Editorial Antioxidants in Longevity and Medicinedownloads.hindawi.com/journals/omcl/2013/820679.pdf · Editorial Antioxidants in Longevity and Medicine ... Zagotta et al. have reported

Hindawi Publishing CorporationOxidative Medicine and Cellular LongevityVolume 2013, Article ID 820679, 3 pageshttp://dx.doi.org/10.1155/2013/820679

EditorialAntioxidants in Longevity and Medicine

Nilanjana Maulik,1 David McFadden,1 Hajime Otani,2 Mahesh Thirunavukkarasu,1

and Narasimham L. Parinandi3

1 Department of Surgery, University of Connecticut Health Center, Farmington, CT-06030, USA2Department of Internal Medicine, Kansai Medical University, Moriguchi City 570-8507, Japan3Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Dorothy M. Davis Heart & Lung Research Institute,The Ohio State University College of Medicine, Columbus, OH 43210, USA

Correspondence should be addressed to Nilanjana Maulik; [email protected]

Received 9 September 2013; Accepted 9 September 2013

Copyright © 2013 Nilanjana Maulik et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Oxidative stress has emerged as a critical player in thepathogenesis and pathophysiology ofmany diseases in exper-imental animal models and humans. The oxidative stresstheory of aging emphasizes that a progressive and irre-versible escalation of oxidative damage caused by reactiveoxygen species (ROSs) exerts severe influence on the criticalaspects of the biology of aging and contributes to impairedphysiological functions, increased incidence of diseases, andshortening of life span. The focus of this special issue is toidentify avenues that affect both the life span and age-relateddiseases in humans. In order to accomplish this, expertsin the field have contributed original research articles andreviews focusing on the current state of understanding ofthe molecular pathology of oxidative stress underlying thebiology of aging and age-related diseases and development ofstrategies to alleviate or treat these conditions.

S. Gazman-Beltran et al. demonstrate that a naturalantioxidant, nordihydroguaiaretic acid (NDGA) attenuatesthe oxidative stress-induced decrease of CD33 expression inhuman monocytes, which is decreased in diabetic patientsunder oxidative stress.The antioxidantmechanism of NDGAappears to be multifactorial and includes the increasedavailability of glutathione and activation of nuclear factorE2-related factor-2 (Nrf2), which is known to orchestrateantioxidative and cytoprotective responses to oxidative stress.NDGA appears to be an effective antioxidant to preventchronic inflammation induced by monocytes.

Recently, studies conducted with dietary polyphenols onneurological disorders have shown promising results. K. S.

Bhullar and H. P. V. Rupasinghe have reviewed the effect ofpolyphenols on age-related neurological disorders and dis-cussed the role of polyphenols inmultiple signaling pathways,includingPI3K/Akt,Nrf2/HO1PPAR, STAT,NF-𝜅B,HIF, andMAPK. All of the pathways can alleviate oxidative damageand inflammation. This review article offers insights intothe complex interactions of polyphenols with intracellularsignaling pathways in neuronal cells and provides novelapproach to neurological disorders.

Resveratrol is a calorie restriction (CR) mimetic agent.CR reverses many of the obesity-related increases in inflam-matory cytokines. I. Zagotta et al. have reported that PAI-1 gene expression is increased in adipose tissue in obesesubjects, and this is critically involved in chronic inflam-mation of blood vessels that leads to atherosclerosis andcardiovascular disease. PAI-1 gene is found to be upregulateddue to inflammatory conditions associated with obesity.Resveratrol treatment has been shown to suppress the PAI-1 gene in human inflamed adipose tissue. Interestingly, theeffect of resveratrol onPAI-1 is notmediated bymodulation ofPI3 K/Akt, SIRT1,AMPK, andNrf2 or reactive oxygen species(ROS) but proceeds through the inhibition of the NF-𝜅Bpathway.This suggests that resveratrol inhibits the generationof inflammatory cytokines in the adipose tissue via a novelanti-inflammatory pathway.

Advanced glycation end products (AGEs) play a crucialrole in senescence. B. Buttari et al., have demonstrated thatresveratrol may be effective in treating autoimmune diseasesthat are intimately related to the activation of dendritic cells

2 Oxidative Medicine and Cellular Longevity

(DCs) with the AGEs. B. Buttari et al. have also shown thatresveratrol pretreatment of human monocyte-derived DCsprevents the activation of DCs in response to the AGE-albumin.The mechanism is by inhibiting the DCmaturationand proinflammatory cytokine expression associatedwith theinhibition of NF-𝜅B activation. Because the specific recep-tor for AGE (RAGE) is down-regulated in the resveratrol-pretreated DCs, resveratrol inhibits oxidative stress andinflammatory response at the level of RAGE upstream ofPI3K/Akt, MAPK, or NF-𝜅B.This finding is interesting sincethe NF-𝜅B pathway is modulated by resveratrol in otherbiological systems. This unique pharmacological action ofresveratrol on DCs that are activated by AGEs is a subject forfurther investigation.

