# Longevity and healthspan drug trials

[Home](../README.md) · [Metabolic health and longevity](../WATCHLIST.md#metabolic-health) · [Calendar](../MILESTONES.md)

Tags: [Drugs and biologics](../BROWSE.md#drugs)

## Current state

VITAL-H’s registered functional-healthspan protocol remains without results. A newly recovered sponsor first-dose report for SenoMune concerns advanced cancer and lacks a verified public protocol/oversight; it is not healthy-adult longevity evidence. Biomarker and animal results remain separate from human healthspan benefit.

Status: active. Initial evidence brief completed 2026-09-12; ongoing monitoring follows this baseline.

## Questions to follow

- Follow formal human trials aimed at aging biology, healthspan, multimorbidity, frailty, or longevity.
- Metformin is an initial research focus. Investigate TAME and other relevant human trials, verifying whether each is proposed, funded, registered, recruiting, completed, or reporting results.
- Discover other human-stage geroscience drugs; do not include routine animal-only lifespan findings.
- Distinguish clinical outcomes from changes in epigenetic clocks or other unvalidated surrogate markers. Do not describe a biomarker improvement as proven lifespan extension.
- Track enrollment, milestones, efficacy, null results, safety, and whether results apply to people without the disease for which a drug is already used.

## Programs and next milestones

### Focused update — 2026-11-10

<span class="note-anchor" id="note-2026-11-10-senomune-first-human-claimed-baseline"></span>

#### Recovered lead: sponsor reports a first human senolytic-immunotherapy dose

**Source date:** 2026-11-02. **Evidence:** Sponsor-only first-dose claim; public protocol and oversight not verified. **Appraisal:** November 10 scheduled run, completed November 11 UTC; source dates are not retrieval dates.

The original **November 2** sponsor release says the first **SenoMune-0257** recipient was treated **October 29** in Mexico in an investigator-initiated advanced-cancer study. The company describes a nine-amino-acid peptide intended to induce immune recognition of senescent cells. This is a newly recovered human-stage lead, not a proven anti-aging therapy or a healthy-adult healthspan trial.

The checked disclosure supplies no registered protocol identifier, patient denominator beyond the first dose, complete design, ethics/regulatory authorization, dose schedule, endpoints or human safety/efficacy results. A public protocol and formal oversight were not independently verified in this run. The company’s earlier SenoVax animal results concern a different product and are not substituted for human SenoMune evidence. **U.S. status:** Investigational; no U.S. approval or treatment-access recommendation is established. Next: verified protocol/oversight and human results, with no announced date.

**Next milestones:** Verified protocol/oversight and first human safety results: date unknown.

**Sources:** [Source 1](https://www.prnewswire.com/news-releases/first-human-administration-of-senolytic-immunotherapy-to-fight-cellular-aging-announced-by-immorta-bio-302926449.html).

**Coverage and remaining gaps:** Focused, incomplete review. All pages of the specified U.S. registry discovery and saved identifiers were retrieved; retrieval is not full appraisal. Global registers, every paper/supplement and the complete regulatory/harms census remain incomplete. Full-success and baseline flags stay unchanged. [Run record](../updates/2026-11-10_scheduled_research_update.md).

### Focused update — 2026-11-06

<span class="note-anchor" id="note-2026-11-06-vitalh-healthspan-protocol"></span>

#### VITAL-H registers a large functional-healthspan trial

**Source date:** 2026-11-06. **Recorded in this review:** November 6, 2026.

**Evidence:** New trial-registry protocol.

**What changed:** NCT07923630, first posted November 6, is a Phase 2b double-blind randomized, double-dummy placebo-controlled plan for 1,200 community-dwelling adults aged 60–75, BMI20–40, without diabetes (HbA1c<6.5%) or major specified cardiovascular disease. It separately tests daily dapagliflozin 10 mg and oral semaglutide starting 1.5 mg, titrated to 4 mg as tolerated, against placebo for 36 months plus 6 months follow-up. Primary is change in the Short Physical Performance Battery, covering balance, walking and chair stands; VO2 peak is secondary. These are functional measures, not lifespan or proven disability-free survival.

**Limitations:** The current protocol has no rapamycin arm, unlike the March 4 investigator announcement of 726 adults and four arms. Do not merge the earlier proposal into the current trial. Registry says not yet recruiting; the undated Barshop page places VITAL-H under Studies Currently Recruiting. Actual enrollment/start remains unresolved despite that discrepancy.

**Safety:** No efficacy or safety results. Exclusions include diabetes, eGFR<45, major cardiovascular disease and recurrent UTI, limiting generalization.

**U.S. status:** Both drugs have existing disease-specific FDA approvals; neither is FDA-approved to extend healthspan in generally healthy adults.

**Next milestones:** VITAL-H estimated start: 2027-01 (Registry estimate); VITAL-H estimated primary completion: 2030-12 (Registry estimate); VITAL-H estimated final completion: 2031-02 (Registry estimate)

**Sources:** [ClinicalTrials.gov](https://clinicaltrials.gov/study/NCT07923630); [Primary source](https://barshopinstitute.uthscsa.edu/clinical-trials/); [Primary source](https://news.uthscsa.edu/ut-san-antonio-to-lead-38-million-national-trial-testing-drugs-to-extend-healthspan/).

<span class="note-anchor" id="note-2026-11-05-rapamycin-transplant-survival-null"></span>

#### Large transplant cohort finds no adjusted survival advantage with rapamycin

**Source date:** 2026-11-05. **Recorded in this review:** November 6, 2026.

**Evidence:** Peer-reviewed observational human study.

**What changed:** The November 5 GeroScience paper compares 4,885 kidney-transplant recipients prescribed an mTOR inhibitor with 6,589 not prescribed one, all alive with functioning grafts at one year. Median follow-up was about 11 years. Propensity-weighted median survival age with follow-up beyond graft failure was 64.6 versus 64.3 years; difference 0.3 years (95% CI −1.6 to 2.0). This did not show an adjusted survival advantage.

**Limitations:** Observational treatment selection, unmeasured confounding and changing drug exposure prevent a causal conclusion. Transplant immunosuppression and generally daily exposure differ from intermittent lower-dose use in healthier adults. This does not prove that all future rapamycin geroscience regimens fail.

Exposure was classified as an mTOR inhibitor (Rapamune, Zortress or generic sirolimus), rather than an exclusively single-compound randomized rapamycin regimen.

