Klotho
A natural anti-ageing protein your body produces, named after the Greek goddess who spun the thread of life. Mice without it age extremely rapidly; mice with extra Klotho live up to 30% longer. Recent research shows it counters the majority of the 12 hallmarks of ageing — reducing cellular senescence, oxidative damage, fibrosis, and inflammation. Recombinant human Klotho is in early clinical trials. Currently more of a research target than a usable therapeutic.
Dosage
Phase 1 only — no established human therapeutic dose
Dosages shown are for research reference only. Always consult a qualified healthcare provider.
Half-Life
Recombinant alpha-Klotho: approximately 10-15 hours (estimated from primate studies)
Half-Life Calculator →Administration
Recombinant alpha-Klotho: subcutaneous or intravenous injection (clinical trial settings only)
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Effects
Anti-Aging
Counters majority of the 12 hallmarks of aging in preclinical research; mice with elevated Klotho live up to 30% longer.
Anti-Inflammatory
Inhibits NF-kB and NLRP3 inflammasome — directly targets inflammaging.
Cognitive Protection
Endogenous Klotho levels correlate with cognitive function; therapeutic potential under study.
Anti-Fibrotic
Inhibits TGF-beta signalling, mitigating organ fibrosis in animal models.
Mechanism of Action
Klotho is a single-pass transmembrane protein primarily expressed in the kidney, parathyroid gland, and choroid plexus, with a soluble form (s-Klotho) cleaved from the membrane and circulating systemically as an endocrine factor. It exists in three forms — alpha-Klotho (the most studied, anti-ageing form), beta-Klotho (which partners with FGF21), and gamma-Klotho — each with distinct receptor partnerships and tissue effects.
At the receptor level, alpha-Klotho is the obligate co-receptor for fibroblast growth factor 23 (FGF23), enabling FGF23 to bind and activate FGFR1 receptors in the kidney to regulate phosphate excretion. This makes Klotho a central node in mineral metabolism. Beyond this canonical role, soluble Klotho exerts numerous endocrine effects: it inhibits the IGF-1/insulin signalling pathway (a conserved longevity mechanism shared with caloric restriction), enhances expression of antioxidant enzymes via FoxO transcription factor activation, suppresses Wnt signalling (reducing stem cell exhaustion), inhibits TGF-beta signalling (preventing fibrosis), and blocks NF-kB and NLRP3 inflammasome activation (reducing inflammaging).
The ageing phenotype connection is striking: mice lacking Klotho develop multi-organ ageing — atherosclerosis, osteoporosis, skin atrophy, cognitive decline — within weeks of birth, while mice with elevated Klotho expression live up to 30% longer than controls. In humans, circulating Klotho levels decline with age, and lower levels associate with increased mortality and chronic disease risk in observational studies. Recombinant alpha-Klotho is in early clinical development as a potential therapy for chronic kidney disease, cognitive decline, and broader age-related diseases. The 2026 research wave around Klotho has positioned it as one of the most promising single-protein interventions in the longevity field, though no therapeutic Klotho product is yet approved for human use.
Regulatory Status
Not approved for any indication. Recombinant alpha-Klotho is in early Phase 1 clinical trials for chronic kidney disease and cognitive decline. Products sold outside formal clinical trials as 'Klotho' are of highly uncertain authenticity.
Risks & Safety
Common
limited human safety data. Animal studies show generally good tolerability.
Serious
theoretical risk of altering phosphate and calcium homeostasis (Klotho is a critical regulator of FGF23 signalling); unknown effects on cancer biology in long-term use.
Rare
allergic reactions to recombinant protein. Quality and authenticity of any product sold as Klotho outside formal clinical trials should be considered highly uncertain.
Compare Klotho With
Research Papers
5Published: March 29, 2026
AI Summary
This review links low soluble Klotho to endothelial dysfunction and vascular calcification, suggesting Klotho protects against atherosclerosis. The clinical implications remain hypothesis-generating rather than proven.
Published: May 2, 2026
AI Summary
A meta-analysis of 30 studies (2,765 people) found exercise reliably raises circulating soluble Klotho, with resistance training showing the largest effect. Evidence quality is mostly low-moderate, so findings should be interpreted cautiously.
Published: April 30, 2026
AI Summary
A large meta-analysis (109 studies) found higher α-Klotho levels were associated with lower frailty risk, better grip strength, and better bone density. The link to cognitive outcomes was inconsistent, and most data are observational.
Published: April 30, 2026
AI Summary
This review summarizes how Klotho supports cerebrospinal fluid balance, synaptic plasticity, and resistance to oxidative stress, and links lower Klotho to cognitive decline. It is a mechanistic synthesis rather than a clinical trial.
