--- title: "Klotho Evidence | Lionheart Longevity Investor Relations" description: "Klotho and whole-body health: potential benefits by health area, with the type of evidence and primary-study references." url: https://investors.lionheartlongevity.com/science/klotho-evidence --- Science # Klotho and Whole Body Health Potential benefits by health area, the type of evidence behind each, and the primary studies. Most entries concern α-Klotho. β-Klotho is a distinct protein and is explicitly labeled where relevant. Low-Klotho associations and deficiency models do not prove that increasing Klotho benefits people. This guide summarizes research rather than demonstrated benefits of a Lionheart treatment. [ Evidence table (PDF)](https://investors.lionheartlongevity.com/docs/lionheart-klotho-evidence-table.pdf)[What is Klotho therapy? →](https://investors.lionheartlongevity.com/company/technology#klotho-therapy) ## Brain, hair and behavior | Health area | Potential role and supporting evidence | Refs. | | -------------------- | ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------- | | Hair loss | Human tissue / deficiencyMay help maintain hair-follicle growth. Silencing Klotho in cultured human follicles inhibited growth and promoted premature regression. Clinical prevention of hair loss has not been established. | [1](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-1) | | Dementia risk | Human genetic associationMay be associated with lower Alzheimer-related cognitive decline in certain genetic groups. KL-VS heterozygosity was linked to reduced progression to mild cognitive impairment or Alzheimer disease in APOE4 carriers; this does not establish prevention of all dementias. | [2](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-2) | | Alzheimer’s disease | Human association / low KlothoMay support resilience against Alzheimer pathology. Lower cerebrospinal-fluid Klotho was observed in Alzheimer disease; a protective genetic association was found in selected APOE4 carriers. Raising Klotho has not been shown here to prevent or treat human Alzheimer disease. | [2](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-2), [3](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-3) | | Parkinson’s disease | Animal interventionMay protect dopamine-producing neurons. Klotho reduced nigrostriatal injury in a toxin-induced rat model. Reduced Parkinson disease incidence or progression in people remains unproven. | [4](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-4) | | Cognition and memory | Nonhuman-primate interventionMay improve memory performance. A low-dose peripheral Klotho injection improved cognition in aged rhesus macaques. This supports therapeutic investigation, rather than established human memory enhancement. | [5](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-5) | | Addiction tendencies | β-Klotho • genetics / animalsβ-Klotho participates in the FGF21 pathway regulating alcohol preference. Human KLB genetics and mouse experiments support an alcohol-specific role; broad reductions in addiction tendencies or clinical addiction recovery are not established. | [6](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-6) | ## Strength, senses, skin and lungs | Health area | Potential role and supporting evidence | Refs. | | ------------------ | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------ | | Muscle strength | Human association / low KlothoMay support preservation of strength. Lower plasma Klotho was associated with poorer grip strength and greater decline in knee strength in older adults. These observational findings do not prove supplementation increases strength. | [7](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-7), [8](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-8) | | Vision loss | Animals / cells / deficiencyMay help preserve retinal function and protect retinal pigment epithelium from oxidative stress. Klotho-deficient mice had impaired retinal function; cell experiments support protective mechanisms. Prevention of human vision loss is unproven. | [9](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-9), [10](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-10) | | Hearing loss | Animals / human associationMay support auditory function. Deficient mice developed hearing abnormalities, and human observational work links serum Klotho with hearing outcomes. Human treatment or prevention of hearing