Klotho: The Longevity Protein, and What Science Knows So Far
Klotho: The Longevity Protein, and What Science Knows So Far
The short answer: Klotho is a protein and hormone, encoded by the KL gene and made mainly in the kidney and brain, that helps regulate phosphate and vitamin D. Mice without it age fast, mice with extra klotho live longer, and levels fall with age. No approved klotho therapy or proven supplement exists.
Key Takeaways
- Klotho is named after one of the Greek Fates who spun the thread of life. It works both as a membrane protein and as a hormone that circulates in blood.
- The strongest evidence is from animals and genetics: klotho-deficient mice age prematurely [1], and mice engineered to overproduce it live roughly 20 to 30 percent longer [2].
- In people, a gene variant called KL-VS is linked to better cognition [4], and low blood klotho tracks with higher mortality [6]. These are associations, not proof that klotho caused the difference.
- Exercise is the best-supported way to modestly raise your own klotho [7]. Supplements sold as “klotho boosters” are unproven.
- Evidence grade: Early. Compelling biology and genetics, but no human klotho therapy has been approved and no supplement has been shown to extend human lifespan. Verdict: a serious research target, not a treatment you can buy.
What is klotho?
Klotho is a protein made mostly in the kidneys and in the choroid plexus of the brain, with smaller amounts elsewhere. It was discovered in 1997 when researchers found that mice carrying a defect in a single gene developed a syndrome that looked strikingly like accelerated human aging: short lifespan, hardened arteries, thinning skin, weak bones, and infertility [1]. They named the gene klotho, after the Greek Fate who spins the thread of human life.
The gene, written as KL in humans, produces a protein that exists in two main forms. One sits anchored in the cell membrane and acts as a co-receptor. The other is a soluble version, clipped free and released into blood, spinal fluid, and urine, where it behaves like a circulating hormone [2][3]. That soluble form is what most human studies measure when they talk about “klotho levels.”
What does klotho actually do in the body?
Its best-defined job is helping the body manage minerals. Membrane klotho partners with a bone-derived hormone called FGF23 and its receptor to control how much phosphate the kidneys keep or excrete, and to regulate active vitamin D [3]. When this system breaks down, phosphate handling and vitamin D metabolism go wrong, which is one reason klotho biology overlaps so heavily with kidney disease and aging.
The soluble hormone form appears to have broader effects. In laboratory work it influences insulin and IGF-1 signaling, dampens certain inflammatory and growth pathways, and helps protect cells against oxidative stress [2][3]. Many of these pathways are the same ones tied to aging across species, which is why klotho keeps showing up in longevity research.
Why is klotho called a longevity protein?
Three lines of evidence earned it the label. First, remove it and animals age early [1]. Second, add more of it and they live longer: mice engineered to overproduce klotho lived meaningfully longer than normal mice, and the protein acted as a hormone repressing insulin and IGF-1 signals, a mechanism linked to longer life in many species [2]. Third, klotho declines with age in humans, and lower blood levels have been associated with a higher risk of death in older adults [6]. Together, biology and genetics point the same direction, even though none of it proves that raising klotho will extend a human life.
Does klotho affect the brain and memory?
This is the most talked-about part of klotho research. A 2014 study found that people carrying one copy of a KL gene variant called KL-VS tended to score better on tests of thinking and memory, and that mice engineered to make more klotho learned and remembered better, with stronger connections in memory-related brain circuits [4]. Carrying two copies of the variant, oddly, does not carry the same benefit, so the genetics are not simple.
The headline-grabbing follow-up came in 2023. Researchers gave aged monkeys a single injection of klotho and saw improved performance on memory tasks. Notably, a low dose worked while a high dose did not, an unusual pattern that underlines how early this science is [5]. These are short-term animal experiments, not evidence that injecting klotho helps human patients.
How is klotho linked to kidney and heart health?
Because the kidney is the main source of klotho, kidney disease and low klotho travel together. As kidney function falls, klotho drops early, and researchers view that decline as both a marker and a possible driver of the phosphate imbalance, vascular calcification, and cardiovascular strain seen in chronic kidney disease [3]. In the general older population, the InCHIANTI study found that adults in the lowest third of blood klotho had roughly 1.8 times the risk of dying over six years compared with those in the highest third, even after accounting for other factors [6]. Again, this is an association. Low klotho may be a symptom of underlying decline rather than its cause.
Can you actually raise your klotho?
Somewhat, and the most reliable lever is exercise. A 2022 systematic review and meta-analysis pooling 12 studies found that regular exercise training significantly raised soluble klotho levels across different populations [7]. The effect is real but modest, and it fits the broader picture that fitness supports healthy aging through many overlapping pathways, not klotho alone.
