Loading
What changed between revision 1 and revision 2, compared over the article's markdown source with its frontmatter — so a change to status, evidence or reversibility shows up as the edit it is.
Older · revision 1
Import· initial corpus import, not an edit
Initial import of content/klotho.md — the filesystem corpus, unchanged. Not an edit.
16.8 kB
Revision 1
Revision 2
lines 7–13 → 7–136 unchanged lines not shown
categories: ["longevity", "genetics"]categories: ["longevity", "genetics"]tags: ["aging", "longevity", "kidney", "fgf23", "cognition", "mouse studies", "hormones"]tags: ["aging", "longevity", "kidney", "fgf23", "cognition", "mouse studies", "hormones"]summary: "A gene and hormone whose loss shortens mouse lifespan and whose best-demonstrated job is phosphate control, proposed as a longevity factor on largely non-human evidence."summary: "A gene and hormone whose loss shortens mouse lifespan and whose best-demonstrated job is phosphate control, proposed as a longevity factor on largely non-human evidence."updated: "2026-08-23"updated: "2026-10-28"humanEvidence: "In people the evidence is observational: KL-VS genotype and serum klotho track cognition and mortality inconsistently across cohorts, and no trial of administered klotho has reported results."humanEvidence: "In people the evidence is observational: KL-VS genotype and serum klotho track cognition and mortality inconsistently across cohorts, and no trial of administered klotho has reported results."access: "Not available as a therapy; two phase 1 studies of klotho gene and mRNA delivery were registered by 2026, one of them dosing volunteers outside United States regulatory jurisdiction."access: "Not available as a therapy; two phase 1 studies of klotho gene and mRNA delivery were registered by 2026, one of them dosing volunteers outside United States regulatory jurisdiction."------lines 85–91 → 85–9171 unchanged lines not shown
Administration studies bypass the genetics by injecting the protein. In mice, peripherally delivered klotho fragments improved cognition and synaptic measures. The most-cited extension of that work gave rhesus klotho protein to aged rhesus monkeys and reported improved memory performance after a single low dose, with no benefit at a high dose.[^castner2023] The dose-response inversion is unusual, the group was small, and the study measured memory rather than lifespan or any [[healthspan]] endpoint. It remains the closest thing to a human-relevant demonstration.Administration studies bypass the genetics by injecting the protein. In mice, peripherally delivered klotho fragments improved cognition and synaptic measures. The most-cited extension of that work gave rhesus klotho protein to aged rhesus monkeys and reported improved memory performance after a single low dose, with no benefit at a high dose.[^castner2023] The dose-response inversion is unusual, the group was small, and the study measured memory rather than lifespan or any [[healthspan]] endpoint. It remains the closest thing to a human-relevant demonstration. Two human studies were on the registry by 2026, neither with results.[^trials2026] Minicircle, a company that dosed volunteers with a plasmid follistatin construct in an earlier and widely reported episode of offshore [[biohacking]], registered a 24-person, single-arm, non-placebo-controlled phase 1 of an injectable klotho plasmid, with the record stating that administration occurs outside United States jurisdiction while assessments happen in Texas. Klothea Bio registered a randomised, placebo-controlled phase 1b of an α-klotho mRNA formulated in [[lipid-nanoparticles]]. The contrast between the two designs is the whole argument about how [[gene-therapy-for-aging]] should be tested, and it is visible in the registry entries themselves.Two human studies were on the registry by 2026, neither with results.[^trials2026] Minicircle, a company that dosed volunteers with a plasmid follistatin construct in an earlier and widely reported episode of offshore [[biohacking]], registered a single-arm, non-placebo-controlled phase 1 of an injectable klotho plasmid that enrolled 14 people, with the record stating that administration occurs outside United States jurisdiction while assessments happen in Texas. Klothea Bio registered a randomised, placebo-controlled phase 1b of an α-klotho mRNA formulated in [[lipid-nanoparticles]]. The contrast between the two designs is the whole argument about how [[gene-therapy-for-aging]] should be tested, and it is visible in the registry entries themselves. Delivery is unsettled. Klotho has been pursued as recombinant protein, as mRNA, and as a gene delivered by [[aav-vectors]] under the general approach described in [[somatic-gene-therapy]]. Each raises a different durability and reversibility question, and none has cleared it. Two authors of the monkey study founded a company to continue developing klotho therapeutics, and a corporate sponsor of that work held patent applications on klotho for cognition.[^castner2023] Commercial interest in the molecule runs well ahead of the human evidence for it, a pattern the field also produced around [[senolytics]] and around [[parabiosis-and-young-blood|young-blood transfusion]].Delivery is unsettled. Klotho has been pursued as recombinant protein, as mRNA, and as a gene delivered by [[aav-vectors]] under the general approach described in [[somatic-gene-therapy]]. Each raises a different durability and reversibility question, and none has cleared it. Two authors of the monkey study founded a company to continue developing klotho therapeutics, and a corporate sponsor of that work held patent applications on klotho for cognition.[^castner2023] Commercial interest in the molecule runs well ahead of the human evidence for it, a pattern the field also produced around [[senolytics]] and around [[parabiosis-and-young-blood|young-blood transfusion]]. removed, struck through added, underlinedLine numbers count the serialised markdown of each revision, frontmatter included.
119 lines are the same in both revisions, and 107 of them are not shown. Neither revision here is necessarily the current article — read Klotho for the text this wiki stands behind today.