Anti-Aging Medicine: Sup Notes 3a | 3b1 | 3b2 | 3b4 | 3b5 | Product B Explorer | 3b6
One, Two, Three,...Infinity: A Lucky Strike.
Telomerase is a 123 Kilodalton enzyme.
Rejuvenation via Cyclic Telomerase Activation (7)

Phase I: For 0 < t < 57.967123 = t0, B = 1,
Model Age = Bt.
Phase II: For 57.967123 < t < 64.3, B = - 5.2 years/yr,
Model_Age = B(delta_t) + t0 = (B/12)N + 57.967123,
N = 1, 2, 3,...,76 months, using astragalus extracts.
Phase III: For 64.3 < t < infinity, B = 0,
Model Age = 25.
Press for Age Transformation's FLIGHT PLAN.

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Highlight Links 3a
[74s] Hair Loss, TERT, Saw Palmetto with Beta-sitosterol, Finasteride, Dutasteride, & PABA.
[75s] Carbonylation of Proteins.
[76s] Nanomedicine.
[77s] Microglia in the Aging Brain are telomere-limited, subject to replicative senescence.
[78s] Jekyll-Hyde Formulas for Life Extension, including Turmeric with Pepper, Cocoa powder drinks, Wasabi, and Astragalus.
[79s] Rejuvenation to produce anti-aging transformations.
[80s] Notes on The Anti-Aging Solution by Giampappa, Pero, and Zimmerman.

Highlight Links 3b1 - Telomerase Inhibitors
[81s] Life Extension via Telomere Extension in Vivo, with Cells that Respond to Telomerase Gene Transduction.
____Telomerase Inhibitors (1)-(73) with hyperlinked numeric and alphabetic selection guides.

Highlight Links 3b2 - Telomerase Activators
____Telomerase Activators (1)-(185), with hyperlinked numeric and alphabetic selection guides.
[81s/6b] Astragalalus-based small-molecule telomerase activators and others.
[81s/6d] 230 base pairs of telomere growth per 3 months of treatment with TA-65. - TA Sciences, Greta Blackburn letter.
____More Telomerase Activators (7)-(22).

Highlight Links 3b4 - Telomerase Activators
____Still More Telomerase Activators (23)-(64).

Highlight Links 3b5 - Telomerase Activators
____Still More Telomerase Activators (65)-(132).
____Telomere Measurement.
____Telomerase Expression Measurement.
[81bs] Senile purpura.

Highlight Links 3b6 - Telomerase Activators
____Further Telomerase Activators (154) - (185).

