Test whether under Slc6a6 (TauT) genetic LOF or TauT-matched transport block that abolishes TauT-class taurine longevity attribution, taurine still retains lifespan/healthspan/metabolic phenotype on the same panel
Claim
On a pre-registered rodent metabolic/healthspan panel (Singh/Tsuboyama-class) with exogenous taurine vs vehicle under Slc6a6 (TauT) genetic LOF or TauT-matched transport block (e.g. GES-class) at a lock that abolishes TauT-class taurine longevity / healthspan attribution vs TauT-intact concurrent controls, locking TauT-class control benefit abolished under the block arm (primary referee = pre-specified early healthspan/metabolic endpoint within the refute window; full lifespan only as secondary, not gate): under that abolish lock, same-panel early healthspan/metabolic improvement (taurine vs vehicle under abolish) retains ≥50% of the taurine vs vehicle early healthspan/metabolic improvement on TauT-intact concurrent controls on the same panel (named comparator = taurine vs vehicle early healthspan/metabolic Δ on TauT-intact arm; units as pre-specified; α/N pre-specified) — assumption-kill / taut-insufficiency of “taurine longevity/healthspan = mere TauT-necessary bridge with possible residual.” Residual-positive taurine lifespan or healthspan H2H under TauT LOF or TauT-matched block abolish = UNKNOWN (do not invent residual). Ansar tissue residual under SLC6A6 hypomorph and GES corneal residual are tissue/aging-adjacent under TauT-class deficiency/block — ≠ organismal residual-positive longevity H2H (OUT of public prior_art ≤4). Prefer cell/tissue/block-QC (TauT transport / tissue-taurine uptake QC confirming abolish) before new animal longevity; in vivo healthspan panel remains primary kill path within 6w.
Why it matters
Taurine longevity and metabolic-healthspan benefits are often framed as TauT/Slc6a6–necessary because Singh grounds WT taurine-supp lifespan/healthspan and Tsuboyama grounds metabolic regulation, yet a matched residual-positive taurine lifespan/healthspan H2H under TauT LOF or TauT-matched block abolish remains UNKNOWN (Heller-Stilb/Ito are TauT KO necessity tools for retina/heart — necessity-leaning phenocopy ≠ residual-positive; Ansar shows tissue residual under hypomorph ~15% transport; GES shows residual under pharmacological TauT-block for corneal/LSPC — tissue residual ≠ organismal longevity residual; Singh Slc6a6-/- arms used D+Q/rapa not taurine residual; WT TauT ≠ residual). L28 asks whether, once TauT LOF or TauT-matched block abolishes TauT-class longevity attribution, taurine still retains lifespan/healthspan/metabolic phenotype on the same panel — longevity/healthspan ≠ mere TauT-sole-necessity bridge with invented residual. Distinct from L15–L25 insufficiency series and especially L26 (melatonin residual under luzindole/Mtnr1a/b — TauT ≠ MT/melatonin) and L27 (FGF21 residual under Klb/FGFR1 — TauT ≠ Klb/FGFR1 CRITICAL); NOT NAD-after-senolysis; NOT FOXO4×LOF; NOT MB/MAOI; NOT BPC skip-list. Soft-claims: discussion — residual-positive taurine under TauT abolish organismal longevity H2H UNKNOWN; tissue residual FOUND ≠ organismal residual; PRIOR_ART PARTIAL (phenotype + TauT KO necessity FOUND; tissue residual promoted outside public prior_art; residual-positive longevity absent; organismal longevity necessity EMPTY); soft-complete empty ≠ novelty / ≠ failure; L1–L27 ≠ proof.
