Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages

Guan, Chenyang, Ryu, Seungjin, Dong, Mingze, Zhu, Yitao, Maeda, Rae, Youm, Yun-Hee, Mohanty, Subhasis, Kim, Hee-Hoon +15 more·2026·Cell

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TL;DR

Aging increases circulating taurine in humans and mice rather than decreasing it, and further elevating taurine in aged mice improves health span and suppresses inflammaging. Mechanistically, NLRP3-specific danger signals trigger taurine efflux from macrophages as an upstream step in inflammasome activation, and restoring taurine prevents trans-Golgi network disassembly and blocks NLRP3 activation.

Key findings

  • Serum taurine was significantly higher in older adults (females and males) in the Yale New Haven Hospital cohort, and higher in aged (28-month) vs. young (2-month) male C57BL/6N and C57BL/6J mice; tissue taurine was higher in aged heart, spleen, lung, kidney, liver, VAT, and SAT, but not BAT or skeletal muscle. Plasma taurine did not differ by age (Mayo cohort).
  • Taurine supplementation (8,000 mg/kg in water, 4 months) in 20-month-old male mice doubled serum taurine, modestly improved glucose homeostasis, significantly enhanced rotarod performance and grip strength, reduced serum and liver IL-1β, and lowered liver IL-18 and IL-6; scRNA-seq of VAT SVF showed downregulation of TNF-α signaling, interferon response, IL-6 signaling, and complement cascade.
  • NLRP3 activators (ATP, hypotonic stress, MSU, C6-ceramide, nigericin, imiquimod) all induced taurine efflux from macrophages, dropping within 5 min of ATP and preceding IL-1β secretion; efflux was unaffected by deletion of *Nlrp3*, *Asc*, or *Gsdmd* or by MCC950, but did not occur with poly(dA:dT), transfected LPS, or flagellin.
  • Taurine supplementation dose-dependently inhibited IL-1β secretion, caspase-1 cleavage, ASC oligomerization, and GSDMD cleavage across NLRP3 stimuli, independently of K+ efflux and Nrf2, and suppressed constitutive NLRP3 activity in FCAS (L351P) and MWS (A350V) BMDMs; it improved survival in lethal LPS endotoxemia, with no added benefit over MCC950 alone.
  • Myeloid-specific *Csad* or *Cdo1* deficiency combined with taurine-free diet/culture reduced intracellular taurine and increased IL-1β, caspase-1, and IL-18 responses; in humans, 1 year of ~14% caloric restriction (CALERIE-II) increased SAT hypotaurine and taurine and FMO1/2 and CSAD expression, and decreased SAT IL-18, ASC, and NEK7.

Methods

  • Human samples: serum from Yale New Haven Hospital young (21–35 y) and older (≥65 y) adults (n = 71 for metabolomics; n = 45 kit-based), plasma from the Mayo Clinic Biobank (n = 65), and SAT/plasma from 14 CALERIE-II participants completing 1 year of ~14% CR (RNA-seq n = 8).
  • Mouse work: C57BL/6N and C57BL/6J mice, including aged (20–28 month) taurine supplementation, scRNA-seq of VAT SVF (control n = 8, taurine n = 10 pooled; 19,904 cells), BMDM and peritoneal macrophage assays, knockout/floxed lines (*Nlrp3*, *Asc*, *Gsdmd*, *Nrf2*, *Cth*, *Slc6a6*, *Csad*, *Cdo1*, *Nlrp3*^L351P, *Nlrp3*^A350V), IAV infection, and in vivo LPS, LPS+ATP, MSU peritonitis, and endotoxic shock models.
  • Readouts: LC-MS/UPLC-MS and IC-MS/LC-MS/MS metabolomics, ELISA/multiplex cytokines, immunoblotting, ASC cross-linking, ICP-MS intracellular K+, LDH release, confocal TGN38/NLRP3 imaging, TEM, and GSEA (GSEAPy, hallmark gene sets); statistics by t test, one-way ANOVA with Holm-Šidák, or log-rank test.

