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Proteomic profile of the dentine pellicle modified with plant polyphenols and fluoride.

OBJECTIVES: Despite its protective role, the dentine pellicle has rarely been studied, therefore we aimed to map out the proteomic profile of in vitro dentine pellicles before and after modification. MATERIALS AND METHODS: A total of 135 human dentine specimens were prepared. After initial pellicle formation with 150 µl pooled human saliva (37 °C, 30 min), the dentine specimens were immersed in one of 9 pellicle modification solutions (2 ml/specimen): deionized water (non-modified pellicle), SnCl2/NaF/AmF (commercial solution containing 800 ppm Sn2+ and 500 ppm F-), NaF solution (500 ppm F- ), and six polyphenol solutions (2 mg / ml) with or without 500 ppm F-: blueberry extract (BBE and BBE + F-), green tea extract (GTE and GTE + F-) and grape seed extract (GSE and GSE + F-). After another aliquot of saliva (150 µl, 37 °C, 60 min), the pellicles were harvested with sodium dodecyl sulphate by rubbing with cotton balls, and taken to proteomic analyses by Liquid Chromatography-Tandem Mass Spectrometry after tryptic digestion. RESULTS: A total of 382 proteins were identified in all the proteomic analyses for all groups. Pellicle modification with fluoride, either NaF or SnCl2/NaF/AmF, led to the presence of 12 or 14 exclusive proteins, respectively, whereas modification with the solutions containing polyphenols presented less exclusive proteins (4-6 proteins). The number of exclusive proteins was even lower for when polyphenols and fluoride (GTE + F- and GSE + F-) were used, with lower abundance of proteases. CONCLUSIONS: We conclude that NaF and SnCl2/NaF/AmF significantly modify the proteome of the dentine pellicle. The combination of fluoride with polyphenols further lowers the abundance of proteins and proteases, which explains the positive effect of these solutions on the dentine pellicles. CLINICAL RELEVANCE: Plant extract solutions with fluoride can significantly modify the proteomic structure of the dentine pellicle, which clarifies the mechanism of action of polyphenols on the protection of dentine demineralization.

Humans

Human milk oligosaccharides and polyphenols: Mechanisms, effects, and applications in allergies.

Human milk offers the best nutrition to the infant, which is crucial for the child's proper development and health status across the lifespan. Besides providing the substances optimally supplying the baby with energy and building materials, breast milk contains several immunometabolically active components. Those include molecules fully de novo synthesized by the mother, such as human milk oligosaccharides (HMO), and substances of nonhuman origin, transferred to the infant through mother's milk, such as dietary plant polyphenols. In this review, we outline the basic biology of HMO and polyphenols and deeply characterize their effects on the development of allergic disorders on the basis of available literature reporting data from in vitro, animal, and human studies. Further, we review the abundance of HMO and polyphenols, commonly present in mother's milk, and their mutual interactions in the context of the mechanisms underlying predisposition to, or protection against, the development of allergies. Finally, we discuss the potential of HMO and polyphenols in allergy prevention and therapy.

Humans

Transcription factor NtELF3 promotes the polyphenol accumulation by targeting NtFLS-1 and NtCHIL-2 genes in tobacco.

Tobacco (Nicotiana tabacum L.) is an important economic crop, from which polyphenols are crucial for regulating its growth and development as well as shaping its quality. However, few genes associated with polyphenol accumulation have been cloned from tobacco, and the molecular mechanisms underlying this process remain poorly understood. Here, we found that the tobacco transcription factor EARLY FLOWERING 3 (NtELF3), which is highly expressed in tobacco leaves, positively regulates the accumulation of chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, rutin, scopoletin, and total polyphenols in tobacco middle leaves. The metabolomic and transcriptomic analyses of middle leaves showed that a total of 177 differentially accumulated metabolites and 7409 differentially expressed genes (DEGs) were identified in ntelf3-1 mutant versus wild type, respectively. Further investigation identified that 17 DEGs were involved in phenylpropanoid metabolic and flavonoid metabolic processes. Combined analysis indicated that the phenylpropanoid and flavonoid biosynthesis pathways were also co-enriched in kyoto encyclopedia of genes and genomes enrichment analysis. Molecular biology experiment demonstrated that NtELF3 directly binds to the promoters of NtFLS-1 and NtCHIL-2 that are both associated with phenylpropanoid and flavonoid biosynthesis, and promotes their expression. Taken together, our results not only provide new theoretical support for in-depth understanding of the regulatory mechanisms underlying polyphenol accumulation in tobacco, but also offer excellent genes and germplasm resources for tobacco quality breeding.

