Senescence Abstracts 5


Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans.
            (Hubbard et al., 2004)  Download
BACKGROUND:  Quercetin, a flavonoid present in the human diet, which is found in high levels in onions, apples, tea and wine, has been shown previously to inhibit platelet aggregation and signaling in vitro. Consequently, it has been proposed that quercetin may contribute to the protective effects against cardiovascular disease of a diet rich in fruit and vegetables. OBJECTIVES:  A pilot human dietary intervention study was designed to investigate the relationship between the ingestion of dietary quercetin and platelet function. METHODS:  Human subjects ingested either 150 mg or 300 mg quercetin-4'-O-beta-D-glucoside supplement to determine the systemic availability of quercetin. Platelets were isolated from subjects to analyse collagen-stimulated cell signaling and aggregation. RESULTS:  Plasma quercetin concentrations peaked at 4.66 microm (+/- 0.77) and 9.72 microm (+/- 1.38) 30 min after ingestion of 150-mg and 300-mg doses of quercetin-4'-O-beta-D-glucoside, respectively, demonstrating that quercetin was bioavailable, with plasma concentrations attained in the range known to affect platelet function in vitro. Platelet aggregation was inhibited 30 and 120 min after ingestion of both doses of quercetin-4'-O-beta-D-glucoside. Correspondingly, collagen-stimulated tyrosine phosphorylation of total platelet proteins was inhibited. This was accompanied by reduced tyrosine phosphorylation of the tyrosine kinase Syk and phospholipase Cgamma2, components of the platelet glycoprotein VI collagen receptor signaling pathway. CONCLUSIONS:  This study provides new evidence of the relatively high systemic availability of quercetin in the form of quercetin-4'-O-beta-D-glucoside by supplementation, and implicates quercetin as a dietary inhibitor of platelet cell signaling and thrombus formation.


Coenzyme Q10 Prevents Senescence and Dysfunction Caused by Oxidative Stress in Vascular Endothelial Cells.
            (Huo et al., 2018) Download
Oxidative damage in endothelial cells is proposed to play an important role in endothelial dysfunction and atherogenesis. We previously reported that the reduced form of coenzyme Q10 (CoQ10H2) effectively inhibits oxidative stress and decelerates senescence in senescence-accelerated mice. Here, we treated human umbilical vein endothelial cells (HUVECs) with H2O2 and investigated the protective effect of CoQ10H2 against senescence, oxidative damage, and reduction in cellular functions. We found that CoQ10H2 markedly reduced the number of senescence-associated β-galactosidase-positive cells and suppressed the expression of senescence-associated secretory phenotype-associated genes in H2O2-treated HUVECs. Furthermore, CoQ10H2 suppressed the generation of intracellular reactive oxygen species (ROS) but promoted NO production that was accompanied by increased eNOS expression. CoQ10H2 prevented apoptosis and reductions in mitochondrial function and reduced migration and tube formation activity of H2O2-treated cells. The present study indicated that CoQ10H2 protects endothelial cells against senescence by promoting mitochondrial function and thus could delay vascular aging.

Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats.
            (Ishisaka et al., 2011)  Download
Quercetin is widely distributed in vegetables and herbs and has been suggested to act as a neuroprotective agent. Here, we demonstrate that quercetin can accumulate enough to exert biological activity in rat brain tissues. Homogenates of perfused rat brain without detectable hemoglobin contaminants were treated with β-glucuronidase/sulfatase and the released quercetin and its methylated form were analyzed using high-performance liquid chromatography (HPLC) with three different detection methods. Both quercetin and the methylated form were detected in the brain of quercetin-administered rats using HPLC-UV and HPLC with electrochemical detection and were further identified using HPLC-tandem mass spectrometry. Oral administration of quercetin (50mg/kg body wt) attenuated the increased oxidative stress in the hippocampus and striatum of rats exposed to chronic forced swimming. The possible transport of quercetin derivatives into the brain tissue was reproduced in vitro by using a rat brain capillary endothelial cell line, a model of the blood-brain barrier. These results show that quercetin could be a potent nutrient that can access the brain and protect it from disorders associated with oxidative stress.


Healthy aging: The ultimate preventative medicine.
            (Kaeberlein et al., 2015)  Download
Age is the greatest risk factor for nearly every major cause of mortality in developed nations. Despite this, most biomedical research focuses on individual disease processes without much consideration for the relationships between aging and disease. Recent discoveries in the field of geroscience, which aims to explain biological mechanisms of aging, have provided insights into molecular processes that underlie biological aging and, perhaps more importantly, potential interventions to delay aging and promote healthy longevity. Here we describe some of these advances, along with efforts to move geroscience from the bench to the clinic. We also propose that greater emphasis should be placed on research into basic aging processes, because interventions that slow aging will have a greater effect on quality of life compared with disease-specific approaches.