**Safety:** Not a randomized safety comparison; specific dose/adherence and long-term exposure were not captured, and more than half of causes of death were unavailable.

**U.S. status:** No new approval; sirolimus has transplant uses, not a longevity indication.

**Next milestones:** Prospective geroscience functional/survival evidence: date unknown (No reliable date verified)

**Sources:** [Primary source](https://link.springer.com/article/10.1007/s11357-026-02643-8).

**Coverage and remaining gaps:** focused_incomplete; Focused incomplete appraisal. All pages of specified ClinicalTrials.gov discovery were downloaded, plus all176 unique saved named IDs across these ten topics; retrieval does not equal appraisal. Full worldwide literature/non-U.S.-registry, regulatory-label, harms/hold/discontinuation census and original conference/podcast recordings remain incomplete. Preserve full successful-check timestamps and incomplete sleep baseline flags.; VITAL-H recruitment sources disagree; actual enrollment unknown. TAME funded launch/status and full prospective geroscience baseline remain incomplete. The new transplant study cannot resolve healthy-adult intermittent dosing.

**Informal-source coverage:** Original Vitaei PEARL24month claim reread; no matching primary follow-up verified. New November 4metformin/SGLT2/f , asting Reddit post repeats a narrative review, not a new trial outcome. Podcast corpus incomplete.

[Full coverage record](../updates/2026-11-06_scheduled_research_update.md).


### Focused update — 2026-11-03

<span class="note-anchor" id="note-2026-11-03-fmt-biological-aging-randomized-protocol"></span>

#### A placebo-controlled FMT study targets aging biomarkers

**Source date:** 2026-11-03. **Recorded in this review:** November 3, 2026.

Human Biome's NCT07912164 plans 68 adults aged 45–80 with metabolic/pre-disease abnormalities and accelerated aging markers. The randomized masked comparison uses multidose FMT capsules after neomycin/metronidazole preparation versus placebo capsules and placebo antibiotics; both receive bowel cleansing. Active antibiotic preparation means any difference cannot be attributed solely to microbiota capsules.

The primary responder definition is either a ≥5% reduction in DunedinPACE or a ≥25% reduction in at least one eligible elevated inflammatory marker at week 13 and/or 26. This disjunctive biomarker composite does not measure years lived, avoided age-related disease or established durable physical/cognitive benefit. No efficacy or comparative safety result is posted.

First public November 3, the record is not yet recruiting, with estimated start December 2026 and primary/final completion December 2027. Full donor-screening/protocol details were not independently appraised. Registration does not validate anti-aging commercial claims.

**U.S. status:** Investigational for aging; no verified U.S. anti-aging approval or availability.

**Next milestones:** FMT aging-biomarker trial estimated start: 2026-12 (Registry estimated month; not yet recruiting); FMT aging-biomarker trial primary/final completion: 2027-12 (Registry estimated month; public readout unknown).

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07912164).

**Coverage and remaining gaps:** focused_incomplete. Paginated retrieval is not complete appraisal. Not every returned record, all non-U.S. registers, full papers/supplements, conference audio or original podcasts were reviewed; full successful-check timestamps and incomplete baseline flags must remain unchanged.; FMT is a small planned biomarker experiment; full donor-screening, protocol and safety plan not independently appraised. Active antibiotics versus placebo antibiotics prevent isolating an FMT-only effect.; TAME launch/funding and all rapamycin/metformin clinical-function/harms evidence remain incompletely appraised; a recent repost of DEMFOS is already in baseline.

**Informal-source coverage:** Original saved Reddit/statement chains selectively revisited; no distinct new source-grounded rumor or material status transition selected. Long-form podcasts and talks were not exhaustively reviewed.

[Full coverage record](../updates/2026-11-03_scheduled_research_update.md).


### Focused update — 2026-10-30

<span class="note-anchor" id="note-2026-10-30-tirzepatide-proteomic-brain-age-protocol"></span>

#### A small trial will test tirzepatide against a proteomic brain-age measure

**Source date:** 2026-10-30. **Recorded in this review:** October 30, 2026.

**NCT07906041**, first posted October 30 by Atria Research/Global Health Institute, plans 22 participants randomized open label to tirzepatide or usual care. Weekly dosing begins at **2.5 mg** with increases separated by at least four weeks to a maximum **10 mg**, for six months.

The primary outcome is change in a blood-protein machine-learning estimate of **brain-age gap**, with the between-group comparison also specified. This is a modeled biomarker, not a direct measurement of brain rejuvenation, dementia prevention, daily function or lifespan. Even a favorable clock change would need independent validation against meaningful outcomes.

The registry lists **enrolling by invitation**, an **October 2026 estimated start**, **April 2028** estimated primary completion and **September 2028** final completion. It does not verify an actual first dose. Cross-link the metabolic topic without duplicating this event.

**U.S. status:** Tirzepatide has existing disease-specific U.S. approvals; a longevity, brain-age or dementia-prevention indication is not established by this protocol.

**Next milestones:** Proteomic brain-age trial primary completion: 2028-04 (Registry estimate).

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07906041).

<span class="note-anchor" id="note-2026-10-30-elite-actual-completion-no-results"></span>

#### ELITE registry now records completion, with results still absent

**Source date:** 2026-10-30. **Recorded in this review:** October 30, 2026.

The October 30 update to **ELITE / NCT07475546** changes the saved gerotherapeutic-combination study to **completed**, with **26 actual participants** and actual primary/final completion **April 9, 2026**. No results are posted.

The three-month open-label pilot compares a multi-drug/supplement combination, a more comprehensive combination including rapamycin, and a vitamin-control regimen, with exercise/behavioral interventions also differing. Outcomes include VO₂ max, cognitive-task scores, inflammatory-age measures and DXA lean tissue. The registry's Phase 3 label does not make this 26-person pilot definitive evidence of healthspan benefit.

This closes an elapsed completion-status question, not the efficacy question. No inference about individual drug effects, disease-free survival or lifespan should follow until outcomes and harms are available.

**U.S. status:** No geroscience or lifespan-extension U.S. indication established.

**Next milestones:** ELITE results posting/publication: date unknown (Completed study; results date unknown).

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07475546).