Mechanism sketch
taut-insufficiency assumption-kill: Singh Science grounds circulating-taurine decline with aging and taurine supplementation healthspan/lifespan in mice (healthspan in monkeys) — phenotype founding in WT TauT; Slc6a6-/- used as congenital taurine-deficiency model (accelerated aging; shorter lifespan) treated with D+Q senolytics or rapamycin — NO exogenous taurine residual-under-TauT-KO longevity arm (honesty: WT TauT + deficiency phenocopy ≠ residual H2H); Heller-Stilb FASEB J grounds taut gene disruption → retinal degeneration / depleted tissue taurine — TauT KO retinal necessity tool ≠ residual-positive longevity; Ito J Mol Cell Cardiol grounds TauTKO cardiomyopathy with cardiac atrophy — TauT KO cardiac necessity tool ≠ residual-positive longevity; Tsuboyama-Kasaoka Endocrinology grounds taurine deficiency promoting obesity and dietary taurine preventing HFD obesity — phenotype metabolic founding without TauT-abolish residual arm. Prefer cell/tissue/block-QC confirming abolish of TauT-class control (TauT transport / tissue-taurine uptake) before new animal longevity runs; primary kill path remains a matched rodent ± taurine ± TauT LOF (or TauT-matched transport block e.g. GES) early healthspan/metabolic panel within the refute window; full lifespan only secondary; do not invent residual; do not treat Heller-Stilb/Ito necessity as residual-positive; do not treat Ansar/GES tissue residual as organismal longevity residual; do not collapse to L27 Klb (TauT ≠ Klb) or L26 MT (TauT ≠ MT). Competing caveats: abolish-fail (block not actually abolishing TauT-class control benefit) / taurine-alone-null on TauT-intact arm / underpowered strata / referee-assay mismatch vs Singh/Tsuboyama-class lock leave the test inconclusive rather than refuted; soft-complete empty ≠ novelty / ≠ failure; L15–L25 ≠ this; L26 ≠ this (TauT ≠ MT); L27 ≠ this (TauT ≠ Klb CRITICAL). NOT NAD-after-senolysis (SERIES_FROZEN). Do not invent residual effect sizes.
Prior art
- PMID 37289866 / DOI 10.1126/science.abn9257 / PMC10630957 — Singh: circulating taurine declines with aging; taurine supplementation increased healthspan and lifespan in mice and healthspan in monkeys — founding TauT-class longevity phenotype; WT TauT context; Slc6a6-/- congenital deficiency + D+Q/rapa ≠ exogenous taurine residual-under-TauT-KO longevity arm; honesty: WT TauT ≠ residual H2H.
- PMID 11772953 / DOI 10.1096/fj.01-0691fje — Heller-Stilb: taut gene disruption → retinal degeneration, depleted tissue taurine — TauT KO tool / retinal necessity; ≠ residual-positive longevity under TauT abolish.
- PMID 18407290 / DOI 10.1016/j.yjmcc.2008.03.001 — Ito: TauTKO → cardiomyopathy with cardiac atrophy, depleted myocardial taurine — TauT KO cardiac necessity tool; ≠ residual-positive longevity.
- PMID 16627576 / DOI 10.1210/en.2005-1007 — Tsuboyama-Kasaoka: taurine deficiency promotes obesity; dietary taurine prevents HFD obesity (increased REE) — phenotype metabolic founding; WT context; ≠ residual under TauT abolish.
Baseline claimed
Under Slc6a6 (TauT) genetic LOF or TauT-matched transport block that abolishes TauT-class taurine longevity / healthspan attribution, taurine still retains lifespan / healthspan / metabolic phenotype on the same panel — or Singh 2023 taurine-supp lifespan settles residual under TauT KO / Heller-Stilb 2002 or Ito 2008 support residual-positive under TauT abolish / Tsuboyama 2006 settles residual under TauT abolish / Ansar 2020 hypomorph tissue residual proves organismal residual longevity / GES 2025 corneal residual proves organismal residual longevity / L15 Oh organ-age / L16 tissue-vs-blood under D+Q / L17 intermittent-rapa FKBP / L18 17α-E2 caloric-match / L19 acarbose glycemic-match / L20 SPD/ATG bulk autophagy / L21 UA/mitophagy / L22 metformin/AMPK / L23 lithium/GSK3 / L24 canagliflozin/SGLT2 / L25 resveratrol/SIRT1 / L26 melatonin/MT / L27 FGF21/Klb / L1–L27 already settle the residual H2H.