NtCHIL

Serum polyphenol oxidase activity (ceruloplasmin) in conventional laboratory animals and man.

The optimum pH for ceruloplasmin as polyphenol oxidase (EC 1.10.3.2) activity was determined in human serum (pH 5.4) and the serum of conventional laboratory animals--the rat (pH 5.2), mouse (pH 5.2), hamster (pH 5.3), guinea pig (pH 5.4), multimammate mouse (pH 5.2) and rabbit (pH 5.4). Determined at the optimum pH in 0.1M acetate buffer polyphenol oxidase activity fell in the sequence: rat--man--rabbit--mouse--multimammate mouse--hamster--guinea pig. Ceruloplasmin polyphenol oxidase activity was inhibited by 0.1M phosphate buffer in the mouse, rat and multimammate mouse, but not in the other species. It was inhibited by 0.05M citrate and 0.1M phthalate buffer in all the species tested.

Animals

Network pharmacology-based prediction and experimental validation of the anti-hyperuricemic effects of oolong tea polyphenols.

OBJECTIVE: This study aimed to identify candidate therapeutic targets of oolong tea polyphenols (TP) against hyperuricemia (HUA) using network pharmacology and bioinformatics, and to validate the predicted molecular mechanism through in vivo experimentation. METHODS: Drug and disease targets were retrieved from public databases, and overlapping targets were identified by Venn diagram analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the shared targets, and a protein-protein interaction (PPI) network was constructed to identify hub genes. For in vivo validation, an HUA mouse model was established by 15 days of oral potassium oxonate (PO) administration. Model mice then received TP by gavage at low (0.5 g⋅kg-1⋅d-1), medium (1 g⋅kg-1⋅d-1), or high (2 g⋅kg-1⋅d-1) doses for an additional 15 days. Serum biochemical markers, histopathological changes, and pathway-related protein expression were assessed by enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (HE) staining, and western blot analysis, respectively. RESULTS: Network pharmacology analysis identified 59 overlapping targets between TP and HUA; GO and KEGG enrichment analyses revealed that these targets were primarily associated with hormone metabolism and the PI3K-AKT signaling pathway. In the animal experiment, TP dose-dependently reduced serum uric acid (SUA) levels in hyperuricemic mice. At the molecular level, low and medium doses of TP suppressed phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR), whereas the high dose paradoxically activated this pathway and concomitantly elevated interleukin-1β levels. These findings indicate that TP modulates uric acid metabolism through a non-monotonic, dose-dependent mechanism. CONCLUSION: By combining network pharmacology with animal experiments, this study identified the PI3K/AKT/mTOR signaling pathway as a likely mediator of the anti-hyperuricemic action of oolong tea polyphenols (TP). A medium dose of TP achieved the most balanced outcome, attenuating inflammation and preserving hepatic and renal architecture; the high dose, by contrast, paradoxically elevated interleukin-1β (IL-1β) and overactivated PI3K/AKT/mTOR signaling, underscoring the importance of dose calibration. These data suggest that a medium dose of TP may represent a feasible dietary strategy against hyperuricemia. Further work-including monomer identification, direct target validation, and clinical evaluation-is warranted to confirm and extend these preclinical findings.

PI3K/Akt/mTOR signaling pathway

Dietary Polyphenol Acteoside-Related Molecular Signatures in Clear Cell Renal Cell Carcinoma: Multi-Omics Profiling and Functional Validation of IMPDH1.

