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PlantBioactivesasNaturalPanacea
AgainstAge-inducedDiseases
NutraceuticalsandFunctionalLeadCompoundsforDrug Development
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PlantBioactivesas NaturalPanacea AgainstAge-induced Diseases
NutraceuticalsandFunctionalLead CompoundsforDrugDevelopment
Editedby
KantiBhooshanPandey
CSIR-CentralSalt&MarineChemicalsResearchInstitute,Bhavnagar, Gujarat,India
MaitreeSuttajit
ThaiVegetarianAssociation,Changpuak,ChiangMai,Thailand
SeriesEditor ChukwuebukaEgbuna
Elsevier
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2.Anti-agingstrategies,plantbioactives,anddrug
2.5Plantsrichinbioactives:strategicpossibilitytodevelop
2.6Plantbioactivesreportedtoprotectagainstskinphotoaging
2.7Futuretrends
3.Nutrigenomics,plantbioactives,andhealthyaging
UchennaEstellaOdoh,ChukwumaMichealOnyegbulam, Theodoramba,ObinnaSabastineOnugwu,IkennaChikeokwu andLonginusC.Odoh
4.Plantbioactivesinbalancingglucosehomeostasis
SuparnaMandal,RavichandraShivalingappaandSambeAshaDevi
4.5Epigenetic-mediatedprotectivemechanismsofgrapeseed proanthocyanidinextractandgreentea
5.Plantbioactivesinimmunemodulationandtheirrole
YaseminAydin,YaseminUlkuDikbasanandBanuOrta-Yilmaz
5.4Inflammaging
5.4.1Molecularlevel89
5.4.2Cellularlevel90
5.4.3Systemiclevel90
5.5Immunecellskewing
5.5.1Molecularlevel91
5.5.2Cellularlevel92
5.5.3Systemiclevel92
5.6Decliningyouthfactors
5.7Plantbioactivemolecules
5.7.1Modeofactionofplantbioactivemolecules97
5.8Modulationofimmunefunctionbyplantbioactive moleculesandantiagingeffects
5.9Conclusionandfutureperspectives
6.Plantbioactives,genes,andlongevi
ManisekaranHemagirri,Shanmugapriya,YengChen, JagatR.KanwarandSreenivasanSasidharan
6.1Introduction
6.2Agingandprocessofaging
6.4Longevitygenesinfluencinglongevityinhumans
6.4.1Longevitygene114
6.4.2Sirgenes114
6.4.3Telomerasereversetranscriptasegene115
6.4.4DAF-16gene116
6.5Plantextractsandtheirbioactivesinregulationoflongevity genes
6.6Plantbioactivesandagingintervention
7.Hormeticeffectsofplantbioactivesonhealthy
PimpisidKoonyosying,NarisaraParadeeand SomdetSrichairatanakool
7.1Introduction
7.1.1Hormesisoradaptivestressresponses129
7.1.2Hormeticversusantioxidantresponses130
7.1.3Antiagingandhormesis131
7.2Hormeticeffectsofplantbioactives
7.2.1Bioactivesfromgreentea132
7.2.2Bioactivesfromcoffee135
7.2.3Bioactivesfrom Perillafruits
7.3Futureprospects
7.4Conclusion
7.5Acknowledgements
8.Anti-agingeffectofpolyphenols:possibilitiesand challenges 147
WittayaChaiwangyen,OradaChumphukam, NapapanKangwan,KomsakPinthaandMaitreeSuttajit
8.1Introduction
8.2Chemistryandclassification
8.3Anti-agingpropertiesofpolyphenolsandmechanisms 148
8.3.1Epigeneticmodification148
8.3.2MicroRNAmodulationsandregulations153
8.3.3Antioxidantactivity155
8.3.4Anti-inflammationactivity158
8.3.5Anti-glycationactivity161
8.4Futuretrends:possibilitiesandchallenges 163 8.5Conclusion 166 References 166
9.Plantpolyphenolsinbalancingtheredoxstate duringaging 181
SandeepSingh,GeetikaGargandSyedIbrahimRizvi
9.1Introduction
9.2Redoximbalance,oxidativestress,andaging
9.3Roleofpolyphenolsinmaintainingredoxstatus
9.4Roleofpolyphenolsinage-relateddisordersdueto redoximbalance
9.4.1Neurodegenerativediseases186
9.4.2Cardiovasculardiseases186
9.4.3Diabetes187
9.4.4Obesity187
9.4.5Cancer188
9.5Futuretrends 188 9.6Conclusion 189
10.Mechanismsinvolvedinpreventionofdementiaand promotionofhealthyagingbyresveratrol
BrahmKumarTiwariandKantiBhooshanPandey 10.1Introduction
10.3Resveratrol,FrenchParadox,aging,anddementia 200
10.4Mechanismsinvolvedinpreventionofdementiaby resveratrol 201
10.5Clinicaltrialsofresveratrolonneurodegenerativediseases 204
10.6Futureprospectiveandconclusion 206 References 206
11.Aninsightintoplantpolyphenolsinpreventionof brainaging 215
PadmanabhSingh,ArpitaKonarandM.K.Thakur
11.1Introduction 215
