An Optimum Anti-Aging Program

An Optimum Anti-Aging Program Dosages: [62s] and Medicines and Dosages 2011

Free Radical Defense for Cell Membranes and DNA with Antioxidants, Anti-Glycating Drugs, and Diet
See my medicine program for February, 2011 with photos. I am beginning to suspect that the ideal anti-aging program uses Vitamin C with bioflavonoids [LifeExtension], perhaps from 1000 mg C per day up to the Linus Pauling maximum dose of 18000 mg per day, in which case bioflavonoids reduce any overdose effects of Vitamin C on white blood cells. Dr. Al Sears claims that 500-1500 mg of vitamin C, taken twice a day, helps to preserve telomere length in mitotic cells, which is accelerated by free radical damage promoting premature stress-induced senescence. However, it is clear that cyclic telomerase activation is required to implement telomere rejuvenation resembling time travel backwards in time. Grape seed extract [LifeExtension, Links] helps Vitamin C penetrate cell membranes better. I get my grape seed extract now in a fancy SolarRay brand of resveratrol including grape seed extract and red wine extract and take 2500 mg of vitamin C every day. Resveratrol (a telomerase inhibitor and SIRT1 activator) should be taken with a source of quercetin [113] like onions, apple slices, or red grapes to improve bioavailability and probably with chunk light tuna to provide NAD [Wikipedia/NAD⁺, Links/Niacin], which enables its sirtuin-activating properties. This will retard the shortening of the genetic clock telomeres in the nucleus that cause nuclear DNA aging [30]. High-gamma Vitamin E (gamma tocopherol to ensure peroxynitrite quenching) and perhaps R-dihydro lipoic acid or alpha lipoic acid should also be taken to cover free radicals dissolved in lipids, since vitamin C only dissolves in water, whereas alpha lipoic acid is soluble in both lipids and water. This should result in superior protection for mitochondrial DNA and cellular aging due to mtDNA aging [Books]. These days I get about 1000 mg of alpha lipoic acid daily, which also effectively opposes the formation of Advanced Glycation End products [Books] that accelerate the formation of free radicals. Acetyl L-Carnitine [Index] 500mg with 200mg Alpha Lipoic Acid [Index] three times a day fights cell sugar damage (glycation of proteins), improves neurite growth, stimulates mitochondrial metabolism, and improves mental energy, vigilance, and perceptual focus. Antioxidant and iron-chelating curcumin is a "Sirius" anticancer star, but today I also get plenty of anticancer odorless garlic (a telomerase inhibitor) and garlic oil, and am worrying about how garlic may be taken otherwise. Heavy metals like mercury from fish or your fillings should be chelated with N-acetyl-cysteine (NAC), curcumin, or perhaps with carnosine. The antioxidant preservative BHT (butylated hydroxytoluene, LifeExtension/BHT) recommended by Dr. Denham Harman helps mice to live 45% longer, so perhaps we should consider using it [Links, Patents, Books; Papers/antioxidant BHT, Patents, Books].
