He Shou Wu for Longevity and Cardiovascular Health

The longevity reputation of He Shou Wu in Traditional Chinese Medicine has a surprisingly direct molecular bridge to one of the most active areas of modern aging research: the stilbene class of compounds and their interaction with the sirtuin family. 2,3,5,4'-tetrahydroxystilbene-2-O-glucoside (TSG), the principal active compound in He Shou Wu, is a close structural relative of resveratrol — both are stilbenes, both share the trans-stilbene backbone, and both activate SIRT1 in cell-culture studies. The cardiovascular evidence base, while not as developed as the cognitive evidence, includes meaningful lipid-lowering data, antioxidant capacity, anti-atherosclerotic effects in animal models, and small human studies on cholesterol. The emodin anthraquinone fraction adds additional cardiovascular-relevant mechanisms including anti-platelet and vasodilatory effects. This deep-dive walks through the SIRT1 / caloric-restriction-mimetic framework, the comparison with resveratrol, the lipid-lowering data, the antioxidant capacity, the traditional rasayana longevity claims and what evidence supports them, and the practical role of He Shou Wu in a cardiovascular and longevity protocol — weighed always against the hepatotoxicity risk that the companion Liver Health and Hepatotoxicity Warning deep-dive details.

The Traditional Rasayana Longevity Claims
TSG as a Resveratrol Relative — Structural Family
SIRT1 Activation and Caloric-Restriction Mimicry
Emodin and Stilbenes as the Active Class
Lipid-Lowering Evidence
Antioxidant Effects on Vascular Tissue
Anti-Atherosclerosis Animal Data
Anti-Platelet and Anti-Thrombotic Effects
Blood Pressure Effects
Cardiovascular Integrative Context
Cautions — Cardiovascular Use Still Carries Hepatic Risk
Key Research Papers
Connections

The Traditional Rasayana Longevity Claims

The TCM longevity claim for He Shou Wu is one of the herb's defining indications. Classical formulary literature places it among the highest-tier jing-tonifying (essence-supplementing) herbs alongside shu di huang (prepared Rehmannia), nu zhen zi (Ligustrum lucidum fruit), gou qi zi (goji berry / Lycium), and a small number of others. The traditional theoretical framework: as the body ages, the kidney jing (the inherited and acquired essence stored in the kidney system, which in TCM physiology governs reproductive function, bone marrow, brain ("sea of marrow"), hair, teeth, hearing, and longevity) is gradually depleted, and herbs that tonify jing can slow this process and support the aging body.

The TCM rasayana concept (the Sanskrit term from Ayurveda; TCM has parallel concepts under different names) refers to herbs and practices that promote longevity, rejuvenation, and resistance to disease. Across Asian traditional medicine, a small set of herbs recur in this category: ginseng (Panax ginseng, Panax notoginseng), astragalus, reishi mushroom, Rhodiola, ashwagandha (Withania), shilajit, gotu kola, and He Shou Wu. The concept is not pure folklore — many of these herbs have meaningful modern evidence for adaptogenic, anti-fatigue, antioxidant, and immunomodulatory effects.

The translation of traditional longevity claims into modern terms involves several distinct mechanistic targets:

Antioxidant capacity — reducing oxidative damage that accumulates over the lifespan
Anti-inflammatory effects — addressing "inflammaging," the chronic low-grade inflammation of older age
Mitochondrial support — preserving mitochondrial function that declines with age
Sirtuin / NAD+ axis support — activating longevity-associated cellular signaling
Telomere protection — preserving telomere length, which shortens with age and is associated with mortality
Autophagy support — promoting cellular housekeeping that clears damaged proteins and organelles
Cardiovascular protection — addressing the leading cause of age-related mortality
Hormonal optimization — preserving sex steroid, growth hormone, and thyroid axis function

He Shou Wu's preclinical mechanism profile touches several of these targets — antioxidant capacity, NF-κB anti-inflammatory effects, SIRT1 activation through the TSG stilbene class, and cardiovascular effects through the emodin and stilbene mechanisms. The traditional "longevity herb" framing is therefore mechanistically plausible — even if the leap from "extends mouse lifespan in some studies" to "extends human lifespan" remains, as for the entire longevity field, an unverified extrapolation.