**Coverage and remaining gaps:** Focused partial appraisal through October 30, 2026. Complete retrieval of the specified query and saved named records; incomplete worldwide review. No full successful-check or baseline-completion claim.. Focused appraisal only. All pages of the specified ClinicalTrials.gov query were retrieved, but not every returned record underwent full results/harms appraisal. This is not complete worldwide coverage.; Independent non-U.S. registry searches, a comprehensive publication/hold/discontinuation census, and complete original conference/podcast audio and transcripts remain incomplete. Full successful-check timestamps and incomplete sleep baseline flags must remain unchanged.; AFAR TAME page again returned 404; funded launch and actual first dosing cannot be refreshed. No new verified TAME efficacy result.; ELITE has no posted results despite now completed status. MAVRIC/other saved geroscience dates are not treated as actual starts or readouts.; Proteomic age and inflammatory-age measures are not validated replacements for demonstrated function, disease-free survival or longevity.

**Informal-source coverage:** Re-read the original Vitaei PEARL 24-month claim; no matching original 24-month clinical report was verified, and the offered citation remains unrelated as previously documented. Targeted rapamycin/metformin Reddit searches did not supply a new selected, attributable human-trial update.

[Full coverage record](../updates/2026-10-30_scheduled_research_update.md).


### Focused update — 2026-10-27

<span class="note-anchor" id="note-2026-10-19-trigonelline-nad-protocol"></span>

#### Trigonelline protocol tests NAD biomarkers rather than healthspan

**Source date:** 2026-10-19. **Recorded in this review:** October 27, 2026.

A newly appraised dsm-firmenich Phase 1 protocol, **NCT07880925**, plans 60 generally healthy adults aged 40–70 in six parallel groups: daily trigonelline **150/300/450/600 mg equivalents**, NMN **600 mg**, or placebo for **four weeks**. The corresponding trigonelline-monohydrate masses are 170/340/510/680 mg, so these units should not be conflated.

The primary endpoint is whole-blood NAD+ change. PK, NAD-related metabolites, inflammatory biomarkers and short-term tolerability are secondary/exploratory. It does not test lifespan, frailty, durable strength/function or reduced chronic disease. Sponsor descriptions of NAD biology are rationale rather than demonstrated clinical benefit.

First posted October 19, the record is not yet recruiting, with **October 2026** estimated start and **January 2027** primary/final completion. Actual initiation remains unverified. This closes a prior unappraised discovery lead and is not new efficacy news.

**U.S. status:** Trial registration is not FDA approval for longevity or proof that supplements extend healthspan.

**Next milestones:** Trigonelline study initiation: 2026-10 (Elapsed/current registry estimate; actual start unverified); Trigonelline primary completion: 2027-01 (Registry estimate).

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07880925).

**Coverage and remaining gaps:** Focused partial review; all pages of specified ClinicalTrials.gov discovery retrieved and selected relevant records appraised. Worldwide full-topic review and baseline completion are NOT claimed.. Focused partial appraisal only. Complete ClinicalTrials.gov query retrieval is not exhaustive worldwide evidence review; independent non-U.S. registries, full conference audio/slides, all publications and a complete holds/discontinuations/harms census remain incomplete. Do not advance full successful-check timestamps or sleep baseline-complete flags.; TAME current funded/registered initiation not verified; AFAR direct page failed previously and indexed fundraising text is insufficient.; No actual REPROGRAM readout inferred from an elapsed October forecast. Complete healthspan-outcome literature and metformin harms review remains incomplete.

**Informal-source coverage:** Re-read Vitaei April11 PEARL24-month claim. It still asserts a follow-up; the offered DOI10.1111/acel.14056 remains unrelated to the claimed clinical report. Prior status persists: follow-up unconfirmed and citation contradicted as support. Targeted metformin/rapamycin/REPROGRAM/TAME informal searches yielded no validated new readout or funded start.

[Full coverage record](../updates/2026-10-27_scheduled_research_update.md).


### Focused update — 2026-10-23

<span class="note-anchor" id="note-2026-06-17-reprogram-baseline-protocol"></span>

#### REPROGRAM is a short biomarker experiment, not a metformin healthspan trial result

**Recovered baseline, not new October news.** The June 17 REPROGRAM protocol (ISRCTN47919839) plans 60 healthy adults aged at least 70, randomized to metformin modified-release 1,500 mg/day, fisetin 100 mg/day or spermidine 15 mg/day for three weeks. There is no placebo arm. The primary endpoint is an adipose-tissue cellular-senescence assay, not survival, multimorbidity or durable function.

The protocol gives an actual September 24, 2025 recruitment start and forecasts enrollment/data/reporting windows in 2026. An October 8 Neuro-Oncology abstract describes a 60-person cohort and analysis planned for autumn 2026; it is not a metformin healthspan efficacy readout. Elapsed forecast windows should be revisited rather than marked completed. The direct ISRCTN holding page was inaccessible during this check; the published protocol and HRA summary were available. No TAME funding completion, current start or clinical result was verified. No U.S. longevity indication follows from these sources.

**Sources:** [Source 1](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0346347); [Source 2](https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/reprogram/); [Source 3](https://academic.oup.com/neuro-oncology/article/28/Supplement_2/noag233.049/8875820).

**Coverage and remaining gaps:** Focused incomplete coverage. All pages of the specified ClinicalTrials.gov discovery query and saved named records were retrieved on 2026-10-20; retrieval is not exhaustive appraisal of every record or worldwide evidence. Do not advance full successful-check timestamps. Original source dates remain unchanged. Independent non-US registries, complete conference tables/audio, and a comprehensive harms/discontinuation census remain incomplete.; ClinicalTrials.gov discovery: 56 records across 1 retrieved pages; final retrieval errors: []. Named records also retrieved successfully.; Sleep incomplete baselines used 90-day context through October 20; other topics used the last full successful check minus seven days. Earlier October 16 focused checks did not reset that window.; NCT07880925 trigonelline study was discovered October 19: planned four-week NAD biomarker study, not proven healthspan benefit. Lead retained for later appraisal. TAME direct page returned 404 again; indexed fundraising text is not evidence of current funding or trial start.; No dedicated October 21–23 longevity delta completed.

**Informal-source coverage:** Original informal sources were sampled on October 20; not a comprehensive podcast, social-media, or anonymous-source search. Reposts were not treated as independent confirmation. No resolved claim was inferred from source silence. Vitaei PEARL 24-month claim unchanged; its offered DOI remains unrelated, so prior unconfirmed/contradicted-citation status remains. TAME start/funding not verified.