In addition, one should also take broccoli sprouts to combat cancer and tumor formation with sulphoraphane [Index, Links, Books]. I get lots of broccoli with indole-3-carbinol in salads and broccoli sprouts rich in sulphoraphane at least once a month. One should take a multivitamin pill like CENTRUM Performance daily to supply essential vitamins and trace elements like selenium shown to be effective in cancer suppression. It takes one atom of selenium to form the cytoplasmic kind of superoxide dismutase (SOD) antioxidant. Selenium is also found in the endogenous antioxidant glutathione, and is of course required for its synthesis in the body. Another cytoplasmic kind of superoxide dismutase, CuZnSOD, is formed by an atom of copper and an atom of zinc. The mitochondrial type, MnSOD, is formed by an atom of manganese. Supplements featuring bioavailable SOD [52] such as wheat sprouts [64s], SODzyme, and GliSODin may be taken with mind-sharpening SOD-boosters such as nootropic Huperzine A [65s], Ashwagandha [63s], or Deprenyl [92]. Furthermore, calories should be restricted by the reduction of saturated fats, high-sugar foods and high-glycemic load foods [70s]. Try celery for breakfast, or celery with cooked tomato paste to get plenty of lycopene in to guard against colon cancer, and avoid the meat fats giving rise to the carcinogenic secondary bile products that cause it by nourishing carcinogen-producing bacteria. Omega-3 fatty acids from fish and fish oils good for your heart should be substituted for omega-6 fatty acids. DHA is brain food, and it is best to get it in pure form, since the EPA in ordinary fish oil raises your triglyceride levels. The sulforaphane in broccoli, the selenium in CENTRUM, the resveratrol and quercetin in red grapes, and the capsaicin in red chili peppers will help prevent cancer complications involving cells with telomeres that we want to preserve at robust length. Greater-than-RDA levels of folic acid and B-vitamins such as B12 and B6 should help deflect methylation problems and glucose toxicity in glycation [62s]. Lipid-soluble benfotiamine [Books], the lipid soluble-form of vitamin B1, is found in trace amounts onions, so I wolf down an onion sandwich every day. (Be sure to mind your breath spray while you're at it.) Using a benfotiamine pill for a dose of 100 mg or more is preferable to taking trace quantities of it found in onions, garlic, shallots, or leeks. Also, pumping up via weight lifting every day using a 3-day split routine to cover the entire body increases the HGH human growth hormone level, and stimulates the pituitary gland or the pineal gland into behaving as if you are a useful specimen that ought to be preserved. It improves your carnosine reservoir, if that is actually a factor. It's best to take whey protein to enhance your HGH levels, and to get micronized creatine monohydrate for quality muscle contractions. Include an amino stack to optimize HGH, which opposes cortisol, an aging accelerator we must foil with HGH and DHEA (dehydroepiandrosterone). To this you may add other antioxidants such as vitamins A and vitamin E, blueberries with other dopamine enhancers like Deprenyl for your brain, and other phytochemicals described below [25] including curcumin (from turmeric, and with black pepper added to improve curcumin bioavailability), green tea, grape seed extract, garlic, red grape skins, pecans, walnuts, tomatoes, spinach, and red chili peppers. I use a low-fat blueberry yogurt with plenty of whey protein in it that is just 80 calories per cup, delicious, and full of anthocyaninin antioxidants. To this I add a 3-tablespoon chilled cocoa powder in water drink daily for PQQ, chocholate polyphenols, and flavonols, remembering how chocolates were used by super centenarian Madame Jeanne Louise Calment for effective life extension. Like Jeanne, I go over my skin with extra virgin olive oil frequently, and get plenty of cooked tomato paste to up the antioxidant lycopene input. Raspberry seeds and mixed nuts contain anticancer ellagic acid and should be taken. The polyphenol resveratrol found in red grape skins has been shown to increase the lifespan of yeast, worms, flies, and no doubt of 122 year old aging record holder Madame Jeanne Louise Calment, so eat red grapes and supplement your intake of resveratrol. Quercetin (a telomerase inhibitor and SIRT1 activator) improves resveratrol bioavailability [Papers], so take it with quercetin-rich apple slices or red grapes. Madame Jeanne Louise Calment was also fond of her olive oil [76], containing the powerful antioxidant hydroxytyrosol and anticancer compounds squalene