_______________________________________________________ ________ Originally published in Dr. Robert Rowen's Second Opinion Newsletter, June 200 Dr. Robert Rowen !hat does the 200" Nobel #ri$e in %edicine ha&e to do with you and %e' ( lot) *his particular pri$e concerned a %a+or disco&ery about how you and , grow old. !hat's %ore, it gi&es us real insight in how we can re&erse the aging process with ine-pensi&e supple%ents and an easy treat%ent you can do at ho%e. On October ., 200", three (%ericans won the pri$e /or a disco&ery they %ade in the "00s. !hat was the disco&ery' *he telo%ere. *he telo%ere is the 1tail1 o/ each chro%oso%e in your cells. 2or decades, scientists thought that this section was +ust +un3 4non/unctional5 DN(. 6ut recent disco&eries ha&e /ound +ust the opposite. *his seg%ent o/ your DN( is critical /or healthy cell di&ision and /unction. (nd /or healthy, youth/ul li&ing. DN( pro&ides the te%plate /or all your proteins and en$y%es. 6ut, the telo%ere does not code /or these. ,t acts %ore li3e the cap to your shoelace. !ithout the cap, your shoelace would unra&el and beco%e useless. *he telo%ere is li3e the handle o/ the chro%osone where the DN( transcribing en$y%es attach. *hese en$y%es acti&ate gene /unction. *hat leads to %a3ing proteins and en$y%es. 6ut, with the telo%ere, there's a proble%. 7ach ti%e your cell di&ides, the telo%ere shortens. 7&entually, it shortens so %uch that the chro%oso%e can't /unction. !hen this happens, the DN( coil can /igurati&ely 1unra&el.1 ,t beco%es useless. *elo%ere length is absolutely critical /or how your chro%oso%es beha&e 8 and how %any ti%es the cell can di&ide. *he shorter the telo%ere, the less gene acti&ity you ha&e. !hen you were young your telo%eres were long. (s you age, and your cells di&ide, all your telo%eres shorten, e-cept /or reproducti&e cells. ,/ they shortened, we would be born 9uite old a/ter +ust a /ew generations. ( special en$y%e called telo%erase can restore telo%eres. *elo%erase is /ully /unctional in reproducti&e cells. Ste% cells also ha&e signi/icant a%ounts o/ telo%erase. *hat's because they are responsible /or replacing cells and need to di&ide /re9uently. :owe&er, e&en their telo%erase acti&ity wanes with age. Ste% cells get old as well. ;ost o/ your cells co%e into the world with a preset nu%ber o/ di&isions 4around <05. (s your telo%eres shorten, your cells lose their ability to generate the en$y%es and proteins o/ youth. !hen your telo%eres get too short, your cell beco%es senescent. *hat %eans it no longer di&ides. ,t's old and /eeble. ,n other words, telo%ere shortening is a %a+or 3ey to the aging process) :ealthy telo%ere /unction 3eeps you at a healthy distance /ro% cancer. *his is the yin and yang o/ aging. !e are not %eant to li&e /ore&er. =ells nor%ally are not %eant to di&ide /ore&er. =ancer cells are the e-ception. *hey ha&e /igured out a way to acti&ate telo%erase so that they can di&ide inde/initely. ,/ we could /igure out a way to do that with our healthy cells, it would 3eep us %ore youth/ul, while at the sa%e ti%e, it would ward o// cancer. *he process beco%es 1unhealthy1 when, due to /actors ,'&e discussed in these pages 4such as to-ins, stress, and bad nutrition5, your cells brea3 /ree o/ >od? designed controls. !ouldn't it be great i/ we could slow your telo%ere shortening process, or acti&ate telo%erase' *he latter would lengthen your telo%eres. !ell, there is a way. :igher le&els o/ ho%ocysteine see% to inacti&ate telo%erase. @ou can lower ho%ocysteine with &ita%ins 62, 6< and /olic acid. ,/ these don't lower your ho%ocysteine, consider other %ethylating supple%ents li3e S(;e, ;S; and betaine. *hey %ight do the +ob /or your particular bioche%istry. #lease consult your integrati&e physician about this. Other supple%ents ,'&e discussed and reco%%ended in these pages can enhance telo%erase acti&ity. >reen tea is %y /a&orite be&erage. ,t supports longer telo%eres. *hose who drin3 the e9ui&alent o/ three cups per day ha&e telo%eres, on a&erage, /i&e years longer 4younger5 than those drin3ing only a 9uarter cup per day. @ou 3now how %uch , ra&e about green tea. , drin3 it al%ost e&ery day. Aita%in D is another o/ %y reco%%ended nutrients. ,t, too, can lengthen telo%eres. Scientists e-a%ined a group o/ wo%en aged B? 0", with an a&erage age o/ C".C. !o%en with the highest le&els o/ &ita%in D had telo%eres /i&e years longer than wo%en in the lowest concentrations. (nd, this was a twin?based study helping to re%o&e any genetic pre?bias to the study. 6ut there %ight be so%ething /ar %ore power/ul than any supple%ent out there /or %odulating telo%erase acti&ity. ,t's so%ething ,'&e told you about %any ti%es in the past. ,t's %y belo&ed o-idation therapy) :ow and why %ight o-idation therapy induce longer telo%eres' ,t has to do with the en$y%e SOD. SOD 4supero-ide dis%utase5 is an antio-idant en$y%e. ,t's absolutely critical /or protecting cells /ro% routine co%bustion o/ o-ygen, carbon, and hydrogen. O$one sti%ulates SOD. *his protects and pro%otes greater telo%erase acti&ity. ,n 2002, a >er%an study showed that higher le&els o/ e-tracellular SOD slowed telo%ere shortening. 6ut that's not all. O-idation therapy also increases the nitric o-ide 4NO5 in your endothelial cells. *hese are the cells that line your arteries. NO 3eeps your arteries dilated. (nd higher NO le&els increase telo%erase acti&ity. ;y o$one %entor and researcher, Aelio 6occi, wrote that o$one therapy %ay acti&ate your own critical ste% cells. :e said it induces NO synthesis. *his can pro%ote regeneration o/ tissues su//ering /ro% a lac3 o/ o-ygen. ,'&e ta3en o-idation therapy inter%ittently throughout the years. ;y lab and blood pressure nu%bers belie %y chronological age. 4:owe&er, , credit %y Di&ing 2oods Diet the %ost.5 !ith this in/or%ation, ,'% now ta3ing o$one on a regular basis 4at least once a wee35, by rectal insu/lation. , could do it by ,A, but ,'&e chosen the /or%er. Rectal insu//lation is so%ething you can do at ho%e as well. O$one 1%odulates1 your bioche%ical processes. *hat %eans it helps your body per/or% at its ideal le&el. Drugs don't %odulate. *hey /orce things, which can result in terrible to-ic e//ects. Donge&ity Resources in =anada 4B00?.CE?EE"B5 %a3es o$one water puri/iers. 6y si%ply attaching a catheter to the o$one line, you can direct the gas into your lower intestine rather than a /las3 o/ water. Rectal o$one is not as potent as blood o$one therapy. 6ut, scientists repeatedly ha&e shown its e//ecti&eness on circulation, i%%une acti&ity, and anti?in/ection. 