[Full coverage record](../updates/2026-10-23_scheduled_research_update.md).


### Focused update — 2026-10-16

No additional finding was selected from these checked sources. Coverage remains incomplete; this is not a full-topic “no news” conclusion.

**Remaining gaps:** Read current canonical scope, shared summaries, state and assigned topic notes. Bounded registry discovery covered September 5–October 16, 2026; prior October 13 findings were deduplicated. Full-topic successful-check dates remain unchanged.; Retrieved all 53 records across 1 pages of the bounded ClinicalTrials.gov query, plus 13 named records. Selected relevant new/changed protocols were appraised; downloading all records does not establish exhaustive safety/results review.; Europe PMC original-literature discovery failed with HTTP 503 for this topic. Targeted primary-source web searches supplied a partial fallback. Worldwide literature, regulators, international registries and complete original conference/podcast recordings remain incomplete.; RESTOR, metformin, rapamycin, MAVRIC, ELITE and saved senolytic programs were refreshed. No extra formal result selected in this bounded review. AFAR TAME direct retrieval failed again; do not infer funding or actual initiation. Completed frailty/aging trials without new results remain pending, not negative results. Full worldwide geroscience and harms review remains incomplete.

**Informal-source coverage:** Reopened original Vitaei PEARL 24-month claim; offered citation mismatch and unconfirmed underlying follow-up remain unchanged, with no repeat alert. Informal longevity search results did not supply a new matching primary paper or attributable launch leak selected. Full recordings/transcripts remain incomplete.

[Full coverage record](../updates/2026-10-16_scheduled_research_update.md).


### Focused update — 2026-10-13

<span class="note-anchor" id="note-2026-10-13-elite-retrospective-registration"></span>

#### ELITE adds a retrospectively registered healthy-aging combination trial

**New registry disclosure, not a new treatment start — ELITE, NCT07871799.** Sheba Medical Center in Israel randomized **31 adults aged 50–80 without diabetes**, BMI≥25, to eight weeks of **metformin 425 mg/day plus semaglutide 0.25 mg/week** or **metformin 425 mg/day plus empagliflozin 10 mg/day**. Both groups also received investigational AgeBiotics AB-01/AB-02 and digital monitoring.

Primary is eight-week change in a muscular–immune–cognitive composite; secondary measures include component scores, digital associations, harms and adherence. The open-label active-versus-active design has no placebo/usual-care group, cannot isolate metformin or the shared products, and does not measure lifespan or delayed major age-related disease. Algorithmic response states were reviewed but **did not reassign treatment** during this pilot.

The record first appeared **October 13, 2026**, after actual conduct **November 17, 2025–February 25, 2026**. It lists completed with 31 actual participants, **no posted results**; late registration limits verification of prospective endpoint selection. These regimens/products have no established U.S. healthy-aging indication. Next: original protocol chronology, full human results and safety; no release date announced.

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07871799).

**Remaining gaps:** Read current canonical scope, shared summaries/state and assigned topic notes. September 5–October 13 overlap preserves the September 12 full-review dates; October 6/9 entries were deduplicated. All pages of each bounded ClinicalTrials.gov query were downloaded, and named records plus selected relevant new/changed protocols were appraised. This is focused partial review, not a worldwide full literature/regulator/safety census; successful full-topic dates must remain unchanged.; Bounded query retrieved 45 records across 1 pages; incidental studies excluded. Named topic records refreshed: 12. Full older evidence, international registries, comprehensive harms and all original conference/podcast recordings remain gaps.; TAME direct page returned HTTP 404 again; indexed official AFAR still describes fundraising/planning, but its stale crawl is not a fresh launch check. No funded/actual start inferred. Disease-specific TRUTH MASH source retained once under liver. Full mTOR/senolytic original publications and safety review incomplete.

**Informal-source coverage:** Reopened actual Vitaei April 11 PEARL 24-month claim; same unrelated citation persists, so clinical follow-up remains unconfirmed with contradicted offered support, no new alert. Original secondary report claims not independent corroboration; targeted Reddit longevity searches did not yield a new source-verified development claim selected. Full audio incomplete.

[Full coverage record](../updates/2026-10-13_scheduled_research_update.md).


### Focused update — 2026-10-09

**Related evidence:** [Small randomized senolytic MASH trial reports a biopsy signal and more adverse events](13_liver.md#note-2026-10-01-truth-senolytics).

No additional finding was selected from the reviewed sources. Coverage remains incomplete; this is not a full-topic “no news” conclusion.

**Remaining gaps:** Window: September 5–October 9, 2026, retaining the seven-day overlap from the last full successful check on September 12. October 6 findings were deduplicated.; 93 named NCT records across the ten topics and ten discovery queries downloaded successfully through the ClinicalTrials.gov public API. Download is not a claim that all fields/safety/results were exhaustively appraised.; Focused review only. Do not advance full successful-check timestamps or label incomplete remaining searches as no news.; All 47 matches in the bounded longevity registry discovery were downloaded; broad terms still include disease-specific programs and not a comprehensive global geroscience census. Named RESTOR, MAVRIC, metformin/everolimus and IPACE-HIV records refreshed.; AFAR TAME official page retrieval failed again. Funded launch cannot be refreshed. Full original audio and complete mTOR/senolytic safety/publication census remain gaps.; Newly recovered TRUTH MASH trial belongs to liver; disease-specific biopsy response does not complete the longevity baseline or establish healthier/longer life.

**Informal-source coverage:** Revisited PEARL24month claim: newly located USA Longevity Today page asserts September 17 Nature Aging primary publication; direct page fetch failed, matching Nature Aging paper not located in exact search. This is another unconfirmed assertion, not independent corroboration of prior Vitaei claim; no repeat efficacy alert. Oct9 Futurology framing of MASH cure reviewed against original paper. Audio not fully reviewed.

[Full coverage record](../updates/2026-10-09_scheduled_research_update.md).