Protective effects of quercetine on the neuronal injury in frontal cortex after chronic toluene exposure.
            (Kanter, 2013)  Download
The aim of this study was designed to evaluate the possible protective effects of quercetine (QE) on the neuronal injury in the frontal cortex after chronic toluene exposure in rats. The rats were randomly allotted into one of the three experimental groups, namely, groups A (control), B (toluene treated) and C (toluene-treated with QE), where each group contains 10 animals. Control group received 1 ml of normal saline solution, and toluene treatment was performed by the inhalation of 3000 ppm toluene in an 8-h/day and 6-day/week order for 12 weeks. The rats in QE-treated group was given QE (15 mg/kg body weight) once a day intraperitoneally for 12 weeks, starting just after toluene exposure. Tissue samples were obtained for histopathological investigation. To date, no histopathological changes of neurodegeneration in the frontal cortex after chronic toluene exposure in rats by QE treatment have been reported. In this study, the morphology of neurons in the QE treatment group was well protected. Chronic toluene exposure caused severe degenerative changes, shrunken cytoplasm and extensively dark picnotic nuclei in neurons of the frontal cortex. We conclude that QE therapy causes morphologic improvement in neurodegeneration of frontal cortex after chronic toluene exposure in rats. We believe that further preclinical research into the utility of QE may indicate its usefulness as a potential treatment on neurodegeneration after chronic toluene exposure in rats.


Intermittent heterochronic plasma exchange as a modality for delaying cellular senescence-a hypothesis.
            (Kiprov, 2013)  Download
The population of baby boomers (age 60-65) is rapidly increasing globally. The aging of the human body is associated with the decline of cellular function which leads to the development of a variety of diseases. The increased demand for health care for the aging population creates significant financial burden to any healthcare system. Developing strategies and health intervention methods to ameliorate this situation is paramount. Experiments utilizing heterochronic parabiosis in mice have demonstrated that replacing the aging cellular milieu with the plasma of a young experimental animal leads to reversal of cellular senescence. This article describes a hypothetical model of intermittent heterochronic plasma exchange in humans as a modality for heterochronic parabiosis in an attempt to delay cellular senescence.

Tocotrienol-Rich Fraction (TRF) Treatment Promotes Proliferation Capacity of Stress-Induced Premature Senescence Myoblasts and Modulates the Renewal of Satellite Cells: Microarray Analysis.
            (Lim et al., 2019) Download
Human skeletal muscle is a vital organ involved in movement and force generation. It suffers from deterioration in mass, strength, and regenerative capacity in sarcopenia. Skeletal muscle satellite cells are involved in the regeneration process in response to muscle loss. Tocotrienol, an isomer of vitamin E, was reported to have a protective effect on cellular aging. This research is aimed at determining the modulation of tocotrienol-rich fraction (TRF) on the gene expressions of stress-induced premature senescence (SIPS) human skeletal muscle myoblasts (CHQ5B). CHQ5B cells were divided into three groups, i.e., untreated young control, SIPS control (treated with 1 mM hydrogen peroxide), and TRF-posttreated groups (24 hours of 50

Anti-inflammatory Activity of Tocotrienols in Age-related Pathologies: A SASPected Involvement of Cellular Senescence.
            (Malavolta et al., 2018) Download
Tocotrienols (T3) have been shown to represent a very important part of the vitamin E family since they have opened new opportunities to prevent or treat a multitude of age-related chronic diseases. The beneficial effects of T3 include the amelioration of lipid profile, the promotion of Nrf2 mediated cytoprotective activity and the suppression of inflammation. All these effects may be the consequence of the ability of T3 to target multiple pathways. We here propose that these effects may be the result of a single target of T3, namely senescent cells. Indeed, T3 may act by a direct suppression of the senescence-associated secretory phenotype (SASP) produced by senescent cells, mediated by inhibition of NF-kB and mTOR, or may potentially remove the origin of the SASP trough senolysis (selective death of senescent cells). Further studies addressed to investigate the impact of T3 on cellular senescence "in vitro" as well as in experimental models of age-related diseases "in vivo" are clearly encouraged.

