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Telomeres, Aging and Disease: Deleterious Effects of ...€¦ · cells, and some immune cells,...

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Review Article Nancy B. Ray, PhD, Science Of3icer, McCord Research unique region on the end of chromosomes known as the telomere is associated with aging. Telomere length has been used as a prognostic indicator for age-related mortality and morbidity risk in humans, and strikingly, it has been shown that older adults with below average leukocyte telomere length have more than a three-fold increased risk for early mortality 1 . Telomeres consist of repeating hexamer DNA sequences and a unique protein complex (shelterin) that protects chromosome ends from being recognized as DNA double-strand breaks that can trigger DNA damage responses. The telomeric DNA also folds back on itself to forms loops that protect the telomere ends and prevent chromosome end fusions. In humans the average telomere length ranges from 10 to 15 kilobases. In normal human cells excluding germ cells, stem cells, and some immune cells, telomeres shorten with each cell division during the typical aging process due to incomplete replication of the 3’ end of chromosomes and DNA degradation. This shortening or attrition continues until the telomere reaches a critical length that results in cell-cycle arrest and senescence or apoptosis. Telomere attrition represents a molecular clock that limits the replicative capacity of normal cells. If apoptosis does not occur and cells continue to divide, the resultant genomic Telomeres, Aging and Disease: Deleterious Effects of Stress and a Lack of Sleep A *McCord Research has three U.S. and worldwide patents pending on this research instability causes chromosomal abnormalities including chromosome-end fusions 2 . Decreased telomere length has been associated with several diseases including dyskeratosis congenita, ataxia-telangiectasia, Fanconi anemia, and cancer 2,3,4 . Shortened telomeres have also been associated with oxidative stress, in3lam- mation, psychological stress, and lack of sleep 5,6,7,8,9,10,11 . It has been suggested that oxidative stress is a major cause of telomere shortening 5 . Telomeres are susceptible to oxidative stress that causes telomere shortening beyond molecular clock-associated attrition, due to the higher content of guanine nucleotides in telomeres, which are sensitive to free-radical damage 6 .
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Page 1: Telomeres, Aging and Disease: Deleterious Effects of ...€¦ · cells, and some immune cells, telomeres shorten with each cell division during the typical aging process due to incomplete

Review Article

NancyB.Ray,PhD,ScienceOf3icer,McCordResearch

unique region on the end of chromosomes known as the telomere

is associated with aging. Telomere length has been used as a prognostic indicator for age-related mortality and morbidity risk in humans, and strikingly, it has been shown that older adults with below average leukocyte telomere length have more than a three-fold increased risk for early mortality1. Telomeres consist of repeating hexamer DNA sequences and a unique protein c o m p l e x ( s h e l t e r i n ) t h a t p r o t e c t s chromosome ends from being recognized as DNA double-strand breaks that can trigger DNA damage responses. The telomeric DNA also folds back on itself to forms loops that protect the telomere ends and prevent chromosome end fusions. In humans the average telomere length ranges from 10 to 15 kilobases.

Innormalhumancellsexcludinggermcells,stemcells,andsomeimmunecells, telomeresshortenwith each cell division during the typical agingprocess due to incomplete replication of the 3’endofchromosomesandDNAdegradation. Thisshortening or attrition continues until thetelomere reachesa critical length that results incell-cycle arrest and senescence or apoptosis.Telomere attrition represents a molecular clockthat limits the replicative capacity of normalcells. If apoptosis does not occur and cellscontinuetodivide,theresultantgenomic

Telomeres, Aging and Disease: Deleterious Effects of Stress and a Lack of Sleep

A

*McCordResearchhasthreeU.S.andworldwidepatentspendingonthisresearch

instability causes chromosomal abnormalitiesincludingchromosome-endfusions2. Decreased telomere length has been associatedwith several diseases including dyskeratosiscongenita,ataxia-telangiectasia,Fanconianemia,and cancer2,3,4. Shortened telomeres have alsobeen associated with oxidative stress, in3lam-mation, psychological stress, and lack ofsleep5,6,7,8,9,10,11. It has been suggested thatoxidative stress is a major cause of telomereshortening5. Telomeres are susceptible tooxidativestressthatcausestelomereshorteningbeyondmolecularclock-associatedattrition,dueto the higher content of guanine nucleotides intelomeres, which are sensitive to free-radicaldamage6.

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Review ArticleIn addition, oxygen free radicals and reactiveoxygenspecies(ROS)canproducesingle-strandbreaksinDNA,whicharenoteffectivelyrepairedin telomeres12. DNA damage responsestriggered by damaged telomeres may alsoenhance mitochondrial dysfunction andoxidative stress4. Viniferamine® supplementscontain potent antioxidant ingredients that canhelpdecreaseoxidativestressandin3lammationincluding oleuropein from olives13, trans-resveratrol from grapes14, EGCG from greentea15, curcumin from turmeric16, sulforaphanefrom broccoli17, melatonin18, N-acetyl-L-cysteine19, methylsufonlymethane20, and L-Taurine21.

As previously described, telomere attritioncontinues with aging until cells becomesenescent. Cellular senescence is a state ofproliferative arrest, in which cells have ceaseddividing but remain metabolically active andnon-apoptotic. Senescent cells secrete growthfactors and pro-in3lammatory cytokinestriggeredbypersistentDNAdamage responses.Cytokinessecretedbysenescentcellshavebeenassociated with tissue dysfunction, in3lam-mation,andage-relateddiseases4.

Chronic in3lammation is also thought to resultfrom oxidative stress, and has been linkedwithmany diseases including cardiovascular disease,diabetes, and neurodegenerative diseases suchas Alzheimer’s disease and Parkinson’s disease22,23,24. Furthermore,shorttelomereshavebeenlinked with diseases associated with chronicin3lammation including diabetes, cardiovasculardisease, Alzheimer’s disease and as mentionedpreviously, cancer25,26,27,4. The powerfulantioxidants in Viniferamine® supplements canreduceoxidativestress thatmay lead tochronicin3lammation.