loss has not been demonstrated by these studies. | [11](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-11), [12](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-12) | | Skin wrinkles | Preliminary human topical studyA topical Klotho-containing serum showed improvement in visible photoaging in a pilot study. This preliminary product study does not establish that Klotho alone reduces wrinkles or that systemic Klotho has the same effect. | [13](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-13) | | Lung deterioration | Animals / cells / deficiencyMay help maintain lung integrity and resistance to smoke-related cellular injury. Gene disruption caused emphysema in mice; extracellular Klotho reduced smoke-induced cell death in cultured human lung cells. Human lung protection remains investigational. | [14](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-14), [15](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-15) | | Cancer risk | Tumor tissue / laboratoryMay have tumor-suppressive activity in some cancer contexts. Human breast-cancer tissue and laboratory models showed reduced Klotho expression and growth-inhibiting effects. Lower cancer incidence or effective cancer treatment from raising Klotho is not established. | [16](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-16) | ## Cancer and organ health | Health area | Potential role and supporting evidence | Refs. | | ------------------------------- | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------ | | Heart and cardiovascular health | Human associationMay be associated with better cardiovascular health. Higher circulating Klotho was associated with lower prevalence of cardiovascular disease in adults. Observational evidence does not establish prevention of heart attacks, stroke or heart failure. | [17](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-17) | | Kidney health | CKD / animal interventionMay protect kidney function and reduce consequences of chronic kidney disease. Low Klotho accompanies CKD, and experimental deficiency worsened injury and calcification; overexpression was protective in mice. Human therapeutic benefit remains investigational. | [18](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-18) | | Bladder health | Animals / human associationMay support bladder function. Klotho-mutant mice had altered voiding and bladder contractility; lower serum Klotho was associated with urinary incontinence severity in women. Clinical improvement from raising Klotho remains unproven. | [19](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-19), [20](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-20) | | Pancreas health / diabetes | Animal intervention / islet evidenceMay help preserve insulin-producing pancreatic β-cells. Pancreatic α-Klotho expression improved β-cell preservation and glucose regulation in a type 2 diabetes mouse model. “β-cell” refers to the cell type, not β-Klotho. | [21](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-21) | | Liver health | Animal / peptide interventionMay reduce liver fibrosis through α-Klotho-related signaling. Deficiency and liver-injury models support a protective role; a Klotho-derived peptide reduced experimental fibrosis. A peptide result is not proof of whole-protein treatment efficacy in people. | [22](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-22) | ## Endocrine function, joints and repair | Health area | Potential role and supporting evidence | Refs. | | ------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ----------------------------------------------------------------------------- | | Pineal gland health | Indirect evidence onlyA direct pineal-health benefit is not established in the sources reviewed. Melatonin improved memory-related outcomes in Klotho-deficient mice, but this does not show that Klotho improves pineal function, melatonin production or pineal calcification. | [23](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-23) | | Thymus health | Mixed / mechanistic evidenceSystemic Klotho deficiency can coincide with thymic abnormalities, but a targeted study found thymic epithelial support of T-cell development did not require Klotho. Improved thymus function or rejuvenation should remain an unconfirmed hypothesis. | [24](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-24) | | Sexual health | Human hormone associationMay be related to hormone balance in men. Serum