and oleic acid, so take more olives and olive oil with antioxidant lycopene or tomato juice. Extra virgin olive oil has fewer toxic impurities than cooked olive oil, and since olive oil lowers LDL and raises HDL cholesterol, it is the optimum component for salad dressings. Just add the spices and hold the vinegar, as it does not help the antioxidant problem by making your pH more basic. The polyphenols found in green tea [25a] may also be responsible for long lives, so take it, but never on an empty stomach. Not eating mammals will reduce the level of cholesterol deposits on the inside of your veins and arteries by reducing toxic homocysteine levels due to incomplete methylation of methionine from red meat [69s]. Trimethylglycine (TMG) might be taken instead to improve methylation without generating a lot of homocysteine. I think tuna fish or mackerel fish with favorable omega-3 fatty acids should be substituted for mammal meat, such as Salmon, Herring, Mackerel, and Bluefish. Remember, your blood pressure goes up as the inverse of the fourth power of the inside radius of your veins and arteries, and we need to prevent strokes and heart attacks from this source, as well as from hypertension due to high salt levels or nervous stress associated with high cortisol levels. Cooking eggs in sesame oil lowers blood pressure partly via its sesame lignans. Some skim milk each day can provide the 9 essential amino acids histidine, lysine, tryptophan, phenylalanine, leucine, isoleucene, threonine, methionine and valine from casein, the principal protein in milk, from which the rest of the 20 or 24 (L.Pauling) important amino acids may be synthesized internally. This also provides calcium to guard against old age shrinkage [102], which also requires vitamin D and HGH. Separate taking skim milk from eating dark chocolate by at least an hour [25], as milk interferes with absorption of dark chocolate polyphenol antioxidants. Soy protein food products and soy isoflavones have many benefits, lowering cholesterol and triglycerides, and tending to prevent cancer, cardiovasular disease, osteoporosis, menopausal syndromes, high blood pressure, metabolic syndrome, and type 2 diabetes. 25 grams of soy protein per day (20-90 mg of soy isoflavones) is an effective dose for lowering cholesterol. Soy milk comes in many flavors and without solid bulk is quite slimming. (However, 1/2 gallon soy milk per day for 2 days can cause constipation and burning urinary tract that would be worrisome to a dog.) Eat the world's healthiest foods and understand their properties and compositions. (See Linus Pauling on Micronutrients.) Melatonin [1], shown to be effective in anti-aging medicine, should be taken before bedtime only. Experimenters found that mice fed extra melatonin lived 20 percent longer than control mice. Curcumin mixed with black pepper to improve bioavailability should also be taken for its excellent neuroprotective and anticancer properties. Otherwise, pre-rinse teeth before brushing with antiplaque mouthwash to prevent build-up of tartar and ward off inflammation associated with Alzheimer's disease [72], brush with an anticavity and whitening fluoride toothpaste like Ultrabrite to prevent tooth decay, spit it out, then use a remineralizing and enamel-hardening mouthwash, which keeps the teeth in an environment with the pH > 5.5, preventing the deminaralization associated with dental caries. Floss at least once a day to clean the proximal surfaces of teeth, and be sure to brush all tooth surfaces. Use an age-defying skin cream with CoQ10, DMAE, carnosine or astragaloside IV to fight wrinkles and cellular wastes in your skin. Grape seed oil also helps with lines around the eyes. Note that Ubiquinone (CoQ10) [39] controls lipofuscin (waste buildup in the cell), a cellular senescence mechanism distinct from telomere shortening. Wastes associated with lipid peroxidation accelerate free radical damage and should be flushed out with CoQ10, DMAE, centrophenoxine, or Piracetam. I find DMAE inexpensive and take 300 mg/day when I can to work on the cellular aging mechanism involving cell membrane penetrability to potassium. Ubiquinone is widely available as the health food store supplement CoQ10 (coenzyme Q) and probably should be taken to cover for lipofuscin cellular senescence, which gradually turns your heart black as time goes on. The new super bioavailable ubiquinol CoQ10 is about 8x better milligram per milligram. As I recall, CoQ10 tags a glycolized protein lipofuscin waste molecule with 3 CoQ10 molecules, so that the waste molecule is excreted by the cell. Acetyl L-carnitine can also