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categories: ["longevity", "genetics"]categories: ["longevity", "genetics"]tags: ["gene therapy", "aav", "telomerase", "klotho", "follistatin", "aging", "self-experimentation"]tags: ["gene therapy", "aav", "telomerase", "klotho", "follistatin", "aging", "self-experimentation"]summary: "The use of delivered genes to modify aging biology systemically, demonstrated in mice with telomerase and other constructs and untested in any controlled human trial."summary: "The use of delivered genes to modify aging biology systemically, demonstrated in mice with telomerase and other constructs and untested in any controlled human trial."updated: "2026-07-28"updated: "2026-10-28"humanEvidence: "No controlled trial has tested any of these constructs against aging in people; the human record is unregulated self-administration reported by press release, plus early-phase follistatin trials in muscular dystrophy."humanEvidence: "No controlled trial has tested any of these constructs against aging in people; the human record is self-administration and single-arm offshore studies without published results, plus early-phase trials in muscle and eye disease."access: "Available through no approved route; pay-to-participate ventures in permissive jurisdictions have offered telomerase and follistatin constructs, one at a reported price of about a million dollars per participant."access: "Not approved for any aging indication; offshore ventures have charged for unapproved telomerase and follistatin constructs at reported prices from about $25,000 to $1 million per dose."reversibility: "context"reversibility: "context"issues: ["The BioViva, Libella, and Honduras episodes are described without citations.", "The klotho monkey result and the OSK mouse lifespan claim are stated without sources."]issues: ["The klotho monkey result is stated without a source.", "Minicircle's announced 2026 commercial klotho offering is not covered pending a primary source."]------ ```infobox```infoboxlines 60–68 → 60–7241 unchanged lines not shown
The newest line delivers reprogramming factors rather than a single protein. Vectors carrying OSK, theThe newest line delivers reprogramming factors rather than a single protein. Vectors carrying OSK, thethree-factor subset of the [[yamanaka-factors]] that omits the oncogene MYC, have been reported tothree-factor subset of the [[yamanaka-factors]] that omits the oncogene MYC, have been reported toextend remaining lifespan in mice treated in old age, in studies with small cohorts that have not beenextend remaining lifespan in mice treated in old age: one study gave an inducible AAV-OSK system toindependently replicated. This work sits at the intersection of gene therapy andmale mice aged 124 weeks and reported a 109% increase in median remaining lifespan, a result that has[[epigenetic-reprogramming]]; the dosing and duration questions are those ofnot been independently replicated.[^macip2024] In 2026 an OSK construct entered a registered humantrial aimed at a disease rather than at aging: Life Biosciences' ER-100, an AAV vector carryingdoxycycline-controlled OSK injected into one eye, began an open-label phase 1 safety study inglaucoma and ischaemic optic neuropathy.[^registry2026] This work sits at the intersection of genetherapy and [[epigenetic-reprogramming]]; the dosing and duration questions are those of[[partial-reprogramming]].[[partial-reprogramming]]. > [!caution] Mice are not the hard case> [!caution] Mice are not the hard caselines 101–125 → 105–14232 unchanged lines not shown
## Unregulated human use## Unregulated human use Because no legitimate trial exists, the human record has been written by people outside the system.Because no controlled trial for aging exists, the human record has been written largely outside conventional oversight. In 2015 the chief executive of the company BioViva, Elizabeth Parrish, received AAV constructsIn September 2015 the chief executive of the company BioViva, Elizabeth Parrish, received two genecarrying telomerase and a myostatin inhibitor outside the United States and reported subsequenttherapies outside the United States, reportedly in Colombia: follistatin, a myostatin inhibitor,lengthening of leukocyte telomeres measured by a commercial assay. The result was never peerinjected into muscle, and an intravenous viral vector carrying telomerase.[^regalado2015] BioVivareviewed, the assay is noisy, and one person is not a study.later announced, by press release, lengthening of her leukocyte telomeres measured by a commercialassay. The result was not published in a journal, the assay is noisy, and one person is not a study. In 2019 Libella Gene Therapeutics announced a pay-to-participate telomerase gene therapy offered inIn 2019 Libella Gene Therapeutics offered an AAV telomerase gene therapy at a clinic in Zipaquirá,Colombia at around a million dollars per participant, a structure that inverts the ethics of clinicalColombia, at $1 million per dose,[^swain2019] a pay-to-participate structure that inverts the ethicsresearch by charging subjects for an unproven intervention. No results have been published.of clinical research by charging subjects for an unproven intervention. Its registry entries, eachfor five participants, were last updated in 2019 and report no results.