Published: March 12, 2026
AI Summary
This review maps Klotho onto most hallmarks of aging, arguing it cuts inflammation, oxidative stress, fibrosis and cellular senescence. The evidence is largely preclinical, with human therapeutic applications still hypothetical.
Frequently Asked Questions
What is Klotho?
A natural anti-ageing protein your body produces, named after the Greek goddess who spun the thread of life. Mice without it age extremely rapidly; mice with extra Klotho live up to 30% longer. Recent research shows it counters the majority of the 12 hallmarks of ageing — reducing cellular senescence, oxidative damage, fibrosis, and inflammation. Recombinant human Klotho is in early clinical trials. Currently more of a research target than a usable therapeutic.
What is Klotho used for?
A natural anti-ageing protein your body produces, named after the Greek goddess who spun the thread of life. Mice without it age extremely rapidly; mice with extra Klotho live up to 30% longer. Recent research shows it counters the majority of the 12 hallmarks of ageing — reducing cellular senescence, oxidative damage, fibrosis, and inflammation. Recombinant human Klotho is in early clinical trials. Currently more of a research target than a usable therapeutic.
What is the dosage for Klotho?
Currently no established human therapeutic dose. Phase 1 clinical trials of recombinant alpha-Klotho are exploring intravenous and subcutaneous dose-escalation protocols. Animal studies have used 10-50 mcg/kg subcutaneous several times per week.
What are the side effects of Klotho?
Common: limited human safety data. Animal studies show generally good tolerability. Serious: theoretical risk of altering phosphate and calcium homeostasis (Klotho is a critical regulator of FGF23 signalling); unknown effects on cancer biology in long-term use. Rare: allergic reactions to recombinant protein. Quality and authenticity of any product sold as Klotho outside formal clinical trials should be considered highly uncertain.
How does Klotho work?
Klotho is a single-pass transmembrane protein primarily expressed in the kidney, parathyroid gland, and choroid plexus, with a soluble form (s-Klotho) cleaved from the membrane and circulating systemically as an endocrine factor. It exists in three forms — alpha-Klotho (the most studied, anti-ageing form), beta-Klotho (which partners with FGF21), and gamma-Klotho — each with distinct receptor partnerships and tissue effects. At the receptor level, alpha-Klotho is the obligate co-receptor for fibroblast growth factor 23 (FGF23), enabling FGF23 to bind and activate FGFR1 receptors in the kidney to regulate phosphate excretion. This makes Klotho a central node in mineral metabolism. Beyond this canonical role, soluble Klotho exerts numerous endocrine effects: it inhibits the IGF-1/insulin signalling pathway (a conserved longevity mechanism shared with caloric restriction), enhances expression of antioxidant enzymes via FoxO transcription factor activation, suppresses Wnt signalling (reducing stem cell exhaustion), inhibits TGF-beta signalling (preventing fibrosis), and blocks NF-kB and NLRP3 inflammasome activation (reducing inflammaging). The ageing phenotype connection is striking: mice lacking Klotho develop multi-organ ageing — atherosclerosis, osteoporosis, skin atrophy, cognitive decline — within weeks of birth, while mice with elevated Klotho expression live up to 30% longer than controls. In humans, circulating Klotho levels decline with age, and lower levels associate with increased mortality and chronic disease risk in observational studies. Recombinant alpha-Klotho is in early clinical development as a potential therapy for chronic kidney disease, cognitive decline, and broader age-related diseases. The 2026 research wave around Klotho has positioned it as one of the most promising single-protein interventions in the longevity field, though no therapeutic Klotho product is yet approved for human use.
How is Klotho administered?
Klotho is administered via recombinant alpha-klotho: subcutaneous or intravenous injection (clinical trial settings only).
What is the half-life of Klotho?
The half-life of Klotho is Recombinant alpha-Klotho: approximately 10-15 hours (estimated from primate studies).
Is Klotho legal?
Not approved for any indication. Recombinant alpha-Klotho is in early Phase 1 clinical trials for chronic kidney disease and cognitive decline. Products sold outside formal clinical trials as 'Klotho' are of highly uncertain authenticity.
Sources. This profile is built from peer-reviewed papers indexed on PubMed, FDA-approved labelling where available, and published clinical guidelines. The 5 primary sources used are listed in the Research Papers section above, each linked to its PubMed entry. See our editorial standards for how we research and review peptide profiles.
Last reviewed. by the Peptide Reference Editorial Team. Spot an error? Email a correction.
Not medical advice. Information on this page is for educational and research reference only. Many peptides covered are not approved for human use. See our full medical disclaimer.
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