be used to undo protein glycolization that results from sugar damage [47] to proteins. Both CoQ10 and Acetyl L-carnitine are substances normally found in the body and both improve your mental energy and perceptual focus. Acetyl L-carnitine plus alpha lipoic acid is sometimes prescribed. Studies showed that old rats behaved like young ones then. "ALT-711" (Alagebrium) has also been proposed as a cure for glycolized proteins. Finally, chromium picolinate can supply a chromium molecule essential for the cleaving of insulin, and has been shown to increase the life span of laboratory mice 15%. However, there are fears it can be dangerous to DNA and that it is mainly good for loosing weight. In any case, a low-glycemic load, low-sugar diet is preferred to deflect chronic low-grade inflammation [70s]. Perhaps at least 500 mg per day of carnosine [69], a naturally-occurring substance in fast-twitch muscle fibers present in red meat, poultry, and fish, should be added to this program. High doses of carnosine can be taken, up to 500 mg per kg of body weight in a single serving without toxic effect. Some authors recommend 500mg to 2000 mg per day, and I suspect 500 mg every three hours would be best, although this more than most of us can afford. Additional anti-aging therapies should be considered. A homocysteine screen including TMG (trimethylglycine), vitamin B6, B12, and folic acid will not only protect you against atherosclerosis, but will help preserve telomere length, like the antioxidants on our list. NSAIDS [Links] are neuroprotective against Parkinson's disease and other neurodegenerative disorders, but NSAIDS can also cause ulcer problems, so I am not taking them. Inflammatory COX-2 enzymes can be inhibited with curcumin in turmeric or from gingerols in ginger without hitting the stomach-protective COX-1 enzyme. Tart cherries might also be an effective substitute for NSAIDs, which can cause ulcers if they inhibit COX-1 like aspirin. Old age diseases like macular degeneration [Index] [101] can be guarded against by taking lutein and zeaxanthin, found in orange juice, egg yolks, lettuce, and supplements along with a homocysteine shield to stop associated atherosclerotic plaque. Some curry powder, curcumin, or turmeric should be taken (with black pepper to provide piperine for improved curcumin bioavailability) to chelate copper and iron and head off mitochondrial aging, dementia, heart disease, and cancer (12). Alpha Lipoic Acid may be the best commonly available thing for mitochondrial aging, and I get my inexpensive brand of it from Wal-Mart these days. Another important drug in mitochondrial membrane maintenance is definitely ubiquinol CoQ10, the new "super bioavailable CoQ10" eight times as bioavailable as standard ubiquinone CoQ10. To repair hydroxyl-radical damage to cell membranes, I use DMAE, and am considering Centrophenoxine, which is more expensive and more difficult to obtain in the USA. A phospholipid exchange using phosphatidylcholine (lecithin) is also a promising route to cell membrane repair.

Protecting Aging Cardiomyocytes & Vasculature
Cardiomyocyte aging of heart muscle cells [Links, Books, Books2, LifeExtension] is perhaps best repaired using ubiquinol CoQ10 (Life Extension's super bioavailable CoQ10), pomegranate juice or extract, DMAE, DHEA, resveratrol, carnosine, gamma tocopherol, vitamin E, bilberry extract, and alpha lipoic acid in combination with a low-calorie Mediterranean diet [Books] including a good deal of lycopene, fish, and olive oil together with a program of healthy exercise and plenty of antioxidant cocoa powder. Heart problems (cardiovascular disease) begin to converge toward the end of a lifetime, while the primary earlier cause of death seems to be cancer. Also, I note that Geron lists cardiomyocytes and vasculature as benefiting from pulsed-on-then-off telomerase activation treatments [81s] featuring astragalosides, cycloastragenol, or ginsenoside RH1. Vitamin C to prevent degeneration of collagen, a low-sugar diet with carnosine, vitamin B1, and benfotiamine to oppose glycation, and turmeric with curcumin to prevent free radical Fenton reactions should help prevent degeneration of heart tissue, which should also be protected by avoiding alcohol, which promotes ceroid (lipofuscin) deposits, and by avoiding the smoke of cured tobacco, browned poultry skins, and other food browned by the Maillard reaction, all of which import fully-formed advanced glycation end products into tissue. Bilberry extract strengthens capillary walls, and fortifies the brain against stroke, in addition to protecting vasculature in the heart.