7&en gi&en rectally, ,'% sure its e//ects will result in greater SOD production, su//icient to trigger %ore telo%erase acti&ity. @ou can read %ore about using o$one at ho%e on %y website. @ou also can cheaply assist telo%erase acti&ity with the /ollowing supple%entsF *a3e @es 72(), /our to si- capsules daily in di&ided doses. *hen ta3e seleniu% 4200?C00 %cg daily5, 3eep your ho%ocysteine below 0 4with the a/ore%entioned supple%ents5, and adhere to a %ostly Di&ing 2oods diet 4which is rich in SOD5. =onsider green tea capsules 4one daily5. (nd %a3e sure your &ita%in D le&el is in the upper 9uarter o/ your lab's re/erence range. @ou can order @es 72(), green tea capsules, and &ita%in D /ro% (d&anced 6ionutritionals 4B00?0"?EE".5. ,/ you are interested in ha&ing your white blood cell telo%eres e&aluated, Spectracell Daboratories has a con&enient test. #lease call B00?220?.220 to ha&e a test 3it %ailed to you and your blood drawn in your own ho%e. No doctor's appoint%ent necessary. , +ust did the test. ,t's &ery easy. (nd ,'% delighted to report that %y anti?aging li/estyle wor3s. ;y telo%eres are the length o/ the a&erage E. year old G and ,'% <0) No wonder , can al%ost 3eep up with %y 2B?year?old daughters on an arduous 0 %ile cross?country s3i trail. Re/F =irculation Research. 2000HB0F.C0H 6r. J. Nut. 200 January 40E545H (% J. =lin Nutr. 2000, No&e%berHB<4.5H O$one, ( New Drug, Springer 200.. Dr. Rowen is a #hi 6eta Iappa graduate o/ Johns :op3ins Jni&ersity and the Jni&ersity o/ =ali/ornia at San 2rancisco. :e has been board certi/ied and recerti/ied by the (%erican 6oards o/ 2a%ily #ractice and 7%ergency ;edicine. :e is currently certi/ied by the (%erican 6oard o/ =linical ;etal *o-icology. :e also ser&ed on the (las3a State ;edical 6oard. Dr. Rowen is 3nown as 1*he 2ather o/ ;edical 2reedo%1 /or pioneering the nation's /irst statutory protection /or alternati&e %edicine in ""0. Dr. Rowen also edits Second Opinion, an alternati&e %edicine newsletter. :e /ocuses on big brea3throughs that really wor3, o/ten years be/ore they're co&ered anywhere else. *o subscribe, &isit the Second Opinion newsletter web site or call B00?0"?ECC.. ,/ you are interested in a personal phone consultation with Dr. Rowen, please call his ad%inistrati&e o//ice in =ali/ornia at 000?.0B?00B0 40F00 a.%. 8 EF00 p.%. #S*, ;on?*hurs.5 /or a schedule and rates. ______________________________________________________________________ __________ Telomeres and Telomerase in Antiaging Science S*7#:7N :OD* ;D, Distinguished #ro/essor o/ ;edicine 47%erite5, Scienti/ic (d&isor, Natural =linician DD= and Aitacost.co% *he 6asics *elo%eres are DN( caps on linear chro%oso%es that /unction to pre&ent aberration or loss genetic in/or%ation during cell di&ision. *hese Kprotecti&e regions o/ DN( shorten with repeated cell di&ision in so%atic cells. *he en$y%e telo%erase 4a re&erse transcriptase5 acts to e-tend telo%eres and reduce their attrition. Shortened telo%eres %ay reach a point where they cannot support nor%al di&ision o/ chro%oso%es, resulting in cell senescence 4replicati&e arrest5 and abnor%al chro%oso%al /unction. *hese changes can result in altered or loss o/ nor%al /unctions o/ genes, cancer propagation, i%%une dys/unction, aging o/ tissues and the e%ergence o/ chronic disease. ,/ telo%ere shortening correlates with age and telo%erase can sustain or lengthen telo%ere, then si%ple logic dictates that inter&entions to %odulate the telo%ereLtelo%erase Kduo present a pro%ising and no&el strategy /or anti?aging or disease pre&ention or treat%ent. !hile ta%pering with telo%eres and telo%erase enchant %any scientists and clinicians, %atters are not 9uite as si%ple as so%e indi&iduals %ay ha&e hitherto supposed. Obser&ations on *elo%ere *a%pering *elo%ere length and telo%erase e-pression appear to be lin3ed in %any, but not all studied species o/ li/e. !hile telo%eres shorten with age, so%e people start with longer telo%eres than others. Shortened telo%eres tend to Kpush a cell towards senescence prior to apoptosis 4cell death5. *elo%erase acti&ity %ay lengthen telo%eres, but this en$y%e is /ound to be e-pressed pre/erentially in cancer, certain ger% cells and ste% cells 4i%%ortal cells5. *his lea&es an unanswered 9uestion Kwill direct telo%erase induction lead to cancer' !e 3now relati&ely little about selecti&e telo%erase enhancers 4www.tasciences.co%, www.geron.co%5. *his selecti&e approach /or telo%ere support is an i%portant target /or phar%aceutical or nutraceutical de&elop%ent as the potential longe&ity pro%oting properties o/ telo%ere support e%erge. Shortened telo%eres e-ert a Ktelo%ere position e//ect which alters genetic e-pressions at the cellular le&el. ,n this circu%stance, DN( repair genes do not e-ert opti%u% /unction and those genes that pro%ote cellular aging %ay e%erge. *he aging cell with its shortened telo%ere, see%s to lead to a circu%stance that /acilitates or /a&ors %ista3es. :owe&er, one %ust pause and thin3 about the induction o/ cellular senescence with age as a potential de/ense %echanis% against the occurrence o/ age?related cancer. Senescence and apoptosis ser&e both aging and disease pre&ention options. *he gene that regulates telo%erase e-pression is Ksilenced in healthy cells. KSwitching on or Kswitching o// this gene, to a &ariable degree, in possible by genetic %anipulations and the ad%inistration o/ certain co%pounds. *elo%ere loss or co%pro%ise is not consistently shown to be telo%erase dependent and it %ay not always show a linear relationship with ad&ancing years. 2or e-a%ple, loss o/ telo%ere length is accelerated in childhood 4up to the age o/ 20 years5 and %anage%ent in the elderly 4greater than <. years5. !hile telo%erase is not e-pressed in %ost so%atic cells, so%e cells 4e-panding i%%unocytes, ger% cells and cancer cells5 e-press high le&els o/ telo%erase. Does telo%erae shortening in laboratory tests o/ white blood cells 4*?ly%phocytes5 %irror telo%ere shortening in other cell types' *elo%eres loss is associated with sedentary li/estyles, o-idati&e stress, cancer, insulin resistance and chronic in/la%%atory diseaseM to na%e a /ew disorders, but so%e degree o/ Kchic3en and egg argu%ents pre&ail. *o add to the conundru%, laboratory studies o/ ger%inal centers, that produce 6 cells 4ly%phocytes5, show that telo%ese length that can increase, in spite o/ intense cell replication. 