What Is Klotho? The Longevity Protein Explained

Klotho is one of the most studied proteins in longevity science — a molecule your own body makes that tends to fall as you age, and that laboratory animals cannot seem to grow old normally without. Here is what klotho actually is, what the evidence does and does not show, and how it fits alongside the better-known cellular-energy pathways we write about at SOMA HEALTH.

What klotho is, in plain terms

Klotho is a protein encoded by a gene first described in 1997 by a Japanese research team led by Makoto Kuro-o. They named it after Clotho, the figure in Greek myth who spins the thread of human life — a fitting choice, because mice unable to make the protein aged dramatically fast, while mice engineered to make extra lived noticeably longer. That single pair of findings is why klotho is often called a "longevity protein," and why it has drawn decades of follow-up research.

There are a few related forms. The one most people mean by "klotho" is alpha-klotho, which is produced mainly in the kidneys and in parts of the brain. A closely related protein, beta-klotho, sits mostly in the liver and fat tissue and does a different job. Alpha-klotho exists in two guises: a membrane-bound form anchored to the surface of cells, and a soluble form that is clipped off and released into the bloodstream and spinal fluid, where it can travel and act at a distance. It is this circulating, soluble klotho that most human studies measure when they talk about someone's "klotho level."

What klotho does in the body

Klotho wears more than one hat. Its best-understood role is as a co-receptor: the membrane-bound form partners with receptors for a hormone called FGF23 to help regulate phosphate and vitamin D balance. This is why the kidneys, which manage mineral balance, are such a major source of the protein. But the soluble form that circulates appears to have wider, more general effects on how cells handle stress — influencing signaling pathways tied to oxidative stress, growth signaling, and the behavior of several hormone systems.

In the laboratory, those effects translate into the aging phenotypes that made klotho famous. Animals short on klotho show a cluster of problems that resemble accelerated aging: weaker muscle, thinner bone, stiffer blood vessels, and shortened lifespan. Restore or boost klotho, and several of those measures improve in the same models. Importantly, almost all of the dramatic lifespan and rejuvenation results come from preclinical research — genetically modified mice, cell cultures, and, in a smaller number of striking studies, aged monkeys given klotho and tested on memory tasks. Those are powerful clues about biology, not proof of what a supplement or injection would do for a healthy person. We think it is worth stating that plainly rather than letting the mouse results stand in for human ones.

Klotho and healthy aging in humans

Human work on klotho is mostly observational — researchers measure klotho in people's blood and look for patterns, rather than giving klotho and watching what changes. Within that limit, the patterns are consistent and interesting. Circulating klotho tends to decline across adulthood, and in several large population studies people with higher klotho levels have, on average, better physical function, stronger grip and walking performance, and better scores on tests of memory and processing. Some cohorts have also linked higher klotho to healthier cardiovascular and kidney measures.

The honest caveat is that association is not causation. People with higher klotho might simply be healthier for other reasons — more active, better-nourished, fewer chronic conditions — and the klotho could be a marker rather than a cause. Teasing those apart requires trials that actually change klotho and measure the result, and in humans those are still scarce. So klotho is best understood today as a credible biomarker of biological resilience with strong mechanistic backing, not as a proven lever you can pull. If you want a deeper primer on why chronological age and biological age diverge, our explainer on biological age pairs naturally with this one.

Can you raise your own klotho?

This is where the practical interest lies, and where the evidence is genuinely encouraging even if it is early. The most reproducible finding is that exercise — particularly regular aerobic activity — is associated with higher circulating klotho, and several small human studies report that a bout or a program of exercise can nudge klotho upward. The effect sizes vary and not every study agrees, which is typical for an emerging field, but the direction of travel fits what we already know: movement is the single most reliable input for cellular and metabolic health across the board. Diet quality, sleep, and avoiding chronic inflammation are plausible contributors too, though the human data there are thinner.

How klotho relates to mitochondria and urolithin A

It is tempting to lump every longevity molecule together, but klotho and urolithin A work on different parts of the picture, and it helps to keep them straight. Klotho is a signaling protein your body produces and releases; its effects ripple across hormone and stress-response systems. Urolithin A, by contrast, is a compound your gut bacteria make from the ellagitannins in foods like pomegranates and walnuts, and its best-studied job is supporting mitophagy — the cellular housekeeping process that clears out worn-out mitochondria so fresher, better-functioning ones can take their place.

There is real mechanistic logic to why both matter for the same goal. Klotho-deficient animals show mitochondrial problems in muscle and other tissues, and some researchers propose that part of klotho's benefit flows through healthier mitochondria downstream. Urolithin A comes at mitochondrial quality from the opposite direction, acting directly on the recycling machinery. We want to be careful here, though: there is no human evidence that taking urolithin A raises klotho, and we are not claiming it does. They are complementary ideas about cellular aging, not the same mechanism wearing two names.

What the urolithin A side has that the klotho side mostly lacks is human trial data. In the first-in-human study, Andreux and colleagues (2019, Nature Metabolism) found urolithin A was safe and well tolerated up to 1,000 mg per day and produced a mitochondrial gene-expression signature in older adults. Singh and colleagues (2022, Cell Reports Medicine) tested 500 mg and 1,000 mg arms in middle-aged adults over four months and reported improvements in muscle strength and exercise performance, and Liu, D'Amico and colleagues (2022, JAMA Network Open) reported better muscle endurance in older adults. A 2025 randomized, placebo-controlled trial published in Nature Aging found that about 28 days of urolithin A supported the mitochondrial health of immune cells in midlife adults — relevant to the low-grade inflammation of aging sometimes called inflammaging. The foundational mitophagy-and-muscle work by Ryu and colleagues (2016, Nature Medicine) remains preclinical — worms and rodents — and should be read as mechanism, not human proof.

The practical takeaway

Klotho is a reminder that your body already makes molecules that shape how you age, and that lifestyle — especially consistent movement — can influence them. It is not something you can currently buy and swallow in a meaningful, evidence-backed form; the supplements marketed around "klotho activation" rest on thin human data, and we would steer you away from spending on promises that outrun the science. The sturdier, more actionable longevity levers available today are the unglamorous ones: regular aerobic and resistance exercise, sleep, a polyphenol-rich diet, and, where it fits, a clinically studied compound like urolithin A that targets a well-characterized mitochondrial pathway with human trials behind it.

If you came to klotho through a general interest in aging biology, our hallmarks of aging overview puts it in context alongside the other major mechanisms, and our urolithin A guide covers the mitochondrial side in depth. If you are deciding between products, our roundup of the best urolithin A gummies walks through what actually matters — dose, testing, and form.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. This guide is educational and is not a substitute for advice from a qualified healthcare provider.