Chondrocyte senescence, joint loading and osteoarthritis.
            (Martin et al., 2004)  Download
cellular level is not completely understood, but both aging and loading-induced stresses have been shown to undermine cell functions related to the maintenance and restoration of the cartilage matrix. Based on precedents set by studies of other age-related degenerative diseases, we have focused our laboratory work on senescence as the cause of age-dependent decline in chondrocytes and on the impact of excessive mechanical stresses in promoting senescence. We hypothesized that senescent chondrocytes accumulate with age in articular cartilage and we propose that excessive mechanical stress plays a role in this process by promoting oxidative damage in chondrocytes that ultimately causes them to senesce. To test this hypothesis, we measured cell senescence markers (beta-galactosidase expression, mitotic activity, and telomere length) in human articular cartilage chondrocytes, and determined the effects of chronic exposure to oxidative stress on chondrocyte growth and senescence. In addition, we measured the effects of abnormally high levels of mechanical shear stress on the release of oxidants in cartilage explants. We found that senescent chondrocytes accumulated with age in articular cartilage. In vitro studies showed that chronic oxidative stress caused by repeated exposure to peroxide, or by growth under superphysiologic oxygen tension caused chondrocyte populations to senesce prematurely, before extensive telomere erosion occurred. Mechanical shear stress applied to cartilage explants considerably increased the production of oxidants. These observations support the hypothesis that senescence accounts for age-related decline in chondrocyte function and indicate that mechanically induced oxidative damage plays a role in this process. This suggests that new efforts to prevent the development and progression of osteoarthritis should include strategies that slow the progression of chondrocyte senescence or replace senescent cells.

The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet.
            (Mitchell et al., 2014)  Download
The prevention or delay of the onset of age-related diseases prolongs survival and improves quality of life while reducing the burden on the health care system. Activation of sirtuin 1 (SIRT1), an NAD(+)-dependent deacetylase, improves metabolism and confers protection against physiological and cognitive disturbances in old age. SRT1720 is a specific SIRT1 activator that has health and lifespan benefits in adult mice fed a high-fat diet. We found extension in lifespan, delayed onset of age-related metabolic diseases, and improved general health in mice fed a standard diet after SRT1720 supplementation. Inhibition of proinflammatory gene expression in both liver and muscle of SRT1720-treated animals was noted. SRT1720 lowered the phosphorylation of NF-κB pathway regulators in vitro only when SIRT1 was functionally present. Combined with our previous work, the current study further supports the beneficial effects of SRT1720 on health across the lifespan in mice.

Effect of quercetin on traits of the metabolic syndrome, endothelial function and inflammation in men with different APOE isoforms.
            (Pfeuffer et al., 2013)  Download
BACKGROUND AND AIMS:  The polyphenol quercetin may prevent cardiovascular diseases due to its vasorelaxant and anti-oxidative properties. We investigated the effects of quercetin on risk factors of atherosclerosis, biomarkers of inflammation and oxidative stress, depending on the apolipoprotein E (APOE) genotype. METHODS AND RESULTS:  In a double-blind crossover study 49 healthy male subjects with APOE genotype 3/3 (n = 19), 3/4 (n = 22) and 4/4 (n = 8) consumed 150 mg/d quercetin or placebo for 8 weeks each, intermitted by a three-week washout phase. After each intervention, endothelial function, anthropometry, metabolic and inflammatory parameters were measured in the fasting and postprandial state following a standardized lipid-rich meal. Endothelial function was not changed. In all subjects combined, quercetin significantly decreased waist circumference (P = 0.004) and postprandial systolic blood pressure (P = 0.044). Postprandial triacylglycerol concentrations were significantly decreased and HDL-cholesterol concentrations increased after quercetin as compared to placebo consumption (P = 0.025). Quercetin also moderately increased levels of TNFα (P = 0.024). There was a significant gene-diet interaction for waist circumference and for body mass index (BMI). CONCLUSIONS:  Quercetin supplementation improved some risk factors of cardiovascular disease, yet exerted slightly pro-inflammatory effects. Genotype-dependent effects were seen only on waist circumference and BMI.