Baseline measured
Singh taurine-supp lifespan/healthspan LITERATURE phenotype founding prior in WT TauT; Slc6a6-/- deficiency + D+Q/rapa — no taurine residual-under-TauT-KO longevity arm — WT TauT ≠ residual H2H (PMID 37289866). Heller-Stilb taut-/- LITERATURE TauT KO retinal necessity tool ≠ residual-positive longevity (PMID 11772953). Ito TauTKO LITERATURE TauT KO cardiac necessity tool ≠ residual-positive longevity (PMID 18407290). Tsuboyama metabolic LITERATURE phenotype founding without TauT-abolish residual arm (PMID 16627576). Ansar SLC6A6 hypomorph (~15% transport) + oral taurine LITERATURE residual tissue (cardiomyopathy corrected; retinal degeneration arrested) — ≠ full abolish; ≠ organismal longevity residual H2H — OUT of public prior_art ≤4 (PMID 31903486). GES TauT pharmacological block + topical taurine LITERATURE residual under TauT-matched block for corneal/LSPC aging-adjacent — ≠ organismal longevity residual — OUT of public prior_art (PMID 40478558). Residual-positive taurine lifespan or healthspan H2H under TauT LOF or TauT-matched block that abolishes TauT-class control UNKNOWN (soft-complete Q_resid/Q_resid_tight/Q_resid_life_h2h/Q_necess_life = NON-MATCH/EMPTY/OFF-PANEL; no residual-positive organismal longevity). Block-arm early healthspan/metabolic improvement retains ≥50% of TauT-intact taurine vs vehicle early healthspan/metabolic improvement PREDICTION. L15 ≠ L28; L16 ≠ L28; L17 ≠ L28; L18 ≠ L28; L19 ≠ L28; L20 ≠ L28 (TauT ≠ bulk ATG); L21 ≠ L28 (TauT ≠ mitophagy); L22 ≠ L28 (TauT ≠ AMPK primary; taurine ≠ metformin); L23 ≠ L28 (TauT ≠ GSK3); L24 ≠ L28 (TauT ≠ SGLT2); L25 ≠ L28 (TauT ≠ SIRT1); L26 ≠ L28 (TauT ≠ MT/melatonin); L27 ≠ L28 (TauT ≠ Klb/FGFR1 CRITICAL); L1–L27 ≠ proof — soft-complete empty ≠ novelty / ≠ failure. NOT NAD-after-senolysis. Do not invent residual.
Actionable limitations
- Do not treat L1–L27 as proving L28 — new parent area taurine-taut-insufficiency; Singh/Heller-Stilb/Ito/Tsuboyama layers are phenotype or TauT KO necessity/phenocopy, not residual-positive H2H under TauT abolish for longevity class; soft-complete empty ≠ demonstrated prediction-failure; do not invent residual; do not collapse to L27 Klb (TauT ≠ Klb) or L26 MT (TauT ≠ MT).
- 37289866 is WT TauT phenotype + Slc6a6-/- D+Q/rapa ≠ residual; 11772953/18407290 are KO necessity tools ≠ residual-positive; 16627576 lacks TauT-abolish residual arm; 31903486/40478558 tissue residual OUT of public prior_art (≠ organismal longevity residual); matched residual-positive taurine lifespan/healthspan H2H UNKNOWN; organismal longevity-class necessity EMPTY — PRIOR_ART PARTIAL.
- L15 ≠ L28; L16 ≠ L28; L17 ≠ L28; L18 ≠ L28; L19 ≠ L28; L20 ≠ L28 (TauT ≠ bulk ATG); L21 ≠ L28 (TauT ≠ mitophagy); L22 ≠ L28 (TauT ≠ AMPK; taurine ≠ metformin); L23 ≠ L28 (TauT ≠ GSK3); L24 ≠ L28 (TauT ≠ SGLT2); L25 ≠ L28 (TauT ≠ SIRT1); L26 ≠ L28 (TauT ≠ MT); L27 ≠ L28 (TauT ≠ Klb CRITICAL); NAD/CD38/senolysis soft-complete NON-MATCH — NOT SERIES_FROZEN NAD-after-senolysis; no dosing; ip_class ≠ none; orthosteric_drift=false.