ROS derived from the mitochondria activates the redox-sensitive transcriptional factor, nuclear respiration factor-2(NRF2). NRF2-induced mitochondrial biogenesis improvesthe function of electoral transfer chain (ETC) and preventsROS generation in mitochondria. Thus, the agents that canactivate NRF2 are attractive in ameliorating oxidative stress-induced pathology. X. Miao et al. have demonstrated thatan NRF2 activator MG132 has prevented the aortic injuryin type-1 diabetic mice, suggesting that activation of NRF2represents a promising approach for hyperglycemia-inducedvascular complications.

Aging is related to circadian rhythm disruption. Theconcept of chrononutrition raised by M. Garrido et al. hasprompted development of a strategy that takes timing oftryptophan-enriched food intake into account when deliver-ing antioxidative medicine. Chrononutrition studies suggestthat along with the content of food, the time of ingestion isessential for the natural functioning of the circadian system,which stimulates melatonin secretion at night. Melatoninproduces circadian rhythm and acts as a potent antioxidantand ROS scavenger. It also inhibits ROS generation bypreventing the electron leakage from mitochondria, therebystimulating the antioxidative defense system. Thus, it isanticipated that administration of melatonin either directlyor indirectly from food enhances one’s antioxidant status.

A review article described by H. Otani opens a newavenue for antioxidative medicine. Although ROS is involvedin many pathological phenomena in humans with advancedage, antioxidative medicine is not always successful in allevi-ating human disease. The limitation of general antioxidantsin preventing oxidative stress-induced diseases is attributedto ROS playing a pivotal role in generating redox signaling.This is necessary formaintaining homeostasis and generatingadaptive response to lethal oxidative damage. Thus, antioxi-dants must be more site specific to eliminate only harmfulROS and leave beneficial ROS. Recent new drugs used fortreating lifestyle-related diseases such as hypertension, hyper-lipidemia, and hyperuricemia possess a pleiotropic effect thatis designated as the site-specific antioxidant against endothe-lial NADPH oxidase and xanthine oxidase. Antioxidants thatspecifically reduce mitochondrial ROS generation will alsobe putative drugs to ameliorate age-associated disease andprolong lifespan.

Mitochondrial generation of ROS is intimately relatedto aging. Eliminating the harmful production of ROS from

mitochondria represents a powerful strategy to prevent cel-lular senescence.The review article authored by K. Shinmurahighlights the importance of preventing mitochondrial gen-eration of ROS. Age-relatedmitochondrial dysfunction is dueto oxidative stress-mediated accumulation of somationmuta-tion in mitochondrial DNA. A growing body of evidencesuggests that caloric restriction (CR) mediates attenuationof mitochondrial oxidative damage via decreasing the pro-duction of mitochondrial ROS rather than by enhancing theantioxidant defense. K. Shinmura suggests that sirtuin mightbe involved in the CR-induced attenuation of mitochondrialoxidative damage. This review article concludes that CR-mimetic agents, such as resveratrol and sirtuin activators, arepromising agents to improve the mitochondrial function andprolong lifespan, although their exactmechanism(s) of actionshould be carefully examined.

Myocardial reperfusion injury is mediated at least inpart by oxidative stress. Yet, there have been no antioxi-dants that unequivocally confer benefit in the postischemicheart in the clinical setting, although numerous agents havebeen shown to exert cardioprotective effects on animalmodels of ischemia/reperfusion injury. Angelos et al. havedemonstrated that the neutrophil esterase inhibitor sivelestatreduces the infarct size and improves cardiac function in anisolated rat heart that lacks neutrophils. The cardioprotectiveeffect of sivelestat appears to be mediated by nitric oxide,which has consistently been implicated in the cardioprotec-tion against myocardial ischemia/reperfusion injury. Futureclinical trials using sivelestat are warranted to test whetherthis clinically available drug is indeed effective in ameliorat-ing myocardial reperfusion injury in humans.

G. Grosso et al. have advocated in favor of the healthbenefits of red orange on the basis of research on experi-mental models and epidemiological evidence. The authorsargue that the beneficial effects of the red orange fruit maybe exerted through the synergistic actions of the naturalproducts present in the fruit. These natural products possessantioxidant actions, which may protect against oxidativedamage, and the total beneficial actions of all the naturalproducts (antioxidants) present in the red orange fruit couldbe more effective than an individual antioxidant.

The lack of mitochondrial superoxide dismutase (Mn-SOD) leading to the loss of hearing during aging has beenclearly demonstrated by M. Kinoshita et al. With the use ofMn-SOD heterozygous knockout mice as the experimentalmodel of mitochondria-derived oxidative stress, the authorshave shown that loss of Mn-SOD by half appears to elevatethe oxidative stress in the cochlea to a certain degree, but thatmay not be adequate to speed up the age-induced damageof the cochlea. Nevertheless, the role of Mn-SOD in themitochondria that scavenges the superoxide radical in theoxidative stress that leads to loss of hearing during aging hasbeen attempted in this study.