Limitations

  • Stated: whether K+ and taurine efflux act in parallel or intersect in inflammasome assembly is unresolved; why taurine efflux is selective for NLRP3-activating stimuli is unclear; taurine reduction in vivo does not produce lethal uncontrolled inflammation and is not analogous to gain-of-function NLRP3 autoactivation; whether aging *Cdo1*- or *Csad*-deficient mice accelerates inflammaging or shortens lifespan remains to be determined; the identity of the macrophage taurine transporter is unknown (SLC6A6 and SLC36A1 excluded); the role of N-acetyltaurine is speculative; and randomized controlled trials are needed to test taurine's direct anti-inflammaging effects.
  • Evident from the text: experiments were conducted without blinding except for intracellular potassium and human serum taurine measurements, and no sample size calculations were performed prior to in vivo experiments; the in vivo mouse work reported here used male mice (with one female cohort for LPS-induced IL-1β), and the human CR analysis rests on a small subset (n = 14 metabolomics, n = 8 RNA-seq) of the CALERIE-II trial.

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Crossref · 10.1016/j.cell.2026.09.061

Cites

Statistics

Nothing to recompute.

Claims the paper makes

29 of 40 cited sources checked · 16 supported · 1 flagged · accuracy not yet measured

  • Premisecitation
    § 6 Cell 190, 1–18, January 7, 2027

    Trans-Golgi network disassembly is a key upstream event in NLRP3 inflammasome activation by diverse danger signals.

    “Trans-Golgi network (TGN) disassembly is a key upstream event in NLRP3 inflammasome activation by diverse danger signals.58”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [58] Chen, 2018, PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation, Nature source
  • Premisecitation
    § 5 to 50 mM.1,2 A recent study proposed that declining taurine

    Inflammaging is driven in part by NLRP3 inflammasome activation.

    “Inflammaging is driven in part by NLRP3 inflammasome activation,5–8”
    Quote in the paperSubstantial claim2 of 4 sources checked
    • cites [5] Camell, 2017, Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing, Nature source
    • cites [6] Youm, 2013, Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging, Cell Metab. source
    • cites [7] Latz, 2018, NLRP3 inflammasome activation in inflammaging, Semin. Immunol. source
    • cites [8] Bauernfeind, 2016, Aging-Associated TNF Production Primes Inflammasome Activation and NLRP3-Related Metabolic Disturbances, J. Immunol. source
  • Premisecitation
    § 8 Cell 190, 1–18, January 7, 2027

    BMDMs carrying disease-relevant Nlrp3 mutations (L351P and A350V, corresponding to human L353P and A352V) confer constitutive NLRP3 activity.

    “Using BMDMs carrying disease-relevant Nlrp3 mutations (L351P and A350V, corresponding to human L353P and A352V) that confer constitutive NLRP3 activity,60”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [60] Brydges, 2009, Inflammasome-mediated disease animal models reveal roles for innate but not adaptive immunity, Immunity source

      The Results sections on mouse-strain development and inflammasome function identify A350V and L351P as the mouse counterparts of the disease-associated human mutations and show enhanced IL-1β release from mutant cells without added ATP. But the experiments described use bone-marrow-derived dendritic cells (BMDCs) and peritoneal macrophages, not BMDMs. The paper calls constitutive inflammasome activity a hypothesis; it reports unstimulated IL-1β release only for L351P BMDCs, not for both mutations. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Findingown data
    § 15 min, and IL-1β appeared by 45 min, even without a classical

    Taurine supplementation reduces IL-18 and LDH release.

    “and it similarly reduced IL-18 and LDH release (Figures S3B and S3C).”
    Quote in the paperSubstantial claim
  • Findingown data
    § RESULTS

    The same NLRP3 stimuli trigger taurine efflux in unprimed BMDMs without eliciting IL-1β secretion.

    “The same stimuli also triggered taurine efflux in unprimed BMDMs without eliciting IL-1β secretion (Figures 2H and S2G).”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 26
  • May combine two claims. 34
  • The quote only partly states this claim. 2
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premiseown data
    § 18 Cell 190, 1–18, January 7, 2027

    CALERIE Phase 2 calorie restriction group participants accomplished 14% of the intended calorie restriction.

    “CR group participants accomplished 14% of CR.”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [29] Spadaro, 2022, Caloric restriction in humans reveals immunometabolic regulators of health span, Science source
    • cites [66] Kraus, 2019, 2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial, Lancet Diabetes Endocrinol. source

      The Results section (“Intervention adherence, body weight and composition”; page unavailable) reports that the CR group averaged 11.7% calorie restriction over the two-year intervention, not 14%. The Methods state that the prescribed target was 25%. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [67] Mishra, 2026, Exoproteome of calorie-restricted humans identifies complement deactivation as an immunometabolic checkpoint reducing inflammaging, Nat Aging source
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § 2 Cell 190, 1–18, January 7, 2027

    NLRP3 inflammasome activation initiates assembly and caspase-1 activation, leading to GSDMD-mediated pore formation, release of IL-1β and IL-18, and pyroptotic cell death.