11.1.1Anatomical,biochemical,andmoleculartriggers ofbrainaging216
11.2Phytochemicalsasnutraceuticalsforhealthybrainaging 218
11.2.1Polyphenols218
11.2.2Polyphenolsandepigeneticregulationofgene expression225
11.2.3Bioavailabilityofpolyphenols225
11.3Conclusionandfutureperspectives 227
12.Plantpolyphenolsintheregulationofion channelsduringagingandinduceddiseases 235
BanuOrtaYilmaz,BuseYilmazandYaseminAydin 12.1Introduction
12.2.1Classificationofpolyphenols237
12.2.2Beneficialeffectsofpolyphenolsonhumanhealth237
12.3Agingprocess 240
12.4Thefunctionsofionchannels 240
12.4.1Maintypesandbiologicalrolesofionchannels241
12.4.2Effectsofpolyphenolsonionchannels244
12.5Potentialmechanismsofpolyphenolsintheregulationof ionchannelsrelevanttoagingintervention 245
12.6Conclusionandperspectives
13.Teacatechinsaspotentantioxidantand anti-inflammatoryagents:possibilitiesofdrug developmenttopromotehealthyaging 253 PracheeDubey
13.1Introduction 253
13.2Structureandsourcesofteacatechins 254
13.3Teacatechinsandanti-agingeffects:mechanismsofaction 254
13.3.1Antioxidantactivityofteacatechins255
13.3.2Anti-inflammatoryactivityofteacatechins258
13.4Antioxidativeandanti-inflammatorypropertiesof teacatechinsinpreventingagingandage-relateddiseases 258
13.4.1Cognitivedeclineanddementia258
13.4.2Cardiovasculardiseases260 13.4.3Cancer261
13.4.4Otherage-dependentdiseases262
13.5Futuretrendsandconclusion
14.Functionalfoods,bioactives,andcognitive impairmentsduringaging 271
PrabhakarSinghandMohammadMurtazaMehdi
14.1Introduction 271
14.2Cellularbiomolecules,oxidativestress,aging,and cognitivedysfunction 273
14.3Functionalfoods 274
14.4Bioactivesfromfunctionalfoods,cognitiveimpairments, andaging 274
14.5Dietarypolyphenols,cognitiveimpairments,andaging 275
14.5.1Resveratrol276 14.5.2Curcumin277
14.5.3(-)-Epigallocatechin-3-gallate279 14.5.4Caffeine280
14.6Vitaminsincognitiveimpairmentsduringaging
14.7Otherbioactivesinfunctionalfoodsduringaging
14.8Conclusionandfutureremarks
15.Functionalfoodsinimprovingbonehealth duringaging 287
SuphachaiCharoensin,PeraphanPothacharoen, OrawanWanachewin,PrachyaKongtawelertandMaitreeSuttajit
15.1Introduction:commonboneandjointchangesduringaging 287
15.2Bonesandtheirassociatedcomponents
15.3Nutritionforboneandjointhealth 289
15.3.1Essentialbone-buildingminerals289
15.4Childhoodandadolescence:theagetostartingstrong bonehealth
15.5Age-relatedboneandjointdegenerationinagingpeople 295
15.5.1Hormonalregulationofcalcium295
15.5.2Alterationsinconnectivetissue296 15.5.3Osteoporosis297
15.5.4Joint,inflammation,andosteoarthritis297
15.5.5Maintainingboneandjointhealthwithfunctional foods298
15.5.6Sesame298
15.5.7Phytochemicals299 15.6Futureprospects 300 15.7Conclusion
16.Dietaryrestriction,vegetariandiet,andaging intervention
MaitreeSuttajit,SubramanianThangaleela,BhagavathiSundaram SivamaruthiandSuphachaiCharoensin
16.1Introduction
16.2Calories,balancedenergy,overweight,andobesity
16.3.1Dietrestrictionmechanismandhealthbenefits310
16.3.2Caloricrestrictionmechanismandhealthbenefits311
16.3.3Intermittentfastingmechanismandhealthbenefits313
16.3.4Religiousdietaryrestriction315
16.4Theroleandnewinsightsofvegetarianandvegandiets
17.Plantbioactivesaspromisingtherapeuticagentsin Parkinson’sdiseasetargetingoxidativestressduring aging 329
NidhiSachan,BrijeshSinghChauhanandSaripellaSrikrishna 17.1Introduction 329
17.2Aging:animportantcontributoryfactorforParkinson’s disease 330
17.2.1EarlyonsetParkinson’sdisease330
17.2.2LateonsetParkinson’sdisease334
17.3TreatmentstrategiesforParkinson’sdisease 335 17.4Flavonoids:promisinganti-Parkinson’sdiseasecompounds 336
17.4.1Baicalein337
17.4.2Curcumin339
17.5Conclusionandfutureprospective
18.Novelplantbioactives,theirantiagingpotencies: realityandpromises 359
UmahRaniKuppusamyandBavaniArumugam
18.1Introduction
18.2Thehallmarksofaging 360
18.2.1Oxidativestressandaging360