2urther%ore, so%e studies i%ply that telo%ere loss %ay not always e-hibit a clear correlation with certain cells history o/ replicati&e acti&ity. *hese /actors, and other concerns, %ay 9uestion the sensiti&ity and speci/icity o/ so%e %easures o/ telo%ere length as a reliable %easure%ent o/ physiological age. *he telo%ereLtelo%erase literature is replete with pro%ises o/ the potential bene/it o/ targeted therapeutic inter&entions. !hile no phar%aceutical is appro&ed /or telo%ere %odulation, natural approaches are e%erging with the use o/ speci/ic dietary supple%ents 4e.g. (stragalus e-tracts5. !hile this long ter% sa/ety or e//icacy o/ nutraceutical inter&entions /or telo%ere support re%ain un3nown, the desirability o/ telo%ere retention or lengthening strategies are so appealing that the use o/ sa/e and si%ple strategies to achie&e this outco%e see%s to be a reasonable inter&ention. =linical *elo%ere Support #rocesses that %ay increase loss o/ net telo%ere length or rebuilding o/ a shortened telo%ere 4*able 5. Se&eral /actors act to shorten telo%ere length and so%e are a%enable to corrections are shown in *able . *able . 2(=*OR =O;;7N* >ender *end to be longer in wo%en (ge =hildren ha&e longer telo%eres (ge o/ parents Older parents %ay de&iate shorter telo%eres to their o//spring 4e.g. Dolly the sheep5 Sedentary li/estylesN 7-ercise tends to cause retained telo%ere length =hronic ,n/la%%ationN =lear e&idence e.g. rheu%atoid disease O-idati&e StressN 7%erging studies on antio-idants /or retention o/ telo%eres ;enopause and (ndropauseN #redictable loss o/ telo%ere length with %ilestones o/ aging. :or%one dependency o/ telo%ere length disco&ered. *elo%eraseN (cti&ity can be induced ,nsulin resistanceN 7%erging association with telo%ere shortening. ;etabolic Syndro%e O and *ype 2 Diabetes are clearly a disorder o/ pre%ature aging. *able. 2actors that alter telo%ere length. *he asteris3 4N5 denotes so%ewhat a%enable to inter&ention A Telomere Support Protocol Research data and clinical outco%e obser&ations per%it the reco%%endation o/ a clinical protocol /or telo%ere support 4*able 2.5. *he e-istence o/ other Knatural protocols /or telo%ere lengthening 4e.g. the #atton #rotocol, www.tasciences.co%5 %ay be superseded by a %ore co%prehensi&e approach to telo%ere support and age %anage%ent. *his proposed protocol /or the natural clinician is best su%%ari$ed in line ite% state%entsF P Di/estyle =hange ;any positi&e li/estyle changes %ay inhibit telo%ere shortening. *hese include opti%u% nutrition, weight control, stress reduction, withdrawal o/ substances o/ abuse 4si%ple sugar, tobacco, alcohol, unnecessary prescription or o&er the counter or illicit drugs5 and the restoration o/ nor%al sleep patterns.4*able .5 P Dietary Supple%ents ( nu%ber o/ nutraceutical are associated with supporting telo%ere structure and /unction including, speci/icallyF e-tracts o/ >ing3o biloba, (stragalus, =hinese >inger root, &ita%in D, /olic acid 4and perhaps Aita%in 625, nicotina%ide and o%ega E /atty acids 4*able 2.5. Studies i%ply that ta3ing %ulti&ita%in and or antio-idant use %ay be associated with enhanced telo%ere length or inter/erence with telo%ere shortening. 7le&ated le&els o/ blood ho%ocysteine should be addressed 42olic acid, Aita%in 62 etc.5. NTRA!"T#!A$ "%#D"N!"&'AS"&()R S" Astragulus (stragalosides 4cycloastragenol5 or the speci/ic %olecule *(?<. are proposed as telo%eres. ( clinical trial that showed i%pro&e%ents in i%%une /unction, eyesight, se-ual /unction and s3in color characteristics. 4Re&iewed at *(Sciences.co% accessed 2ebruary <, 2005. )mega * (atty Acids ,n a group o/ patients with coronary heart disease there was a in&erse relationship between blood le&els o/ %arine o%ega E /atty acids and telo%ere shortening o&er a /i&e?year inter&al. 4Rai%in 2, et al, J(;(, E0E, 2.0?2.0, 2005 Antio+idants *he rate o/ telo%ere shortening is %odulated by o-idati&e stress 4certain in &itro5 4Saret$3i >, Aon Qglinic3i, *, (nn N@ (cad Sci, ".", 2C?", 20025. 6reast cancer ris3 %ay be a//ected by telo%ere length in wo%en with low inta3e o/ antio-idants or antio-idant supple%ents 4 Shen J et al, ,nt. J. =ancer, 2C, <E0?CE, 200"5 %itamin D ,igher %itamin D concentrate in seru% are associated with longer telo%ere length 4Richards J6 et al, (%. J. =lin. Nutr., B<, ., C20?C2., 20005 (olate-'./ (olate status alters telo%ere length in a non?linear %anner probably by its e//ects on the integrity o/ DN( and epigenetic in/luences 4=attaneo #D, et al, J Nutr., E", 0, 20E?20B, 200"5 #las%a ho%ocysteine ele&ation due to /olate and &ita%in 62 de/iciency is associated with decreased telo%ere length in older %ales 46ull =2 et al, Re+u&enation R. Sep. 2B, 200"5 Nicotinamide Nicotina%ide e-tends the li/espan o/ hu%an /ibroblasts as a presu%ed conse9uence o/ reduce %itochondrial production o/ reacti&e o-ygen species 4Iang :* et al, (ging =ell, ., C2E?E<, 200<5 Multivitamins 7pide%iological e&idence associates %ulti&ita%in use with longer telo%ere length 4Ou, R et al, (% J =lin Nutr. B", <, B.0? <E, 200"5 !hinese 0inger Root 7&idence is e%erging that ginger root %ay support telo%erase lengthening and ha&e other bene/icial actions. Alpha&tocopherol De%onstrated to inhibit telo%ere shortening and retain telo%erase acti&ity in %icro&ascular endothelial cells in the brain. 4*ana3a @ et al, J. =ell 6ioche%, 02, E, <B"?00E, 20005 N&acetylcysteine N?acetylcysteine bloc3s the nuclear e-port o/ h *7R* into cell cytoplas% and sdelays replicati&e senescence o/ endothelial cells that are attracted by reacti&e o-ygen species 4:aendeler J, et al =linc. Res, "C, 0<B?00., 200C5 Statins *reat%ent with statins increases ly%phocyte telo%ere length 46rouillette S! et al, Dancet, E", 00?C, 20005 Statins inter/ere with redo- balance o/ endothelial cells 4:aendeler J et al, =lin Res, "C, 0<B?00., 200C5 and 4Spyridopolens ,, et al circulation, 0, EE<? EC2, 200C5 0ing1o 2ilo2a 7-tracts o/ >ing3o biloba e-tracts ha&e been show to delay the onset o/ cellular senescence by acti&ating #E3L(3t signaling pathways that aug%ent telo%erase acti&ity 4Ou D et al, D O et al, J =ardio&asc. #har%acol, C?",?., 20005. *able 2. (n e%erging e&idence base /or nutraceuticals that support the structure and /unction o/ telo%eres. Dietary supple%entation is not a substitute /or speci/ic dietary guidelines in the 9uest /or telo%ere support. ,n brie/, the anti?aging, telo%ere supporting diet should in&ol&eF P Reductions in si%ple carbohydrate inta3e with increase in dietary /iber inta3e 4to counter insulin resistance5. P Nutrient dense /ood selections that are low in calories. =alorie restriction enhances %a-i%u% and a&erage li/espan and this process %ay be enhanced by the use o/ calorie restriction %ionetic co%pounds. P :igh antio-idant load in a diet rich in /ruit and &egetables. ;ulti&ita%ins ta3en in greens, berries, /ruit and &egetable %i-es are a pre/erred /or% o/ general nutritional support. #hytonutrients are &ita%in co?