### Focused update — 2026-10-06

<span class="note-anchor" id="note-2026-09-23-rapamycinmri"></span>

#### Older rapamycin cardiac MRI substudy has an October completion estimate

**Historical baseline addition, reviewed October 6; registry update September 23, 2026.** NCT04742777 is a 20-person, open-label single-group phase 2 cardiac MRI substudy of eight weeks of rapamycin in clinically stable adults aged 70–95. Primary measures include systolic/diastolic function and aortic compliance. ACTIVE_NOT_RECRUITING, actual start February 1, 2022, estimated primary/final completion October 16, 2026; no results posted. This is an older human geroscience program newly recovered for the watch. Its lack of placebo and imaging endpoints cannot establish longer lifespan or general healthspan. Rapamycin has no aging indication established here; safety and published results remain pending.

[Source 1](https://clinicaltrials.gov/api/v2/studies/NCT04742777) · [Source 2](https://clinicaltrials.gov/study/NCT04742777)

**Coverage:** 2026-10-06: human longevity October2026 rapamycin metformin senolytics trials; 2026-10-06: PEARL24month AgingCell exact paper source-chain follow-up; 2026-10-06: direct NCT07520110/NCT06658093/NCT05835999/NCT07144293/NCT04742777

**Remaining gaps:** September5–October6 overlap plus older program recovery; direct RESTOR, MAVRIC, everolimus and IPACE-HIV records rechecked. No new material efficacy finding in these focused sources; incomplete broad coverage.; AFAR TAME page fetch failed; funded launch cannot be refreshed. AgelessRx Oct5 updated explainer repeats the pilot and does not provide verified larger-trial initiation; no new efficacy event. Full senolytic/mTOR registry census and original audio incomplete.

**Informal-source coverage:** Vitaei Apr11 claim revisited and its primary link checked: unrelated2023 cellular-aging paper. October Reddit AMPK items are preclinical and excluded. Full Kaeberlein/Attia/other original podcasts not appraised.

[Full coverage record](../updates/2026-10-06_scheduled_research_update.md).


### Focused update — 2026-10-02

No additional material finding was verified in this focused pass. Coverage remains incomplete; this is not a full-topic “no news” conclusion.

**Coverage:** human longevity metformin rapamycin senolytics September2026 October 2026; MAVRIC NCT07520110 original registry; Reddit longevity trial September2026.

**Remaining gaps:** MAVRIC remains NOT_YET_RECRUITING in September8 record despite elapsed September28 estimated start. No actual initiation verified. Full refresh of all senolytic/mTOR registries, TAME funding, RESTOR and original podcast recordings incomplete. Search results mainly reviews/preclinical stories, not a completed new lifespan trial.

**Informal-source coverage:** September4 metformin Reddit item repeats a review, not new TAME results. Existing PEARL 24-month-paper claim not confirmed; no repeat alert.

**Next update:** Everolimus and IPACE-HIV results undated; MAVRIC September 28 estimated start remains unconfirmed.

[Full coverage record](../updates/2026-10-02_scheduled_research_update.md).

### Focused update — 2026-09-29

#### Completed everolimus aging study awaits results

**Source date:** 2026-09-04. **Event date:** 2026-06-30. **Date basis:** Registry update date; older completed-study baseline. **Evidence:** Baseline addition from trial registry. **Baseline addition; not new news.**

An additional controlled geroscience study is completed, with no results posted. NCT05835999: Phase 2, actual enrollment 106 including a young reference group. Older insulin-resistant/prediabetic adults were randomized to daily everolimus, weekly everolimus or placebo for 24 weeks; primary endpoint is peripheral insulin sensitivity. Primary completion was June 30, 2026; registry updated September 4.

**Limitations:** Completion does not demonstrate benefit. Total registry enrollment includes reference participants, not necessarily 106 randomized older adults. This is metabolic physiology, not lifespan or multimorbidity prevention.

**Safety:** Adverse events, metabolic labs and lipids are tracked; no results posted.

**U.S. status:** No approved longevity indication.

**Next milestone:** Results publication or posting undated.

[Everolimus aging primary registry](https://clinicaltrials.gov/study/NCT05835999).

**Coverage:** TAME/rapamycin/senolytic discovery; fresh everolimus, PEARL and MAVRIC registries; original PEARL publication checked against a dubious secondary story.

**Remaining gaps:** TAME actual funded launch remains unverified. MAVRIC still not yet recruiting despite September28 estimated start. RESTOR and worldwide geroscience census incomplete; no full podcast sweep.

**Informal-source coverage:** A September19 blog asserts a September17 Nature Aging 24-month PEARL paper, but no such original was found; the verified primary report is April4,2025, 48 weeks in Aging. Excluded unsupported claim from findings, retained as source-quality gap. https://usalongevitytoday.com/rapamycins-first-randomized-human-aging-trial-posts-its-data/ . Current forum material largely recycled preclinical/mechanistic claims.

**Next update:** Everolimus and IPACE-HIV results undated; MAVRIC September 28 estimated start remains unconfirmed.

[Full coverage record](../updates/2026-09-29_scheduled_research_update.md).

### Focused update — 2026-09-27

#### Completed senolytic trial will test physical function in older adults with HIV

**Source date:** 2026-09-15. **Event date:** 2026-08-26. **Evidence:** New-to-watch completed-trial registry. **Baseline addition; not newly initiated research.**

IPACE-HIV adds a controlled human senolytic program focused on frailty and function, with results not yet posted. NCT07144293 / A5426: Phase 2, 82 actual participants, randomized double-blind dasatinib plus quercetin versus matched placebos. Adults ≥50 with longstanding controlled HIV and frailty/prefrailty. Actual completion August 26, 2026.

**Limitations:** Completion is not efficacy evidence; cannot generalize to healthy aging or lifespan. Registration first posted August 2025, before study start.

**Safety:** Primary outcomes include grade ≥2 adverse events, premature discontinuation through 24 weeks and gait-speed change at 12 weeks; no results available.

**U.S. status:** No approved senolytic longevity indication.

**Next milestone:** Posted results or publication undated; monitor physical-function and safety together.

[IPACE-HIV primary registry](https://clinicaltrials.gov/study/NCT07144293).

**Related findings:**

- [OCTOPUS stops metformin arm in progressive MS for insufficient promise](15_autoimmune.md#programs-and-next-milestones).

**Coverage:** TAME direct status, metformin/rapamycin/senolytic discovery; IPACE-HIV primary registry, INSPIRE-COPD-E and MAVRIC original records.