Clear cell renal cell carcinoma (ccRCC) is characterized by substantial metabolic and molecular heterogeneity, but the disease-relevant programs associated with acteoside, a dietary polyphenol, remain poorly understood. We integrated predicted acteoside targets with bulk, single-cell, and spatial transcriptomic data from ccRCC and combined molecular subtyping with cross-cohort machine-learning analysis. Acteoside-related signatures were preferentially enriched in malignant compartments and increased with tumor grade and stage. Consensus clustering identified two molecular subtypes with distinct biological and clinical features. C1 was associated with immune activation, metabolic activity, and more favorable survival, whereas C2 showed greater genomic instability, reduced renal epithelial differentiation, and poorer outcomes. We further benchmarked multiple machine-learning strategies and established a 10-gene prognostic model that retained predictive performance across independent cohorts, with IMPDH1 emerging as the strongest risk-associated feature. Functional experiments confirmed the biological relevance of IMPDH1: its knockdown suppressed ccRCC cell proliferation, DNA synthesis, colony formation, and migration, whereas overexpression produced the opposite effects. Together, these findings indicate that acteoside-related molecular signatures capture clinically relevant heterogeneity in ccRCC and provide a framework for linking dietary-polyphenol-related molecular space with tumor biology. The identification and functional validation of IMPDH1 further highlight its potential importance in ccRCC progression.

IMPDH1

Acute pre-exercise oral intake of cacao polyphenols attenuates central fatigue development during sustained low-intensity ankle dorsiflexion exercise in healthy young male adults.

This double-blind, randomized, crossover study investigated whether acute cacao polyphenol (CP) ingestion attenuates neuromuscular fatigue in 19 healthy young male adults. After consuming CP or placebo, participants performed sustained isometric ankle dorsiflexion at 25% of maximal voluntary isometric contraction (MVIC) torque until task failure. Neuromuscular function (MVIC torque, voluntary activation [VA%], doublet torque) and electromyographic activity were assessed before, immediately after, and during recovery (1 and 5&#x2009;min). Salivary chromogranin A and &#x3b1;-amylase were measured at baseline and 1&#x2009;min post-task. Only VA% and chromogranin A showed significant condition &#xd7; time interactions (p&#x2009;=&#x2009;0.027-0.039). VA% significantly decreased from before to immediately after the task and 1&#x2009;min post-task in both conditions (p&#x2009;&#x2264;&#x2009;0.002), with significantly higher values in the CP condition than in placebo immediately after and 1&#x2009;min post-task (p&#x2009;&#x2264;&#x2009;0.037). Chromogranin A significantly increased from baseline to 1&#x2009;min post-task in the placebo condition (p&#x2009;<&#x2009;0.001) but not in the CP condition (p&#x2009;=&#x2009;0.083). These findings suggest that acute CP ingestion attenuates the decline in central motor drive and autonomic stress responses following strenuous exercise, without altering performance or peripheral recovery, supporting its potential as a nutritional strategy for modulating central fatigue.

Humans

EWAS in a polyphenol dense, DNA methylation-targeted, controlled diet and lifestyle study.

BACKGROUND: Dietary and lifestyle factors can influence DNA methylation patterns. We previously reported epigenetic age attenuation following a controlled study using an 8-week polyphenol-dense, DNA methylation-targeted diet and lifestyle intervention in healthy males (Methylation Diet and Lifestyle Study), with phytonutrient/polyphenol-rich foods (green tea, oolong tea, curcumin, garlic, and berries) being most predictive of this effect. METHODS: Here we conducted an epigenome-wide association study (EWAS) in 38 participants from the Methylation Diet and Lifestyle Study. The intervention included a dietary pattern intentionally rich in substrate and cofactor nutrients for methylation pathways, and components known to alter DNA-methyltransferase (DNMT) enzyme activity. In line with prior EWAS studies with small sample sizes where FDR-significant findings are unlikely, we used pre-specified nominal P-value thresholds (0.001, 0.0001) for the exploratory analyses. RESULTS: At P < 0.001 (unadjusted), 676 differentially methylated loci (DML) were identified in the intervention group versus 286 in controls. At P < 0.0001 (unadjusted), 50 DML were identified in the intervention group compared to 13 in controls. Fifteen DML were in transcription start site-proximal regions of genes including those involved in zinc homeostasis and nutrient sensing, development and pluripotency, proteostasis and genome stability, tumor suppression, and synaptic function. A group-by-time interaction analysis identified 70 intervention-specific DML at P < 0.0001, with nominal enrichment including autophagy, mTOR signaling, and chromatin remodeling pathways. A regional DMR analysis identified 128 within-group and 129 interaction-specific DMRs. DMR functional enrichment analyses revealed convergent nominal associations with lipid metabolism (alpha-linolenic acid, lipoic acid, biosynthesis of unsaturated fatty acids, PPAR signaling, cholesterol homeostasis), central energy metabolism (TCA cycle, glycolysis/gluconeogenesis, pentose phosphate, pyruvate), and nutrient sensing (PI3K-Akt, mTOR, AMPK, autophagy as well as other pathways). As expected for the limited cohort size and short intervention duration, none of the single CpG findings or enrichment analyses survived multiple test correction and are therefore considered exploratory and hypothesis-generating only. CONCLUSION: This EWAS identified a larger number of nominally changing CpGs in the intervention group compared to controls as well as biologically coherent methylation changes. These findings provide mechanistic hypotheses for previously observed epigenetic age attenuation. Replication in larger cohorts, longer intervention durations, and functional validation remain essential.