/actors and pro&ide an antio-idant /ood. P 7nrich sources o/ o%ega E /atty acids in acti&e /or%s e.g. cold water, /ish, sal%on etc. P Decreased sources o/ saturated /at, hydrogenated oils and trans? /atty acids. P (&erage balance protein inta3e with rotation a%ong %eat, dairy, &egetable and /ish protein sources 4not greater than g%L3g o/ body weight per day, unless otherwise indicated5. P ,nter%ittent short periods o/ /asting and %ethods /or body deto-i/ication 4dietary and otherwise5 %ay support telo%ere structure and /unction. P Disease ;anage%ent ( clear association e-ists between co%%on diseases 4cancer and degenerati&e diseases5 and shortening o/ telo%ere length e.g. cardio&ascular disease 4altherosclerosis5, hypertension, insulin resistance 4;etabolic Syndro%e O5, diabetes %ellitus and diseases associated with cogniti&e decline 4de%entia5. ;eticulous %anage%ent o/ co?%orbid conditions is obligatory. ;etabolic Syndro%e O and diabetes are classic disorders o/ pre%ature aging. P ?;iscellaneous 2actors 7&ery atte%pt should be %ade to tac3le the /ollowing issues with appropriate %edical inter&entionsF. (tte%pts to eli%inate coronary heart disease and atherosclerosis ris3 /actors %ust be applied e.g. reduce DDD 4target S"0 %gTU, reduce o-idi$ed and dense particle si$e DDD, increase :DD. =ontrol blood glucose 4i%portant in both established and pre?diabetes or ;etabolic Syndro%e O5, control blood pressure, 3eep blood ho%ocysteine in chec3, reduced chronic in/la%%ation 4%onitor =?Reacti&e #rotein, %aintain :S?=R#S. ,nstitute an e-ercise progra% is obligatory, lin3ed to le&els o/ aerobic /itness 4pro/essional trainers reco%%ended5. =ontrol o/ weight with holistic inter&entions o/ diet, e-ercise, beha&ior %odi/ication and supple%ent ad+uncts are %andatory. ,nter&entions that support ste% cell /unctions, increase nitric o-ide signaling, i%pro&e %itochondrial /unction, deto-i/y the body and opti%i$e hor%onal controls 4e.g. bio? identical hor%one therapy5 %ay be &aluable ad+uncti&e approaches to telo%ere support. =onclusion ,n %y educational colu%ns on natural therapeutics, , ha&e /ocused on three &ery i%portant issues in anti?aging or regenerati&e %edicine. *hese areas include ste% cell support, the use o/ calorie restriction %i%etics and support /or telo%ere structure and /unction 4*he (nti? (ging *rilogy5. , belie&e that these three areas o/ longe&ity %edicine interdigitate in a %anner that creates the %ost i%portant and pro%ising /rontier /or Kturning bac3 the cloc3 in the /ield o/ aging %edicine. *his article is abstracted /ro% Dr3 ,olt4s new 2oo1 entitled the Anti&Aging Trilogy 5www3hiom3org6
VVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVV VV Docated at the tips o/ each o/ our C< chro%oso%es, telo%eres help protect DN( and are particularly i%portant during cell di&ision. *elo%eres ha&e recei&ed a lot o/ notoriety due to their relationship with aging. *hese protecti&e structures shorten with each cell di&ision, e-posing DN( to potential danger. ,n ti%e, telo%eres get too short to shield DN(. *hatWs when cells stop wor3ing, /unction poorly or, e&en worse, de&elop disease. *hereWs a lot o/ research being conducted on ways to preser&e telo%eres. ;uch o/ this wor3 /ocuses on telo%erase, an en$y%e that helps rebuild telo%eres a/ter cell di&ision. So%e researchers propose that boosting telo%erase %ay be a way to preser&e telo%ere /unction and increase longe&ity and health. :owe&er, thereWs another side to the coinF *oo %uch telo%erase acti&ity %ay be associated with cancer /or%ation, because it allows cells to replicate uncontrollably. 6ut other studies debun3 this lin3. !hat researchers are suggesting o&erall is that healthy telo%ere /unction, li3e so %any other co%ple- syste%s in the body, re9uires a care/ul balance. 2urther%ore, itWs beco%ing clear that telo%ere /unction is in/luenced by nu%erous en&iron%ental and li/estyle /actors and that shortened telo%eres can lead to a nu%ber o/ chronic, degenerati&e diseases. Ob&iously, %ore research is needed, but data suggests that preser&ing telo%ere health can play a role in %aintaining long?ter% &itality. Ris3y 6usiness *elo%eres can be pre%aturely shortened by %any /actors. 7n&iron%ental to-ins, stress, s%o3ing and an unhealthy diet play a part. Shortened telo%eres ha&e been lin3ed to cancer, heart disease, in/la%%ation, insulin resistance, osteoarthritis, obesity and de%entia. ,tWs not entirely clear whether shortened telo%eres are causing these conditions. Still, thereWs ob&iously a relationship. ( study conducted at the Jni&ersity o/ Jtah /ound that people with shorter telo%eres ha&e a shorter li/e e-pectancy. ,n particular, they see%ed to be susceptible to heart disease and in/ections. ( %ore co%prehensi&e study conducted in Den%ar3 showed that reduced length increases the chance o/ pre%ature death by 2. percent. *a3ing (ction #reser&ing telo%eres is not a %agic health bullet. ,/ we eat poorly, s%o3e, drin3 hea&ily and neglect e-ercise, thereWs no a%ount o/ telo%ere support that will guarantee protection. On the other hand, i/ we de&elop a healthy li/estyle and control 3nown disease %ar3ers, li3e blood pressure and chronic in/la%%ation, supporting telo%ere length can co%ple%ent these e//orts. (s always, the starting point is diet and e-ercise. 7at plenty o/ /ruits and &egetables, drin3 lots o/ /iltered water, and choose lean proteins and healthy /ats. (dopt a sustainable e-ercise progra%F bris3, E0? %inute wal3s pro&ide e-cellent cardio&ascular support. DonWt /orget stress reduction. *here are a nu%ber o/ studies lin3ing stress to shortened telo%eres. (gain, weWre not sure whether this is cause or e//ect, but it hardly %atters. 7e 1now that stress releases the hormone cortisol and can cause chronic in8lammation along with other degenerative e88ects3 )n the other hand9 a study 8rom researchers in !ali8ornia 8ound that positive 8eelings9 such as those produced 2y meditation9 seem to activate telomerase3 They also 8ound that people who sustained :good 8eelings; had healthier telomeres3 ,n other words, we should adopt acti&ities that 9uiet the %ind and help center us. ;editation, yoga, *ai =hi, wal3ing in nature or swi%%ing a /ew laps in the pool can all be bene/icial. ,%portant Supple%ents *here are a wide &ariety o/ herbs and nutrients that ha&e been lin3ed to healthy telo%eres. (stragalus has been used /or centuries in traditional %edicines. Recent research has shown that (stragalus boosts i%%une /unction. (t present, at least two phar%aceutical co%panies are /ocusing on this herbWs potential to preser&e telo%eres. Aita%ins also see% to play a role. Se&eral &ita%ins, speci/ically &ita%in D, appear to boost telo%ere length. (ntio-idants, which can be /ound in &ita%ins and other sources, are also i%portant. O-idati&e stress is lin3ed with shortened telo%eresH ar%ing the body against this pro?in/la%%atory process is