Klotho is a protein that can make you more intelligent and live longer. Read on about how to increase it.


What is Klotho (Protein)?

Klotho is a protein that circulates in the blood and brain throughout life. It declines with age, in conjunction with cognitive deficits [1, 234].

It is an anti-aging and health-promoting protein. When increased, it extends lifespan and when it’s decreased, it decreases lifespan [5, 6].

Klotho increased intelligence by as much as 3% or a 6 point IQ boost [7].

It also helps you regenerate muscle (by inhibiting TGF) [8].

People with genetic variants with higher levels of Klotho had a lower risk of heart disease [9].

Klotho suppresses insulin and IGF-1 pathways in mice [10].

Klotho suppresses the production of biologically active vitamin D (calcitriol) (decreases 1alpha-hydroxylase) [11].

Klotho significantly enhances our antioxidant balance [12].

Mouse Studies on Klotho

UPDATED 032414 Klotho Graphical Abstract

Mice bred for higher levels of Klotho:

  • Had increased lifespan (between 19% and 31%) [5]
  • Were more resistant to oxidative stress [13]
  • Performed better in multiple tests of learning and memory [5]
  • Better memory, indicated by more long-term potentiation, a form of synaptic plasticity [5]
  • Had enhanced synapses and glutamate receptors [5]
  • Doubled GluN2B levels (NMDAR subunit) in the mouse hippocampus [14]. GluN2B enhances cognition [151617] and dysfunction of this subunit contributes to Alzheimer’s [14, 18].

Mice bred to have lower levels of Klotho experience:

  • Early postnatal death [14]
  • Less myelination [19]
  • Synapse shrinkage [20]
  • Cognitive impairment [21]
  • Infertility [13]
  • Osteoporosis [13]
  • Accelerated aging [22]
  • Heart disease [22]
  • Impaired vessel Nitric Oxide, less vasodilation and angiogenesis [22]
  • Increased production of Calcitriol/Active vitamin D and higher blood calcium and phosphorous, which might be the cause of premature aging in one study [11].
  • Increased ADH and Aldosterone [23]. One study says that the excessive formation of Calcitriol in Klotho-deficient mice results in volume depletion outside cells, which contributes significantly to the shortening of life span [23].

How to Increase Klotho

  • Exercise – in both humans and mice. Klotho only increases post exercise in people who completed a 16-week training program, with younger people having a bigger increase than older people. Based on mouse studies, it’s believed that muscle injury and new muscle cell secrete Klotho [8, 8].
  • Vitamin D (Calcitriol) increases Klotho. However, Vitamin D supplements apparently don’t work in humans to increase Klotho, even when calcitriol goes up. In dialysis patients, vitamin D supplements actually decrease Klotho [24, 25, 26, 27].
  • Insulin increases klotho. This is one downside to a really low carb diet [28].
  • PPARgamma activators [13, 29].
  • Activated charcoal by binding to a toxin that decreases klotho (Indoxyl sulfate) [30].
  • Probiotics such as Acidophilus + L Lactis in aging mice [31].
  • Cordyceps reverses the Angiotensin II decrease klotho [32].
  • Gentian root extract – might simply stabilize some part of the process after its production [33].
  • ACE inhibitors
  • Statins (HMG -CoA reductase inhibitors) – might simply stabilize some part of the process after its production [34, 35, 33].

What Decreases Klotho


The following decrease klotho:

  • Psychological stress and depression. Women under high chronic stress had low klotho compared with low-stress controls. Depressed people had even lower klotho levels [36, 36].
  • Inflammation [37]
  • Oxidative stress (such as H2O2) [38]
  • Angiotensin II [32]
  • Indoxyl sulfate, a product of protein degradation [39, 40]
  • In dialysis patients, vitamin D supplements decrease Klotho [27]

Klotho SNPs

If you have your genetic data sequenced, you can find out whether you have a high or low producing variation of the Klotho Gene.

The most significant Klotho SNP is:

  1. rs9536314

If you want to analyze your genome, SelfDecode is the best tool out there to do that.

SelfDecode is a sister company of SelfHacked. The proceeds from your purchase of this product are reinvested into our research and development, in order to serve you better. Thank you for your support.

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