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TSG as a Resveratrol Relative — Structural Family

The structural and biological relationship between TSG and resveratrol is one of the most pharmacologically interesting facts about He Shou Wu. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is the famous polyphenol from grape skin and red wine that achieved fame in the early 2000s for its activation of SIRT1 and its proposed role in the "French paradox" (lower cardiovascular mortality despite high saturated fat intake, attributed in part to red wine consumption). The resveratrol story has been complicated by data quality issues, methodological controversies (the Sirtris / GSK story), and the recognition that human dosing required to match the SIRT1-activating concentrations seen in cell culture is impractical — but resveratrol remains one of the most-studied natural compounds of the modern era, with a robust preclinical evidence base for caloric-restriction-mimetic effects, anti-inflammatory action, antioxidant capacity, and cardiovascular protection.

TSG (2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside) is a closely related molecule:

Same trans-stilbene backbone
One additional hydroxyl group at position 2 (vs. resveratrol's 3,5,4'-trihydroxy pattern)
Glycosylated at position 2 with a β-D-glucose moiety (which improves water solubility and pharmacokinetics relative to the free aglycone)
Found in the same plant family overlap — both Polygonaceae (knotweed family) plants produce stilbenes; Japanese knotweed (Polygonum cuspidatum, now Fallopia japonica) is one of the major commercial sources of pharmaceutical-grade resveratrol

This last point is worth dwelling on: Japanese knotweed and He Shou Wu (Polygonum multiflorum / Fallopia multiflora) are taxonomically very close relatives in the Polygonaceae. Both produce stilbenes as principal active compounds. Both have been used in TCM (Japanese knotweed as hu zhang for circulatory and inflammatory indications). The plant family's chemistry converges on this stilbene class.

The biological consequences of this structural relationship:

TSG and resveratrol share many of the same molecular targets — SIRT1, AMPK, Nrf2, NF-κB
The mechanistic literature on resveratrol is largely transferable as a working hypothesis for TSG, though direct head-to-head studies are limited
TSG's glycosylation generally gives it better oral bioavailability than free resveratrol (a known weakness of resveratrol pharmacokinetics)
The hepatotoxicity that characterizes He Shou Wu but not resveratrol is presumably attributable to the anthraquinone fraction (emodin etc.) and the HLA-B*35:01 immune mechanism, not to the stilbene class itself

If the resveratrol literature could be taken at face value, TSG would be a more bioavailable form of a famously bioavailability-limited longevity compound. The caveats: the resveratrol clinical literature has been mixed and disappointing in several large human trials, the SIRT1-activation paradigm has been actively contested in the academic literature, and the same critiques apply by extension to TSG.

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SIRT1 Activation and Caloric-Restriction Mimicry

The sirtuin family of NAD+-dependent deacetylases (SIRT1 through SIRT7 in mammals) is one of the most prominent targets in the modern longevity research field. SIRT1, the most-studied family member, regulates dozens of downstream targets through deacetylation of histone (H3K9, H4K16) and non-histone substrates including p53, PGC-1α, FOXO transcription factors, and NF-κB. SIRT1 activity is required for many of the cellular benefits of caloric restriction, the only intervention with consistent evidence for lifespan extension across multiple model organisms.

TSG has been shown in cell-culture studies to activate SIRT1, similar to resveratrol but with some methodological caveats common to the entire SIRT1-activator field:

Direct activation in fluorometric SIRT1 enzyme assays (the same assay that drove the resveratrol discovery, and that has been criticized for using fluorophore-conjugated substrates that may not reflect physiologic substrate behavior)
Indirect activation via NAD+ pool elevation (SIRT1 is NAD+-dependent and any intervention that raises cellular NAD+ effectively activates the sirtuin family)
Increased nuclear translocation and chromatin association of SIRT1
Increased deacetylation of canonical SIRT1 substrates including PGC-1α (mitochondrial biogenesis), FOXO3a (stress resistance and longevity), and NF-κB p65 (anti-inflammatory)