The influence of cellular senescence on intracellular vitamin C transport, accumulation, and function.
            (Saitoh et al., 2018) Download
In humans, vitamin C (VC) accumulates at higher concentrations in cells than in plasma, and this intracellular accumulation appears critical to several important physiological functions. However, although VC accumulation decreases in the elderly, the influence of cellular senescence on the transport, accumulation, and function of VC is poorly understood. In this study, we investigated the effects of supplementation with both ascorbic acid (AsA) and dehydroascorbic acid (DehAsA) on the uptake and accumulation of VC, AsA, and DehAsA into cells and the effect of AsA on the levels of intracellular reactive oxygen species (ROS) in human fibroblast TIG-1 cells. We also assessed how that supplementation affected senescence-associated changes in intracellular VC transport and accumulation. AsA supplementation significantly increased intracellular levels of AsA, DehAsA, and total VC (i.e., reduced AsA plus oxidized DehAsA) in senescent cells compared with young cells. DehAsA supplementation also significantly increased intracellular AsA and total VC levels in senescent cells, but not DehAsA, and the increases were less than after adding AsA. Among the molecules related to VC accumulation, the mRNA and protein expressions of sodium-dependent VC transporter 2 (SLC23A2) were increased in senescent cells. Furthermore, intracellular peroxide and superoxide anion levels were higher in senescent cells, with AsA supplementation markedly attenuating spontaneous intracellular peroxide accumulation. Overall, our results therefore suggest that VC transport and accumulation improved in senescent human fibroblast TIG-1 cells due to the adaptive upregulation of sodium-dependent VC transporter 2 in response to increased ROS levels. We conclude that adequate supplementation with AsA can effectively mitigate senescence-associated intracellular ROS.

Polychlorinated biphenyls induced oxidative stress mediated neurodegeneration in hippocampus and behavioral changes of adult rats: anxiolytic-like effects of quercetin.
            (Selvakumar et al., 2013)  Download
Polychlorinated biphenyls (PCBs) are extremely toxic environmental contaminant speculated to accelerate neurochemical and behavioral damages. Developmental and behavioral development relies on the proper functioning of the endogenous neurotransmitters that remain the pivotal target of neurotoxicants. This study intent to evidence the neuroprotective efficacy of quercetin against PCBs induced hippocampal degeneration. Animals were sorted into four (n=6), Group I: received corn oil (vehicle) intraperitoneally (i.p.); Group II: received quercetin 50 mg/kg bwt (gavage); Group III: were induced with Aroclor 1254 (commercial mixture of PCB) at 2 mg/kg bwt (i.p); Group IV: received quercetin 50 mg/kg bwt (gavage) and along with PCBs 2 mg/kg bwt (i.p.) for 30 days. Cognitive behaviors such as learning and memory were assessed by 8-arm radial maze behavior test throughout the experimental period. Subsequently, anxiety and stress were studied by open field test at the termination of experiment. Hippocampal tissue and blood were collected after the intended experimental period to analyze the levels of oxidative stressors, antioxidants in tissue and estimation of neurotransmitters. Perhaps, PCBs evoke detrimental deterioration of the neurotransmitters and integrative antioxidant defense by elevation of reactive oxygen species (ROS). Concurrent treatment with quercetin prominently suppresses the oxidative stressors, improved the levels of enzymatic antioxidants and neurotransmitter levels significantly at the level of p<0.05. Behavioral analysis claims drastic revitalization of cognitive functions like learning and memory on treatment with quercetin. The results coalesced depicts neurotoxicity stimulated by PCBs is augmented by simultaneous quercetin administration.


Testosterone is essential for skeletal muscle growth in aged mice in a heterochronic parabiosis model.
            (Sinha et al., 2014)  Download
As humans age, they lose both muscle mass and strength (sarcopenia). Testosterone, a circulating hormone, progressively declines in aging and is associated with loss of muscle mass and strength. The surgical joining of a young and old mouse (heterochronic parabiosis) activates Notch signaling and restores muscle regenerative potential in aged mice. We hypothesize that testosterone is at least one of the factors required for the improvement seen in muscles in old mice in heterochronic parabiosis with young mice. To test this hypothesis, we established the following heterochronic parabioses between young (Y; 5 months old) and old (O; 22-23 months old) C57BL6 male mice: (1) Y:O; (2) castrated Y:O (ØY:O); (3) castrated + testosterone-treated Y:O (ØY + T:O). A group of normal young mice received empty implants, and old mice were used as controls. Parabiotic pairings were maintained for 4 weeks prior to analysis. Serum testosterone levels were three-fold higher in young than in old mice. The ØY + T:O pairing demonstrated significantly elevated levels of serum testosterone and an improvement in gastrocnemius muscle weight, muscle ultrastructure, muscle fiber cross-sectional area, and Notch-1 expression in old mice. These changes were not present in aged mice in the ØY:O pairing. These data indicate that testosterone has a critical role in mediating the improved muscle mass and ultrastructure seen in an experimental model of heterochronic parabiosis.

