Peptide Profile
Klotho
alpha-Klotho · a-Klotho · soluble Klotho · KL protein fragment
Klotho is an endogenous transmembrane protein and circulating hormone encoded by the KL gene, expressed primarily in kidney distal tubules and brain choroid plexus, that functions as a co-receptor for fibroblast growth factor 23…
- Routes
- subcutaneous, intravenous
Educational research information — not medical advice. Review primary sources and consult a qualified professional before any decision.
Educational research tools — not medical advice.
What Klotho is
About Klotho
Acts as a co-receptor for FGF23, regulating phosphate and vitamin D metabolism. As a circulating hormone, inhibits insulin/IGF-1 signaling to extend lifespan, activates Nrf2 antioxidant pathways, and suppresses TGF-β fibrotic signaling.
Klotho is an endogenous transmembrane protein and circulating hormone encoded by the KL gene, expressed primarily in kidney distal tubules and brain choroid plexus, that functions as a co-receptor for fibroblast growth factor 23 (FGF23) and as a systemic anti-aging regulatory factor; circulating alpha-klotho levels decline progressively with age and have been associated with accelerated aging phenotypes, cognitive decline, and increased cardiovascular mortality in large human cohort studies. Soluble klotho exerts pleiotropic protective effects including suppression of IGF-1 and Wnt signaling, reduction of oxidative stress and inflammation, regulation of calcium-phosphate homeostasis via FGF23 co-signaling, and neuroprotective effects relevant to brain aging; mouse models overexpressing klotho live approximately 30% longer while klotho-deficient mice develop premature aging syndromes, establishing it as a key longevity regulator in mammals. Human epidemiological and cohort data — including a systematic review and meta-analysis and a large PNAS cohort study — support significant associations between higher circulating klotho levels and better cognitive performance, lower dementia incidence, and reduced cardiovascular mortality, establishing klotho as a robust human biomarker of healthy aging. Exogenous klotho has no FDA approval and no human interventional trial data; while preclinical administration of recombinant klotho has shown promising anti-aging effects in animal models, the compound remains an active research target rather than an established therapeutic, and its use as an administered agent in humans is not supported by any published clinical evidence.
Klotho Benefits & Research Areas
What the evidence says about Klotho
Research Evidence
based on 8 studies · most recent 2026
Regulatory Status
- Availability Status
- Research Only
- FDA Status
- Not Evaluated
Regulatory status reflects publicly available information and may change. This is not legal or medical advice.
Research Sources
8 sources cited · 1 strong · 2 moderate · 5 weak
1 Meta-analysis · 2 Cohorts · 1 Review · 4 Animals
Klotho protein and cognitive function: a systematic review and meta-analysis
Asian Journal of Psychiatry · 2025
A systematic review and meta-analysis of studies totaling 6,645 participants found a significant positive correlation between klotho protein levels and cognitive function, with subgroup analyses confirming significance for α-klotho measured in serum and plasma, supporting klotho as a biomarker of cognitive aging and a candidate longevity-promoting target.
Association between soluble Klotho levels and calcification propensity T50 in patients with hemodialysis: a cross-sectional study.
Sci Rep · 2026
Klotho heterozygosity does not modify cognitive decline in APOE ε4 carriers: analysis of a large biobank cohort
Proceedings of the National Academy of Sciences · 2025
In a large biobank cohort of 320,861 participants, APOE ε4 homozygous carriers showed significantly greater cognitive decline than heterozygotes; klotho heterozygosity did not independently modify cognitive trajectories after controlling for APOE genotype, providing important context for interpreting klotho's cognitive benefits within the broader longevity genetic risk framework.
Show 5 more sources ↓
VSIG4 Expression During Renal Aging Is Accelerated by Type 2 Diabetes in Mice.
Life (Basel) · 2026
# Summary Research found that VSIG4 expression increases during kidney aging in mice, with this process accelerated in type 2 diabetic mice compared to non-diabetic controls. This study demonstrated that urinary VSIG4 levels correlate strongly with kidney damage markers and may reflect age-related kidney changes, while klotho expression—a known marker of kidney aging—progressively declined over time.
Gene deletion of Klotho in the dentate gyrus does not affect the number of adult-born granule cells.
Sci Rep · 2026
# Summary Research found that removing the Klotho gene specifically in the dentate gyrus—a brain region involved in memory formation—did not alter the production or number of newly generated neurons in adult mice. This study demonstrated that despite Klotho's known roles in aging and neuroprotection, it is not required for maintaining the normal rate of adult neurogenesis in this particular brain structure.
Vitamin D attenuates Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and downregulates hepatic gluconeogenesis in obesity.
J Nutr Biochem · 2026
Podocyte mPGES-2 Determines Renal Aging and Contributes to Senile Osteoporosis.
Aging Cell · 2026
From Longevity Genetics to Precision Interventions: Integrating Nutrigenomics and Epigenetic Mechanisms of Ageing.
Genes (Basel) · 2026
Klotho Side Effects & Safety Considerations
Research-use compound with limited human data. Evidence strength varies — see the Evidence section.
No established clinical contraindications. This is an investigational compound with limited human data and has not been evaluated by the FDA for safety in this context. Consult a qualified clinician.
Consult a qualified healthcare professional before making any health decisions. This information is educational only and does not constitute medical advice.
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Frequently Asked Questions — Klotho
Klotho is an endogenous transmembrane protein and circulating hormone encoded by the KL gene, expressed primarily in kidney distal tubules and brain choroid plexus, that functions as a co-receptor for fibroblast growth factor 23 (FGF23) and as a systemic anti-aging regulatory factor; circulating alpha-klotho levels decline progressively with age and have been associated with accelerated aging phenotypes, cognitive decline, and increased cardiovascular mortality in large human cohort studies. Soluble klotho exerts pleiotropic protective effects including suppression of IGF-1 and Wnt signaling, reduction of oxidative stress and inflammation, regulation of calcium-phosphate homeostasis via FGF23 co-signaling, and neuroprotective effects relevant to brain aging; mouse models overexpressing klotho live approximately 30% longer while klotho-deficient mice develop premature aging syndromes, establishing it as a key longevity regulator in mammals.
neuroprotection, cardiovascular protection, anti-aging, cognitive support, anti-fibrotic.
Research on Klotho primarily documents effects related to neuroprotection and cardiovascular protection and anti-aging and cognitive support and anti-fibrotic. These are areas covered in preclinical and clinical literature — individual response varies and effects depend on context of use.
For Klotho, its FDA status is not evaluated by the FDA, and it is designated for research use only. Regulatory status reflects publicly available information and may change. This is not legal or medical advice.
A systematic review and meta-analysis of studies totaling 6,645 participants found a significant positive correlation between klotho protein levels and cognitive function, with subgroup analyses confirming significance for α-klotho measured in serum and plasma, supporting klotho as a biomarker of cognitive aging and a candidate longevity-promoting target.
How to get Klotho
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