[74s] Hair Loss, hTERT, Saw Palmetto with Beta-sitosterol, Finasteride, Dutasteride, & PABA.
Most recently, extra TERT in mouse skin has been shown to affect stem cells in a way that promotes hair growth, so that perhaps small molecule telomerase activators may be useful in promoting human hair growth. Vince Giuliano states in his blog on hair follicle theory that his hair has been returning since using an astragaloside IV supplement. Terraternal markets astragaloside IV skin cream, and I have been using GAIA Herbs astragalus extract in glycerin at 30 drops per 1 mg of astragalosides on my scalp since it became available again in August 2010. See Kavita Y. Sarin, Peggie Cheung, Daniel Gilison, Eunice Lee, Ruth I. Tennen, Estee Wang, Maja K. Artandi, Anthony E. Oro, & Steven E. Artandi, 2005, Conditional telomerase induction causes proliferation of hair follicle stem cells, Nature 436, 1048-1052 (18 August 2005). In other words, astragalosides from astragalus extract or ginsenoside Rh1 from Korean Ginseng Extract may be useful in restoring hair. (However, Korean red ginseng extract is a net telomerase inhibitor, probably due to ginsenoside Rh2 content.) Astragalosides, in particular, are known to promote stem cell proliferation, as required according to research at Artandi Labs. See also Ramirez et al., 1997 on telomerase expression in human hair follicles [Papers, Books]. "Intuition suggests that telomerase intervention might effectively restore hair growth in elderly males." - Michael Fossel, Cells, Aging, and Human Disease, p.160. Fossel also notes that among progerics, whose fibroblasts exhibit short telomeres, baldness is almost universal. Toxicology literature and experiments in progress seem to indicate that astragalus extract in glycerin at 30 drops/mg of astragalosides, say formerly GAIA astragalus extract, may be applied directly to the skin and scalp. In treatment with telomerase activators [81s], skin constitution is restored to young skin after about 20 population doublings are added. (Fossel, p.156). Note that TA Science's TA-65 (probably cycloastragenol) can add 230 base pairs to blood granulocyte telomeres in vivo in just 3 months. For typical cells on the average, 20 doubling x 50(bp/doubling) = 1000 base pairs, so that a couple of years would be typically required, since telomerase is turned on for just two 3-month periods in a year using the TA Sciences Patton Protocol. That is, they get 460 bp/year, so that 1000/460 = 2.174 > 2 years should be required to thoroughly rejuvenate typical cells with TA-65. After 3 or 4 years of plenty of astragaloside application, we should probably expect to have achieved serious rejuvenation effects. Since 460 >> 50, we may seem to feel the aging clock ticking backwards in time with a rejuvenation rate of up to -9 years per year, although I recently seem to see about -5.2 years/year using Telomere Remodeling with Cyclic Telomerase Activation for Age Transformation. See (7)/Rejuvenation Rates.
Saw Palmetto, when combined with Beta-sitosterol [Links/Saw Palmetto with Beta Sitosterol, Ray Sahelian's with remarks on hair loss, LifeExtension], has been shown to treat hair loss and baldness by blocking dihydrotestosterone formation from testosterone, which happens when saw palmetto or finasteride (Wikipedia, Proscar, Proscar for hair loss, ProcepiaTM [Links]) blocks 5-alpha-reductase. Dihydrotestosterone is thought to kill off hair folicles. Blocking the formation of dihydrotestosterone is also used to block prostate cancer. According to Jerry Brainum (Iron Man, March 2010) writing on prostate cancer, green tea also blocks the formation of dihydrotestosterone. I have been using green tea on my own scalp in 2010 for the last 2 weeks of the month, applying astragalus extract in glycerin for the first two weeks of the month. A new, potent dual 5-alpha-reductase inhibitor of both type I and type II enzymes (there are two isoforms of 5-alpha-reductase) that halts dihydrotestosterone (DHT) production is the relatively expensive Dutasteride (Avodart) [Links/Dutasteride, Images/Dutasteride, Links/Avodart, Images/Avodart, Wikipedia/Dutasteride, Books/Dutasteride, LifeExtension], which is more effective at stopping hair loss than Finasteride. "Scalp DHT was decreased 38% for Propecia/Finasteride compared to 54% for 0.5mg Dutasteride." It turns out that Dutasteride [Images] inhibits both the type 1 and type 2 enzymes responsible for the conversion of testosterone to DHT (dihydrotestosterone), which Finasteride [Images] did not do. Also, topical hair lotions containing saw palmetto have been devised to treat hair loss.
See Life Extension on treatments for hair loss [Links, Books, Papers, Patents]. See also IAAS/Dercos containing the chemical Aminexil, and the IAAS Hair Program. See Inhouse Pharmacy on these and other drugs for treating hair loss. "6-24 grams of PABA (Para-AminoBenzoic Acid, Links) per day for six weeks caused dramatic hair color change and hair regrowth in 5 patients out of 20. With markedly grey hair (hair color returned to grey within three to four weeks of ceasing PABA treatment)... 200 mg of PABA per day for two months resulted in marked darkening of the hair in nearly all participants." I note that "Excessive levels of PABA are stored in the body and may cause liver damage". Since 50 mg is a typical supplement dosage, I suppose 6-24 grams/day may eventually cause liver damage. Melancor [Links] is now formulated to inhibit 5-alpha-reductase to fight receding hairlines, and also promotes dark hair coloration with melanin. See also NuHair. A pharmacist at Walmart recommended Rogaine for treating hair loss, a preparation which contains minoxidil [description, Wikipedia, Books, Papers, LifeExtension], and I noticed another brand that was a considerably more economical, "equate", which also contained minoxidil. These preparations are applied topically and are supposed to regrow hair. Men's Rogaine is a 5% solution, women's is a 2% solution. Dillons makes relatively inexpensive minoxidil solutions available. Rogaine (minoxidil) treatment must be continued for a couple of months to see results, and must be continued thereafter to maintain results. No one quite understands how minoxidil works, however. The amino acid L-Lysine treats various types of hair loss by inhibiting 5-alpha-reductase, although its application to hair loss is covered by a US Patent. Green tea contains catechins that also work by inhibiting 5-alpha-reductase. The amino acid L-arginine is required to produce nitric oxide, which is used by hair follicles to maintain and promote new hair growth, so that it is sometimes applied in hair regrowth formulas. For more on the pharmacology of balding and hair loss treatment, see LifeExtension/Balding. The article notes that eunuchs or she males have low levels of testosterone and do not lose scalp hair via the 5-alpha-reductase testosterone-to-dihydrotestosterone conversion mechanism.