DNA methylation

Polyphenol-Rich Opuntia ficus-indica Cladodes: An Integrated Metabolomic, In Vivo and In Silico Study Supporting Their Hypolipidemic and Hepatoprotective Effects.

Background: Hyperlipidemia is a major risk factor for cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD), and is closely associated with oxidative stress. Opuntia ficus-indica (OFI) cladodes are recognized as a rich source of bioactive phytochemicals; however, the molecular mechanisms underlying their metabolic benefits remain incompletely understood. Objectives: This study aimed to comprehensively evaluate the hypolipidemic and hepatoprotective potential of a polyphenol-rich O. ficus-indica cladode extract (OCE) using an integrated approach combining in vivo evaluation, untargeted metabolomics (UHPLC-Orbitrap-MS/MS), molecular docking, and ADMET prediction. Methods: Hyperlipidemic mice fed a high-fat diet (HFD) were treated with OCE, while molecular docking was performed on ten major annotated phytochemicals against twelve key proteins involved in lipid metabolism and cholesterol homeostasis, including HMGCR, FAS, PPAR&#x3b1;, PCSK9, and NPC1L1, using simvastatin as the reference compound. Results: OCE treatment significantly improved plasma and hepatic lipid profiles, improved glucose homeostasis, and markedly reduced hepatic malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. Histopathological analysis further supported a pronounced hepatoprotective effect, with a substantial reduction in hepatic steatosis. Untargeted metabolomics enabled the annotation of 102 metabolites, putatively identifying piscidic acid as the predominant phenolic constituent together with a diverse profile of flavonoids and phenolic acids. Molecular docking supported the potential contribution of these phytochemicals to the regulation of lipid metabolism through favorable interactions with multiple therapeutic targets, while ADMET prediction suggested an overall favorable pharmacokinetic and toxicity profile despite the lower intestinal permeability predicted for glycosylated derivatives. Conclusions: Overall, these findings support O. ficus-indica cladodes as a promising source of dietary bioactive compounds with potential applications in the nutritional management and prevention of hyperlipidemia and related cardiometabolic disorders.

Animals

Column chromatography of plant polyphenols on weak anion exchangers.

Mixtures of phenols and cinnamic acid derived plant polyphenols are separated on several WAX cellulose materials and on DEAE Sephadex. Reference mixtures are also split up into the following distinct groups: phenolic carboxylic acids--neutral o-dihydroxy phenolics--neutral non o-dihydroxy phenolics. Quantitative recoveries are obtained, while no isomerizations occur with the pH labile plant phenolics. It is suggested that these materials can be used for preparative scale purification of plant phenolics, or for cleaning up plant extracts prior to HPLC examination.

Chromatography, High Pressure Liquid

Free polyphenols and multi-omics traits underlying antioxidant variation across Paeonia lactiflora leaf cultivars.