    “This initiates inflammasome assembly and caspase-1 activation, leading to gasdermin-D (GSDMD)-mediated pore formation, the release of interleukin (IL)-1β and IL-18, and pyroptotic cell death.27”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] Barnett, 2023, A 360° view of the inflammasome: Mechanisms of activation, cell death, and diseases, Cell source
  • May combine two claims.

    Findingcitation
    § RESULTS

    NLRP3 inflammasome activation increases glycolytic metabolites such as fructose 1,6-biphosphate via PFK-1 and reduces NAD, with no change in cystine or betaine.

    “NLRP3 inflammasome activation also increased glycolytic metabolites45 such as fructose 1, 6-biphosphate via phosphofructokinase-1,46 alongside reduced nicotinamide adenine dinucleotide (NAD) (Figure 2A), a key cofactor in redox reactions,47 with no change in cystine (the oxidized dimeric form of cysteine) or betaine, an organic osmolyte in the methionine cycle (Figures 2B and Figure S2C).”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [45] Mills, 2016, Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages, Cell source

      The Results section, under “Glycolytic ATP production,” reports that LPS boosts glycolysis in macrophages, supporting the general glycolysis point attached to citation 45. It does not establish that NLRP3 inflammasome activation increases glycolytic metabolite concentrations. The PFK-1 and NAD statements have separate citations, while the cystine and betaine observations refer to the citing paper’s figures; they are not attributed to this source. Page numbers are unavailable in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [46] Amara, 2021, Selective activation of PFKL suppresses the phagocytic oxidative burst, Cell source
    • cites [47] Shim, 2021, Intracellular NAD+ Depletion Confers a Priming Signal for NLRP3 Inflammasome Activation, Front. Immunol. source
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § 2 Cell 190, 1–18, January 7, 2027

    Multiple longevity interventions in rodents are associated with rewiring of the transsulfuration pathway that feeds into taurine synthesis.

    “Multiple longevity interventions in rodents have been associated with the rewiring of the TSP that feeds into taurine synthesis.34–38”
    Quote in the paperNot a substantial claim3 of 5 sources checked
    • cites [34] Tyshkovskiy, 2019, Identification and Application of Gene Expression Signatures Associated with Lifespan Extension, Cell Metab. source

      In Results and Discussion, under “Common gene signatures of longevity interventions” (page unavailable), the paper reports increased hepatic expression of Cth after most lifespan-extending interventions in mice. That supports a change in one sulfur-metabolism gene, but the passage links Cth to glutathione and H2S production; it does not establish rewiring of the transsulfuration pathway feeding into taurine synthesis. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [35] Uthus, 2006, Methionine flux to transsulfuration is enhanced in the long living Ames dwarf mouse, Mech. Ageing Dev. source

      The Discussion (p. 444–450; specific page unavailable) reports greatly enhanced transsulfuration flux in long-lived Ames dwarf mice, supporting this source as one example of altered transsulfuration associated with longevity. It does not address taurine synthesis or establish the claim across multiple longevity interventions; its discussion of a downstream product focuses on glutathione. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [36] Tyshkovskiy, 2023, Distinct longevity mechanisms across and within species and their association with aging, Cell source
    • cites [37] Rao, 1990, Role of the transsulfuration pathway and of gamma-cystathionase activity in the formation of cysteine and sulfate from methionine in rat hepatocytes, J. Nutr. source
    • cites [38] Lee, 2025, Cysteine depletion triggers adipose tissue thermogenesis and weight loss, Nat. Metab. source
  • Classified as probably not a substantial claim.

    Premisecitation
    § 5 to 50 mM.1,2 A recent study proposed that declining taurine

    Reduction of NLRP3 extends lifespan in mice.

    “reduction of NLRP3 extends lifespan in mice,11,12”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [11] Marín-Aguilar, 2020, NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice, Aging Cell source
    • cites [12] Navarro-Pando, 2021, Inhibition of the NLRP3 inflammasome prevents ovarian aging, Sci. Adv. source
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § 10 Cell 190, 1–18, January 7, 2027

    FMO2 has been shown to extend lifespan in Caenorhabditis elegans.

