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

If you want to interpret your genes, you can use SelfDecode.



Klotho is a protein that circulates in the blood and brain/spine throughout life (R).  It declines with aging in conjunction with cognitive deficits (RR2R3).

Klotho increased intelligence by as much as 3% or 6 point IQ boost (R).

Klotho also helps you regenerate muscle (by inhibiting TGF) (R).

Klotho is an anti-aging and health-promoting protein.   When increased, it extends lifespan (R) and when it’s decreased, it decreases lifespan (R).

Klotho diminishes age-related heart disease (R).

Klotho suppresses insulin pathways (R).

Klotho suppresses the production of Calcitriol/Active vitamin D (decreases 1alpha-hydroxylase gene expression) (R).

Klotho significantly enhances our antioxidant balance (specifically the thioredoxin/peroxiredoxin (Trx/Prx) system with the greatest effect on the induction of Prx-2) (R).

Mouse Studies on Klotho

UPDATED 032414 Klotho Graphical Abstract

Mice bred for higher levels of Kloth0:

  • Had increased lifespan (between 19% and 31%) (R)
  • Were more resistant to oxidative stress (R)
  • Performed better in multiple tests of learning and memory (R)
  • Better memory, indicated by more long-term potentiation, a form of synaptic plasticity (R)
  • Had enhanced synapses and glutamate receptors (R)

Mice bred to have lower levels of Klotho experience:

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

How to Increase Klotho

Screenshot 2015-01-06 22.59.14

  • Exercise – in both humans and mice (R)….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 (R).
  • Calcitriol/Active vitamin D increases Klotho (R, R2). However, Vitamin D supplements apparently don’t work in humans to increase Klotho, even when calcitriol goes up (R). In dialysis patients, vitamin D supplements actually decrease Klotho (R).
  • Insulin increases klotho (R).  This is one downside to a really low carb diet.
  • PPARgamma activators (R, R2)
  • Statins/Red yeast rice (HMG -CoA reductase inhibitors) (R, R2) – might simply stabilize some part of the process after its production (R).
  • Activated charcoal by binding to a toxin that decreases klotho (Indoxyl sulfate) (R)
  • Gentian root extract– might simply stabilize some part of the process after its production (R),
  • Probiotics such as Acidophilus + L Lactis in aging mice (R).
  • Cordyceps reverses the Angiotensin II decrease klotho (R).
  • ACE inhibitors

What Decreases Klotho


The following decrease klotho:

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

Klotho SNPs

Get your 23andme to find out your Klotho Gene.  You must sign up for SelfDecode to see if you’re a high or low klotho producer.

The most significant Klotho SNP is:

  1. RS9536314

Other Klotho SNPs:

  1. RS211239
  2. RS2249358
  3. RS577912
  4. RS648202
  5. RS650439

Technical Aspects of Klotho


  • Increased total protein levels of the NMDAR subunit GluN2B (R). GluN2B enhances cognition (RR2R3) and dysfunction of this sub-unit contributes to Alzheimer’s (R,R2). Klotho elevation nearly doubled GluN2B levels in post-synaptic density (PSD) fractions in the mouse hippocampus (R)
  • Suppresses Wnt (R), Regulates ion channel clustering (R) and transport (R), Promotes FGF23 function (R)…

Health Tools I Wish I Had When I Was Sick

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.

That’s why I decided to create tools that will help others cut down the guesswork:

  • Lab Test Analyzer – a software tool that will analyze your labs and tell you what the optimal values are for each marker — as well as provide you with actionable tips and personalized health and lifestyle recommendations to help you get there.
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  • SelfHacked Secrets – an ebook where we examine and explain the biggest overlooked environmental factors that cause disease. This ebook is a great place to start your journey if you want to learn the essential steps to optimizing your health.
  • SelfHacked Elimination Diet course – a video course that will help you figure out which diet works best for you
  • Selfhacked Inflammation course – a video course on inflammation and how to bring it down
  • Biohacking insomnia – an ebook on how to get great sleep
  • Lectin Avoidance Cookbook – an e-cookbook for people with food sensitivities
  • BrainGauge – a device that detects subtle brain changes and allows you to test what’s working for you
  • SelfHacked VIP – an area where you can ask me (Joe) questions about health topics


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