Eye lens in aging and diabetes: effect of quercetin.
            (Stefek and Karasu, 2011)  Download
Old age is accompanied by a number of pathological eye conditions. Cataract is the most common age-related eye complication. Because the lens becomes naturally more opaque over time, aging is the most important risk factor for developing cataract, which is a major cause of blindness in the world. Cataractogenesis is also one of the earliest secondary complications of diabetes mellitus. The lens is a closed system with limited capability to repair or regenerate itself. Current evidence supports the view that cataractogenesis is a multifactorial process. Oxidative stress and its sequelae are clearly involved in the etiology of senile cataract, whereas mechanisms related to glucose toxicity, namely oxidative stress, processes of nonenzymatic glycation, and enhanced polyol pathway contribute significantly to the development of the eye complications under conditions of diabetes. There is an urgent need for inexpensive, nonsurgical approaches to the treatment of cataract. Recently, considerable attention has been devoted to the search for phytochemical therapeutics. Several pharmacological actions of natural flavonoids may operate in preventing cataract because flavonoids are capable of affecting multiple mechanisms or etiological factors responsible for the development of sight-threatening ocular diseases. The flavonol quercetin is the most widely consumed flavonoid in the human diet. In this article, quercetin is reviewed as an agent that could reduce the risk of cataract formation via affecting multiple pathways pertinent to eye lens opacification, including oxidative stress, nonenzymatic glycation, the polyol pathway, lens calpain proteases, and epithelial cell signaling. In addition, the bioavailability of quercetin to the lens is considered.

Administration of L-arginine plus L-citrulline or L-citrulline alone successfully retarded endothelial senescence.
            (Tsuboi et al., 2018) Download
L-citrulline and L-arginine supplementation has been shown to have several beneficial effects on the cardiovascular system. Nitric oxide (NO) protects against the progression of atherosclerosis and is synthesized by nitric oxide synthase (NOS), which converts L-arginine (L-Arg) into L-citrulline (L-Cit). Our previous study revealed that chronic administration of a combination of L-Cit and L- Arg has a better therapeutic effect on high cholesterol-induced atherosclerosis in rabbits. We investigated how L-Arg and L-Cit affect endothelial function, aging and atherosclerosis. Following a 3-day stimulation of human umbilical venous endothelial cells (HUVECs) with high glucose (HG: 22 mM) and L-Arg (300 μM), L-Cit (300 μM) or L-Arg plus L-Cit (LALC: each 150 μM) supplementation, endothelial senescence and function were evaluated. These amino acids were also administered to dyslipidemic type 2 diabetic (ZDFM) rats fed a high cholesterol diet. They were fed L-Arg or L-Cit or LALC for four weeks. Aortic senescence was investigated by measuring senescence-associated ß-galactosidase (SA-ß-gal), telomerase activity, DNA damage and p16INK4a protein expression. Only L-Cit and LALC supplementation retarded the HG-induced endothelial senescence, as evaluated by SA-ß-gal activity, a widely used marker of cellular senescence, p16INK4a expression, a senescence-related protein, and DNA damage. Under HG conditions, L-Cit and LCLA restored telomerase activity to levels observed under normal glucose (NG) conditions. Under HG conditions, L-Cit decreased ROS production, as measured by CM-H2DCFDA and the expression of p67phox, a major component of NADPH oxidase. Under HG conditions, L-Cit and LALC increased NO production, as measured by DAF-2AM. Endothelial NO synthase (eNOS) and phosphorylated eNOS were decreased under HG conditions and L-Cit and LALC significantly increased these levels. Arginase 2 protein expression increased under the HG conditions, and L-Cit and LALC significantly attenuated this effect. In ZDFM rats, SA-ß-gal activity was detected on the aortic endothelial surface; however, L-Cit and LALC reduced these levels. L-Cit and LALC both decreased the proportion of senescent cells. Furthermore, treatment with LALC for 4 weeks increased plasma NO production. Therefore conclusively, L-citrulline supplementation rescued NO levels better than L-arginine supplementation by inhibiting ROS production and arginase 2 protein expression. Consequently, L-Cit and LCLA supplementation retaeded HG-induced endothelial senescence.