Recently, (Feb 2010) the Life Extension Foundation has been marketing Super-Absorbable Tocotrienols, featuring tocotrienols together with co-extracted phytonutrients including squalene, phytosterols, and trace amounts of mixed carotene. Within 8 months, nearly all subjects in a study including 30 volunteers showed marked improvements in hair thickness and density. According to LEF, "The adult scalp loses about 100 hairs every day. Starting at age 40, hair follicles shrink, causing hair to grow thinner, or worse, not at all.... Using a supplement with tocotrienols can be pivotal in addressing the various physiological mechanisms that lead to thinning hair."

See also Hair Loss is Reversible by Tom Hagarty, Immortalhair.org, and Vince Giuliano's notes on the problem at Anti-Aging Firewalls: More Research Insight on Gray Hair and Adult Stem Cell Reproduction. Also see Vince's Anti-Aging Firewalls Blog.
Google Links: Baldness and Saw Palmetto, Treating Hair Loss, Beta Sitosterol [Vitacost/Beta Sitosterol].
Google Books: Baldness and Saw Palmetto, Treating Hair Loss.
Life Extension Search: Hair Loss Treatment, Hair Greying Treatment, Dihydrotestosterone, Hair Follicle Microenvironment, Catechins, Nitric Oxide, Blocking 5-alpha-reductase, Saw Palmetto, Dutasteride.
IAAS Hair Improvement Program.
Hair Transplant Solutions: [Medical Hair Restoration All-Stars, Links, Books, Amazon, LifeExtension/Hair Transplants].

Greying of Hair [Refs6, Index]: Tyrosine [Wikipedia, Links; Links/food sources of tyrosine] may be supplemented to support melanin synthesis, counteracting the greying of hair. [Links]. A tyrosine kinase inhibitor named Gleevec [Links, Images/Gleevec, Books/Gleevec] has reversed grey hair in some patients. Other vitamins, minerals, and chemicals are useful in anti-greying hair treatments [Links, Papers, Books, Patents]. Melancor may be used to more directly supplement melanin. See also footnote [48].
Tyrosine [Wikipedia, Links] is not one of the 8 essential amino acids, but is present to some degree in skim milk and cheeses. (Warning: cheeses 70% fat, except for cottage cheese, which has the highest concentration of tyrosine and is just 2% milkfat.) I note that tyrosine kinase inhibitors like Gleevec [Images] are given for greying of the hair and cancer of the colon, so that perhaps tyrosine supplementation would be useful for those suffering from these disorders. In aging specimens, synthesis of tyrosine from hydroxylation of phenylalanine [Wikipedia] may be degraded. Note that phenylalanine must be abundantly supplied for tyrosine to be synthesized in animal tissues. "Phenylalanine is contained in most protein rich foods, but especially good sources are dairy products (curd, milk, cottage cheese), avocados, pulses and legumes (particularly peanuts and lima beans), nuts (pistachios, almonds), seeds (piyal seeds), leafy vegetables, whole grains, poultry, fish and other seafoods." - Wikipedia.
Greying hair [Wikipedia/hair color, Wikipedia/Grey Hair] is sometimes described as due to stem cell failure that no longer renews a melanocyte hair coloring cell in the hair follicle, so that the melanocyte dies and the hair turns white. This was a news story in 2004. I believe I have observed that hair follicle melanocyte stem cell renewal via telomerase activation with astragalosides can restore the melanocyte to the hair follicle after the transition has taken place. I have suggested in Age Transformation that perhaps
(1) Terraternal Astragaloside IV skin cream,
(2) Astragalus Membranaceus Root Extract in glycerin,
(3) IGF-1 liposome spray, or
(4) Progesterone skin creams
might be used for hair follicle melanocyte stem cell renewal by direct application to the scalp, via a favorable effect on the hair follicle microenvironment. (See Hair Clippings after 32 months of oral administration of astragalosides as described in Age Transformation and Rejuvenation via Cyclic Telomerase Activation. I suspect that costimulation with astragalosides applied to the scalp in a skin cream such as Terraternal Astragaloside IV skin cream or measures (1) through (4) above would have produced somewhat better results.) I note that Geron and Telomolecular Nanotechnologies seemed to believe that white hair can be restored to normal dark hair using telomerase activation [Links/hair restoration with telomerase, article]. There are products on the market now that claim to restore hair and hair color with telomerase activation, such as iGrowHair Telomerase [Links/telomerase excreting acidophilus, Wikipedia/Lactobacillus Acidophilus: improves immune function]. I seems fairly definite after 14 months that my hair is getting darker as I experiment with telomerase activation, but then my hair looks dark after a shower when it is wet, and greyer later... (See Hair Clipping Detail/Water Wet after 32 months) perhaps explaining ancient popular belief in baptism. Just plunking a handful of water on the top of my head makes me look 5-10 years younger - it must help! On the average, 50% of persons have 50% grey hair by age 50 [Hisama, Chromosomal Instability and Aging, p.565], about the density of grey I now display. The density of hair growth is still slightly down from peak, and skin firmness and skin tone are improved, but still a bit degraded from prime. I conjecture that more intensive application of astragalosides in glycerin to the scalp would be useful. Unfortunately, a liposome cream for topical astragaloside application is not available off-the-shelf, but must be specified as a custom preparation [Links/custom liposome creams, Books; Links/liposome creams, Books, Papers, Patents]. However, NOW Foods manufactures a Liposomal IGF-1 Spray that might be suitable, and astragalus membranaceus root extract in glycerin may provide an adequate solution, as may progesterone skin creams or Terraternal Astragaloside IV skin cream.