We also take 4-6 grams of L-arginine [Links] per day with 1 gram of L-citrulline [Links] (found in watermelon rind) to generate nitric oxide (NO) from nitric oxide synthase from bodybuilding exercises for maintaining the heart, following Nobelist Dr. Louis B. Ignarro's program outlined in NO More Heart Disease. Gamma tocopherol may be taken to protect the cell membrane against peroxynitrides. In addition, one takes the 4 antioxidants vitamin C, alpha lipoic acid, folic acid, and vitamin E. The L-citrulline helps maintain the NO supply for a longer period of time than results from the use of L-arginine alone,allowing NO to reach more cells. From studies by Vasa and Hayashi [Vasa, et al., 2000, Hayashi, et. al, 2006], we recognize that nitric oxide lengthens telomeres in the vascular endothelium, rejuvenating senescent cells there, tending to deflect heart attack, stroke, and atherosclerosis. This can also rejuvenate the thymus gland, allowing it to produce fresh T-lyphocytes. On the other hand, [Erusalimsky JD, 2009] indicates that NO activates SIRT1, not telomerase, to perform it's life-extending tricks, a contention also supported by [ Hong Y, Quintero M, Frakich NM, Trivier E, Erusalimsky JD, 2007].
Vitamin D [Index, Links/Vitamin D; Links/vitamin D and telomere loss, Books, Papers] attenuates telomere loss rates in leukocytes and many other cells. However, it is a telomerase inhibitor that might interfere with a telomerase activator if taken at the same time. According to William Falloon of Life Extension Magazine, men with low vitamin D levels suffer 2.47 x more heart attacks. He recommends 1000 IU per day, which is inexpensive. A 142% reduction in heart attacks was seen with vitamin D. Women deficient in vitamin D have a 253% increased risk of colon cancer, and women with the lowest level of vitamin D had a 222% increased risk of breast cancer. Men with higher levels of vitamin D have a 52% reduced incidence of prostate cancer. vitamin D also helps prevent strokes.

Chromosome Reconstruction with Telomerase Activation and DNA Repair
TA-65 (4x8 mg/day), Terraternal cycloastragenol (25 mg/day) or an equivalant telomerase activator [Index] (7) may be used to reconstruct short telomeres with cyclic telomerase activation. RevGenetics Astral Fruit NF contains more than 2.5 mg of cycloastragenol/cap, in addition to supplemental telomerase activators like aqueous extract of Purslane, Haritaki, and astragalus extract. The people's small molecule telomerase activator [81s/6b, List] is GAIA Herbs Astragalus Root Extract in glycerin (1 mg astragalosides/30 drops), taken at greater than 5 mg of astragalosides per day (> 150 drops/day), two weeks on and two weeks off, continuing over the course of a year, with 2 grams of chitosan to improve bioavailability. According to recent Chinese experiments on Beagle dogs that could tolerate 2.85–19.95 g/kg, we suspect that quite large doses of Astragalus Root Extract may be taken. Alternatively, I take at least 6 x 200 mg Solaray Astragalus Root Extract capsules per day for 15 days of the month to get > 5 mg astragalosides per day during the "on" part of the treatment cycle. Another alternative is to take 4 capsules of Nature's Way Astragalus Root Extract, available from Herbal Remedies. Note that smaller doses of astragalus root extract are used to deflect virus infections by activating interferon, while we are trying to activate telomerase with higher doses of the same medicine. During the first two weeks of each month on one must avoid telomerase inhibitors [81s] such as garlic, turmeric (curcumin), resveratrol, quercetin, vitamin E, green tea, melatonin, silymarin, and fish oil EPA, applying them during the next two weeks. Since a high-polyphenol diet can produce telomerase inhibitors, during the first two weeks of each month I recommend a low-polyphenol diet during that period. This keeps the cost at about what it was before using telomerase activators [Index, List] to re-extend your telomeres to repair the tip-ends of your aging chromosomes [Index/Gene]. However, this program is not yet well