always bene/icial3 Dong touted /or its ability to boost heart and cogniti&e /unction, o%ega?E /atty acids ha&e also been lin3ed with telo%ere length. ,n one study, lower o%ega?E le&els in the bloodstrea% were associated with accelerated telo%ere shortening. (s noted, en&iron%ental to-ins such as hea&y %etals %ay play a signi/icant role, as well as being har%/ul to health in other ways. *here are a couple o/ supple%ent /or%ulas , reco%%end to help the body re%o&e these pollutants. ( co%prehensi&e, botanical deto-i/ication /or%ula containing &ita%ins, %inerals, astragalus, ging3o, antio-idants and other botanicals helps rid the body o/ to-ins and %ay preser&e telo%ere health. , also reco%%end %odi/ied citrus pectin 4;=#5, which has long been used to re%o&e hea&y %etals and other to-ins. ,n addition, ;=# helps reduce le&els o/ an in/la%%atory protein o/ten associated with cardio&ascular disease and cancer. *his is by no %eans the /inal word on telo%eres. New research will /urther illu%inate these 3ey structures, helping to guide our e//orts to preser&e long?ter% health. ;eanwhile, a si%ple co%%on?sense approach that includes a healthy diet, e-ercise, stress reduction and /ocused supple%entation can go a long way toward preser&ing telo%eres and pro%oting health and longe&ity. VVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVV VVVVVVVV Turning on #mmortality: The De2ate )ver Telomerase Activation 6y !illia% (ndrews, #hD and ;ichael !est, #hD *urning on ,%%ortalityF *he Debate O&er *elo%erase (cti&ation *he role o/ telo%erase in allowing the i%%ortal growth o/ reproducti&e cells is well established in the scienti/ic literature. ,n the laboratory dish, the introduction o/ telo%erase into cultured hu%an cells trans/or%s otherwise aging %ortal cells into i%%ortal cells without trans/or%ing the% into cancer cells. On the heels o/ this disco&ery, s%all %olecule acti&ators o/ telo%erase are being de&eloped /or use in treating cellular aging and at least one nutritional supple%ent is being %ar3eted /or the treat%ent o/ aging. Do these co%pounds really wor3 and are they sa/e' *hat is the 9uestion that was posed to two leaders in the /ield3 (rguing in /a&or o/ the %ar3eting o/ telo%erase acti&ators /or nutritional use is !illia% :. (ndrews, #hD, president X =7O, Sierra Sciences, who pre&iously was director o/ %olecular biology at >eron =orporation where the telo%erase genes were /irst isolated. *a3ing the opposing position is ;ichael D. !est, #hD, who was the /ounder o/ >eron =orporation, and is currently the =7O o/ 6io*i%e, ,nc, which /ocuses on the ste% cell biology and the resetting o/ cell li/e span by cellular reprogra%%ing. Jntil %ore hu%an data are co%piled, the Di/e 7-tension 2oundationY does not ha&e a position, one way or another, on the use o/ this particular telo%ere?e-tending therapy. *he in/or%ation /or this article is written by two highly respected scientists. So%e %e%bers %ay /ind this %aterial technically challenging to co%prehend. Dr. (ndrews !rites in 2a&or o/ M *here is now co%pelling e&idence that the length o/ a personWs li/e span is dictated by the li%ited nu%ber o/ ti%es a hu%an cell can di&ide. *hough the i%%ortal reproducti&e cell can di&ide a li%itless nu%ber o/ ti%es, once the hu%an reproducti&e cell, in the de&eloping e%bryo, turns into a de&elop%ental cell the cloc3 starts tic3ing and the cellWs /ate is doo%ed to a li%ited 0.?00 nu%ber o/ cell di&isions 4the :ay/lic3 Di%it5. Once that li%it has been reached, the cell and all o/ its progeny co%pletely lose the ability to di&ide and then enter a phase called senescence. *he tic3ing cloc3 in this case is /ound at the tips o/ the cellWs chro%oso%es in a region called the telo%ere. ,t is belie&ed that telo%eres %ay ha&e e&ol&ed to pre&ent the unli%ited growth o/ cells by li%iting their li/e span. *elo%eres are %ade up o/ subunits 4or bases5 o/ DN( called (, =, >, and *. ,n the telo%ere, these bases are arranged in si- base repeat units o/ **(>>>. !hen a hu%an is /irst concei&ed, the length o/ the telo%eres a&erages about .,000 bases 4up to 2,.00 **(>>> repeat units5 as %easured by a process called ter%inal restriction /rag%ent length analysis. *he length then begins to decrease at a rate o/ about 00 bases per cell di&ision. 6y the ti%e a person is born, the a&erage telo%ere length has already dwindled to about 0,000 bases and then throughout the rest o/ a personWs li/eti%e the a&erage length o/ the telo%eres gradually decreases to about .,000 bases at which ti%e the personWs cells lose the ability to di&ide. *hese cells are then senescent, and the person su//ers and dies o/ old age. Dr. (ndrews !rites in 2a&or o/ M *elo%eresF a region o/ highly repetiti&e DN( at the end o/ a linear chro%oso%e that /unctions as a disposable bu//er. Aery recently, re%edies ha&e been de&eloped that could possibly alle&iate, abolish, or re&erse this Kup to now ine&itable /ate by acti&ating an en$y%e called telo%erase, which %ay help %aintain telo%ere length. One such re%edy, a nutraceutical called *(?<., is already co%%ercially a&ailable and se&eral people ha&e already signed up to bene/it /ro% its potential to e-tend health span and li/e span. Jn/ortunately, this re%edy also carries with it a potential /or pro%oting cancer. (nd so, we are brought bac3 to the age?old 9uestion, KDo you gi&e a ris3y cure to a dying person, or do you si%ply let the person die because the cure is too ris3y' 7&ery one o/ us is su//ering /ro% this disease, but %ost o/ us are in only the &ery early stages and ha&e the lu-ury not to %a3e this choice so hurriedly. :owe&er, %any o/ the people in the later stages o/ aging /eel that they donWt ha&e this lu-ury and choosing to ta3e *(?<. %ay be what they /eel to be their only recourse to Ksa&ing their li&es. Should these people be depri&ed' Should they be allowed to intentionally increase their ris3 o/ cancer to potentially enhance and prolong their health span and li/e span' !e should let people who are concerned about their age?related deterioration, whether or not in the later stages o/ aging, decide /or the%sel&es. *(?<. is presently the only potential cure /or telo%ere shortening and there wonWt be another one /or a long ti%e co%ing. *hough the data are not o&erwhel%ing enough yet to con&ince scientists that *(?<. is, in /act, e-tending health span and li/e span, they do show a lot o/ pro%ise and are supported on %any theoretical grounds. Di3ewise, as stated abo&e, there are also a lot o/ theoretical grounds /or *(?