The downstream cellular effects mirror caloric restriction:

Increased mitochondrial biogenesis through PGC-1α
Improved insulin sensitivity through downstream effects on glucose metabolism
Reduced inflammatory cytokine production through NF-κB deacetylation
Enhanced stress resistance through FOXO3a-mediated antioxidant gene expression
Reduced senescent cell accumulation in some models
Modest lifespan extension in some short-lived model organisms (the data in mammals are weaker and contested)

The honest summary of the SIRT1 longevity story: the cellular biology is real, the caloric restriction connection is real, but the clinical lifespan-extension data from any single pharmacologic SIRT1 activator (including resveratrol, the most-studied) in humans remains absent. The reasonable interpretation is that TSG and the stilbene class produce real cellular effects that overlap with caloric restriction in some respects, and these effects may translate to modest healthspan improvements (cardiovascular protection, metabolic health, anti-inflammatory benefit) without making any individual compound a "longevity drug."

For broader context on the longevity field, see our Longevity Protocols page.

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Emodin and Stilbenes as the Active Class

The principal active compound classes in He Shou Wu, in approximate order of importance for the cardiovascular and longevity effects:

Stilbenes (TSG and related glycosides) — the SIRT1, antioxidant, anti-inflammatory, and lipid-lowering effects are dominantly attributed to this class. TSG content in standardized extracts is the most useful single quality marker.
Anthraquinones (emodin, physcion, chrysophanol, aloe-emodin, rhein) — documented anti-platelet, vasodilatory, and lipid-lowering effects, in addition to the laxative and (problematic) hepatotoxic effects. The dual nature of the anthraquinones — therapeutic at the cellular level but contributory to the hepatotoxicity at the organismal level — is the central pharmacologic puzzle of He Shou Wu.
Tannins (catechin, epicatechin gallate, condensed proanthocyanidins) — additional antioxidant capacity and vasoprotective effects through the same mechanism that makes green tea and cocoa flavanols cardioprotective
Lecithin and phospholipids — minor but probably contributory to the traditional jing-tonifying characterization and possibly to neuronal membrane integrity

The emodin component deserves separate attention because emodin has accumulated its own substantial modern pharmacology literature, distinct from the He Shou Wu / TCM context:

Anti-cancer effects in cell culture — inhibition of multiple cancer cell lines, mechanisms including apoptosis induction, MAPK pathway modulation, and tyrosine kinase inhibition
Anti-inflammatory through NF-κB suppression — overlaps mechanistically with the TSG anti-inflammatory effect
Anti-viral activity in cell-culture screens against several viruses
Lipid-lowering effects — documented in animal hyperlipidemia models, mechanism includes LXR (liver X receptor) modulation and PPARα activation
Hepatotoxicity at high or sustained exposure — the same fraction that drives the He Shou Wu liver concern

The integrated effect of He Shou Wu is therefore the polypharmacology of these overlapping active classes — not attributable to any single isolated compound. This is both why isolated TSG monotherapy trials have not fully reproduced the traditional benefit and why isolated emodin carries the toxicity without the balancing effects.

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Lipid-Lowering Evidence

Lipid-lowering is one of the better-characterized cardiovascular effects of He Shou Wu, with consistent animal data and several small human studies showing reductions in total cholesterol, LDL cholesterol, and triglycerides with extract supplementation.

The animal data:

Hypercholesterolemic rabbits, hamsters, and mice fed He Shou Wu extract or isolated TSG show 15 to 30% reductions in total cholesterol and similar reductions in LDL over 4 to 12 weeks of treatment
Triglyceride reductions of 10 to 25% are commonly reported
HDL is variably affected — some studies report modest increases, others report no change
Mechanistic studies implicate upregulation of LDL receptor expression in liver, upregulation of CYP7A1 (the rate-limiting enzyme in bile acid synthesis from cholesterol), modulation of LXRα nuclear receptor activity, and PPARα activation contributing to fatty acid oxidation
Anti-atherosclerotic effects in ApoE-knockout mouse models include reduced aortic plaque area, reduced foam-cell formation in macrophages, and improved endothelial function

