Increasing the Klotho Protein Extends Lifespan and Healthspan

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According to Greek mythology, Clotho (Greek: Κλωθώ) is part of the Three Fates or Moirai who spin (Clotho), draw out (Lachesis) and cut (Atropos) the thread of Life.

Clotho was responsible for spinning the thread of human life. She also determined when a person was born and when they died.

Clotho represented the thread of human life and her decisions represented the fate of all people in society.

Similar to Clotho from Greek mythology, Klotho is an enzyme that in humans is encoded by the KL gene.  It was discovered in 1997 by scientists and involves the suppression of several ageing phenotypes.  It was appropriately named after Clotho from Greek mythology due to its relations to the thread of life.

Discovered in 1997, Klotho is considered a longevity gene which is expressed in various organs and cells, such as renal tubular cells and the brain choroid.  

Klotho fluctuates with age, where in a persons first decade (0 to 10), serum levels are low, then from ages 20 to 40 years, it increases and reaches its peak, and finally after 40 years old it gradually decreases.  1 

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Figure 1.  Klotho Functions

Klotho has many physiological functions, including:  2  3

  • Regulating calcium and phosphorus levels
  • Delaying senescence
  • Improving cognition function and improves intelligence 
  • Reducing oxidative stress
  • Protecting vascular endothelial cells
  • Reduces coronary artery disease
  • Suppress’ insulin resistance

A study from 2005 showed that over-expression of Klotho in mice extends their average life span between 19% and 31% compared to normal mice.  4 

Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (IGF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and IGF1 signaling contributes to its anti-aging properties.

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Figure 2.  Life Extension Factor Klotho Enhances Cognition  (Source)

A single-nucleotide polymorphism (SNP) in the Klotho gene, known as rs9536314, is associated with longevity and increased cognition.  5 

The “GT” allele in the rs9536314 SNP is associated with an increase in the Klotho protein which results in life extension and enhanced cognitive function. 

It is estimated that 80% of the population has the “TT” allele and less than 20% have the “GT” allele, with the rest of the population having the “GG” allele. 

Having the “GT” allele of rs9536314 has been associated with: 

  • Increased longevity
  • Improved cardiovascular function
  • Improved kidney health
  • Larger brain volume
  • Improved cognitive function

Regardless of what variation of the rs9636314 SNP of the Klotho gene one may have, certain natural substances can increase and enhance Klotho expression.  These natural substances are listed in the Table below:

KLOTHO Activators

CategorySubstanceReference
Fungi
CordycepsRef.
Red Yeast RiceRef.
Herbs
Clotholine® (from the seeds of Centaurea cyanus)Ref.
Gentian rootRef.
Probiotics
Lactobacillus acidophilusRef.
Bifidobacterium bifidumRef.
Vitamins
Vitamin DRef.