Klotho was positively associated with testosterone in a cross-sectional study. This does not establish improved libido, erections, fertility or sexual performance from increasing Klotho. | [25](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-25) | | Joint health | Human tissue / animalsMay help preserve cartilage integrity. Age-related stiffness reduced α-Klotho expression, and experimental loss compromised chondrocyte function and cartilage in osteoarthritis models. Human pain relief or disease modification remains unproven. | [26](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-26) | | Accelerated wound healing | Animal deficiencyMay support normal repair. α-Klotho-deficient mice had delayed wound healing and aged-skin-like features. Deficiency evidence does not establish accelerated healing beyond normal rates or clinical efficacy of Klotho treatment. | [27](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-27) | ## Circulation, bone, immunity and aging | Health area | Potential role and supporting evidence | Refs. | | ------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------ | | High blood pressure | Animal gene deliveryMay modulate blood pressure and protect the kidney. Klotho gene delivery prevented progression of hypertension in spontaneously hypertensive rats. A blood-pressure-lowering effect from Klotho treatment in people is not established by this study. | [28](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-28) | | Calcification | CKD / animal interventionMay reduce abnormal vascular calcification in CKD. Experimental Klotho deficiency promoted calcification, while overexpression was protective. This does not establish reversal of existing human calcification or benefit for every calcified tissue. | [18](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-18) | | Bone health | Animal gene therapyMay help preserve bone architecture in some aging contexts. Secreted-Klotho gene therapy improved bone measures in mice. Effects depend on phosphate–FGF23 physiology; more Klotho cannot be assumed universally beneficial for bone. | [29](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-29) | | Immunity health | Human cellsMay protect immune-cell function under inflammatory stress. Klotho reduced oxidative stress and immunosenescent-like changes in cultured human monocytes. Stronger immunity or fewer infections in treated people remains unproven. | [30](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-30) | | Gut health | β-Klotho animals / α deficiencyβ-Klotho protected intestinal barrier function in alcohol-exposed mice. Separately, experimental colitis reduced α-Klotho expression. These support pathway research, rather than demonstrated broad gut-health benefits from α-Klotho supplementation. | [31](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-31), [32](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-32) | | Slowing aging | Animal intervention / human associationMay influence longevity and age-related resilience. Klotho overexpression extended mouse lifespan; lower circulating Klotho was associated with higher mortality in older adults. Human lifespan extension or comprehensive slowing of aging has not been established. | [33](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-33), [34](https://investors.lionheartlongevity.com/science/klotho-evidence#ref-34) | ## References Numbered sources correspond to the table rows. Includes observational, experimental and deficiency studies. Reviewed October 11, 2026. 1. 1.[Expression Pattern and Role of Klotho in Human Hair Follicles (2021)](https://pubmed.ncbi.nlm.nih.gov/33911642/) 2. 2.[Association of Klotho-VS Heterozygosity With Risk of Alzheimer Disease in Individuals Who Carry APOE4 (2020)](https://pubmed.ncbi.nlm.nih.gov/32282020/) 3. 3.[Klotho in the cerebrospinal fluid of adults with and without Alzheimer's disease (2014)](https://pubmed.ncbi.nlm.nih.gov/24211693/) 4. 4.[The anti-aging protein klotho alleviates injury of nigrostriatal dopaminergic pathway in 6-hydroxydopamine rat model of Parkinson’s disease: Involvement of PKA/CaMKII/CREB signaling (2017)](https://pubmed.ncbi.nlm.nih.gov/29107062/) 5. 5.[Longevity factor klotho enhances cognition in aged nonhuman primates (2023)](https://pubmed.ncbi.nlm.nih.gov/37400721/) 6. 6.[KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference (2016)](https://pubmed.ncbi.nlm.nih.gov/27911795/) 7. 7.