established. Cycloastragenol at 25 mg/day is probably superior in such a program, and cycloastragenol, the common structural element in the astragalosides, is readily available at this time in TA Sciences TA-65, Terraternal cycloastragenol, Iron Dragon cycloastragenol, and RevGenetics Astral Fruit NF. Note that the astragalosides improve wound healing, and that telomerase activation of stem cells can restore their ability to proliferate. Finally, the DNA repair enhancer Cat's Claw extract is available and some months I can take it for about $10/month in the 2nd part of the month's telomerase activation on-off cycle. I am still doing without the chromatin remodeling factor sodium 4-phenyl butyrate to maybe stretch my telomeres, but I may try it later. Sodium butyrate [Images] is available now in pill form to perhaps accelerate hTERT transcription from the butyrate-expanded chromatin. Sodium 4-Phenylbutyrate, which lengthens the life span of Drosophila, may also be used to expand chromatin for transcription. Supplementing magnesium may help telomeric DNA helicases work better to maintain telomeres, and definitely helps lower blood pressure.

Opening Telomere T-loops for Telomerase Repair and Application of Novel Activators
It has become clear that niacinamide (nicotinamide) improves the expression of tankyrase 1, a telomeric PARP which poly(ADP-ribosyates) the telomere t-loop closure protein TRF1, allowing it to detach from the telomere loop, so that the loop can open and provide access to telomerase. Up to 1 gram/kilogram of niacinamide has been given to experimental animals to boost their tankyrase 1 levels, but the recommended human maximum dose is < 3 grams/day, so I am considering trying nicacinamide in that range. It rarely causes side effects. I am taking nicinamide in the morning to develop adequate levels of NADH for poly(ADP-ribo)sylation of TRF1 in the evening, and to dimenish niacinamide strength in the evening, because niacinamide itself can interfere with the action of PARP enzymes such as tankyrase 1. Upregulating telomerase expression continuously has been observed to lengthen telomeres. Niacinamide is often taken at 1x or 2x 700 mg/day. Niacinamide-treated dermal fibroblasts at 5 mM niacinamide showed 75 population doublings at 25 mM glucose, and 83 population doublings at 5.5 mM glucose, with excursions to 125 population doublings at normal glucose levels according to Kang, et al., 2006. The canonical Hayflick Limit for such cells is 49 population doublings. The earlier cells were treated with niacinamide, the more their life span was extended. Furthermore, tankyrase 1 may become active for removal of TRF1 by phosphorylating tankyrase 1 with insulin. Therefore, the telomerase activator diosgenin contained in Fenugreek seeds and Fenugreek extract (which activatates production of the HIF-1 transcription factor for hypoxia) becomes attractive, because it also contains 4-hydroxyisoleucine, which increases insulin secretions. Insulin secretion boosting is best limited to after a workout, which also boosts levels of heat shock proteins that transport telomerase activating factors into the cellular nucleus. Therefore, Fenugreek seeds or extract and any other telomerase activators should be taken near the conclusion of an evening workout. Furthermore, arginine should probably be taken at < 10 grams 30 minutes to an hour prior to workout along with L-lysine at 1500 mg to boost HGH levels and dilate blood vessels for transport of these factors to cells. Furthermore, Nitric Oxide (NO) from arginine prior to the workout activates telomerase in vascular endothelial progenitor cells as it assists with transport. Forskolin, which should also be taken prior to the workout, darkens hair and upregulates testosterone, so that androgen-sensitive cells such as heart muscle stem cells and hair follicle melanocytes experience telomerase up-regulation. These measures should be introduced during the first 15 days of the month, when telomerase is to be upregulated to lengthen telomeres, before applying telomerase inhibitors for 15 days to maintain anticancer defenses.