Leaves of Paeonia lactiflora are underutilized by-products with potential as natural antioxidant sources. In this study, 18 cultivars were evaluated for phytochemical composition and in vitro antioxidant capacity. Total phenolic content correlated strongly with DPPH and ABTS activities, and the comprehensive antioxidant index identified 'Coral Charm' and 'Hangshao' as representative high- and low-antioxidant cultivars, respectively. Untargeted metabolomics detected 2677 metabolites and identified 908 differential metabolites between the two cultivars. Targeted phenolic profiling quantified 27 compounds, among which 11 differed significantly between the two cultivars. Catechin and epicatechin were enriched in 'Coral Charm', with contents of 6.62 and 0.397&#xa0;ng/mg, respectively, compared with 0.012 and 0.002&#xa0;ng/mg in 'Hangshao'. (+)-Dihydroquercetin was also more abundant in 'Coral Charm', while caffeic acid showed an upward trend. Proteomic analysis identified 423 differentially expressed proteins, mainly associated with secondary metabolite biosynthesis, redox homeostasis, and central carbon metabolism. Integrated analysis identified pyruvate metabolism as the only pathway significantly enriched in both metabolomic and proteomic datasets. Molecular docking predicted favorable binding between representative phenolics and selected proteins. These findings link cultivar-dependent antioxidant variation in peony leaves with free-phenolic accumulation and pathway-level metabolic differences, supporting the selection and utilization of antioxidant-rich peony leaf resources.

Antioxidants

Untargeted metabolomics and proteomics reveals cocoa-mediated mitigation of valproic acid-induced dysregulation in a zebrafish model of autism: pilot study.

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by behavioral impairments and limited therapeutic options. Emerging evidence suggests that plant-derived polyphenols may offer neuroprotective benefits. OBJECTIVES: This pilot study aimed to investigate the therapeutic potential of polyphenol-rich cocoa extract in a valproic acid (VPA)-induced zebrafish model of ASD. METHODS: Zebrafish were exposed to 3&#x202f;&#x3bc;M VPA, cocoa powder providing 2.5 &#x3bc;M (-)-epicatechin, a combination of both, or left untreated. Behavioral phenotyping was conducted using DanioVision and gut morphology was assessed. Untargeted metabolomic and proteomic profiling was performed followed by univariate and multivariate analyses. RESULTS: VPA exposure induced ASD-like behavioral hyperactivity, and severe gastrointestinal abnormalities. Cocoa co-treatment ameliorated both behavioral performance and gut architecture. Metabolomic profiling revealed VPA-associated disruptions in neurotransmission, methylation, mitochondrial function and redox homeostasis. Proteomic profiling showed elevated levels of trafficking protein particle complex subunit 11, proteasomal ubiquitin receptor, betaine-homocysteine S-methyltransferase 1 (BHMT-1), and desmoplakin-A, consistent with genotoxic stress and impaired protein trafficking. Cocoa co-treatment normalized BHMT-1 and desmoplakin-A expression and mitigated broader metabolic dysregulation. CONCLUSION: Collectively, these results suggest that polyphenol-rich cocoa may represent a promising multi-targeted nutraceutical approach for mitigating ASD-related neurodevelopmental and metabolic disturbances.

Animals

Dealcoholized muscadine wine improved skin elasticity and oxidative stress biomarkers without affecting gut microbiome in women over 40 in a randomized controlled trial.

Muscadine wine has a unique polyphenol profile distinct from that of common wine, and limited research exists on its health benefits. This study aimed to investigate the effects of intake of dealcoholized muscadine wine (DMW) on skin health, oxidative stress, inflammatory biomarkers, and the gut microbiome. Seventeen healthy women were randomly assigned to consume 300&#xa0;mL of DMW or a placebo daily for 6&#xa0;weeks, separated by a 3-week washout period, in a randomized, single-blinded, crossover design. Skin health parameters were measured on the face and forearm. Oxidative stress and inflammatory biomarkers were assessed in plasma. Fecal bacterial DNA was sequenced using shotgun sequencing. DMW did not affect UVB-induced erythema compared to placebo. However, it significantly decreased transepidermal water loss and increased facial gross elasticity. Skin elasticity significantly improved on the forearm, whereas other skin parameters were not affected. DMW significantly decreased plasma levels of matrix metalloproteinase-9 and advanced glycation end products compared with placebo. However, the abundance, diversity, and functions of the gut microbiome were not affected. Polyphenol-rich DMW administered for six weeks improved certain skin health parameters and reduced oxidative and inflammatory stress, without affecting the gut microbiome in healthy women.

Humans

Nutrition and longevity - diet in centenarians.