    “which has been shown to extend lifespan in Caenorhabditis elegans.68,69”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [68] Choi, 2023, FMO rewires metabolism to promote longevity through tryptophan and one carbon metabolism in C. elegans, Nat. Commun. source
    • cites [69] Leiser, 2015, Cell nonautonomous activation of flavin-containing monooxygenase promotes longevity and health span, Science source
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § 10 Cell 190, 1–18, January 7, 2027

    SLC36A1 (PAT1) has been reported to transport taurine.

    “As SLC36A1 (PAT1) has also been reported to transport taurine,65”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [65] Anderson, 2009, Taurine uptake across the human intestinal brush-border membrane is via two transporters: H+-coupled PAT1 (SLC36A1) and Na+- and Cl(-)-dependent TauT (SLC6A6), J. Physiol. source
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § DISCUSSION

    Taurine has been linked to protection from inflammation in SARS-CoV-2 viral infection and reduces oxidative damage by formation of taurine haloamines.

    “In addition, taurine has been linked to protection from inflammation in SARS-CoV-2 viral infection and reduces oxidative damage by the formation of taurine haloamines.71,72”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [71] Thomas, 2020, COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status, JCI Insight source

      The Discussion (pp. 12–13) describes taurine as an antioxidant depleted in patients with COVID-19 and proposes taurine supplementation as a potential intervention. It does not show that taurine protects against inflammation during SARS-CoV-2 infection or say that it reduces oxidative damage through formation of taurine haloamines. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [72] Sabaka, 2021, Role of interleukin 6 as a predictive factor for a severe course of Covid-19: retrospective data analysis of patients from a long-term care facility during Covid-19 outbreak, BMC Infect. Dis. source

      The Background and Discussion address COVID-19 inflammation and IL-6 as a marker of severe disease, but do not discuss taurine. Searches for taurine, taurine haloamines, and oxidative damage found no passage supporting either attributed effect. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premiseown data
    § 18 Cell 190, 1–18, January 7, 2027

    238 metabolically healthy adults (BMI 22.0-27.9 kg/m2, age 25-45) were enrolled in CALERIE Phase 2 and randomized to a 25% calorie restriction intervention versus an ad-libitum control group.

    “238 metabolically healthy adults (BMI: 22.0– 27.9 kg/m2, Age: 25–45) were enrolled in the study from Pennington Biomedical Research Center (PBRC, Baton Rouge, LA), Washington University (St. Louis, MO) and Tufts University (Boston, MA) (NCT00427193)”
    • Also stated in: § 18 Cell 190, 1–18, January 7, 2027 · plain
      “Study participants were randomized assigned to the 25% CR intervention versus ad-libitum control group who continued their habitual diet.”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [29] Spadaro, 2022, Caloric restriction in humans reveals immunometabolic regulators of health span, Science source

      The CALERIE-II passages (section labeled Abstract; page unavailable) identify a two-year calorie-restriction study in healthy volunteers and refer to control participants. Our copy does not state that 238 people were enrolled, their specified BMI and age ranges, the three enrollment sites, or random assignment to a 25% restriction target versus ad-libitum control. It reports approximately 14% restriction achieved, which does not establish or rule out a 25% assigned target. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [66] Kraus, 2019, 2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial, Lancet Diabetes Endocrinol. source

      The Results report that 238 participants began baseline assessments, but only 220 were randomized; the claim overstates the number randomized. Methods > Study population supports the BMI range and three clinical centers, and Methods > Treatment assignment and intervention supports the 25% calorie-restriction and ad-libitum arms. The stated age range of 25–45 is not supported: the paper describes men aged 21–50 and women aged 21–47. (LLM, conf=0.92)

      Experimental — accuracy not yet measured
    • cites [67] Mishra, 2026, Exoproteome of calorie-restricted humans identifies complement deactivation as an immunometabolic checkpoint reducing inflammaging, Nat Aging source

      Methods > Human participants identifies CALERIE-II as a multicenter randomized trial involving healthy, non-obese adults. Results > CR rewires the directionality of the human exoproteome toward longevity pathways identifies a Pennington cohort, but the paper describes 42 participants in its proteomics analysis, not the claimed 238 enrollees. Our copy does not substantiate the exact BMI and age ranges, the Washington University and Tufts sites, or a 25% restriction assignment; it reports 14% calorie restriction after two years. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § DISCUSSION

    Prior reports suggest swelling-evoked taurine release in the brain, including astrocytes and neurons.