[75s] Carbonylation of Proteins [Books, LifeExtension] (Glycation of proteins) "As cells age, after many cell divisions, proteasome activity declines (Sitte N et al., 2000; Merker K et al., 2000). At the same time, more and more proteins undergo damage through a process called carbonylation. Thus the proteolytic system becomes increasingly inadequate to deal with the increasing numbers of abnormal or unneeded proteins, which can irreversibly form cross-links and turn cellular processes awry." - LifeExtension, Carnosine and Cellular Senescence, 2001. "Carnosine...both protects proteins from carbonylation and helps reverse proteasomal decline." - LE [Papers, LifeExtension].
[Wikipedia/Glycation, LifeExtension/Glycation]. Why, perhaps the body can be run on fatty acids by processing them with mitochondria to yield ATP, so that sugar levels can be kept quite low. Olive oil might become one's primary source of calories, for instance. However, in reality blood sugar must be kept up to avoid hypoglycemia with symptoms including lethargy, degraded mental functioning, irritibility, and loss of consciousness, even [Wikipedia].

[76s] Links/Nanomedicine, Papers/Nanomedicine, Books/Nanomedicine, Wikipedia/Nanomedicine,
LifeExtension/Nanomedicine

[77s] Microglia in the Aging Brain - Fix from Hemopoietic Stem Cells, perhaps from Bone Marrow. See also [J Neuropathol Exp Neurol. 2006 Mar;65(3):199-203.].
Microglial cells [Wikipedia/Microglial cells, Links, Images, Books, LifeExtension/microglial cells in the aging brain] in the brain divide and are telomere-limited, so that they can undergo only a finite number of cell divisions. There are 4 kinds of glial cells in the brain [Wikipedia, Links, Images, Books, LifeExtension, A4M] in addition to
neurons with axons and dendrites [Links, Images], including
(1) oligodendrocytes [Links, Images] (do not continue mitosis),
(2) astrocytes [Links, Images] (do not continue mitosis),
(3) ependymal cells [Links, Images] (do not continue mitosis), and
(4) microglia [Links, Images] (continue mitosis).
The oligodendrocytes maintain the myelin sheath [Images] around axons, astrocytes transport nutrients to the nerve cells and regulate the external chemical environment, ependymal cells maintain cerebrospinal fluid, and the microglia clean out garbage from failed neurons via phagocytosis. Most glial cells do not continue mitosis, excepting microglia, which are derived from hemopoietic stem cells [Wikipedia, Books, LifeExtension] in bone marrow [Books, Papers] or in the blood of patients with bone marrow treated to release hemopoietic stem cells [PNAS,February 4, 2003,vol. 100,no. 3,1364-1369]. "Microglia are immunocompetent monocytes usually replaced from hemopoietic stem cells that divide and ultimately senesce." - (M.Fossel, p.227). "Microglia...are an increasing source of inflammatory mediators in older human brains, particularly after exposure to amyloid-beta peptide." - (M. Fossel, p.233). According to Michael Fossel, the monocytes play a role not only in microglial inflammation observed in Alzheimer's dementia, but as cells in atherogenesis, and as osteoblasts in osteoarthritis. "Alzheimer's Disease may be a process in which senescing microglial cells become activated and trigger severe inflammatory changes, culminating in neural destruction." (M.Fossel, p.237).
By this time (2007), it seems likely that the best way to preventively treat the problem of microglial cell senescence is with small molecule telomerase activators (7) such as TA-65, astragalus extracts, cycloastragenol, astragaloside IV, or other molecules with similar telomerase-activating properties [81s] that combat cellular senescence by lengthening telomeres at the ends of chromosomes. Astragalus extract is known to improve stem cell numbers and characteristics and to lengthen telomeres. Prior technique that seemed acceptable in the past is described below:
It seems likely that microglial cell death after attaining replicative senescence by telomere clock wind-down can be avoided by inserting hemopoietic adult stem cells containing the patient's own DNA, by transfusion of cells saved earlier and perhaps telomere-extended with telomerase treatment, or by transfusion of blood taken from sources with bone marrow pre-treated to release hemopoietic stem cells [Papers]. Techniques for externally preparing stem cells for implantation into bone marrow [Papers] may be important in saving microglia by treatment to release hemopoietic stem cells [Papers]. For instance, embryonic stem cells [Images] may be prepared by nuclear transfer, extracted from a blastosphere, specialized as hemopoietic stem cells, cultured, and prepared for implantation into bone marrow on a scaffold. It is now also possible to prepare embryonic stem cells from the patient's skin cells (8), specialize them as hemopoietic stem cells, culture them, and have them likewise prepared for implantation into bone marrow on a scaffold. The 2nd method of preparing embyronic stem cells from skin cells via nuclear reprogramming is politically more popular than securing human embryonic stem cells by taking human blastospheres apart. I note that it is desirable to have such cells prepared in excellent condition with long telomeres, perhaps by culturing the cells in the presence of telomerase activators, to safeguard them from replicative senescence. However, telomerase activators are typically so slow (less than |-9| years per year absolute rejuvenation rate) that the telomere extension might be something that must be confined to conservative in situ treatment. The safe rate of telomere growth in base pairs per year for cultured hemopoietic stem cells in vitro should be determined for each telomerase activator or telomerase activation method based on gene therapy, say by insertion of another gene for hTERT into the stem cell genome. Equipment for sorting hemopoietic stem cells after treatment to apply telomerase activation may be useful. Alternatively, the patient's own hemopoietic stem cells [Images] may be extracted, cultured, telomerase treated to re-extend telomeres, and re-implanted in bone marrow with chemistry provided to release some into the blood stream to refresh brain microglia. See stem cell and cord blood treatments [Books] available from The Institute for Cellular Medicine and Aastrom Biosciences. See also US Patent 5004681 on Preservation of fetal and neonatal hemopoietic stem and progenitor cells of the blood: "Reconstitution of the hemopoietic system has been accomplished by bone marrow transplantation.... The present invention is directed to hemopoietic stem and progenitor cells of neonatal or fetal blood, that are cryopreserved, and the therapeutic uses of such stem and progenitor cells upon thawing." In the future, one's own neonatal or fetal blood might be saved for autologous treatment later, although the methylation pattern of early fetal DNA is not exactly the same as the methylation pattern (familiar from epigenetics) that one has in the adult state in most kinds of cells after human development and cellular differentiation. I am trying to determine how seriously this may impact autologous blood transfusions or hemopoietic stem cell transplants. See also Books/Bone Surgery, Books/Bone Marrow Surgery, Books/Bone Marrow Transplants, Books/Culturing Bone Marrow, Books/Bone Marrow Culturing, Books/Hematopoietic Stem Cell Culturing, Books/Peripheral Blood Stem Cell Transplants, Books/Stem Cell Injections.
Also see Human Cells Limited by Replicative Senescence [Links, Papers, Books]. Many human cells such as regular neurons with axons and dendrites do not continue mitosis, and so are not limited by replicative senescence, as opposed to cells like the microglia which continue to divide. However, premature stress-induced senescence modifying gene expression in such cells is a problem that can be partially addressed using hTERT activation techniques. Note that recent diligent research has shown by this time (2007-2010) that neurons and muscle cells do sometimes divide, though rarely. For instance, cardiac myocytes may divide some after a myocardial infarct. (M.Fossel).