18.2.2Linksbetweenreactiveoxygenspeciesandthe hallmarksofaging361
18.3Plantbioactivesandtheirclassification
18.4Novelbioactivecompoundsasantiagingagents 365
18.4.1Novelbioactivesascaloricrestrictionmimetics370 18.4.2Novelbioactivesasmitochondria-localized antioxidants370
18.4.3Gutmicrobiotaastheantiagingtargetofnovel bioactives371
18.4.4NovelGolgi β-galactosidaseaspotentialtargetof novelbioactivesinantiagingtherapy371
18.5Promisingantiagingbioactivesthathavemadeitto humanclinicaltrials 371
18.6Plantbioactivesasantiaging/geroprotectivenutraceuticals: realityandchallengesandfutureperspectives 374
18.6.1Bioavailabilityofthebioactivesandtheirmetabolites374
18.6.2Influenceonthegutmicrobiota376
18.6.3Toxicity,dosage,safety,andshortandlong-terms adverseeffects376
18.6.4Complianceandcontrolinclinicaltrialsandlackof appropriatepanelofantiagingmarkers377
BishnuKumarPandey,KantiBhooshanPandeyand ShailendraKumarSrivastava
19.3.1Nano-emulsion389 19.3.2Nano-liposomes390 19.3.3Nano-polymersomes390 19.3.4Solid-lipidnanoparticles390 19.3.5Micelles390 19.4Nanotechnologyandplantbioactives:promisein anti-agingresearch
19.4.1Nano-resveratrol391
19.4.2Nano-curcumin391
19.4.3Nano-quercetin392
19.4.4Nano-epigallocatechingallate393
19.4.5Nano-genistein393
19.5Nanotechnologyinrefiningtheeffectofbioactivesused inskincare 393
19.6Conclusionandfutureoutlook
20.Trendsintheplant-basedanti-agingdietindifferent continentsoftheworld
RatanaBanjerdpongchai,MaitreeSuttajitand TreetipRatanavalachai
20.1Introduction
20.2Importanceofplant-baseddietsinhealthyaging
20.3Activephytochemicalsversuswholeplant-baseddiets
20.4Thereducedriskofobesityandotherschronicdiseases duringagingbyadoptionofplant-baseddietarypattern
20.5Plant-baseddietsasprebioticspromotingprobiotics 409
20.6Theworld’sagingpopulationsversusplant-based differentdietarypatterns 411
20.7Thestrategiesofplant-baseddietsandhealthyaging establishmentglobally
20.8Trendingdietarypatternsandeffectivenessof plant-baseddietsasanti-agingdiets
21.Functionalfoodsinclinicaltrialsinagingintervention 429 PinarAtukeren
21.1Introduction
21.1.1Definingfunctionalfoods429
21.1.2Cellularsenescenceinaging430
21.2Oxidativestressinaging 431
21.2.1Functionalfoodswhichhaveantioxidantproperties432
21.3Impactoffunctionalfoodsinthemanagementof age-relateddiseases
21.3.1Neurodegenerativediseases434
21.3.2Cancer434
21.3.3Eyemaculardegenerationandcataract435
21.3.4Cardiovasculardiseases435
21.3.5Osteoporosis436
21.3.6Immunologicaldiseases437
22.Plantbioactives,agingresearch,anddrugindustry: proceduresandchallenges
ChalermpongSaenjum,ThanawatPattananandechaand SutasineeApichai
22.2Agingresearchandinterventionalpropertiesofplant bioactives
22.3Challengesindrugdiscoveryanddevelopmentofa platformforplantbioactives
22.3.1Molecularmodeling457 22.3.2Extraction,separation,andstandardization458 22.3.3Organiccultivationofmedicinalplants459 22.4Conclusionandfutureperspective
Listofcontributors
SutasineeApichai DepartmentofPharmaceuticalSciences,FacultyofPharmacy, ChiangMaiUniversity,ChiangMai,Thailand;CenterofExcellencefor InnovationinAnalyticalScienceandTechnologyforBiodiversity-based EconomicandSociety(I-ANALY-S-T_B.BES-CMU),ChiangMaiUniversity, ChiangMai,Thailand
BavaniArumugam DepartmentofBiomedicalScience,FacultyofMedicine, UniversitiMalaya,KualaLumpur,Malaysia
SambeAshaDevi LaboratoryofGerontology,DepartmentofZoology,Bangalore University,Bangalore,Karnataka,India
PinarAtukeren IstanbulUniversity-Cerrahpasa,FacultyofPharmacy,Cerrahpasa MedicalFaculty,DepartmentofMedicalBiochemistry,Istanbul,Turkey
YaseminAydin DepartmentofBiology,FacultyofScience,IstanbulUniversity, Istanbul,Turkey
RatanaBanjerdpongchai DepartmentofBiochemistry,FacultyofMedicine,Chiang MaiUniversity,ChiangMai,Thailand
WittayaChaiwangyen DivisionofBiochemistry,SchoolofMedicalSciences, UniversityofPhayao,Phayao,Thailand