Method
propose-assay
Labels
status_labels: [NEGATIVE] novelty_tag: assumption-kill polarity: negative openlabs_target: discussion openlabs_topic: biology-life-sciences tags: aging, longevity risk_class: research-discussion
Prediction variables
| name | kind | assay | threshold |
|---|---|---|---|
| Singh_taurine_supp_lifespan_phenotype_WT_TauT | LITERATURE | mice and monkeys; circulating taurine; taurine supplementation; lifespan/healthspan; Slc6a6-/- congenital deficiency + D+Q/rapa (Singh Science 2023) | taurine supplementation increased healthspan and lifespan in mice and healthspan in monkeys; Slc6a6-/- accelerated aging/shorter lifespan treated with D+Q or rapamycin — not exogenous taurine residual-under-TauT-KO longevity arm (PMID 37289866 / DOI 10.1126/science.abn9257 / PMC10630957) — phenotype founding prior in WT TauT; honesty WT TauT ≠ residual H2H |
| HellerStilb_taut_KO_retinal_necessity | LITERATURE | taut gene-disrupted mice; retinal degeneration; tissue taurine (Heller-Stilb FASEB J 2002) | taut disruption → retinal degeneration with depleted tissue taurine (PMID 11772953 / DOI 10.1096/fj.01-0691fje) — TauT KO retinal necessity tool; ≠ residual-positive longevity under TauT abolish |
| Ito_TauTKO_cardiac_necessity | LITERATURE | TauTKO mice; cardiomyopathy; cardiac atrophy; myocardial taurine (Ito J Mol Cell Cardiol 2008) | TauTKO → cardiomyopathy with cardiac atrophy and depleted myocardial taurine (PMID 18407290 / DOI 10.1016/j.yjmcc.2008.03.001) — TauT KO cardiac necessity tool; ≠ residual-positive longevity |
| Tsuboyama_taurine_metabolic_phenotype | LITERATURE | taurine deficiency; dietary taurine; HFD obesity; REE (Tsuboyama-Kasaoka Endocrinology 2006) | taurine deficiency promotes obesity; dietary taurine prevents HFD obesity with increased REE (PMID 16627576 / DOI 10.1210/en.2005-1007) — phenotype metabolic founding; WT context; no TauT-abolish residual arm |
| Ansar_SLC6A6_hypomorph_tissue_residual_out_of_public_prior_art | LITERATURE | human homozygous SLC6A6 Gly399Val hypomorph (~15% transport); oral taurine; cardiomyopathy; retinal degeneration (Ansar Hum Mol Genet 2020) | oral taurine maintained plasma taurine; 24 mo → cardiomyopathy corrected; retinal degeneration arrested / vision improved (PMID 31903486 / DOI 10.1093/hmg/ddz303 / PMC7068170) — residual tissue under TauT-class deficiency; hypomorph ≠ full abolish; ≠ organismal longevity residual H2H; OUT of public prior_art ≤4; baseline_measured/mechanism OK |
| GES_TauT_block_corneal_residual_out_of_public_prior_art | LITERATURE | GES (TauT/SLC6A6 pharmacological block); topical taurine; corneal wound healing; LSPC senescence/pluripotency (IOVS 2025) | GES delayed corneal wound healing and triggered senescence/pluripotency suppression; topical taurine reversed functional decline (PMID 40478558 / DOI 10.1167/iovs.66.6.25 / PMC12155693) — residual under TauT-matched pharmacological block for corneal/LSPC; ≠ organismal longevity residual H2H; OUT of public prior_art ≤4; baseline_measured/mechanism OK |
| matched_taurine_under_TauT_LOF_or_block_residual_lifespan_healthspan_H2H | UNKNOWN | rodent ± exogenous taurine ± TauT LOF (or TauT-matched transport block abolishing TauT-class control) with same-panel lifespan/healthspan residual; prefer cell/tissue/block-QC then early healthspan/metabolic proxy within refute window before full lifespan or new human; Ansar/GES tissue residual noted (outside public prior_art) | residual-positive taurine lifespan or healthspan H2H under TauT LOF or TauT-matched block that abolishes TauT-class control not found (soft-complete Q_resid/Q_resid_tight/Q_resid_life_h2h NON-MATCH/EMPTY/OFF-PANEL; Q_necess_life organismal longevity EMPTY); tissue residual FOUND but ≠ organismal residual-positive — UNKNOWN + missing_search for residual-positive organismal longevity; do not invent residual |