Senescent cells: A new Achilles' heel to exploit for cancer medicine
            (Zhang et al., 2019)  Download
Cellular senescence is a typical tumor-suppressive mechanism that restricts the proliferation of premalignant cells. However, mounting evidence suggests that senescent cells, which also persist in vivo, can promote the incidence of aging-related disorders principally via the senescence-associated secretory phenotype (SASP), among which cancer is particularly devastating. Despite the beneficial effects of the SASP on certain physiological events such as wound healing and tissue repair, more studies have demonstrated that senescent cells can substantially contribute to pathological conditions and accelerate disease exacerbation, particularly cancer resistance, relapse and metastasis. To limit the detrimental properties while retaining the beneficial aspects of senescent cells, research advancements that support screening, design and optimization of anti-aging therapeutic agents are in rapid progress in the setting of prospective development of clinical strategies, which together represent a new wave of efforts to control human malignancies or mitigate degenerative complications.

Quercetin protects against high glucose-induced damage in bone marrow-derived endothelial progenitor cells.
            (Zhao et al., 2014)  Download
Endothelial progenitor cells (EPCs), a group of bone marrow-derived pro-angiogenic cells, contribute to vascular repair after damage. EPC dysfunction exists in diabetes and results in poor wound healing in diabetic patients with trauma or surgery. The aim of the present study was to determine the effect of quercetin, a natural flavonoid on high glucose‑induced damage in EPCs. Treatment with high glucose (40 mM) decreased cell viability and migration, and increased oxidant stress, as was evidenced by the elevated levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase in bone marrow-derived EPCs. Moreover, high glucose reduced the levels of endothelial nitric oxide synthase (eNOS) phosphorylation, nitric oxide (NO) production and intracellular cyclic guanosine monophosphate (cGMP). Quercetin supplement protected against high glucose‑induced impairment in cell viability, migration, oxidant stress, eNOS phosphorylation, NO production and cGMP levels. Quercetin also increased Sirt1 expression in EPCs. Inhibition of Sirt1 by a chemical antagonist sirtinol abolished the protective effect of quercetin on eNOS phosphorylation, NO production and cGMP levels following high glucose stress. To the best of our knowledge, the results provide the first evidence that quercetin protects against high glucose‑induced damage by inducing Sirt1-dependent eNOS upregulation in EPCs, and suggest that quercetin is a promising therapeutic agent for diabetic patients undergoing surgery or other invasive procedures.


Therapeutic Potential and Cellular Mechanisms of Panax Notoginseng on Prevention of Aging and Cell Senescence-Associated Diseases.
            (Zhao et al., 2017)  Download
Owing to a dramatic increase in average life expectancy, most countries in the world are rapidly entering an aging society. Therefore, extending health span with pharmacological agents targeting aging-related pathological changes, are now in the spotlight of gerosciences. Panax notoginseng (Burk.) F. H. Chen, a species of the genus Panax, has been called the "Miracle Root for the Preservation of Life," and has long been used as a Chinese herb with magical medicinal value. Panax notoginseng has been extensively employed in China to treat microcirculatory disturbances, inflammation, trauma, internal and external bleeding due to injury, and as a tonic. In recent years, with the deepening of the research pharmacologically, many new functions have been discovered. This review will introduce its pharmacological function on lifespan extension, anti-vascular aging, anti-brain aging, and anti-cancer properties, aiming to lay the ground for fully elucidating the potential mechanisms of Panax notoginseng's anti-aging effect to promote its clinical application.



Hubbard, GP, et al. (2004), ‘Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans.’, J Thromb Haemost, 2 (12), 2138-45. PubMed: 15613018
Huo, J, et al. (2018), ‘Coenzyme Q10 Prevents Senescence and Dysfunction Caused by Oxidative Stress in Vascular Endothelial Cells.’, Oxid Med Cell Longev, 2018 3181759. PubMed: 30116476
Ishisaka, A, et al. (2011), ‘Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats.’, Free Radic Biol Med, 51 (7), 1329-36. PubMed: 21741473
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Tsuboi, T, M Maeda, and T Hayashi (2018), ‘Administration of L-arginine plus L-citrulline or L-citrulline alone successfully retarded endothelial senescence.’, PLoS One, 13 (2), e0192252. PubMed: 29415069
Zhang, B, EW Lam, and Y Sun (2019), ‘Senescent cells: A new Achilles’ heel to exploit for cancer medicine’, Aging Cell, 18 (1), e12875. PubMed: 30450821
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Zhao, LR, et al. (2014), ‘Quercetin protects against high glucose-induced damage in bone marrow-derived endothelial progenitor cells.’, Int J Mol Med, 34 (4), 1025-31. PubMed: 25197782