<. increasing the chances that the person will be a//licted with cancer. (bout B.?".T o/ all cancers e-press telo%erase acti&ity 4but telo%erase acti&ity doesnZt pro&e solely the e-istence o/ a cancer5. ;any research labs are wor3ing &ery hard to de&elop inhibitors o/ telo%erase acti&ity to cure cancer. So, one %ight thin3 that we %ust be out o/ our %inds to now want to intentionally turn telo%erase acti&ity on. 6ut, the data show that telo%erase is, in /act, not the cause o/ cancer. ,nstead, cancers turn on telo%erase e-pression only to e-tend their li/e spanH +ust li3e we want to turn on telo%erase e-pression in our non?cancer cells to e-tend their li/e span. So, weW&e learned a lesson /ro% cancer cells on how to e-tend cellular li/e span. 6ut, true cancer cells already ha&e telo%erase acti&ity. >i&ing so%eone a telo%erase inducer isnWt going to %a3e an i%%ortal cancer %ore i%%ortal. So, itWs not actually the true cancers we are concerned about. *he cancers that are really at issue here are the pre?i%%ortal cancersH that is, the cells that ha&e lost growth control but that donWt e-press telo%erase acti&ity or so%e other i%%ortal pathway 4such as the (D* [alternati&e lengthening o/ telo%eres\ pathway5. 2ortunately, *(?<. is a transient inducer o/ telo%erase acti&ity. =essation o/ ta3ing *(?<. will shut down the e-pression o/ telo%erase acti&ity in cells, including the pre?i%%ortal cancer cells, thus pro&iding opportunities to still treat the pre?i%%ortal cancer cells. *hough, on one hand, the ris3 o/ cancer has still been ele&ated because o/ the e-tended telo%ere lengths, there are also strong reasons to belie&e that the longer telo%eres ha&e also signi/icantly reduced the cancer ris3sH especially in the people su//ering /ro% later stages o/ aging. *hat is, short telo%eres %ay actually be one o/ the %a+or causes o/ cancer. !hen telo%eres are short, they ha&e a higher propensity to induce chro%oso%e rearrange%ents. *his can lead to aberrant e-pression o/ oncogenes and aberrant repression o/ tu%or suppressor genes. ,n addition, our i%%une cells show decreased abilities to target and destroy cancer cells when telo%eres are short. Ieeping telo%eres long should there/ore decrease the incidence o/ cancer and help our i%%une syste%s to /ight cancer. ,tWs hard to 3now i/ the Kpros outweigh the Kcons when considering the cancer issues. *he lac3 o/ a good ani%al %odel that ages by telo%ere shortening %a3es these issues al%ost untestable. So, at this ti%e we can only speculate. ,n the %eanti%e, people are aging, and people are dying o/ old age. ;any cancer sur&i&ors will tell you that cancer is a /ate worse than death. ;any elderly people will tell you that su//ering old age is a /ate worse than death. *here is little doubt that the potential /or increased ris3 o/ cancer due to *(?<. is real. 6ut the potential /or increased ris3 o/ su//ering /ro% old age due to not ta3ing *(?<. is %ore real. Dr. !est !rites (gainstM Recent ad&ances in %olecular and cell biology ha&e allowed spectacular progress in our understanding o/ the %olecular %achinery o/ hu%an aging. !ith this new in/or%ation co%e insights into how that cloc3wor3 can be %odi/ied to slow or e&en re&erse &arious /acets o/ hu%an aging. *he disco&ery o/ the telo%erase gene as a central regulator o/ replicati&e i%%ortality and the K3ey that winds and sets the length o/ telo%eres 4and hence cell replicati&e li/e span5 in hu%an cells has led to great opti%is% about the prospects o/ turning on the gene in the body to e-tend telo%eres and potentially hu%an li/e span. ;any scientists belie&e that the reason telo%erase, and hence cellular i%%ortality, is repressed in the %a+ority o/ cells in the body while being le/t on in the reproducti&e cells is that this allows the hu%an species to continue inde/initely, while repressing the unli%ited growth o/ cells in the process o/ cancer /or%ation. *his conclusion is based in part on the obser&ation that appro-i%ately "0T o/ hu%an %alignant tu%ors show the abnor%al e-pression o/ telo%erase co%pared with nor%al tissues. __________________________________________________________________ The events initiated 2y telomere shortening ;iguel >odinho 2erreira in&estigates *elo%eres, regions o/ DN( at the tips o/ chro%oso%es that protect against the loss or garbling o/ &ital genetic in/or%ation. *elo%eres per/or% this protecti&e /unction through sel/?sacri/ice, gi&ing up bits o/ the%sel&es each ti%e the cell di&ides, beco%ing shorter and shorter until they are too s%all to do their +ob. *his /inal loss o/ /unction has been lin3ed to the deterioration and death o/ cells that occurs as we grow older and %ay underlie the in/ir%ities o/ old age. (n en$y%e called telo%erase pre&ents telo%ere shortening by adding bac3 seg%ents to telo%ere ends. 6ut while this en$y%e plays a /unda%ental role in single?celled organis%s that di&ide inde/initely, it is absent /ro% %ost types o/ hu%an cells. *hat %ay not be such a bad thing. ,n "0 percent o/ cancers analy$ed to date, telo%erase is acti&e, suggesting that the en$y%e helps cancer cells di&ide uncontrollably, a 3ey /actor in %alignancy. Since establishing his *elo%ere and >eno%ic Stability Daboratory at the >ulben3ian Science ,nstitute 4,nstituto >ulben3ian de =i]ncia5 in 200<, >odinho 2erreira has concentrated on understanding the %olecular %echanis%s that underlie telo%ere protection. K,W&e been trying to /igure out how cells cap chro%oso%e endsGthe %echanis%s by which they pre&ent short or da%aged telo%eres, >odinho 2erreira e-plains. #re&iously, he studied /ission yeast, a single?celled organis% whose chro%oso%es are re%ar3ably si%ilar to those o/ hu%ans. Now he wants to e-pand his studies to a %ulticellular organis%, the $ebra/ish, which, li3e hu%ans and /ission yeast, has telo%eres that shorten with age. *wo %ain $ebra/ish pro+ects are ta3ing shape in his lab. ,n one, his group is using a $ebra/ish %odel o/ %elano%a to /ind out whether the cancer can be controlled by inhibiting telo%erase and, i/ so, e-actly when tu%ors are %ost susceptible to antitelo%erase treat%ent. ,n the other line o/ wor3, >odinho 2erreiraWs lab is in&estigating whether telo%ere shortening a//ects only the cell in which it occurs or i/ that cell also signals neighboring cells with the %essage, K:ey, none o/ us is getting any younger, you 3now) K*he idea is that there %ay be ^sentinel organsW that send signals to the rest o/ the body so that aging is a coordinated e&ent in the whole organis%, >odinho 2erreira e-plains. ______________________________________________________________________ _________ Telomerase Therapies in our (uture *elo%ere biology has the potential to e-tend hu%an li/e span, to dra%atically lower rates o/ the great re%aining 3iller diseasesF heart disease, stro3e, and (l$hei%erWs. (ll three diseases increase e-ponentially with age, and their toll will be slashed as we we learn how to address the bodyWs aging cloc3s. @ou would thin3 that the 200" Nobel #ri$e %ight ha&e done %ore to raise the pro/ile o/ research in telo%ere biology, but the /ield re%ains a speciali$ed bac3water o/ %edical research, and /ew biologists 4/ewer doctors5 ta3e it seriously as a panacea /or the diseases o/ old age. ,/ the National ,nstitute o/ :ealth has %oney to put into heart disease and cancer and (l$hei%erWs and #ar3insonWs diseases, there is no better place to in&est than in telo%ere biology. Research on these diseases co%%ands %ulti?billion dollar budgets, because they are considered K%edicine, /unded by N,:, while telo%ere biology is considered Kscience and is /unded by NS2. *he total NS2 budget /or all cell biology is only _2E %illion, and the portion de&oted to telo%ere biology is a /ew %illion. *he pri&ate sector is doing a little better 8 there are se&eral co%panies selling herbs that sti%ulate our own bodies to liberate telo%erase. 