SuphachaiCharoensin DivisionofNutritionandDietetics,SchoolofMedical Sciences,UniversityofPhayao,Phayao,Thailand
YengChen DepartmentofOral&CraniofacialSciences,FacultyofDentistry, UniversityofMalaya,KualaLumpur,Malaysia
IkennaChikeokwu DepartmentofPharmacognosy,FacultyofPharmaceutical Sciences,EnuguStateUniversityofScienceandTechnology(ESUT),Agbani, EnuguState,Nigeria
OradaChumphukam DivisionofBiochemistry,SchoolofMedicalSciences, UniversityofPhayao,Phayao,Thailand
YaseminUlkuDikbasan DepartmentofBiology,InstituteofGraduateStudiesin Sciences,IstanbulUniversity,Istanbul,Turkey
PracheeDubey GovernmentG.I.College,Malwan,Fatehpur,UttarPradesh,India
UchennaEstellaOdoh DepartmentofPharmacognosyandEnvironmentalMedicines, FacultyofPharmaceuticalScences,UniversityofNigeria,Nsukka,Nigeria
GeetikaGarg DepartmentofZoology,SavitribaiPhulePuneUniversity,Pune, Maharashtra,India
xvi Listofcontributors
ManisekaranHemagirri InstituteforResearchinMolecularMedicine (INFORMM),UniversitiSainsMalaysia,USM,PulauPinang,Malaysia
NapapanKangwan DivisionofPhysiology,SchoolofMedicalSciences,University ofPhayao,Phayao,Thailand
JagatR.Kanwar DepartmentofBiochemistry,AllIndiaInstituteofMedical Sciences(AIIMS),Bilaspur,HimachelPradesh,India
ArpitaKonar CSIR-InstituteofGenomics&IntegrativeBiology,NewDelhi,Delhi, India
PrachyaKongtawelert DepartmentofBiochemistry,FacultyofMedicine,Chiang MaiUniversity,ChiangMai,Thailand
PimpisidKoonyosying OxidativeStressResearchCluster,Departmentof Biochemistry,FacultyofMedicine,ChiangMaiUniversity,ChiangMai, Thailand;ClusterofHighValueProductfromThaiRiceandPlantforHealth, ChiangMaiUniversity,ChiangMai,Thailand
UmahRaniKuppusamy DepartmentofBiomedicalScience,FacultyofMedicine, UniversitiMalaya,KualaLumpur,Malaysia
SuparnaMandal LaboratoryofGerontology,DepartmentofZoology,Bangalore University,Bangalore,Karnataka,India
Theodoramba DepartmentofPharmacognosy,FacultyofPharmaceuticalSciences, EnuguStateUniversityofScienceandTechnology(ESUT),Agbani,EnuguState, Nigeria
MohammadMurtazaMehdi DepartmentofBiochemistry,Schoolof BioengineeringandBiosciences,LovelyProfessionalUniversity,Phagwara, Punjab,India
ChukwumaMichealOnyegbulam DepartmentofPharmacognosyand EnvironmentalMedicines,FacultyofPharmaceuticalScences,Universityof Nigeria,Nsukka,Nigeria
LonginusC.Odoh DepartmentofAccountancy,UniversityofNigeria,Nsukka, Nigeria
BanuOrtaYilmaz DepartmentofBiology,FacultyofScience,IstanbulUniversity, Istanbul,Turkey
BishnuKumarPandey DepartmentofPhysics,SPMCollege,Universityof Allahabad,Prayagraj,Allahabad,UttarPradesh,India
KantiBhooshanPandey CSIR-CentralSalt&MarineChemicalsResearchInstitute, Bhavnagar,Gujarat,India
NarisaraParadee OxidativeStressResearchCluster,DepartmentofBiochemistry, FacultyofMedicine,ChiangMaiUniversity,ChiangMai,Thailand
ThanawatPattananandecha DepartmentofPharmaceuticalSciences,Facultyof Pharmacy,ChiangMaiUniversity,ChiangMai,Thailand;CenterofExcellence forInnovationinAnalyticalScienceandTechnologyforBiodiversity-based EconomicandSociety(I-ANALY-S-T_B.BES-CMU),ChiangMaiUniversity, ChiangMai,Thailand
Listofcontributors xvii
KomsakPintha DivisionofBiochemistry,SchoolofMedicalSciences,University ofPhayao,Phayao,Thailand
PeraphanPothacharoen DepartmentofBiochemistry,FacultyofMedicine,Chiang MaiUniversity,ChiangMai,Thailand
TreetipRatanavalachai DepartmentofPreclinicalSciences(Biochemistry),Faculty ofMedicine,ThammasatUniversity,Pathumthani,Thailand
SyedIbrahimRizvi DepartmentofBiochemistry,UniversityofAllahabad, Allahabad,UttarPradesh,India
ObinnaSabastineOnugwu DepartmentofPharmacognosy,Facultyof PharmaceuticalSciences,EnuguStateUniversityofScienceandTechnology (ESUT),Agbani,EnuguState,Nigeria
NidhiSachan CellandNeurobiologyLaboratory,DepartmentofBiochemistry, InstituteofScience,BanarasHinduUniversity,Varanasi,UttarPradesh,India; ToxicogenomicsandPredictiveToxicologyLaboratory,SystemsToxicologyand HealthRiskAssessmentGroup,CSIR-IndianInstituteofToxicologyResearch (CSIR-IITR),VishvigyanBhawan,Lucknow,UttarPradesh,India