**Remaining gaps:** TAME funding/start remains unverified. INSPIRE-COPD-E remains not yet recruiting in stale April record despite elapsed September 1 estimate. MAVRIC remains not yet recruiting with September28 estimatedstart; disease-specific study not lifespan evidence. RESTOR not freshly downloaded; global census and full podcasts incomplete.

**Informal-source coverage:** September 24 r/Aging senolytic-skin headline refers to mice and was excluded; September20 fisetin discussion not a new human-trial result. September25 Kara Fitzgerald show description and wider podcast searches did not disclose a verified new human-program milestone; original audio not reviewed. https://www.reddit.com/r/Aging/comments/1wosuw7/breakthrough_drug_reverses_skin_aging_and/ ; https://podcasts.apple.com/gb/podcast/what-actually-slows-aging-the-science-vs-hype-dr/id1103271110?i=1000791630630

**Next update:** IPACE-HIV results undated. TAME funded start unverified; RESTOR saved July 2028 completion estimate was not newly verified.

[Full coverage record](../updates/2026-09-27_scheduled_research_update.md).

### Focused update — 2026-09-22

#### Rentosertib trial samples show proteomic aging-clock changes

**Source date:** 2026-09-07. **Event date:** 2026-09-07. **Evidence:** Peer-reviewed secondary human biomarker analysis.

A September 7 paper, recovered during the overlap search, reports changes across six proteomic aging clocks after 12 weeks of rentosertib. NCT05938920 was a randomized placebo-controlled IPF Phase 2a trial in China. This secondary analysis used 42 Asian participants, mean age 67.1, from 71 randomized; 43 consented to proteomics and one lacked an end measurement.

**Limitations:** Disease-specific, short, selected biomarker cohort. The authors cannot separate antifibrotic effects from aging biology. No evidence of extended lifespan, improved general healthspan or measured years of rejuvenation; six models are not six independent clinical trials.

**Safety:** Six participants in this proteomics cohort had grade ≥3 adverse events; sensitivity analyses excluded them. Attribution and full parent-trial safety need separate review.

**U.S. status:** No U.S. longevity approval.

**Next milestone:** No verified clinical healthspan readout date; healthy-population validation is needed.

[Nature Biotechnology secondary analysis](https://www.nature.com/articles/s41587-026-03286-y); [NCT05938920 registry](https://clinicaltrials.gov/study/NCT05938920).

**Coverage:** TAME direct status, rentosertib September 7 proteomics paper, rapamycin RESTOR and AgelessRx pilot/APOE4 registry follow-up.

**Remaining gaps:** TAME actual launch/registration remains unverified; official page still fundraises to launch. AgelessRx larger planned 186-person study registration not confirmed; old 30-person record has elapsed unrefreshed estimate. Rentosertib full parent-trial safety not separately reconstructed; proteomic changes are not healthspan outcomes. Senolytic/metformin worldwide registry census and complete podcasts not covered.

**Informal-source coverage:** Targeted Reddit/rapamycin/podcast/TAME searches. Excluded animal-only items and unsupported TAME interim-result blog claims lacking a retrievable original study, conflicting with AFAR launch status. Did not treat search popularity/reposts as corroboration.

[Full coverage record](../updates/2026-09-22_scheduled_research_update.md).

**Next update:** TAME funded initiation remains unverified; RESTOR primary completion is estimated **July 2028**. No dated rentosertib clinical healthspan result is established.

### Focused update — 2026-09-18

#### Rapamycin pilot reports brain-perfusion increases in APOE4 carriers

**Source date:** 2026-09-10. **Evidence:** Peer-reviewed single-arm human pilot.

A four-week study reports a cerebral blood-flow signal in cognitively normal APOE4 carriers; it did not test prevention of dementia or longer life. Twenty-three adults aged 45–65 completed the study: nine APOE4 carriers and 14 noncarriers. They received rapamycin 1 mg/day for four weeks. The primary cerebral blood-flow endpoint increased by more than 15% in multiple regions among carriers; noncarriers had no significant change. Secondary metabolic, inflammatory and microbiome measures were explored. DOI: 10.1177/0271678X261490342.

**Limitations:** There was no placebo or control treatment. Genotype groups were tiny, follow-up lasted four weeks, and multiple exploratory measures were examined. Appraisal was limited to the abstract; detailed safety tables and the registry record were not retrieved.

**Safety:** The abstract describes minimal adverse effects but provides no event counts; long-term safety cannot be inferred.

**U.S. status:** Rapamycin is not approved for longevity or Alzheimer’s prevention.

**Next milestone:** No date for a subsequent trial or readout was verified.

[Original PubMed abstract](https://pubmed.ncbi.nlm.nih.gov/42723264/).

#### Previously inaccessible metformin biomarker trial recovered

**Source date:** 2026-09-03. **Evidence:** Historical evidence recovered.

The September 3 paper resolves a prior access gap but measures cellular biomarkers rather than healthspan. The trial randomized 127 North Indian adults aged 30–60 with prediabetes; 112 completed 24 weeks. Leukocyte telomere elongation was 29.6% with metformin versus 4.4% with placebo (between-group p < .0001). Trial identifier: NCT07302932.

**Limitations:** No survival, disability or disease-incidence endpoint; marked biomarker response needs replication. Registry first posted December 24, 2025, after actual January 30, 2025 completion: retrospective registration. Registry reports 112 enrolled, whereas the publication reports 127 randomized and 112 completers. Preserve those distinctions. December 2026 issue date is not original publication date.

**Safety:** The publisher reports early mild gastrointestinal symptoms in eight participants (14.3%) receiving metformin and two (3.6%) receiving placebo. These resolved without discontinuation, and no serious adverse events occurred. The percentages use completers rather than randomized participants as denominators.

**U.S. status:** No longevity indication.

**Next milestone:** Larger and longer replication studies are undated. TAME remains in fundraising; a funded launch was not verified.

[Original abstract](https://pubmed.ncbi.nlm.nih.gov/42692117/); [Publisher paper and safety excerpt](https://www.sciencedirect.com/science/article/pii/S004763742600093X); [Original trial registry, freshly retrieved September 18](https://clinicaltrials.gov/study/NCT07302932).

#### Safety detail added to already recorded AgelessRx pilot

**Source date:** September 2 pilot; safety detail checked September 18. **Evidence:** Evidence correction to existing pilot.