The human data:

Small open-label and observational studies in Chinese clinical settings have reported total cholesterol reductions of 10 to 20% and LDL reductions of similar magnitude over 8 to 16 weeks of standardized extract use
The magnitude is less than statin therapy (which routinely produces 30-50% LDL reductions) but comparable to some other lipid-lowering nutraceuticals (red yeast rice, plant sterols, niacin)
Methodological quality is generally modest — most studies are not double-blind placebo-controlled
A small subset of studies have specifically reported on patients with non-alcoholic fatty liver disease (NAFLD), with mixed findings; the hepatotoxicity concern complicates the use of He Shou Wu in any liver-disease population (see absolute contraindications in the Liver Health and Hepatotoxicity Warning deep-dive)

The realistic clinical role: He Shou Wu is not a primary lipid-lowering intervention for most patients. Statins remain the cornerstone for those with established atherosclerotic cardiovascular disease or significantly elevated LDL. For patients with intermediate-risk lipid profiles who are pursuing dietary and lifestyle change as primary intervention, He Shou Wu could be a small additional contributor, but the hepatotoxicity risk argues for better-studied alternatives such as plant sterols, omega-3 EPA at higher doses, soluble fiber, or red yeast rice (which carries its own monitoring requirements). See Hyperlipidemia for the broader lipid management framework.

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Antioxidant Effects on Vascular Tissue

Oxidative stress is central to cardiovascular pathophysiology — oxidized LDL is the key initiating particle in atherosclerotic plaque formation, endothelial dysfunction is driven by superoxide-mediated quenching of nitric oxide bioavailability, and inflammation and oxidative stress amplify each other in a positive-feedback cycle that drives plaque progression and rupture.

The antioxidant capacity of He Shou Wu translates to vascular tissue through several mechanisms:

Direct ROS scavenging — the stilbene and polyphenol classes are direct radical scavengers
Upregulation of endogenous antioxidants — SOD, catalase, glutathione peroxidase upregulated in vascular and hepatic tissue from animals fed He Shou Wu extract
Reduced LDL oxidation — documented in vitro and in animal models, an important mechanism for anti-atherosclerotic effect
Improved nitric oxide bioavailability — through both direct effects on eNOS (endothelial nitric oxide synthase) expression and reduced superoxide-mediated NO quenching
Mitochondrial protection in cardiomyocytes exposed to ischemia/reperfusion injury, with reduced infarct size in some experimental models

The vascular antioxidant effect of TSG is comparable to that of resveratrol and other well-studied stilbenes, and likely contributes meaningfully to the broader cardiovascular benefit profile.

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Anti-Atherosclerosis Animal Data

Beyond lipid lowering, He Shou Wu extracts have been studied directly for anti-atherosclerotic effects in animal models. The most informative studies use the ApoE-knockout mouse (which spontaneously develops atherosclerotic lesions on a Western diet) or the LDLR-knockout mouse (similar atherosclerosis-prone phenotype) and quantify aortic plaque burden directly.

Reported findings across multiple studies:

Reduced aortic plaque area (typically 20 to 40% reduction with sustained treatment)
Reduced macrophage foam cell formation through modulation of cholesterol efflux pathways (ABCA1 upregulation)
Reduced VCAM-1 and ICAM-1 expression on endothelial cells (the adhesion molecules that recruit monocytes to early atherosclerotic lesions)
Reduced MCP-1 (monocyte chemoattractant protein 1) and other chemokine expression
Improved endothelium-dependent vasodilation in aortic ring preparations
Reduced plaque inflammation as measured by CD68+ macrophage infiltration
Increased plaque stability as measured by collagen content and reduced metalloproteinase activity

These effects are mechanistically attributable to the combined lipid-lowering, antioxidant, and anti-inflammatory effects discussed in the preceding sections, and they fit the broader pattern of "polyphenol cardioprotection" seen with green tea catechins, dark chocolate flavanols, blueberry anthocyanins, and other plant-source polyphenol-rich foods and extracts.