BACKGROUND: Nutrition plays a central role in the biological mechanisms that shape aging, health span, and longevity. Micronutrients&#x2014;including vitamins, trace elements, and polyphenols&#x2014;support genomic stability, mitochondrial integrity, and antioxidant defense, while dietary patterns rich in plant-based foods modulate inflammation, metabolic regulation, and epigenetic processes. Centenarian populations consuming Mediterranean, Okinawan, Nordic, and Nicoyan diets offer a natural model for understanding how nutrient-rich, minimally processed foods, moderate caloric intake, and balanced lifestyles interact with molecular pathways to extend functional life. MAIN BODY: This review synthesizes current evidence on how micronutrients influence DNA repair, oxidative stress reduction, and mitochondrial protection, particularly through the actions of vitamins C and E, niacin-dependent PARP activity, folate-mediated methylation, and metal cofactors involved in antioxidant enzymes. Plant-based diets rich in fiber and polyphenols enhance microbial diversity and promote beneficial taxa such as Akkermansia and Bifidobacterium, supporting gut barrier integrity and immune balance. Caloric restriction and intermittent fasting activate nutrient-sensing pathways, including AMPK and sirtuins, reduce mTOR activity, and stimulate autophagy, collectively improving cellular resilience. Findings from centenarian regions highlight the convergence of lifestyle, nutrition, and cultural practices that reduce systemic inflammation, maintain metabolic flexibility, and support healthy aging trajectories. CONCLUSIONS: Diet emerges as a decisive modifiable determinant of lifespan and health span. The convergence of molecular nutrition, microbiome composition, and traditional dietary habits underlies the exceptional longevity observed in centenarian populations. Future research should integrate nutrigenomics, metabolomics, and microbiome profiling to clarify causal mechanisms and guide precision nutrition strategies for aging societies.

Humans

Histochemical and biophysical study of cuticle sclerotization in Pycnoscelus surinamensis L. (Blattaria).

The problem of melaninogenesis and quinone tanning of the cuticle was examined by histochemical and biophysical methods (electroparamagnetic resonance: EPR) on normal subjects of Pycnoscelus surinamensis and on subjects with abnormal cuticular colour. The cuticle of abnormal subjects showed a lower content of polyphenolic substances and a greater positivity for the indole group. This suggests that in these insects tanning products can be synthetized differently and not derived from tyrosine but from tryptophan as postulated by Pryor (1955). Furthermore, a higher number of unsaturated aminic groups is found in abnormal subjects. Granules present only in the cytoplasm of the epidermal cells of the abnormal newly moulted subjects may indicate that the polyphenolic compound of tanning, secreted in an inactive form as 4-0, beta-glucoside, is not freed from the beta-glucosidase and remains as such in the cytoplasm.

Animals

Pterostilbene Targets Hallmarks of Aging in the Gene Expression Landscape in Blood of Healthy Rats.

SCOPE: Polyphenols from the phytoestrogen group, including pterostilbene (PTS), are known for their antioxidant, anti-inflammatory, and anti-cancer effects. In recent reports, phytoestrogens attenuate age-related diseases; however, their pro-longevity effects in healthy models in mammals remain unknown. As longevity research demonstrates age-related transcriptomic signatures in human blood, the current study hypothesizes that phytoestrogen-supplemented diet may induce changes in gene expression that ultimately confer pro-longevity benefits. METHODS AND RESULTS: In the present study, RNA sequencing is conducted to determine transcriptome-wide changes in gene expression in whole blood of healthy rats consuming diets supplemented with phytoestrogens. Ortholog cell deconvolution is applied to analyze the omics data. The study discovered that PTS leads to changes in the gene expression landscape and PTS-target genes are associated with functions counteracting hallmarks of aging, including genomic instability, epigenetic alterations, compromised autophagy, mitochondrial dysfunction, deregulated nutrient sensing, altered intercellular interaction, and loss of proteostasis. These functions bridge together under anti-inflammatory effects through multiple pathways, including immunometabolism, where changes in cellular metabolism (e.g., ribosome biogenesis) impact the immune system. CONCLUSION: The findings provide a rationale for pre-clinical and clinical longevity studies and encourage investigations on PTS in maintaining cellular homeostasis, decelerating the process of aging, and improving conditions with chronic inflammation.

Animals