Klotho
Alpha-Klotho (secreted s-KL) and klotho-based therapies
Also known as: s-KL, Soluble klotho, KLTO-202, AKL003, alphaKlothoLR, Klotho peptide
The 'anti-aging gene' protein whose blood levels track with longevity and cognition; a gene therapy (KLTO-202) is heading toward human trials, while products sold online as 'klotho peptide' are not the protein studied.
Overview
Klotho is a transmembrane protein, mostly made in the kidney and brain, whose shed form circulates as soluble klotho. Mice lacking it age rapidly; mice overexpressing it live longer, and in humans higher circulating klotho associates with better cognition and lower mortality. A single injection of klotho improved cognition in aged monkeys in a 2023 Nature Aging study. A 2025 Molecular Therapy study reported a 19.7% lifespan extension in male mice from a single dose of an AAV secreted-klotho gene therapy. In humans, Klothea Bio began a 21-person Phase 1b safety trial of AKL003 (mRNA alpha-klotho) in Honduras in February 2026, Klotho Neurosciences is developing an AAV gene therapy (KLTO-202) for ALS, and Minicircle sells an offshore klotho gene therapy. There is no approved klotho drug. Native alpha-klotho is a roughly 130 kDa protein of 998 amino acids; vendor products sold as 'klotho peptide' or 'alphaKlothoLR' at about $500 for 20 micrograms are short engineered fragments or unrelated peptides, cannot deliver anything close to the doses used in animal studies, and have no published human data.
Mechanism of action
Soluble klotho acts as a co-receptor for FGF23 and modulates insulin/IGF-1, Wnt and oxidative-stress signaling; its decline with age is linked to kidney, vascular and cognitive aging.
Key studies & citations
- Animal1997
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Klotho deficiency causes accelerated aging in mice.
Nature - Animal2005
Suppression of aging in mice by the hormone Klotho
Overexpression extended lifespan by about 20 to 30%.
Science - Animal2023
Longevity factor klotho enhances cognition in aged nonhuman primates
A single low dose improved memory in aged rhesus monkeys.
Nature Aging - Animal2025
Single-dose AAV secreted-klotho gene therapy extends lifespan in adult mice
19.7% lifespan extension in males with bone, muscle and brain benefits.
Molecular Therapy - Human2026
Klothea initiates longevity-focused human trial of klotho therapy (AKL003)
21-adult Phase 1b safety study of mRNA alpha-klotho; no efficacy data yet.
Longevity.Technology - Human2011
Plasma klotho and mortality risk in older community-dwelling adults
Higher circulating klotho associates with lower mortality in observational cohorts.
Journal of Gerontology / meta-analyses
Frequently asked questions
Can you raise klotho naturally?
Exercise, vitamin D sufficiency and some blood-pressure and diabetes drugs have been associated with higher klotho in small studies. None are proven to change outcomes through klotho itself.
What is 'klotho peptide' sold online?
Usually a short synthetic fragment marketed with the klotho name. There are no published human studies showing these products raise klotho or do anything the full protein does.
Is there a klotho drug?
Not yet. AKL003 (mRNA) entered a 21-person safety trial in 2026 and KLTO-202 (AAV gene therapy for ALS) is pre-IND. Nothing has shown a benefit in people.