The current sponsor page reports a serious adverse event omitted from the notebook summary. It does not establish that a new safety event occurred on September 17. The same 90-day pilot enrolled 26 participants and analyzed 18. Seven of 26 participants experienced adverse events, and three withdrew. One myocardial infarction occurred in the multi-therapy arm and was assessed as possibly associated with physical activity. The page now says it was last updated on September 17; earlier findings were first recorded as September 2.

**Limitations:** Bundled intervention, small groups, sponsor-only reporting and attrition; no causal attribution to any drug established. Do not equate unchanged laboratory panels with an absence of adverse events.

**Safety:** The myocardial infarction was a serious adverse event. Mixed cognitive and maximal oxygen-uptake results should also remain visible.

**U.S. status:** No approval of a longevity drug or regimen is established.

**Next milestone:** The sponsor plans a one-year trial with 186 participants; registration and actual start were not confirmed.

[AgelessRx current pilot report](https://agelessrx.com/agelessrx-xprize-pilot-longevity-protocol-results/).

**Coverage:** Rapamycin APOE4 pilot; metformin publication and retrospective registration; AgelessRx safety correction; unchanged TAME fundraising status. RESTOR remains recruiting in its June 1 registry snapshot, with estimated completion in July 2028. This is a focused review, not a complete re-review of every program.

**Remaining gaps:** Rapamycin APOE4 detailed safety/registry not reviewed. Metformin full statistical analysis and registration discrepancy require deeper appraisal. AgelessRx larger finals trial registration/start remains unverified.

**Informal-source coverage:** Rapamycin.news and podcast searches included August 26 Kaeberlein and September 1 Asprey opinions; no new human-program timing claim verified. Animal-only metformin prostate-cancer post excluded.

[Full coverage record](../updates/2026-09-18_scheduled_research_update.md).

### Focused update — 2026-09-14

**2026-09-02 — Older context added: a small combination geroscience pilot.** AgelessRx’s September 2 report describes a randomized 90-day combination pilot: 26 enrolled and 18 analyzed across three small groups. Reported biomarker, lean-mass and quality-of-life signals are exploratory. Multiple drugs and behavioral components changed together; attrition, small samples, missing between-group uncertainty and sponsor involvement limit inference. **This does not establish lifespan extension or isolate any drug’s benefit.** [Sponsor report](https://agelessrx.com/agelessrx-xprize-pilot-longevity-protocol-results/); [NCT07475546](https://clinicaltrials.gov/study/NCT07475546), which still has no posted results. Separately, [RESTOR / NCT06658093](https://clinicaltrials.gov/study/NCT06658093) lists recruiting and estimated July 2028 primary completion; that is not a publication date. AFAR still describes [TAME fundraising to launch](https://www.afar.org/tame-trial). These are focused baseline/status additions, not proof of rejuvenation.

**Coverage:** September 2 AgelessRx 90-day pilot added as preliminary older context; RESTOR recruitment verified from registry. AgelessRx report is sponsor-only, 26 enrolled/18 analyzed, bundled interventions and no precise adjusted between-arm uncertainty; not lifespan evidence. Metformin PMID42692117 original inaccessible, no numerical claim promoted. TAME funded launch remains unverified. Animal-only Genflow SLAB result excluded. This was a focused refresh, not a complete re-review of every program.

Checked sources: [Source 1](https://www.afar.org/tame-trial); [Source 2](https://agelessrx.com/agelessrx-xprize-pilot-longevity-protocol-results/); [Source 3](https://clinicaltrials.gov/study/NCT07475546); [Source 4](https://clinicaltrials.gov/study/NCT06658093).

**Next update:** **No dependable readout date.** Watch TAME funding/start, metformin peer review, and newer rapamycin trial recruitment.

### Tracked programs and current evidence

#### Initial brief — evidence available through 2026-09-12

**Current assessment:** human geroscience has real randomized trials, but the programs below have not established longer human lifespan or a broad, reliable delay in multiple age-related diseases. Several trials have missed their primary endpoint. Favorable molecular or epigenetic measures should remain signals to investigate, not “years of life gained.” These programs are investigational for aging; existing approval of a drug for diabetes, transplantation, or cancer does not establish a longevity indication.

**Metformin / TAME — proposed pivotal trial, launch not confirmed.** AFAR's official TAME page still describes fundraising to launch a planned six-year program involving more than 3,000 adults aged 65–79 at 14 institutions, with Wake Forest coordinating. The intended question is whether metformin delays age-related diseases such as cardiovascular disease, cancer, and dementia. This baseline did not verify an enrolled TAME cohort, a current recruitment registration, or a results date. The right watch trigger is a funded launch, registry entry, and first participant—not a speculative readout countdown. [AFAR's official TAME status](https://www.afar.org/tame-trial).

**Metformin / completed human trials — mixed evidence, dependent on the population.** In the peer-reviewed MET-PREVENT trial, published March 24, 2025, 72 older adults with probable sarcopenia and prefrailty/frailty received metformin or placebo for four months. Walking speed did not improve: adjusted difference 0.001 m/s, 95% CI −0.06 to 0.06. Tolerability was poor; hospital admissions occurred in 12/35 treated participants versus 3/36 controls. This small trial cannot determine the effect in healthier younger adults. Trial: **ISRCTN29932357**. [MET-PREVENT results](https://pubmed.ncbi.nlm.nih.gov/40147475/).

The peer-reviewed July 2026 **DEMFOS trial, NCT04221750**, included 114 older adults with obesity. Adding metformin to an intensive lifestyle program provided no additional six-month physical-function benefit over that program plus placebo (difference 0.1 points, 95% CI −1.2 to 1.4). [DEMFOS results](https://www.sciencedirect.com/science/article/pii/S266675682600067X).

A newer **July 28, 2026 preprint**, **NCT02570672**, reports two years of treatment in 145 older adults with glucose intolerance. A deficit-accumulation frailty index and two methylation clocks improved, but the Fried frailty phenotype did not; weight loss complicated that measure. The participants had prediabetes, and the report is not yet peer reviewed. Watch for peer review, clinical interpretation of the effect size, and independent replication. This is a relevant positive signal alongside the negative trials—not proof of general longevity benefit. [Metformin frailty preprint](https://pubmed.ncbi.nlm.nih.gov/42620010/).