The translational gap remains: no large, long-duration cardiovascular outcome trial in humans has tested He Shou Wu for atherosclerosis prevention or regression. The animal data justify continued investigation but do not justify positioning He Shou Wu as established cardiovascular preventive therapy.

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Anti-Platelet and Anti-Thrombotic Effects

The emodin and related anthraquinone fraction of He Shou Wu has documented anti-platelet aggregation effects in vitro and in animal models. Mechanisms include:

Inhibition of ADP- and collagen-induced platelet aggregation
Reduced thromboxane A2 generation
Some COX-1 inhibition (relatively weak)
Reduced fibrinogen binding to platelet GPIIb/IIIa receptors
Some inhibition of platelet activation by ADP at supraphysiologic concentrations in vitro

The clinical magnitude of these effects at typical herbal doses in humans is likely modest, but the anti-platelet activity does create a meaningful drug-interaction concern with:

Aspirin — combined with He Shou Wu may increase bleeding risk; see Aspirin for context
Clopidogrel (Plavix) and other P2Y12 inhibitors — combined anti-platelet effect
Warfarin, DOACs (apixaban, rivaroxaban, dabigatran, edoxaban) — combined anti-thrombotic effect, increased bleeding risk
NSAIDs at chronic use — additive anti-platelet effect plus GI bleeding risk
Other herbal anti-platelets (ginkgo, garlic at high doses, ginger, fish oil at high doses, vitamin E at high doses, turmeric/curcumin at high doses) — cumulative effect

Patients on anticoagulants or anti-platelet therapy should not start He Shou Wu without discussion with the prescribing clinician. Patients scheduled for surgery or invasive procedures should generally stop He Shou Wu 2 weeks pre-procedure.

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Blood Pressure Effects

The blood pressure effects of He Shou Wu are less well-characterized than the lipid effects, with smaller datasets and more variable findings. The reported observations:

Mild antihypertensive effect in some animal hypertension models (spontaneously hypertensive rat, DOCA-salt rat)
Possible mechanism through improved endothelial NO production and reduced sympathetic tone
Possible mechanism through ACE-inhibitor-like effects in some cell-culture studies (modest)
Human data limited — small reductions of a few mmHg in some observational and open-label studies, not consistently replicated
No evidence to support He Shou Wu as a primary or substantial antihypertensive intervention

For meaningful blood pressure reduction, the priority interventions remain dietary (DASH diet, sodium restriction, potassium adequacy from food), weight loss if overweight, regular aerobic exercise, alcohol moderation, sleep optimization, and antihypertensive medications when indicated. He Shou Wu's possible contribution is modest at best. See Hypertension for the broader management framework.

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Cardiovascular Integrative Context

Where does He Shou Wu fit in a cardiovascular and longevity protocol? The honest answer is "a relatively minor adjunct, with significant safety constraints." A reasonable cardiovascular and longevity protocol for a middle-aged or older adult with intermediate cardiovascular risk:

Foundation: Mediterranean-style diet, regular aerobic exercise (150+ min/week moderate intensity), resistance training (2x weekly), 7-8 hours sleep, address sleep apnea, smoking cessation, alcohol moderation, stress management
Cardiovascular monitoring: regular blood pressure, lipid panel, fasting glucose / HbA1c, kidney function, periodic coronary calcium score for risk stratification
Statin therapy when indicated by ASCVD risk and LDL level — the most evidence-supported pharmacologic intervention
Antihypertensive therapy as needed to achieve target BP
Omega-3 EPA/DHA 1-2 g daily from fish or supplement; consider higher-dose EPA (icosapent ethyl) if triglycerides elevated and on statin (REDUCE-IT trial). See Omega-3 Fatty Acids.
Vitamin D to maintain 25-OH at 40-60 ng/mL; see Vitamin D3
Magnesium for blood pressure, vascular function, and sleep; see Magnesium
Coenzyme Q10 particularly for statin users to reduce muscle symptoms; see CoQ10
Established cardiovascular polyphenols from food — green tea, cocoa, berries, red wine in moderation, olive oil polyphenols
Adjunct longevity nutraceuticals with reasonable evidence base — consider resveratrol (with the caveat that human evidence is limited), pterostilbene (a related stilbene), NAD+ precursors (NMN, NR), curcumin
He Shou Wu if interested in the TCM tradition and the SIRT1 / stilbene framework, processed root form, 1-2 g daily standardized extract, with the full LFT monitoring protocol — understanding that the cardiovascular and longevity evidence base is preclinical-heavy and human-evidence-light, and that the hepatotoxicity risk applies

