membrane co-receptor for FGF23 (regulating phosphate and vitamin D metabolism) and as a circulating hormone once cleaved from the cell surface. The shed form travels through the bloodstream and exerts broad anti-inflammatory and anti-oxidative effects. Higher circulating Klotho is associated with better cardiovascular outcomes and slower cognitive decline in humans.

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 Klotho

Sorted by evidence grade

B+

Zone 2 Cardio

Aerobic exercise consistently increases circulating Klotho

B-

Vitamin D3

VDR activation upregulates Klotho gene expression

B+

Caloric Restriction

CR preserves Klotho levels in aging animals

B-

Sauna

Heat stress may upregulate Klotho expression

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 Klotho protein (UniProt Q9UEF7). 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