# 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

A newly disclosed 31-person ELITE combination pilot measures eight-week function and digital signals, with no posted results or lifespan claim. Larger healthspan evidence remains unsettled; the alleged PEARL 24-month follow-up remains unconfirmed.

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 — 2026-10-16

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).