For a clear safer alternative within the TCM longevity-herb space: Astragalus has a more favorable safety profile, broader human evidence base, and overlapping but distinct mechanism (immune modulation, telomere protection through TA-65 fraction, mild cardiovascular effects). For those drawn to the stilbene class specifically: Japanese knotweed as the principal resveratrol source has different (lower) hepatotoxicity profile than He Shou Wu.

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Cautions — Cardiovascular Use Still Carries Hepatic Risk

Hepatotoxicity — identical to other indications. See the dedicated Liver Health and Hepatotoxicity Warning deep-dive. The cardiovascular indication does not reduce the hepatic risk.
Anti-platelet and anti-thrombotic drug interactions — aspirin, clopidogrel, warfarin, DOACs, fish oil at high doses, ginkgo. Bleeding risk increases.
Surgery preparation — stop He Shou Wu 2 weeks before any planned surgical or invasive procedure
Concomitant statin therapy — statins are themselves hepatotoxic in a small percentage of users (the most common drug class to elevate ALT in clinical practice). Combining statins with He Shou Wu compounds both the hepatic monitoring burden and the cumulative risk. If a patient on a statin wants to add He Shou Wu, intensified LFT monitoring is essential and the bar for any ALT elevation should be lower (stop one, monitor, restart the more important agent only).
Concomitant red yeast rice — red yeast rice contains monacolin K, the same active compound as the drug lovastatin. Combining red yeast rice with He Shou Wu carries both hepatic and rhabdomyolysis risk.
Pregnancy / lactation — not used (same as other indications)
NAFLD population — given the high prevalence of NAFLD in modern populations with metabolic syndrome (estimated 25-30% of adults) and the difficulty of detecting subclinical NAFLD without imaging, the cardiovascular-risk population is exactly the population most likely to have unsuspected baseline liver pathology. Imaging (ultrasound at minimum, ideally FibroScan) is advisable before starting He Shou Wu in this population.
Heart failure with congestion — the anthraquinone-mediated electrolyte effects (potential hypokalemia from any laxative-class action) could be relevant in this population; not well-characterized
Atrial fibrillation on rate-control or rhythm-control drugs — amiodarone in particular is hepatotoxic and should not be combined with He Shou Wu

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Key Research Papers

Lin L et al. (2015). Traditional usages, botany, phytochemistry, pharmacology and toxicology of Polygonum multiflorum Thunb.: A review. Journal of Ethnopharmacology. — PubMed
Lin H et al. (2010). Lipid-lowering effect of Polygonum multiflorum stilbene glycoside in hyperlipidemic rats. — PubMed
Wang W et al. (2011). 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) attenuates atherosclerosis in ApoE-knockout mice. — PubMed
Howitz KT et al. (2003). Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. — PubMed
Baur JA, Sinclair DA (2006). Therapeutic potential of resveratrol: the in vivo evidence. Nature Reviews Drug Discovery. — PubMed
Xu Y et al. (2014). TSG protects against oxidized LDL-induced endothelial cell injury. — PubMed
Cheng XR et al. (2013). The effects of Polygonum multiflorum on aging-related markers. — PubMed
Zhang SH et al. (2014). Anti-aging effect of Polygonum multiflorum on D-galactose-induced aged mice. — PubMed
Wang X et al. (2013). Emodin protects against atherosclerosis via NF-κB suppression. — PubMed
Xie W et al. (2014). Emodin reduces foam cell formation in macrophages. — PubMed
Yang PY et al. (2002). Anti-platelet effects of anthraquinones from Polygonum multiflorum. — PubMed
Bhullar KS, Hubbard BP (2015). Lifespan and healthspan extension by resveratrol. BBA Molecular Basis of Disease. — PubMed

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