6ut this is short?sighted &enture capital, and what we need is /ocused research with a ten?year &ision. *here is good reason to thin3 that telo%ere length is a pri%ary aging cloc3 in the hu%an body. *he body 3nows per/ectly well how to lengthen telo%eres, but chooses not to. (ll we ha&e to do is to signal the body to acti&ate the telo%erase genes that are already present in e&ery cell. O/ course, there is no guarantee that this will wor3, but co%pared to the sluggish rate o/ progress on indi&idual diseases, itWs a pretty good bet, and the target is rather si%ple. ,;:O, itWs worth a crash research e//ort. Ob+ections raised against telo%erase research . K(ging is ine&itable because #hysics tell us that nothing can last /ore&er. *his state%ent re/ers to the Second Daw o/ *her%odyna%ics, which says that closed syste%s, e&ol&ing in isolation, %ust beco%e %ore disordered o&er ti%e. 6ut li&ing syste%s are open, ta3ing in /ree energy in the /or% o/ /ood or sunlight, du%ping their entropy out into the en&iron%ent. *here is no reason that such syste%s cannot %aintain the%sel&es inde/initely. ,ndeed, growth and %aturation would not be possible i/ this law o/ physics applied to open ther%odyna%ic syste%s. Since the "th =entury when the laws o/ ther%odyna%ics were /or%ulated, it has been understood that aging cannot be e-plained /ro% physics, and there/ore co%%ands an e-planation /ro% e&olution. 2. K7&olution has been wor3ing to %a-i%i$e ani%al li/e spans in order to increase /itness. ,t is unli3ely that any si%ple ad+ust%ent to physiology that hu%ans can disco&er will do better than e&olution has done o&er %illions o/ years. ,n /act, e&olution has not wor3ed to %a-i%i$e li/e span, but only to %a3e it su//icient to assure ti%e /or reproduction. (ging is a /or% o/ progra%%ed death, on a /le-ible but /inite schedule. ,t is /i-ed in our genes. *here are %echanis%s o/ aging that ha&e been progra%%ed into li&ing things since the /irst eu3aryotic cells. *elo%ere attrition has been used to ti%e the li/e cycle and /or% a basis /or progra%%ed death /or at least a billion years. ;any species o/ proto$oans do not e-press telo%erase during %itosis 4but only during con+ugation5, so their telo%eres shorten with each reproduction, leading to a li%it o/ a /ew hundred reproductions per cell line. *his %echanis% is the precursor to telo%eric aging that e-ists to the present day in hu%ans and %any other higher ani%als. E. K7-pressing telo%erase will increase the ris3 o/ cancer. *here is a great deal o/ theoretical concern in this direction, which , thin3 is entirely %isguided. ,t is true that cancer cells e-press telo%erase. ,t is not true that e-pressing telo%erase causes a cell to beco%e cancerous. *his relationship is clearly e-plained by two seasoned e-perts 4Shay and !right 205 ,n early studies, the only way o/ increasing telo%erase acti&ity in lab ani%als was to add e-tra genes /or telo%erase. *echnology in the early 2000s did not per%it a gene to be added at a targeted location, but only inserted rando%ly into a chro%oso%e. *a%pering with the structure o/ DN( in this way is 3nown to increase cancer ris3 no %atter what gene is added or subtracted. ,n three o/ these early studies, cancer rates in %ice were increased [, 2, E\. *here are no lab studies to %y 3nowledge in which acti&ating the nati&e telo%erase has increased the ris3 o/ cancer. *he %odern &iew is that Kwhile telo%erase does not dri&e the oncogenic process, it is per%issi&e and re9uired /or the sustain growth o/ %ost ad&anced cancers. Recent perspecti&es /ro% both :ar&ard lab o/ de #inho and the Spanish lab o/ 6lasco /ocus on the potential /or telo%erase to decrease cancer ris3, and these were the &ery people who produced the three studies suggesting caution a decade earlier. (nd there are %any studies showing that 4a5 telo%erase e-pression does not increase cancer ris3 in lab ani%als, and 4b5 short telo%eres are a &ery strong cancer ris3. , belie&e that telo%erase acti&ators will greatly reduce the cancer rate, /irst by eli%inating cells that are pro? in/la%%atory and potentially carcinogenic because their telo%eres ha&e beco%e short, and second by re+u&enating the i%%une syste%, which is our pri%ary de/ense against cancer. , published an article on this sub+ect last year. !hy we %ight e-pect big li/e e-pectancy gains /ro% e-tending telo%eres *his is the a//ir%ati&e 9uestion, thenF what %a3es %e thin3 that telo%ere e-tension will ha&e such a power/ul e//ect on di&erse aspects o/ aging biology' (5 *elo%ere attrition is an ancient %echanis% o/ aging. #rotists were the /irst eu3aryotic cells, and they appeared on earth a billion years ago 4they were a leap up in co%ple-ity /ro% bacteria, which had been around E billion years be/ore5. ,n protists, DN( is linear and hence there are telo%eres and a need /or telo%erase. Since protists reproduce by si%ple cell di&ision, you would not e-pect that the cells would Kage or e&en that the concept o/ aging could ha&e any %eaning /or their li/e cycle. 