    “Prior reports suggest swelling-evoked taurine release in the brain, including astrocytes and neurons.74,75”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [74] Estévez, 1999, Induction of nitric oxide-dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase, Science source
    • cites [75] Haskew-Layton, 2008, Two Distinct Modes of Hypoosmotic Medium-Induced Release of Excitatory Amino Acids and Taurine in the Rat Brain In Vivo, PLoS One source
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Taurine can boost the cellular uptake of small D-peptides by endocytosis or trogocytosis.

    “It has been shown that taurine can boost the cellular uptake of small D-peptides by endocytosis or trogocytosis.81”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [81] Zhou, 2015, Taurine Boosts Cellular Uptake of Small D-Peptides for Enzyme-Instructed Intracellular Molecular Self-Assembly, J. Am. Chem. Soc. source

      The Abstract reports that taurine conjugation boosts uptake of small D-peptides and identifies dynamin-dependent endocytosis and macropinocytosis as uptake pathways. It does not identify trogocytosis; the citing sentence appears to substitute that term for macropinocytosis. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § 18 Cell 190, 1–18, January 7, 2027

    CALERIE Phase 2 is a multi-center, parallel-group, randomized controlled trial recruiting non-obese healthy individuals.

    “CALERIE Phase 2 is a multi-center, parallel group, randomized controlled trial recruiting non-obese healthy individuals.”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [29] Spadaro, 2022, Caloric restriction in humans reveals immunometabolic regulators of health span, Science source

      The study text describes CALERIE as a clinical trial in healthy volunteers and identifies CALERIE-II participants and a control group (section labeled Abstract; page unavailable). It does not state that participants were non-obese or that the trial was multicenter, randomized, and parallel-group. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [66] Kraus, 2019, 2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial, Lancet Diabetes Endocrinol. source
    • cites [67] Mishra, 2026, Exoproteome of calorie-restricted humans identifies complement deactivation as an immunometabolic checkpoint reducing inflammaging, Nat Aging source

      The Methods section (“Human participants”; page not specified) describes CALERIE-II as a multicenter randomized controlled trial and identifies its sampled participants as non-obese and healthy. It does not specify a parallel-group design, so that part of the claim is not verified by our copy. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
  • May combine two claims.

    Findingown data
    § 15 min, and IL-1β appeared by 45 min, even without a classical

    Taurine blocks NLRP3 inflammasome activation in Nrf2-deficient macrophages, indicating an Nrf2-independent mechanism.

    “Notably, taurine also blocked NLRP3 inflammasome activation in Nrf2-deficient macrophages (Figures 3E, S3I, and S3J), indicating an Nrf2-independent mechanism.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data
    § 6 Cell 190, 1–18, January 7, 2027

    Taurine inhibits caspase-1 cleavage in Gsdmd−/− macrophages responding to ATP and hypotonic stress, consistent with taurine acting upstream of caspase-1, prior to GSDMD cleavage.

    “Taurine also inhibited caspase-1 cleavage in Gsdmd− /− macrophages responding to ATP (Figures S4I and S4J) and hypotonic stress (Figures S4K and S4L), consistent with taurine acting upstream of caspase-1, prior to GSDMD cleavage.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data
    § RESULTS

    Taurine supplementation significantly enhances rotarod performance and grip strength in aged mice.

    “Notably, taurine significantly enhanced rotarod performance and grip strength (Figure 1K)”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data
    § RESULTS

    Taurine supplementation upregulates Uba52 and Cmss1 and inhibits B2m in taurine-regulated cells.

    “Top taurine-regulated genes in these cells shared common hubs, including the upregulation of Uba52 and Cmss1 and inhibition of β2 microglobulin (B2m) (Figures 1N and S1Q).”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data
    § RESULTS

    Aging is associated with higher hypotaurine and lower homocysteine, cystathionine, and cysteine sulfinic acid, with no change in cysteine.

    “Aging was also associated with a broader remodeling of the TSP, including higher hypotaurine (Figure S1I) and lower homocysteine, cystathionine, and cysteine sulfinic acid, with no change in cysteine (Figure S1J).”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data
    § Summary

    Taurine supplementation reduces mortality from sepsis and inflammasome-mediated inflammation in aged mice.