ChalermpongSaenjum DepartmentofPharmaceuticalSciences,Facultyof Pharmacy,ChiangMaiUniversity,ChiangMai,Thailand;CenterofExcellence forInnovationinAnalyticalScienceandTechnologyforBiodiversity-based EconomicandSociety(I-ANALY-S-T_B.BES-CMU),ChiangMaiUniversity, ChiangMai,Thailand
SreenivasanSasidharan InstituteforResearchinMolecularMedicine(INFORMM), UniversitiSainsMalaysia,USM,PulauPinang,Malaysia
Shanmugapriya InstituteforResearchinMolecularMedicine(INFORMM), UniversitiSainsMalaysia,USM,PulauPinang,Malaysia
RavichandraShivalingappa DivisionofBiology,IndianInstituteofScience EducationandResearch,Tirupati,AndhraPradesh,India
EwaSikora LaboratoryofMolecularBasesofAging,NenckiInstituteof ExperimentalBiology,PolishAcademyofSciences,Warsaw,Poland
PadmanabhSingh CentreofAdvancedStudy,DepartmentofZoology,Instituteof Science,BanarasHinduUniversity,Varanasi,UttarPradesh,India;Departmentof Zoology,IndiraGandhiNationalTribalUniversity,Amarkantak,Madhya Pradesh,India
PrabhakarSingh DepartmentofBiochemistry,FacultyofScience,VeerBahadur SinghPurvanchalUniversity,Jaunpur,UttarPradesh,India
SandeepSingh DepartmentofBiochemistry,UniversityofAllahabad,Allahabad, UttarPradesh,India;HadassahBiologicalPsychiatryLaboratory,HadassahHebrewUniversityMedicalCenter,Jerusalem,Israel
BrijeshSinghChauhan CellandNeurobiologyLab oratory,Departmentof Biochemistry,InstituteofScience,BanarasHinduUniversity,Varanasi, UttarPradesh,India
BhagavathiSundaramSivamaruthi InnovationCenterforHolisticHealth, Nutraceuticals,andCosmeceuticals,FacultyofPharmacy,ChiangMaiUniversity, ChiangMai,Thailand
SomdetSrichairatanakool OxidativeStressResearchCluster,Departmentof Biochemistry,FacultyofMedicine,ChiangMaiUniversity,ChiangMai, Thailand;ClusterofHighValueProductfromThaiRiceandPlantforHealth, ChiangMaiUniversity,ChiangMai,Thailand
SaripellaSrikrishna CellandNeurobiologyLaboratory,Departmentof Biochemistry,InstituteofScience,BanarasHinduUniversity,Varanasi, UttarPradesh,India
BungornSripanidkulchai FacultyofPharmaceuticalSciences,KhonKaen University,KhonKaen,Thailand
ShailendraKumarSrivastava SamHigginbottomUniversityofAgriculture, Technology&Sciences,Prayagraj,Allahabad,UttarPradesh,India
MaitreeSuttajit DivisionofNutritionandDietetics,SchoolofMedicalSciences, UniversityofPhayao,Phayao,Thailand;ThaiVegetarianAssociation, Changpuak,ChiangMai,Thailand
M.K.Thakur CentreofAdvancedStudy,DepartmentofZoology,Instituteof Science,BanarasHinduUniversity,Varanasi,UttarPradesh,India
SubramanianThangaleela BehaviouralNeuroscienceLaboratory,Departmentof AnimalScience,SchoolofLifeSciences,BharathidasanUniversity, Tiruchirappalli,TamilNadu,India
BrahmKumarTiwari DepartmentofParamedicalSciences,SGTUniversity, Gurugram,Haryana,India
OrawanWanachewin DepartmentofBiochemistry,FacultyofMedicine,Chiang MaiUniversity,ChiangMai,Thailand
BuseYilmaz DepartmentofBiology,InstituteofGraduateStudiesinSciences, IstanbulUniversity,Istanbul,Turkey xviii Listofcontributors
Preface
Extendinglifespan/healthyaginghasbeenthegreatestwishofhumanssince evolution.Inthepastfewdecades,significantadvanceshavebeenseenin theexplorationoftheagingprocess,itscellularbiology,andbiomarkersof aging,whichhaveprovidedspecifictargetsthatcanbeleveragedforpossibleaginginterventions.Thereisnodoubtthataginginterventionismore complicatedthanfindingthecureforotherdiseases,sincetheagingprocess ishighlyheterochronic.Inaddition,variationsintheoriesexplainingthe agingprocess,thestrategiesbeingexercisedforanagingcure,or/andthe promotionofhealthyagingarealsohighlydiverse.However,interveningin agingisalwaysthenextfrontierincontemporarycureandwillremaintobe ofhigherimportancesinceagingnotonlyaffectsthelifestyleoftheindividualsadverselybutalsobringsdependencyonothersandcostlymedical expenses.