Z. Makpol et al. have studied the gene expression-modulating actions of gamma-tocotrienol in the senescenthuman diploid fibroblasts by utilizing the microarray anal-ysis. This study has emphasized on the lipid-soluble antiox-idant (gamma-tocotrienol) actions on the modulation ofgenes associated with the cellular aging and oxidative stress.

Oxidative Medicine and Cellular Longevity 3

This study has demonstrated that gamma-tocotrienol appearsto block cellular aging of human fibroblasts through themodulation of gene expression in the cells. In addition, therole of lipid peroxidation in cellular aging and associated geneexpression is apparent from this study.

D. McCormack and D. McFadden have discussed indepth the antioxidant and disease-modifying actions ofpterostilbene. The antioxidant actions of pterostilbene havebeen connected with cancer protection, treatment of neu-rological diseases, suppression/treatment of inflammation,attenuation of vascular diseases, and improvement of dia-betes. The authors have provided an excellent account onthe clinical use of pterostilbene in prevention/treatment ofseveral disorders and diseases.

A. B. Rodriguez et al. showed that fish oils containing theomega-3 polyunsaturated fatty acids (n3-PUFA) are capableof attenuating the levels of inflammatory cytokines andoxidative stress markers in the serum of multiple sclerosispatients. From this study, the authors have concluded thatthe fish oil supplementation to the multiple sclerosis patientseffectively lowers the levels of inflammatory cytokines andnitric oxide (oxidant), thus leading to the protection againstmultiple sclerosis.

J. Rosado-Perez et al. have shown that physical exerciselike Tai Chi offers beneficial effects in lowering oxidativestress in humans. In their study on Mexican adults, theauthors have revealed that the subjects who have practicedTai Chi have exhibited lower extent of lipid peroxidationand elevated superoxide dismutase activity as compared tothe control individuals. From this study, the authors haveconcluded that Tai Chi is more effective in elevating theantioxidant status in humans as compared to walking.

S. Dande et al. have discussed on the natural antioxidantactions of the commonly consumed foods of plant originin India. In this review, the authors have emphasized onthe domestic processing of plant foods that could affect thequality of the plant foods that are consumed. The authorsdiscussed the importance of polyphenols present in the plantfoods that could act as natural antioxidants.The authors havestated that the domestic processing of plant foods may notalter the content of polyphenols and antioxidant activities inthe plant foods.

In a study on the hypoxia-induced neuroinflammation,Z. Wu et al. have shown that the Brazilian green propolisinhibits the NF-𝜅B activation in the microglia. The authorshave demonstrated that the mitochondrial ROS formationis crucial for the activation of NF-𝜅B activation in themicroglia. Therefore, it appears that propolis could have alsoacted as an antioxidant in attenuating the hypoxia-inducedneuroinflammation in the microglia.

A. L. Zagayko et al. have shown that the grape polyphe-nols increase the activity of high-density lipoprotein (HDL)enzymes in old and obese rats. The authors have revealedthat the activity of paraoxonase, lecithin: cholesterol acyl-transferase (LCAT) in plasma have been lowered and thecholesterol ester transfer protein (CETP) activity has beenelevated in old rats. This study emphasizes the actions ofgrape polyphenols on the elevation of HDL enzymes duringaging.

These papers represent an exciting and insightful snap-shot of current antioxidant research. State-of-the-art, excitingchallenges, which still present many new challenges, arehighlighted in this special issue, which may inspire and helpadvance antioxidant research. We would like to thank allauthors, reviewers, and the editors for producing this specialissue.

Antioxidative medicine has become a practical tool totreat age-associated disease and to prolong the lifespan sinceoxidative stress is critically involved in human aging. Thepurpose of the topics covered in this special issue is to provideadditional opportunities to all the investigators in the field inorder to identify avenues that impact both the life span andage-related diseases in humans. Therefore, the contributionsmade by the experts in this issue as original research articlesand reviews will hopefully stimulate the continuing efforts ofthe investigators to understand and establish the molecularpathology of oxidative stress underlying the biology of agingand age-related diseases and development of strategies toalleviate or treat these conditions.

Nilanjana MaulikDavid McFadden

Hajime OtaniMahesh ThirunavukkarasuNarasimaham L. Parinandi

Submit your manuscripts athttp://www.hindawi.com

Stem CellsInternational

Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014

Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinson’s Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

Documents

Editorial Antioxidants in Longevity and Medicinedownloads.hindawi.com/journals/omcl/2013/820679.pdf · Editorial Antioxidants in Longevity and Medicine ... Zagotta et al. have reported