    “reduces mortality from sepsis and inflammasome-mediated inflammation”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data
    § 6 Cell 190, 1–18, January 7, 2027

    Restoring intracellular K+ with KCl does not prevent taurine efflux, suggesting taurine efflux occurs upstream of inflammasome activation.

    “Restoring intracellular K+ with potassium chloride (KCl), which blocks inflammasome activation, did not prevent taurine efflux (Figures 3C and 3G), suggesting that taurine efflux occurs upstream of inflammasome activation.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data
    § RESULTS

    Taurine levels are significantly higher in aged mouse heart, spleen, lung, kidney, liver, VAT, and SAT, but not in BAT or skeletal muscle.

    “with significantly higher levels in aged heart, spleen, lung, kidney, liver, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) (Figure 1G), but not in brown adipose tissue (BAT) or skeletal muscle (Figure S1L), in mice.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data
    § 6 Cell 190, 1–18, January 7, 2027

    Taurine supplementation inhibits NLRP3 inflammasome activation without affecting K+ efflux.

    “Surprisingly, taurine supplementation inhibited NLRP3 inflammasome activation without affecting K+ efflux (Figure 3F).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data
    § Summary

    Sustained caloric restriction elevates adipose tissue taurine and is accompanied by lower inflammation in humans.

    “In humans, sustained caloric restriction elevates adipose tissue taurine and is accompanied by lower inflammation.”
    • Also stated in: § Highlights · plain
      “Calorie restriction elevates taurine and lowers inflammation in humans”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data
    § Summary

    Taurine restoration in macrophages prevents NLRP3-induced trans-Golgi network disassembly, thereby suppressing NLRP3 inflammasome activation.

    “Taurine restoration in macrophages prevents NLRP3-induced trans-Golgi network disassembly, thereby suppressing NLRP3 inflammasome activation.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data
    § 6 Cell 190, 1–18, January 7, 2027

    Imiquimod does not trigger K+ efflux, and taurine supplementation does not alter intracellular K+.

    “As expected, imiquimod did not trigger K+ efflux, and taurine supplementation did not alter intracellular K+ (Figure S5G).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data
    § 15 min, and IL-1β appeared by 45 min, even without a classical

    Macrophages in taurine-containing medium show neither taurine efflux nor measurable IL-1β.

    “In contrast, macrophages in a taurine-containing medium showed neither taurine efflux nor measurable IL-1β (Figure 2J).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data
    § 6 Cell 190, 1–18, January 7, 2027

    Under hypotonic stress, taurine diminishes cell swelling and partially preserves mitochondrial structural integrity in inflammasome-activated macrophages.

    “Under hypotonic stress, taurine also diminished cell swelling (Figure S7B) and partially preserved mitochondrial structural integrity in inflammasome-activated macrophages (Figures S7C–S7E).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data
    § RESULTS

    Taurine supplementation slightly reduces body weight and fat mass without affecting lean mass in aged mice.

    “slightly reduced body weight and fat mass without affecting lean mass (Figures S1N and S1O)”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data
    § 10 Cell 190, 1–18, January 7, 2027

    The same mice showed no differences in body temperature or weight loss.

    “without differences in body temperature or weight loss (Figure S12O).”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data
    § 10 Cell 190, 1–18, January 7, 2027

    In myeloid-specific Slc6a6-deficient mice, peritoneal macrophages had comparable IL-1β, which remained sensitive to taurine supplementation.

    “but comparable IL-1β, which remained sensitive to taurine supplementation (Figure S11J).”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim.

    Findingown data
    § 10 Cell 190, 1–18, January 7, 2027

    Taurine-free culture reduced intracellular taurine in Cdo1-deficient macrophages.

    “However, taurine-free culture reduced intracellular taurine (Figures 6K and 6L)”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data
    § 10 Cell 190, 1–18, January 7, 2027

    CR reduced IL-1β-inducible genes CCL13 and TNFAIP6, with trends in reduction of CXCL2, IL-8, and CCL2.

    “and reduced the IL-1β-inducible genes CCL13 and TNFAIP6, with a trend in the reduction of CXCL2, IL-8, and CCL2 (Figure 7H).”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data
    § 10 Cell 190, 1–18, January 7, 2027

    Taurine supplementation did not affect body weight.

    “without affecting body weight (Figure S9H).”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data
    § 10 Cell 190, 1–18, January 7, 2027

    CR reduced cysteine and GSH but increased hypotaurine and taurine in SAT.