Althoughtheavailabilityofadvancedagecarefacilitieshasdelayedthe developmentandprogressionofagingcomplications,stillitisnotfeasiblefor alargegroupofthepopulationduetohighcosts.Inaddition,sideeffectsassociatedwiththesesyntheticremedieshaverestrictedtheirfrequentandsafe use.Insuchascenario,asustainablecurewithno/leastsideeffectsistheneed ofthehourtocombattheanticipatedfutureburdenofage-dependent complications.
Bioactivesfromplantsofferremar kablefeaturesincomparisonwith traditionalsyntheticmedicines whichendowbothadvantagesandchallengesfordrugdiscovery.Enormouss caffolddiversity,structuralcomplexity,andhighernumbersofH- bondacceptors/donorsprovidehigher molecularrigiditytothesebioactiv escomparedwithsyntheticcompounds, thesecharacteristicsarevaluableind rugdiscoverytacklingprotein-proteininteractions.
Thepresentbookisacomprehensivedescriptionoftheantiagingpotentialofplant-derivedbioactivecompounds,naturallypresentinfoodsand beverages,anditprovidesanupdateonaginginterventionbasedonnatural compounds,whichmaybeutilizedinplant-baseddrugdiscoveryagainstan agingandassociatedcomplications.Writtenbyaglobalteamofexperts,this bookmaybeanidealresourceforresearchersinthisarea.Thisbookhas22 chapters.Chapter1extendsanexpertopiniononagingprinciplesandinterventionalperspectives.Chapters2and22discussanti-agingstrategiesand
thepossibilityofplantbioactivesinantiagingdrugdiscoveryandthechallengesinvolved.Recently,plantpolyphenolshavegainedglobalinterestin aginginterventionduetotheirstrongantioxidativeandimmunomodulatory effects.However,scatteredandcontradictoryliteraturechallengestheconcurringresults.Chapter8exploresmoreonthistopic.Thebookalsocontainsdedicatedchapters9,12,and13onvariousantiagingmechanismsof actionofdifferentpolyphenols.
Neurologicalimpairmentsincludingcognitivedysfunctionareoneofthe majorcomplicationsduringaging,whichcompromisethehealth/lifespansas wellasthequalityoflifeofolderpopulationssignificantly.Chapters10,11, and17specificallydealwiththetherapeuticeffectsofplantbioactivesin counteractingneuroproblemsamongtheelderly.Chapter4focusesonthe advancesmadeindecipheringtheroleofgrapeseedsandgreenteabioactivesinmaintainingglucosehomeostasisinbloodandthebrainduringaging andattenuatingage-associateddisorders.Theimmunomodulatoryroleof plantbioactivesrelevanceinagingisincorporatedinChapter5.
Functionalfoodsrichinbioactivecompoundsarerecentlygainingmuch attentioninpromotinghealthandenhancinglifespan.Keepingthisrationale inminddedicatedChapters14,15,and21areincludedinthebook,which discussestheeffectivenessoffunctionalfoodsinpreventivecognitive impairmentsandimprovingbonehealthintheelderlyandrealisticresultsin clinicaltrialsinagingintervention.
Nanotechnologicalapproachestoenhancementofbioavailability,targeted deliveryandpreventionofbiotransformation,andmajorconcernsassociated withplantbioactivestodrugdevelopmentarediscussedinChapter19. Chapter20hasbeenincorporatedinthebooktobetterunderstandtheeffects ofdietarypatternsandassociatedbioactivesonagingandlongevityindifferentcontinentsoftheworld.Inadditiontotheestablishedcompounds,the antiagingpotenciesofnovelbioactivesarediscussedinChapter18, highlightingthereality,promises,andchallengesinapplyingthemasnutraceuticalorfunctionalanti-agingmolecules.Dietaryrestriction,vegetarian diet,andtheirrelationshipwithagingareexploredinChapter16.
