Hardly any protein is linked to longevity in ageing research as often as Klotho. In February 2026, the US start-up Klothea Bio began a phase 1b trial of AKL003, an mRNA therapy intended to raise Klotho levels in the blood – for the first time in healthy adults.
What is Klotho?
Klotho was discovered in 1997 by the Japanese researcher Makoto Kuro-o. Mice without a functioning Klotho gene age at high speed: they develop vascular calcification, muscle wasting and osteoporosis early and die young. Conversely, mice that produced more Klotho lived considerably longer in a study published in Science in 2005. In humans, Klotho levels fall with age; in observational studies, low levels are associated with kidney and cardiovascular disease.
The trial
- Product: AKL003, an mRNA packaged in lipid nanoparticles that is intended to make the body produce alpha-Klotho
- Design: randomised, double-blind, placebo-controlled (phase 1b)
- Participants: 21 healthy adults aged between 25 and 75, in a 2:1 ratio of active drug to placebo
- Administration: two infusions about four weeks apart
- Endpoints: primarily safety and tolerability, plus Klotho levels in the blood, inflammatory and metabolic markers, sleep and recovery data and quality of life
With this candidate, Klothea Bio was selected as one of the semi-finalists of the XPRIZE Healthspan competition, which carries a prize of 101 million US dollars.
Why caution is warranted
The trial is taking place at a single centre: the GARM Clinic in Próspera on the island of Roatán (Honduras). Próspera is a special economic zone with its own set of rules, in which several experimental anti-ageing gene therapies have been offered in recent years outside the usual approval pathways. The trial is therefore not regulated by the FDA or the European Medicines Agency (EMA).
All information known so far comes from a company press release; data on the efficacy of AKL003 or on animal experiments have not been published in a scientific journal. With 21 participants, the trial can at best provide initial indications of safety – no conclusions about longevity can be drawn from it.
Conclusion
Klotho remains one of the most exciting targets in ageing medicine. However, whether Klotho levels can be raised safely in humans and whether this brings health benefits must be shown by independently monitored trials with published data.
Note: This article is for general information only and does not replace medical advice. AKL003 is not approved.
Sources
- PackGene: Klothea Bio Launches Phase 1b Trial of AKL003 (23.02.2026, company announcement)
- Kuro-o M et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997, DOI 10.1038/36285
- Kurosu H et al. Suppression of aging in mice by the hormone Klotho. Science 2005, PMC2536606
- PackGene: Roatán Island Pushes Regulatory Boundaries for Anti-Aging Gene Therapies
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