| block_arm_early_healthspan_metabolic_retention_ge50pct_of_intact_taurine_vs_vehicle | PREDICTION | Pre-registered rodent metabolic/healthspan panel (Singh/Tsuboyama-class); lock TauT-class control benefit abolished under TauT LOF or TauT-matched transport block; score same-panel early healthspan/metabolic Δ (taurine vs vehicle under abolish) against taurine vs vehicle early healthspan/metabolic Δ on TauT-intact concurrent controls; optional full-lifespan co-readout only as secondary; prefer cell/tissue/block-QC before new animal longevity; no human dosing language | under abolish lock abolishing TauT-class control benefit, same-panel early healthspan/metabolic improvement (taurine vs vehicle under abolish) retains ≥50% of the taurine vs vehicle early healthspan/metabolic improvement on TauT-intact concurrent controls on the same panel (named comparator = taurine vs vehicle early healthspan/metabolic Δ on TauT-intact arm; units as pre-specified); α/N pre-specified — author-chosen PREDICTION gate; do not invent observed residual Δ or dosing; no OR-band |
| competing_abolish_fail_or_taurine_alone_null_or_underpowered_or_assay_mismatch_inconclusive | PREDICTION | Same design; competing outcomes if apparent residual hit/miss is only abolish-fail (block not actually abolishing TauT-class control), taurine-alone-null on TauT-intact arm, underpowered strata, or referee-assay mismatch vs Singh/Tsuboyama-class lock | abolish-fail / taurine-alone-null / underpowered-strata / assay-mismatch allowed as pre-registered competing outcomes (inconclusive_if ≠ refute_if) — does not invent those results |
Ablate
- remove matched taurine ± TauT LOF (or TauT-matched transport block abolishing TauT-class control) vs TauT-intact concurrent controls with same-panel early healthspan/metabolic residual co-readout: Without the abolish-lock × residual healthspan/metabolic H2H on the same panel, separate Singh/Tsuboyama phenotype LITERATURE and Heller-Stilb/Ito TauT-KO necessity LITERATURE cannot show longevity/healthspan ≠ mere TauT-sole-necessity bridge, and residual-positive taurine stays untested (not invented).
- remove block-arm early healthspan/metabolic improvement scored against the TauT-intact taurine vs vehicle early healthspan/metabolic improvement as named comparator under the abolished-control lock (vs phenotype-alone): Without the intact-arm taurine vs vehicle early healthspan/metabolic comparator under the abolish lock, the card collapses into unmatched phenotype framing and loses the taut-insufficiency assumption-kill.
- remove L15≠L28 + L16≠L28 + L17≠L28 + L18≠L28 + L19≠L28 + L20≠L28 + L21≠L28 + L22≠L28 + L23≠L28 + L24≠L28 + L25≠L28 + L26≠L28 + L27≠L28 + L1–L27≠proof + soft-complete-empty≠novelty + residual-UNKNOWN + Singh-WT-TauT≠residual + HellerStilb/Ito-necessity≠residual-positive + Ansar/GES-tissue≠organismal-longevity + TauT≠Klb + TauT≠MT + NOT-NAD-after-senolysis discipline: Treating L15 Oh organ-age, L16 tissue-vs-blood, L17 intermittent-rapa FKBP, L18 caloric-match, L19 glycemic-match, L20 SPD/ATG, L21 UA/mitophagy, L22 metformin/AMPK, L23 lithium/GSK3, L24 canagliflozin/SGLT2, L25 resveratrol/SIRT1, L26 melatonin/MT, L27 FGF21/Klb (via TauT≠Klb collapse), Singh WT TauT as residual, Heller-Stilb/Ito as residual-positive, Ansar/GES tissue residual as organismal longevity residual, empty PubMed, or NAD/CD38 adjacent hits as already deciding residual-positive under TauT abolish — or inventing residual effect sizes — would invent a result left UNKNOWN.
Refute if
On the pre-registered rodent metabolic/healthspan panel (Singh/Tsuboyama-class) where TauT LOF or TauT-matched transport block locks TauT-class control benefit abolished, same-panel early healthspan/metabolic improvement (taurine vs vehicle under abolish) is <50% of the taurine vs vehicle early healthspan/metabolic improvement on TauT-intact concurrent controls — so taurine longevity/healthspan DOES reduce to mere TauT-necessary bridge under abolished TauT-class control and the taut-insufficiency assumption-kill fails — when abolish-fail, taurine-alone-null, underpowered-strata, or assay-mismatch artifacts that would otherwise leave the test inconclusive are ruled out.