[^registry2026] Since 2023 a company has offered plasmid-based follistatin gene therapy in a special jurisdiction inMinicircle, a Delaware-registered startup, doses volunteers in Próspera, a special economic zone onHonduras, with participants including a prominent longevity entrepreneur. Plasmid delivery is lessthe Honduran island of Roatán with its own regulatory framework, whose legal standing Honduras haspersistent than AAV, which reduces some risks, and the venture has produced self-collected data rathercontested since its Congress voted in 2022 to repeal the law behind such zones. The company recruitedthan controlled evidence.volunteers in 2022 for a plasmid follistatin gene therapy, at one point asking them to buy an NFT totake part.[^clarke2023] That study enrolled 43 people between August 2022 and August 2023, wasregistered only in May 2024, after it had finished, and has posted no results.[^registry2026] InSeptember 2023 the longevity entrepreneur [[bryan-johnson|Bryan Johnson]] received the therapy, thenlisted at about $25,000 per treatment, on Roatán; Minicircle had published no trial data.[^fortune2023]Plasmid delivery is less persistent than AAV, which reduces some risks. In 2025 the company began twofurther single-arm studies, of a klotho plasmid and of klotho combined with follistatin, eachenrolling 14 people; as of October 2026 neither had posted results. A second company, UnlimitedBiotechnology, began an open-label phase 1/2a at a Roatán clinic in June 2026, combining an AAV9follistatin vector with a VEGF plasmid for age-related muscle decline.[^registry2026] These ventures share a pattern: jurisdiction shopping, absent control groups, surrogate endpointsThese ventures share a pattern: jurisdiction shopping, absent control groups, surrogate endpointschosen after the fact, and outcomes announced by press release. They generate no usable knowledge andchosen after the fact, and outcomes announced by press release. Registration on ClinicalTrials.gov,raise the regulatory temperature for the researchers doing the work properly.which the later ventures have adopted, makes their designs visible without adding a control group.They generate little usable knowledge and raise the regulatory temperature for the researchers doingthe work properly. ## What a legitimate path would look like## What a legitimate path would look like lines 166–169 → 183–19240 unchanged lines not shown
[^kurosu2005]: `paper` Kurosu, H. et al. "Suppression of aging in mice by the hormone Klotho." *Science*, 2005. {A transgenic overexpression model rather than a delivered therapy: the mice carried the extra klotho from conception.}[^kurosu2005]: `paper` Kurosu, H. et al. "Suppression of aging in mice by the hormone Klotho." *Science*, 2005. {A transgenic overexpression model rather than a delivered therapy: the mice carried the extra klotho from conception.}[^mendell2015]: `paper` Mendell, J.R. et al. "A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy." *Molecular Therapy*, 2015. {An open-label early-phase trial in a small number of men with Becker muscular dystrophy, with no placebo group.}[^mendell2015]: `paper` Mendell, J.R. et al. "A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy." *Molecular Therapy*, 2015. {An open-label early-phase trial in a small number of men with Becker muscular dystrophy, with no placebo group.}[^musunuru2021]: `paper` Musunuru, K. et al. "In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates." *Nature*, 2021.[^musunuru2021]: `paper` Musunuru, K. et al. "In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates." *Nature*, 2021.[^macip2024]: `paper` Macip, C. C. et al. "Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice." *Cellular Reprogramming*, 2024. {Male mice only, treated from 124 weeks of age; the 109% figure is for median remaining lifespan, not total lifespan.}[^regalado2015]: `news` Regalado, A. "A Tale of Do-It-Yourself Gene Therapy." *MIT Technology Review*, 14 October 2015. https://www.technologyreview.com/2015/10/14/165802/a-tale-of-do-it-yourself-gene-therapy/ {The magazine could not confirm many details: Parrish would not name the country or the doctor, and Colombia comes from people involved with the company.}[^swain2019]: `news` Swain, F. "Buyer beware of this $1 million gene therapy for aging." *MIT Technology Review*, 6 December 2019. https://www.technologyreview.com/2019/12/06/131657/buyer-beware-of-this-1-million-gene-therapy-for-aging/[^clarke2023]: `news` Clarke, L. "This biohacking company is using a crypto city to test controversial gene therapies." *MIT Technology Review*, 13 February 2023. https://www.technologyreview.com/2023/02/13/1068330/minicircle-prospera-honduras-biohacking-follistatin-gene-therapy/[^fortune2023]: `news` Royle, O. R. "Bryan Johnson is being used as a human guinea pig in unproven gene therapy injections worth $25,000 a pop in an island off Honduras." *Fortune*, 21 December 2023. https://fortune.com/2023/12/21/bryan-johnson-human-guinea-pig-unproven-tests-reprogram-human-genes-follistatin-roatan-island-honduras {Reports that Minicircle did not charge Johnson; his claimed results come from his own posts and from Bloomberg, not from a study.}[^registry2026]: `trial` ClinicalTrials.gov records NCT04133649 (Libella, AAV-hTERT), NCT06411366 (Minicircle, follistatin plasmid), NCT07216781 and NCT07285629 (Minicircle, klotho and klotho-follistatin plasmids), NCT07443826 (Unlimited Biotechnology, AAV9-follistatin with VEGF plasmid), and NCT07290244 (Life Biosciences, ER-100), checked October 2026. {All are single-arm or non-randomised and unmasked; none had posted results at the time checked.} removed, struck through added, underlinedLine numbers count the serialised markdown of each revision, frontmatter included.
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