6ut a protist cell lineage can age, and indeed so%e do. *his is the oldest 3nown %echanis% o/ aging, and it is i%ple%ented through withholding telo%erase3 #ara%ecia are an e-a%ple. !hen para%ecia reproduce, their cells si%ply /ission, the DN( replicates, and telo%erase is e-pressed. :ence, telo%eres get shorter with each cell di&ision. #ara%ecia can con+ugate, which is a pri%iti&e /or% o/ se-ual gene e-change. *wo para%eciu% cells %erge, %ingle their DN(, and then separate. ,t is only in the con+ugation process that telo%erase is e-pressed. *here/ore, any cell lineage that does not con+ugate will die out a/ter a /ew hundred generations. *his pre&ents cell colonies /ro% beco%ing too ho%ogeneous. *hus aging is a billion years old, and so%e o/ the genetic %echanis%s o/ aging ha&e been conser&ed and passed on through all the trans/or%ations o/ %ulticellular li/e 4!illia% R =lar3 has written two accessible boo3s [, 2\ on this topic.5 65 *elo%eres shorten with age in hu%ans. *his has been 3nown /or twenty years. =5 #eople with shorter telo%eres ha&e a %uch higher ris3 o/ %ortality. *his was established by Richard =awthon 4200E5 in a paper which too3 the /ield by surprise. Researchers be/ore then had assu%ed on erroneous theoretical grounds that telo%ere attrition, which was 3nown to occur, could not ha&e anything to do with hu%an aging. ,t was assu%ed that the nu%ber o/ cell replications, though li%ited, %ust be su//icient to last through the longest li/eti%e that hu%ans nor%ally e-perience. (/ter all, i/ aging were as si%ple as telo%ere attrition, then the body could sol&e the proble% %erely by e-pressing telo%erase. *his would enhance indi&idual /itness. !hy would not e&olution ha&e /ound such a si%ple e-pedient' 4*he answer, o/ course, is that natural selection /a&ors aging, /or the sa3e o/ the de%ographic stability 8 an e&olutionary /orce not recogni$ed by %ost e&olutionary biologists.5 ,n =awthonWs study, the top ` o/ <0?year? olds in ter%s o/ telo%ere length had hal/ the o&erall %ortality ris3 as the botto% `. =awthon had access to a uni9ue database o/ 20?year? old blood sa%ples, and to %y 3nowledge his study has not been replicated or re/uted these years.
D5 #eople with short telo%eres ha&e a higher ris3 o/ diseases, especially =AD, a/ter ad+usting /or age. *he association with cardio&ascular disease has been consistent, not +ust in =awthonWs original study, but also se&eral other studies [Re/ Re/ Re/\. *here are also associations with de%entia [Re/, Re/\ and with diabetes [Re/, Re/\. 75 (ni%als with short telo%eres also ha&e a higher ris3 o/ %ortality, a/ter ad+usting /or age. *his has been established in se&eral bird species [Re/ Re/ Re/\, and in baboons. ,n 200E, it was already 3nown that long?li&ed species tend to lose telo%ere length %ore slowly, and short?li&ed species lose telo%eres %ore rapidly. 25 ,n li%ited studies with %ice, telo%erase enhancers ha&e led to re+u&enation. 4;ice are e-pected to be a %uch less e//ecti&e target /or this strategy than hu%ans, because to all appearances, aging in hu%ans relies on telo%ere attrition %uch %ore so than in %ice.5 *he /irst e-peri%ent o/ this type was done in 200B. ,n the Spanish lab o/ ;aria 6lasco, *o%as?Doba engineered %ice that were both cancer?resistant and contained an e-tra telo%erase gene, e-pressed in so%e tissues where, e&en in %ice, it would not nor%ally be /ound. =ancer?/ree %ice with the e-tra telo%erase li&ed BT longer than cancer?/ree %ice with only the nor%al gene /or telo%erase. 6ut soon it was disco&ered that all the e-peri%ental precautions around cancer %ay not ha&e been necessary. *he sa%e lab 6ernardes de Jesus 4205 reported that they could increase health span in %ice with the co%%ercial product called *(?<. 4widely ru%ored to be cycloastragenol5 with no increase in the incidence o/ cancer. =ycloastragenol is a wea3 telo%erase acti&ator co%pared to %an?%ade che%icals disco&ered at Sierra Sciences, and e&en co%pared to so%e other herbal e-tracts. Ne&ertheless, the 6lasco lab was able to show that the shortest telo%eres in the %ice were elongated, and that %ar3ers o/ health including insulin sensiti&ity were i%pro&ed by short?ter% treat%ent with *(?<.. 6lascoWs lab then wor3ed with a %ore potent 4though %ore dangerous5 %ethod o/ telo%erase inductionF in/ection with a retro&irus engineered to introduce telo%erase into the nuclear DN( o/ the in/ected cell. K*reat%ent o/ ? and 2?year old %ice with an adeno associated &irus 4((A5 o/ wide tropis% e-pressing %ouse *7R* had re%ar3able bene/icial e//ects on health and /itness, including insulin sensiti&ity, osteoporosis, neuro%uscular coordination and se&eral %olecular bio%ar3ers o/ aging. 46ernardes de Jesus, Aera et al. 2025 *he %ice li&ed ET longer when ((A treat%ent began at age 2 years, and 2CT longer when treat%ent began at year. *here was no increase in cancer incidence. *he %ost dra%atic e-a%ple o/ re+u&enation is /ro% the :ar&ard laboratory o/ Robert de #inho. Nor%ally, %ice 4unli3e people5 e-press telo%erase /reely through their li/eti%es. *hese scientists engineered a %ouse without the nor%al 4always on5 gene /or telo%erase, but instead had a telo%erase gene that could be turned on and o// at will by use o/ a che%ical signal that the e-peri%enters could /eed to the %ice. (s these %ice grew older, they de&eloped %ultiple, se&ere sy%pto%s o/ degeneration in the testes, spleen, intestine, ner&ous syste% and elsewhere. (ll these sy%pto%s were not +ust halted but re&ersed when telo%erase was turned on late in the ani%alsW li&es. *he e//ect on the ner&ous syste% is particularly interesting because ner&e cells last a li/eti%e and do not depend on continual regeneration /ro% ste% cells, the way blood and intestinal and s3in cells do. Ne&ertheless, these %ice with telo%erase turned o// su//ered sensory de/iciencies and i%paired learning that was re&ersed when the e-peri%enters ad%inistered the che%ical signal to turn telo%erase bac3 on3 A Stan8ord-0eron research group wor1ed with :s1in; grown 8rom human cells in a la2 setting. *hey /ound they were able to restore youth/ul elasticity, so/tness and te-ture to the cultured Ks3in by in/ecting the cells with an engineered retro&irus that inserted the gene /or telo%erase. >5 ,n addition to its /unction in lengthening telo%eres, telo%erase also acts as a 3ind o/ growth hor%one. *his /act was suspected as early as the ""0s, and con/ir%ed de/initi&ely in a Stan/ord e-peri%ent [Re/, Re/, Re/, Re/\. ,n this e-peri%ent, %ice were engineered with Kdenatured telo%erase that lac3ed the RN( te%plate /or creating telo%eres. Still, the telo%erase was shown to induce hair growth. *elo%erase has been shown to a//ect a hor%onal signaling pathway called !nt. Other /unctions /or telo%erase are re&iewed by =ong and Shay 4200B5. :5 ,n one hu%an case, huge doses o/ herbal telo%erase acti&ators has led to re+u&enation. , a% recently in touch with a physicist /ro% Iansas who has been ta3ing super?high doses o/ telo%erase?acti&ating herbs and supple%ents /or si- years and clai%s to loo3 and /eel younger, with i%pro&ed athletic per/or%ance. :e %ay be an interesting case study. Ji% >reen has co%%ented on this blog site. *he 6otto% Dine ,n %y opinion, telo%erase acti&ation is a /ield that o//ers the %ost potential /or hu%an li/e e-tension in the ne-t /ew years. *his research is languishing /or lac3 o/ /unds, and /or lac3 o/ attention. Josh ;itteldor/ (ging ;atters