Nutrigenomicsstudiesareimportantinunderstandingtheinteractionof nutrition/foodbioactiveswithlongevitygenes.Chapters3and6discusslongevitygenesandtheirinteractionwithplantbioactives,whichishelpfulin drugdiscovery.Recently,hormesisisintroducedincounterbalancingthe progressiveshrinkageofthehomeodynamicspace,whichistheultimate causeofaging.Chapter7dealswiththehormeticeffectsofplantbioactives inpromotinghealthyagingandlongevity.
Thisbookprovidescutting-edgeupdatedinformationandfutureperspectivesonplantbioactivesasemergingsourcesofleadcompoundsfornew drugdiscoveryagainstagingandrelateddiseases,whichofferpossiblehope forhealthandlongevity.
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WeextendourthankstoallourcontributorswhoprovideduswithsplendidchaptersinthisfieldandElsevier,Inc.formakingeveryefforttopublish thisbook,whenalargegroupofpopulationworldwideisconcernedwiththe age-associatedhealthissues. KantiBhooshanPandey MaitreeSuttajit
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Chapter1
Agingprinciplesand interventionalperspectives
EwaSikora
LaboratoryofMolecularBasesofAging,NenckiInstituteofExperimentalBiology,Polish AcademyofSciences,Warsaw,Poland
1.1Themessageofgeroscience
Agingischaracterizeddemographicallybyincreasedmortalityanddecreased reproductivesuccesswithadvancingage.Sincetheforceofselection declineswithage,aging,accordingtothenotmutuallyexclusiveevolutionarytheories,evolvesduetomutationaccumulation(mutationaccumulation theory)orasabenefittotheearlylifefitness(antagonisticpleiotropytheory) (Flatt&Partridge,2018).
Agingisaseeminglyuniversalbiologicalphenomenon,whichbegins aftersexualmaturityandgraduallyleadstoadeclineinvariousfunctioning (althoughtheexamplesofanimalsthatdolivewithoutcharacteristicsymptomsofdecreasingfunctionalityandreproductionhavebeendescribedand arecategorizedasnegligiblesenescence)(Finch,2009).Withage,thecharacteristicfunctionalchanges,knownasbiological“hallmarks”ofaging, occuratboththemolecularandcellularlevels.Recently,nineindicative hallmarksthatrepresentcommondenominatorsofagingindifferentorganisms,withspecialemphasisonmammalianaging,havebeenproposed. Namely,genomicinstability,telomereattrition,epigeneticalterations,lossof proteostasis,deregulatednutrient-sensing,mitochondrialdysfunction,cellular senescence,stemcellexhaustion,andalteredintercellularcommunication. Accordingtotheauthorswhoproposedthesehallmarks:“amajorchallenge istodissecttheinterconnectednessbetweenthecandidatehallmarksand theirrelativecontributiontoaging,withthefinalgoalofidentifyingpharmaceuticaltargetstoimprovehumanhealthduringagingwithminimalsideeffects”(Lo ´ pez-Ot´ınetal.,2013).
Thesamegoalofimprovingagingconditionswaspursuedbyotherleadersofbiogerontology,whoassumedthatagingisthemainriskfactorfor manygeriatricsyndromes(GSs)andage-relateddiseases(ARDs),suchas
PlantBioactivesasNaturalPanaceaagainstAge-InducedDiseases. DOI: https://doi.org/10.1016/B978-0-323-90581-7.00002-5
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sarcopenia,osteoporosis,frailty,cardiovasculardiseases,metabolicsyndrome,osteoarthritis,neurodegenerativediseases,andsomecommoncancers,suchasbreast,prostate,andcoloncancers.Manyofthemolecularand biochemicalmechanismsthatdeterminetherateofagingwerealsounder investigationinlaboratoriesthatfocusedsolelyonindividualchronicdiseases.Thuscollaborationsbetweenscientistsworkingonagingandchronic diseaseshavebecometheneedofthehour.Accordingly,aninterdisciplinary scienceattheinterfaceofnormalagingandchronicdiseasewascreatedand termed“geroscience.”Geroscienceseesagingastheprimarycauseofmany chronicdiseasesoflaterlife.Thusthepremiseunderlyinggeroscienceisthat bytargetingagingwecanpreventordelaymultiplechronicdiseasesand deathsimultaneously(Kennedyetal.,2014).Indeed,invariousexperimental interventionsinlaboratorymodels,itispossibletoslowandpartiallyreverse thefeaturesofaging(Childsetal.,2015).Thebasicmechanismssharedby agingandARDs/GSshavebeenidentifiedas“sevenpillars,”whichinclude adaptationtostress,lossofproteostasis,stemcellexhaustion,metabolism derangement,macromoleculardamage,epigeneticmodifications,andinflammation(Kennedyetal.,2014).Thegoalofgeroscienceistopromotehealthy aging;however,itisgoodtorealizethathealthspanandlonglifespan(longevity)areintimatelyrelated,asindividualswholiveexceptionallylong tendtobehealthyformuchoftheirlives(Franceschietal.,2018).Onthe otherhand,increasedlifeexpectancyobservedduringthepastfewcenturies (althoughdisturbedrecentlybytheCOVID-19pandemic(Maroisetal., 2020))resultedinincreasedmorbidityanddisabilityinoldandveryoldpeople(Chengetal.,2020).