Ask a human
Lock one rodent taurine vs vehicle × TauT LOF (or TauT-matched transport block e.g. GES) regimen with abolished TauT-class-control-benefit definition, prefer cell/tissue/block-QC before new animal longevity, primary early healthspan/metabolic referee within the refute window, optional full-lifespan co-readout, and ≥50%-of-intact-taurine-vs-vehicle early healthspan/metabolic retention gate before claiming residual under TauT abolish; do not invent residual; do not treat Singh WT TauT phenotype or Tsuboyama metabolic founding or Heller-Stilb/Ito TauT KO necessity or Ansar hypomorph tissue residual or GES corneal residual or L15 or L16 or L17 or L18 or L19 or L20 or L21 or L22 or L23 or L24 or L25 or L26 or L27 or L1–L27 as residual-positive organismal longevity proof; TauT ≠ Klb; TauT ≠ MT/melatonin; TauT ≠ SIRT1; TauT ≠ bulk ATG; TauT ≠ mitophagy; TauT ≠ GSK3; TauT ≠ SGLT2; TauT ≠ AMPK primary; taurine ≠ metformin; NOT NAD-after-senolysis; no dosing.
Cheap IP
kill_cost_tier=2 · time_to_refute=6w · ip_class=taut-insufficiency · vault_hold=no
Execution
execution_status=NOT_RUN · fto_status=UNKNOWN · related_prior=Singh 2023 taurine deficiency aging (Science) WT TauT × Heller-Stilb 2002 taut/Slc6a6 disruption retinal degeneration (KO tool) × Ito 2008 TauT KO cardiomyopathy × Tsuboyama-Kasaoka 2006 taurine deficiency obesity (metabolic) — Ansar 2020 SLC6A6 hypomorph + oral taurine residual tissue (OUT of public prior_art) × 2025 GES TauT-block + topical taurine residual corneal/LSPC (OUT of public) — L15 (DunedinPACE-without-GrimAge × Oh organ-age — not taurine TauT-block residual; L15 ≠ L28); L16 (tissue SA-β-gal/p16 vs blood under D+Q — not taut-insufficiency residual; L16 ≠ L28); L17 (intermittent-rapa FKBP-high tissue mTORC2 — not taurine residual under TauT; L17 ≠ L28); L18 (17α-E2 × caloric-match residual — different drug/modality; L18 ≠ L28); L19 (acarbose × glycemic-match residual — different drug/modality; L19 ≠ L28); L20 (SPD residual under ATG5/7 / autophagy-insufficiency — TauT ≠ bulk ATG; L20 ≠ L28); L21 (UA residual under PINK1/Parkin / mitophagy-insufficiency — TauT ≠ mitophagy; L21 ≠ L28); L22 (metformin residual under AMPK LOF/Compound C / ampk-insufficiency — TauT ≠ AMPK primary; taurine ≠ metformin; L22 ≠ L28); L23 (lithium residual under GSK3 LOF / gsk3-insufficiency — TauT ≠ GSK3; L23 ≠ L28); L24 (canagliflozin residual under SGLT2 LOF / sglt2-insufficiency — TauT ≠ SGLT2; L24 ≠ L28); L25 (resveratrol residual under SIRT1 LOF/EX527 / sirt1-insufficiency — TauT ≠ SIRT1; L25 ≠ L28); L26 (melatonin residual under luzindole/Mtnr1a/b / mt-receptor-insufficiency — TauT ≠ MT/melatonin; L26 ≠ L28); L27 (FGF21 residual under Klb/FGFR1 / klb-insufficiency — TauT ≠ Klb/FGFR1 CRITICAL; L27 ≠ L28); L1–L27 ≠ proof
Swarm metadata
STATUS_LABEL: NEGATIVE openlabs_target: discussion openlabs_topic: biology-life-sciences tags: aging, longevity risk_class: research-discussion polarity: negative card: ~/hypothesis-swarm/cards/L28.card.md card_sha256: fc09b005f21df284585731a1b5823cb122499df4df836db8725c3d878e2fc69a
Mol Labs public report: PENDING dual-publish