What does not have good evidence is the growing market of “klotho booster” pills and injectable peptides sold online. Klotho is a large protein that would be broken down if swallowed, no oral supplement has been shown to raise it reliably, and no klotho product has been approved by any regulator as a treatment. Claims that a capsule will restore youthful klotho and extend your life are not supported by human data.
How does klotho compare to other longevity approaches?
| Approach | What it targets | Human evidence today |
|---|---|---|
| Klotho | Aging hormone, phosphate and vitamin D, brain signaling | Early. Strong animal and genetic data, no approved therapy |
| Exercise | Whole-body, and modestly raises klotho itself | Strong. Consistently linked to longer, healthier life |
| Senolytics | Clearing senescent “zombie” cells | Early. Small human trials underway |
| Rapamycin | mTOR nutrient-sensing pathway | Early to moderate. Strong animal data, off-label human use |
How strong is the evidence, really?
Klotho sits in an honest middle ground. The foundational discovery, the lifespan extension in mice, and the KL-VS cognition genetics are robust and repeatedly cited [1][2][4]. The human data is observational, meaning it shows patterns rather than cause and effect [6]. The most exciting therapeutic results, including the monkey cognition work, are early-stage and have not been tested in human trials [5]. That combination is why serious longevity scientists take klotho seriously while cautioning that it is a research target, not a shelf product.
Frequently asked questions
Is there a klotho supplement or drug I can take?
No approved klotho drug or proven supplement exists as of July 24, 2026. Klotho is a large protein that would be digested if swallowed, and injectable or “booster” products sold online have not been shown in human trials to raise klotho or improve health. Treat all such marketing claims with caution.
What is the KL-VS variant?
KL-VS is a common variation in the KL gene. People with one copy tend to have somewhat higher klotho and, in several studies, better scores on thinking and memory tests [4]. Curiously, having two copies does not carry the same advantage, so researchers are still working out exactly how the variant shapes brain and longevity outcomes.
Does exercise really increase klotho?
Yes, modestly. A 2022 meta-analysis of 12 studies found that regular exercise training significantly increased soluble klotho in blood across varied groups [7]. The rise is meaningful but not dramatic, and it is one of many reasons consistent physical activity supports healthy aging. It remains the best-supported way to influence your own klotho.
Why is it called klotho?
The scientists who discovered the gene in 1997 named it after Klotho, one of the three Fates in Greek mythology who spun the thread of human life [1]. The name reflected their finding that losing the gene shortened lifespan and sped up aging in mice, as if the thread of life had been cut early.
Bottom Line
Evidence grade: Early. Klotho is one of the most compelling molecules in aging research, backed by strong genetics and dramatic animal results, but human evidence is still observational and no klotho therapy has been approved. It is worth understanding for anyone following longevity science, and worth watching as human trials develop. It is not something to buy as a supplement today; the products marketed as klotho boosters are unproven. The practical takeaway is unglamorous but real: regular exercise is the only well-supported way to nudge your own klotho, and it helps healthy aging through many routes at once. Limitations to keep in mind: most positive findings are in mice or monkeys, human associations cannot prove cause, and the genetics of the KL-VS variant are not fully understood.
Related reading
References
- Kuro-o M, Matsumura Y, Aizawa H, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997. https://pubmed.ncbi.nlm.nih.gov/9363890/
- Kurosu H, Yamamoto M, Clark JD, et al. Suppression of aging in mice by the hormone Klotho. Science. 2005. https://pubmed.ncbi.nlm.nih.gov/16123266/
- Kuro-o M. Klotho and the aging process. Korean J Intern Med. 2011. https://pmc.ncbi.nlm.nih.gov/articles/PMC3110841/
- Dubal DB, Yokoyama JS, Zhu L, et al. Life extension factor klotho enhances cognition. Cell Reports. 2014. https://pubmed.ncbi.nlm.nih.gov/24813892/
- Castner SA, Gupta S, Wang D, et al. Longevity factor klotho enhances cognition in aged nonhuman primates. Nature Aging. 2023. https://pubmed.ncbi.nlm.nih.gov/37400721/
- Semba RD, Cappola AR, Sun K, et al. Plasma klotho and mortality risk in older community-dwelling adults. J Gerontol A Biol Sci Med Sci. 2011. https://pubmed.ncbi.nlm.nih.gov/21474560/
- Cavaliere G, et al. A systematic review and meta-analysis demonstrating Klotho as an emerging exerkine. Scientific Reports. 2022. https://pmc.ncbi.nlm.nih.gov/articles/PMC9585050/
Medical disclaimer: This article is for general educational purposes only and is not medical advice. It is not intended to diagnose, treat, cure, or prevent any disease. Klotho is an area of active research with no approved therapy or proven supplement. Do not start, stop, or change any treatment, supplement, or exercise program based on this article. Always consult a qualified healthcare professional about your individual circumstances.