    “Among the top altered metabolites, CR reduced cysteine and GSH but surprisingly increased hypotaurine and taurine (Figures 7B and 7C).”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim.

    Findingown data
    § 10 Cell 190, 1–18, January 7, 2027

    Similar effects were observed across other NLRP3 activators in Cdo1-deficient macrophages.

    “with similar effects across other NLRP3 activators (Figures 6O and 6P).”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data
    § 10 Cell 190, 1–18, January 7, 2027

    Slc6a6−/− BMDMs responded to the NLRP3 stimulator similarly to controls, with comparable IL-1β secretion, caspase-1 release, GSDMD cleavage, LDH release, and ASC oligomerization.

    “Slc6a6− /− BMDMs responded to the NLRP3 stimulator similarly to controls, with comparable IL-1β secretion (Figure S10C), caspase-1 release (Figure S10D), GSDMD cleavage (Figure S10E), LDH release (Figure S10F), and ASC oligomerization (Figure S10G).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data
    § 18 Cell 190, 1–18, January 7, 2027

    Taurine does not inhibit NLRP3 priming, caspase-11, NLRC4, or AIM2 inflammasome activation.

    “Taurine does not inhibit NLRP3 priming, caspase-11, NLRC4 or AIM2 inflammasome activation, related to Figure 4”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data
    § DISCUSSION

    In cross-sectional analyses, taurine did not decline with age; instead, taurine increased in sera of older humans and mice.

    “In our cross-sectional analyses, taurine did not decline with age; instead, taurine increased in the sera of older humans and mice”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data
    § 18 Cell 190, 1–18, January 7, 2027

    The scRNA-seq dataset was annotated into 16 cell types, including adipocytes, adipose stem and progenitor cells (ASPCs), vascular cells, and immune cells.

    “The dataset was annotated into 16 cell types, including adipocytes, adipose stem and progenitor cells (ASPCs), vascular cells and immune cells.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data
    § DISCUSSION

    Taurine efflux is not the consequence of pyroptosis; taurine still effluxes when exposed to NLRP3 activators in Nlrp3−/−, Asc−/−, and Gsdmd−/− macrophages.

    “This efflux is not the consequence of pyroptosis as in Nlrp3− /− , Asc− /− , and Gsdmd− /− macrophages; taurine still effluxes when exposed to NLRP3 activators.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § 2 Cell 190, 1–18, January 7, 2027

    Taurine limits inflammation and preserves cell volume as an organic osmolyte.

    “taurine limits inflammation and preserves cell volume as an organic osmolyte.32”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Warskulat, 1997, Taurine is an osmolyte in rat liver macrophages (Kupffer cells), J. Hepatol. source
  • May combine two claims.

    Interpretationown data
    § 15 min, and IL-1β appeared by 45 min, even without a classical

    Taurine efflux occurs in vivo in response to NLRP3 stimuli, driving downstream NLRP3 inflammasome activation.

    “Together, these data show that taurine efflux occurs in vivo in response to NLRP3 stimuli, driving downstream NLRP3 inflammasome activation.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationown data
    § 6 Cell 190, 1–18, January 7, 2027

    Taurine's anti-inflammasome effect is K+ independent, and taurine and K+ efflux are likely separately regulated pathways converging on NLRP3 inflammasome activation.

    “Together, these results indicate that taurine's anti-inflammasome effect is K+ independent and that taurine and K+ efflux are likely separately regulated pathways converging on NLRP3 inflammasome activation.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationown data
    § 6 Cell 190, 1–18, January 7, 2027

    Taurine supplementation maintains TGN integrity, preventing a key upstream step in NLRP3 inflammasome activation.

    “These data indicate that taurine supplementation maintains TGN integrity, preventing a key upstream step in NLRP3 inflammasome activation.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § DISCUSSION

    Activation of the TSP that generates cysteine and culminates in production of GSH and taurine has previously been associated with pro-longevity interventions.

    “Activation of the TSP that generates cysteine and culminates in production of GSH and taurine has previously been associated with pro-longevity interventions.36,70”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [36] Tyshkovskiy, 2023, Distinct longevity mechanisms across and within species and their association with aging, Cell source
    • cites [70] Mota-Martorell, 2021, Methionine transsulfuration pathway is upregulated in long-lived humans, Free Radic. Biol. Med. source
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § 10 Cell 190, 1–18, January 7, 2027

    Taurine is synthesized from cysteine via CDO1 and CSAD.