Short telomeres have also been linked withchronic psychological stress28. Psychologicalstress,whichcanleadtoanxietyanddepression,can result from many sources including stressrelated to caregiving, low socioeconomic status,or exposure to trauma29. Adults experiencingchronicstresshaveimpairedimmuneresponsesandwoundhealing,aswellaselevated levelsofchronic in3lammation9. Psychological stressincreases the risk of many diseases includingcardiovascular, autoimmune and neurodegener-ativediseases28.

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Review Article

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Viniferamine®Mood Support contains powerfulantioxidantsandothernutritionalingredientstohelp support health and decrease feelings ofanxiety and depression, including magnesium,which has been found to promote feelings ofcalm and wellbeing 29, and curcumin that hasanti-depressant properties30. Viniferamine®Mood Support also includes B vitamins such asfolateandB12.Ithasbeenshowninstudiesthatlow levels of folate are associated withdepressive symptoms31, and B12 de3iciency isassociated with a two-fold increased risk ofseveredepressivedisorders32.

Dif3iculty with sleeping is one of the mostcommonproblemsamongmiddle-agedandolderadults.Olderadultsfrequentlytakelongertofallasleep,wakemoreofteninthenight,andhavealowerquality of sleep thanyounger individuals.Disruptionoftheregularsleep-wakecycle,whichis regulated by the circadian rhythm, has beenshown to affect immune functions, and sleepdeprivation has been shown to increasecirculating levelsof in3lammatorymarkers33. Inaddition, increasing evidence suggests thatrotating night shifts and sleep deprivation arepotential risk factors for metabolic disorders,cardiovascular disease, and cancers34. Shorterdurationsinsleephavealsobeenassociatedwithshortertelomerelengthsincomparisontolongerdurations33,34. Viniferamine® Sleep Support includes a naturallevel of melatonin, which is well known for itsimportant role in maintaining the circadianrhythm. In addition, melatonin has immunestimulatory effects and anti-in3lammatoryfunctions18. Viniferamine® Sleep Support alsoincludesmagnesium and vitaminD,which bothhelp support sleep and immune functions35,36.Furthermore, vitamin D helps regulatein3lammatoryresponses37,andmagnesiummayplayaroleinregulatingtheseresponses38.

Viniferamine® Sleep Support also includescurcumin, which has been associated withpotentialincreasesintelomerelength39.

References1.PLoSOne2011;6:e19687.2.CurrOpinOncol2013;25:93-98. 3. FEBS J 2013; 280: 3180-3193. 4. CancerEpidemiol Biomarker Prev 2011; 20: 1238-1250. 5. ExpGerontol2007;42:1039-1042.6.FreeRadBiolMed2011;50: 730-735. 7. PLoS One 2014; 9: e87348. 8.Psychoneuroendocrinol 2006; 31: 277-287. 9. MolPsychiatry2014; 10.JAgingRes2011;2011:ID721390.11.PLoSOne2012;7:e47292.12.SciAdvEnvironToxicolExotoxicolIssues2010(www.chem-tox-ecotox.org)13.IntJMolSci2014;15:18508-18524.14.MolNeurobiol2010;41: 375-383. 15. Oxid Med Cell Long 2012; 2012: ID560682.16. IntJBiochemCellBiol2009;41:40-59.17. JNutr Biochem 2014; 25: 824-833.18.FASEB J 2010; 24:3603-3624. 19. Biochim Biophys Acta 2013; 1830:4117-4129.20.JIntSocSportsNutr2012;9:46-21.AdvExpMedBiol2013;775:19-2722.WorldJCardiol2014;6:462-477.23.DiabetesMetabSyndrObes2014;7:25-34.24.CurrNeuropharmacol2009;7:65-74.25.AgingMale2012;15:54-58.26.NutrMetabCardiovascDis2014;27.Neuromolecular Med 2013; 15: 25-48. 28. Nature 2012;490:169-171.29.BrainBehavImmun2012;26:573-579.30. Sci World J 2009; 9: 1233-1241. 31. Biol Psychiatry2005; 58: 679-685. 32. Am J Psychiatry 2000; 157:715-721.33.SLEEP2014;37:65-70.34.PLoSOne2011;6: e23462. 35. Nutrients 2013; 5: 2502-2521. 36. Eur JClinNutr2003;57:1193-1197.37.AmJClinNutr2007;86: 1430-1425. 38. Nutr Res 2006; 26: 193-196. 39.Mutation Res 2009; 661: 25-34. 40. Clin Therapeutics2012; 34: 849-856. 41. Eur J Pharmacol 2010; 641:199-206.42.IntJCardiol2013;162:199-209.

Higher serum levels of and treatment withv i tamin D are associated with longertelomeres37,40. All Viniferamine® supplementsinclude EGCG from green tea, which has alsobeenfoundtoinhibittelomereattrition41,42. In summary, many of the ingredients includingantioxidants and vitamins in the Viniferamine®supplements canhelpdecreaseoxidative stress,in3lammation,psychologicalstressanddif3icultysleeping, which are all associated with shorttelomeres.Inaddition,vitaminD,curcumin,andEGCG have been linked with longer telomeres.Thelengthoftelomereshasbeencorrelatedwithage-related morbidity and mortality risks.Viniferamine® supplements can help keep cellshealthy including immune cells,which can helpreducethelikelihoodofdiseasesassociatedwithoxidativestressandin3lammation.

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Review Article

www.viniferamine.comCopyright 2017 McCord Research, Coralville, IA

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