**Rapamycin / sirolimus — human testing is progressing, efficacy remains unsettled.** The peer-reviewed 48-week **PEARL trial, NCT04488601** (April 4, 2025), found no significant improvement in its primary visceral-fat outcome. Some secondary, sex-specific signals favored treatment; adverse and serious adverse events were similar between groups. The investigators were employees/shareholders of the sponsoring commercial clinic. These exploratory signals need independent confirmation. [PEARL results](https://pubmed.ncbi.nlm.nih.gov/40188830/).

The April 2026 **RAPA-EX-01 trial, ACTRN12624000790549**, randomized 40 adults aged 65–85 during a 13-week exercise program. Sirolimus did not significantly improve the primary chair-stand outcome; sensitivity analyses favored placebo. Adverse-event counts were higher, including one possibly drug-related pneumonia. This cautions against assuming that mTOR inhibition improves exercise adaptation. [RAPA-EX-01 results](https://pubmed.ncbi.nlm.nih.gov/41985884/). UT Health San Antonio announced an NIA-funded dose/schedule program on March 16, 2026, including a planned approximately 84-person randomized cohort treated for six months with six months' follow-up. Watch actual recruitment, dosing comparisons, functional outcomes and infection/metabolic safety; no readout date was verified. [Institutional trial announcement](https://news.uthscsa.edu/large-rapamycin-clinical-trial-launches-at-ut-health-san-antonio/).

**Senolytics / dasatinib plus quercetin — early clinical evidence, no established healthspan benefit.** A 2024 peer-reviewed randomized phase 2 study in 60 postmenopausal women, **NCT04313634**, missed its primary 20-week bone-resorption-marker endpoint. Short-lived secondary bone-formation changes and exploratory subgroup findings do not demonstrate fracture prevention or systemic rejuvenation. Watch replicated clinical outcomes and safety rather than isolated changes in senescence markers. [Nature Medicine trial](https://www.nature.com/articles/s41591-024-03096-2), [trial record](https://clinicaltrials.gov/study/NCT04313634).

#### When to expect the next useful update

| Program | Timing and confidence | What would change the assessment |
| --- | --- | --- |
| TAME | **No reliable launch or readout date verified.** AFAR still describes fundraising to launch. | Funding/registration, confirmed first participant, then a credible enrollment and follow-up schedule. |
| Metformin frailty preprint | **No announced peer-review/publication date.** The preprint is already available. | Peer-reviewed analyses and replication of the mixed clinical findings. |
| Rapamycin / RESTOR, NCT06658093 | **No reliable results-publication date verified.** The March 2026 institutional announcement describes six months of treatment plus six months of follow-up for its longest cohort; that is participant duration, not a countdown from the announcement. [RESTOR record](https://clinicaltrials.gov/study/NCT06658093). | Dose/schedule findings, functional outcomes, and sufficiently long safety follow-up. |
| Senolytics | **No dependable next class-wide readout date established in this focused brief.** | Larger randomized studies with sustained functional or disease outcomes. |

No analyst-generated date is being substituted for a sponsor or registry milestone.

## Rumors and informal signals

<span class="note-anchor" id="note-2026-04-11-pearl24month"></span>

### PEARL 24-month claim cites an unrelated cellular-aging paper

**Informal-source follow-up — checked October 6, 2026.** Vitaei’s April 11, 2026 article, with the byline “Prof. Marco Lindqvist, PhD” (identity/credentials not independently verified), claims a 24-month PEARL rapamycin follow-up in Aging Cell in early 2026. Its “PEARL 24-month follow-up” source link is DOI 10.1111/acel.14056. That DOI resolves to Braunger and colleagues’ “Transcriptional changes are tightly coupled to chromatin reorganization during cellular aging,” first published December 7, 2023, studying cellular-aging datasets rather than a PEARL follow-up.

**Status:** The offered citation is contradicted as support for that claim. The purported clinical follow-up itself remains unconfirmed; this mismatch does not prove no other publication exists. Preserve the original claim, source date and attribution. Do not include the blog’s inflammatory, lean-mass or adverse-event numbers as trial evidence. Next: a retrievable matching primary paper or author/sponsor clarification.

[Source 1](https://vitaei.com/articles/pearl-rapamycin-trial) · [Source 2](https://doi.org/10.1111/acel.14056) · [Source 3](https://onlinelibrary.wiley.com/doi/10.1111/acel.14056)

Stable key: `PEARL24month_Vitaei_2026-04-11_claim`.

## Dated history

### 2026-10-02 — Scheduled focused review

0 newly recorded findings or milestones; primary evidence, uncertainty and incomplete coverage are detailed above and in the [run record](../updates/2026-10-02_scheduled_research_update.md). Full-topic successful-check dates remain unchanged.

- **2026-09-29:** 1 sourced entries, 0 cross-topic links and 0 informal-source checks. [Coverage and gaps](../updates/2026-09-29_scheduled_research_update.md).

- **2026-09-27:** 1 sourced entries and 1 cross-topic links from a focused scheduled check. [Coverage and remaining gaps](../updates/2026-09-27_scheduled_research_update.md).

- **2026-09-22:** Focused scheduled research retry; 1 sourced entries and 0 cross-topic links. [Coverage and gaps](../updates/2026-09-22_scheduled_research_update.md).

### Dated findings

- **2026-09-12:** Established the initial brief using sponsor/institutional status, trial records, original trial publications, and one explicitly labeled preprint. No human lifespan benefit established for the programs reviewed. TAME launch remains unverified; this is a focused baseline, not an exhaustive registry census.

### 2026-09-14 — Ad-hoc focused review

September 2 AgelessRx 90-day pilot added as preliminary older context; RESTOR recruitment verified from registry. Original event dates and sources are recorded above; unchanged historical trial results remain dated. AgelessRx report is sponsor-only, 26 enrolled/18 analyzed, bundled interventions and no precise adjusted between-arm uncertainty; not lifespan evidence. Metformin PMID42692117 original inaccessible, no numerical claim promoted. TAME funded launch remains unverified. Animal-only Genflow SLAB result excluded.

### 2026-09-18 — Scheduled focused review

Rapamycin APOE4 pilot; metformin publication and retrospective registration; AgelessRx safety correction; unchanged TAME fundraising status. RESTOR remains recruiting in its June 1 registry snapshot, with estimated completion in July 2028. Original event dates, safety and limitations are retained in the September 18 update above. The complete-topic successful-check date was not advanced because the listed gaps remain. [Run record](../updates/2026-09-18_scheduled_research_update.md).