    “Because taurine is synthesized from cysteine via CDO1 and CSAD (Figure S12A)”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data
    § 18 Cell 190, 1–18, January 7, 2027

    In the scRNA-sequencing analysis, possible doublets (cells with more than 8000 genes) and low-quality cells (mitochondrial reads greater than 15% of total counts) were filtered out.

    “We filtered out possible doublet with number of genes per cell larger than 8000. We further filtered out low-quality cells with mitochondria reads larger than 15% of the total counts.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning
    § 18 Cell 190, 1–18, January 7, 2027

    Treated BMDMs were washed with PBS at least 3 times to rule out culture medium taurine contamination before taurine measurement.

    “Treated BMDMs were washed with PBS at least 3 times to rule out the culture medium taurine contamination.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § DISCUSSION

    Intracellular vitamin C is 0.008 μmol/108 cells.

    “Intracellular vitamin C is 0.008 μmol/108 cells.78”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [78] Emadi-Konjin, 2005, Measurement of intracellular vitamin C levels in human lymphocytes by reverse phase high performance liquid chromatography (HPLC), Clin. Biochem. source
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § 18 Cell 190, 1–18, January 7, 2027

    No sample size calculations were performed prior to conducting in vivo experiments.

    “No sample size calculations were performed prior to conducting in vivo experiments.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § 18 Cell 190, 1–18, January 7, 2027

    The averaged CPS relative standard deviations for the potassium measurements were 0.7%.

    “The averaged CPS RSDs for the K measurements were 0.7%.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § 18 Cell 190, 1–18, January 7, 2027

    All animal experiments were performed in accordance with institutional regulations after protocol review and approval by Yale University's Institutional Animal Care and Use Committee.

    “All animal experiments were performed in accordance with institutional regulations after protocol review and approval by Yale University's Institutional Animal Care and Use Committee.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning
    § DISCUSSION

    Prior work typically centrifuged blood at 17,000-20,000 × g to obtain plasma or serum; these high forces may compromise cell integrity and thereby contribute to potential variability across studies.

    “Unlike our studies, prior work typically centrifuged blood at 17,000–20,000 × g to obtain plasma or serum4,73; these high forces may compromise cell integrity and thereby contribute to potential variability across studies.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [4] Fernandez, 2025, Is taurine an aging biomarker?, Science source
    • cites [73] Jankowski, 2025, Aged mice exhibit widespread metabolic changes but preserved major fluxes, Cell Metab. source
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § 18 Cell 190, 1–18, January 7, 2027

    Experiments were conducted without blinding, except for measurements of intracellular potassium and human serum taurine levels, for which the investigator was blinded to group allocation.

    “Experiments were conducted without blinding, except for measurements of intracellular potassium and human serum taurine levels, for which the investigator was blinded to group allocation.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given
    § 18 Cell 190, 1–18, January 7, 2027

    All studies using CALERIE Phase 2 samples were performed under a protocol approved by the Pennington institutional review board with informed consent from participants.

    “All studies were performed under the protocol approved by the Pennington institutional review board with the informed consent from participants.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § 18 Cell 190, 1–18, January 7, 2027

    All experiments were repeated at least three independent times.

    “All experiments were repeated ≥3 independent times.”
    Quote in the paperNot a substantial claim
55 of 55
  • The paper relies on this without support.

    Multiple pathways control inflammasome activation in vivo.

    “Given that multiple pathways control inflammasome activation in vivo”
  • The paper relies on this without support.

    Macrophages can import extracellular taurine.

    “Because macrophages can import extracellular taurine”
2 of 2

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Authors
Guan, C., Ryu, S., Dong, M., Zhu, Y., Maeda, R., Youm, Y.-H., Mohanty, S., Kim, H.-H., Orliaguet, L., Dlugos, T., Smith, S. R., Ravussin, E., Onyuru, J., Hoffman, H. M., Siebel, S., Wang, A., Wang, Y., Kluger, Y., Shaw, A. C., Kanneganti, T.-D., LeBrasseur, N., Sugiura, Y., & Dixit, V. D.
Venue
Cell
Publisher
Elsevier BV
Published
2026-10
ISSN
0092-8674
Language
en
Funders
National Institute on Aging

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