Agingistheresultofacontinuousinteractionbetweenanindividual’s “geneticmakeup”andenvironmentalfactors,characterizedbylifelongdamageaccumulationandprogressivelossoftissueandorganfunctionality (Kirkwood,2017).Indeed,longevityhasheritablecomponents,however, theirinfluencehasbeenoverestimatedforalongtime,andisnowthoughtto benomorethan10%(Melzeretal.,2020).AlsoARDshaveaheritability component,butitdependsverymuchonthetypeofdisorder(Tenesa& Haley,2013).Nonetheless,relativelylowheritabilityofthedurationoflifespanstrengthensthelong-lastingassumptionthatagingisaplasticprocess, whichcanbemodifiedbylifestyleandenvironment(Kirkwood,2017).Thus prolongingnotonlylifespanbut,firstofall,healthspan,ispossible,since accordingtogeroscience(letusrepeat)both“physiological”and“pathological”agingsharethesamebasicmolecularandcellularmechanisms,and shouldbeconsideredasthesameprocessbutoccurringwithadifferentrate dependingondiversegeneticbackgroundandlifestyle(Franceschietal., 2018).Fromtheplethoraofanimalandhumandatacollectedsofar,it emergesthatthereareseveralcommonmolecularandcellulartargets,which atleastpartiallyoverlapwithcommonaginghallmarks,andwhichcanbe modifiedbylifestyle.Theseincludespecialdiets,food,nutrition,physical
activity,andpharmacologicalapproach.Someofthebeneficialinterventions andtheirtargetsarebrieflyreviewedbelow.
1.2Rejuvenationbydiet
AnoldChineseproverbsays:showmewhatyoueatandI’lltellyouwho youare.Itcanbeparaphrasedasfollows:showmewhatandhowyoueat, andIwilltellyouwhatageyouare.Wemeanthebiologicalage,whichis differentfromthecalendarage.Eachofushasourownaginghistoryreflectingourgeneticbackgroundandlifestyle.Thematteristofollowtherulesof life,whichwillallowustodieyoungaslateaspossible.Epidemiological, clinical,andpreclinicalstudiesactuallyshowedthatwhatweeatandhow muchweconsumecontributestodeterminingourhealthspan(Ekmekcioglu, 2020).Manipulationofanutritionallybalanceddiet,whetherbyalteringthe caloricintakeormealtiming,canleadtoadelayintheonsetandprogressionofdiseasesandincreaselifeinmostorganisms(DiFrancescoetal., 2018).
Thebeneficialeffectsofcaloricrestriction(CR)onlifespanhavebeen discoveredmorethanacenturyago(Osborneetal.,1917).Later,thepositiveeffectofCRonhealthspanandlifespanhasbeendocumentedinmany modelorganisms,suchasyeast, Caenorhabditiselegans, Drosophilamelanogaster,mice,andprimates,pointingtothestrongevolutionaryconservationofthecommonmechanismsconnectingfoodintaketolongevity(De Cabo&Mattson,2019).CRinvolvesa20% 40%reductionincalorie intakewithoutcausingmalnutrition.Also,inhumans,datafromobservationalandrandomizedclinicaltrialsindicatethatCRelicitsthesame mechanismsandbeneficialeffectsasinanimalmodelsoflongevity. ModerateCRinhumansamelioratesmultiplemetabolicandhormonalfactorsthatareimplicatedinthepathogenesisoftype2diabetes,cardiovascular diseases,cancer,andneurologicaldisorders,theleadingcausesofmorbidity, disability,andmortality(Dorlingetal.,2020;Mostetal.,2017).
Foodprovidesuswithnutrientsandenergynecessaryforgrowth,reproduction,andthesustainenceoflife.Moreover,nutrientsregulatemanyprocessesonthemolecular,cellular,andorganismallevelsviaso-callednutrient signalingpathways,whichinfluencetheagingprocess.Genetic,pharmacological,ordietaryinterventionstargetingnutrientsignalingpathwayshave beenshowntoattenuateaginginmanyorganisms(Johnson,2018).Theinsulin/insulin-likegrowthfactor1(IGF-1)signalingpathway(ILS)wasthefirst definedgeneticpathwayregulatingagingandARDsinmodelorganisms (Kenyon,2011).Additionalplayershavesincebeenidentified,suchas mTOR(mechanistictargetofrapamycin),AMPK(50 AMP-activatedprotein kinase),andsirtuins,asrobustmediatorsoftheprotectiveeffectsofdietary restriction(Johnson,2018).Allthesesignalingpathwaysaresomehow interconnected.