[Relationship of low plasma klotho with poor grip strength in older community-dwelling adults: the InCHIANTI study (2012)](https://pubmed.ncbi.nlm.nih.gov/21769735/) 8. 8.[Low Plasma Klotho Concentrations and Decline of Knee Strength in Older Adults (2016)](https://pubmed.ncbi.nlm.nih.gov/26359247/) 9. 9.[The age-regulating protein klotho is vital to sustain retinal function (2013)](https://pubmed.ncbi.nlm.nih.gov/24045987/) 10. 10.[Klotho Regulates Retinal Pigment Epithelial Functions and Protects Against Oxidative Stress (2013)](https://pmc.ncbi.nlm.nih.gov/articles/PMC3810551/) 11. 11.[Expression of Klotho protein in the inner ear (2002)](https://pubmed.ncbi.nlm.nih.gov/12204354/) 12. 12.[The significance of serum Klotho to hearing loss: a potential protector under noise pollution (2023)](https://pubmed.ncbi.nlm.nih.gov/37700133/) 13. 13.[A Pilot Study Evaluating Efficacy of a Topical Klotho Anti-Aging Serum to Treatable Visible Photoaging (2025)](https://pubmed.ncbi.nlm.nih.gov/40911741/) 14. 14.[Disruption of the klotho gene causes pulmonary emphysema in mice. Defect in maintenance of pulmonary integrity during postnatal life (2000)](https://pubmed.ncbi.nlm.nih.gov/10615062/) 15. 15.[Soluble extracellular Klotho decreases sensitivity to cigarette smoke induced cell death in human lung epithelial cells (2015)](https://pubmed.ncbi.nlm.nih.gov/26100223/) 16. 16.[Klotho: a tumor suppressor and a modulator of the IGF-1 and FGF pathways in human breast cancer (2008)](https://pubmed.ncbi.nlm.nih.gov/18762812/) 17. 17.[Plasma Klotho and Cardiovascular Disease in Adults (2011)](https://pmc.ncbi.nlm.nih.gov/articles/PMC3486641/) 18. 18.[Klotho deficiency causes vascular calcification in chronic kidney disease (2011)](https://pubmed.ncbi.nlm.nih.gov/21115613/) 19. 19.[Micturition defects and altered bladder function in the klotho mutant mouse (2020)](https://pubmed.ncbi.nlm.nih.gov/32699807/) 20. 20.[The relationship between serum alpha-klotho levels and urinary incontinence in middle-aged and older females: insights from NHANES (2024)](https://pmc.ncbi.nlm.nih.gov/articles/PMC11577013/) 21. 21.[In vivo pancreatic β-cell-specific expression of antiaging gene Klotho: a novel approach for preserving β-cells in type 2 diabetes (2015)](https://pubmed.ncbi.nlm.nih.gov/25377875/) 22. 22.[Klotho-derived peptide 1 ameliorates hepatic fibrosis induced by αKlotho deficiency and liver injury (2026)](https://pubmed.ncbi.nlm.nih.gov/41608630/) 23. 23.[Melatonin Attenuates Memory Impairment Induced by Klotho Gene Deficiency Via Interactive Signaling Between MT2 Receptor, ERK, and Nrf2-Related Antioxidant Potential (2015)](https://pmc.ncbi.nlm.nih.gov/articles/PMC4438546/) 24. 24.[Thymic epithelial cell support of thymopoiesis does not require Klotho (2018)](https://pmc.ncbi.nlm.nih.gov/articles/PMC6275142/) 25. 25.[The relationship between klotho, testosterone, and sexual health parameters among US adult men (2024)](https://pubmed.ncbi.nlm.nih.gov/37648906/) 26. 26.[Age-related matrix stiffening epigenetically regulates α-Klotho expression and compromises chondrocyte integrity (2023)](https://pubmed.ncbi.nlm.nih.gov/36627269/) 27. 27.[Wound healing delays in α-Klotho-deficient mice that have skin appearance similar to that in aged humans – Study of delayed wound healing mechanism (2016)](https://pubmed.ncbi.nlm.nih.gov/27037022/) 28. 28.[Klotho gene delivery prevents the progression of spontaneous hypertension and renal damage (2009)](https://pubmed.ncbi.nlm.nih.gov/19635988/) 29. 29.[Long-term effects of s-KL treatment in wild-type mice: Enhancing longevity, physical well-being, and neurological resilience (2025)](https://pubmed.ncbi.nlm.nih.gov/39988871/) 30. 30.[Klotho protects human monocytes from LPS-induced immune impairment associated with immunosenescent-like phenotype (2017)](https://pubmed.ncbi.nlm.nih.gov/28478304/) 31. 31.[Intestinal epithelial β Klotho is a critical protective factor in alcohol-induced intestinal barrier dysfunction and liver injury (2022)](https://pmc.ncbi.nlm.nih.gov/articles/PMC9352463/) 32. 32.[Downregulation of aging-related Klotho gene in experimental colitis: the role of TNF and IFN-γ (2010)](https://pmc.ncbi.nlm.nih.gov/articles/PMC3454518/) 33. 33.[Suppression of aging in mice by the hormone Klotho (2005)](https://pubmed.ncbi.nlm.nih.gov/16123266/) 34. 34.[Plasma klotho and mortality risk in older community-dwelling adults (2011)](https://pubmed.ncbi.nlm.nih.gov/21474560/)