[78s] Jekyll-Hyde Formulas for Life Extension
Press for Longevity Potions.
Music[2]:
Things Have Changed.
Jekyll-Hyde solutions make your nose wrinkle up like the Wolfman as you drink them down, and will not make you popular in the world that eats for the taste of things, but I know of four that are great for life extension:
(1) Turmeric or Curry Powder with Black Pepper (1 tablespoon) and water in a wine glass. This will get you the superantioxidant and DNA-protector curcumin [LifeExtension, Books] you want with better bioavailability for great anticancer protection, exepting perhaps for colon cancer. Note that turmeric, which contains curcumin, is a telomerase inhibitor (7).
(2) Cocoa powder (2 heaping tablespoons) [LifeExtension] with water in a wine glass.
This one gets you the stronger-than-tea antioxidant PQQ (Pyrroloquinoline Quinone) that supercentenarian Jean Calment believed in as she consumed her chocolates, olive oil, and resveratrol-rich red wine for life extension, with minimum fats. Jean consumed 5 pounds of chocolate per week to get her chocolate antioxidant protection to a high level. This may be sweetened with stevia [Wikipedia] or other sweeteners. Unsweetened, this drink is best taken chilled from the refrigerator door after for a couple of hours to cool out. Then you get chocolate antioxidant punch that tastes great! "Cocoa [Index] is rich in antioxidant flavonoids called flavanols, which include:
(1) procyanidins,
(2) epicatechins, and
(3) catechins,"
explains Harold Schmitz, PhD, director of science at Mars, Inc. Studies have shown that people with high blood levels of flavonoids have lower risk of heart disease, lung cancer, prostate cancer, asthma, and type 2 diabetes. Several studies in animals and humans have shown the heart-healthy effects of chocolate's antioxidants. One of these studies, led by Penny Kris-Etherton, PhD, RD, distinguished professor of nutrition at Penn State University, found that people who ate a diet rich in cocoa powder and dark chocolate had lower oxidation levels of bad LDL cholesterol, higher blood antioxidant levels, and 4 percent higher levels of good HDL cholesterol." See Life Extension's product Endothelial Defense, which contains "CocoaGold". I thought perhaps that cocoa may promote telomerase activation in endothelial cells via Nitric Oxide generation promoted by cocoa, since Nitric Oxide activates telomerase. However, cocoa dietary polyphenols (catechins) make cocoa and chocolate telomerase inhibitors to avoid during the first 15 days of a 30-day treatment cycle of telomerase ON, then OFF designed to lengthen telomeres for rejuvenation. It is known to promote blood flow for 8 hours after ingestion and to reduce platelet aggregation leading to atherosclerosis. Chocolate is thought to improve cerebral blood flow for a couple of hours after ingestion, opposing dementia. This drink can be improved by mixing the cocoa with cinnamon and cloves, sugarless apple cider, pomegranate juice, or cranapple-pomengranate juice. So far, I like it best chilled and thoroughly mixed with cranapple-pomegranate juice. I get best results with straight cocoa in water if I mix it, then pour it into a container to chill, because the result looks cleaner, with less cocoa clinging to the edges of the glass.
(3) Wasabi powder (1/2 teaspoon) with water in a wine glass, great DNA-protector [LifeExtension].
Wasabi (Japanese Horseradish) [Books/Wasabi and aging] is a great SOD-mimetic that imitates SOD (Superoxide Dismutase) [Books] and protects you from superoxide and cancer. Remember, the lifetimes of primates are proportional to their SOD concentrations per kilogram. However, taking Wasabi can produce fume-dilated nostrils reminescent of the smoking nose of a Chinese dragon, so experiment and use the appropriate mixture.
Small Molecule Telomerase Activators: 
The Holy Grail of Anti-Aging Medicine.(4) Astragalus Extract in Water (GAIA Herbs, formerly available Extra Strength Astragalus Extract, 77 drops for 5 mg astragalosides, or regular Astragalus Extract, 30 drops/mg of astragalosides, 150 drops for 5 mg of astragalosides.) (7), [81s/6b], Dosages [63s], see also Astragalus & Toxicology. [Alternatively, I have substituted 1200 mg/day of Solaray Astragalus Root Extract to cover the 5 mg of astragalosides, which requires 6 x 200 mg capsules per day in a cyclic protocol featuring 15 days on, then 15 days off. Most recently I have added to this 5 droppers full of Herb Pharm Astragalus Extract per day during the same period, to better guarantee astragaloside concentration. Although this exceeds the recommended dose according to Solaray, I believe from toxicology studies that it is safe enough. Reconstructing cellular telomeres using activation of telomerase closes chromosomal t-loops in senescent cells, restoring the youthful phenotype and patterns of gene expression at a rejuvenation rate of up to -0.75 years per month (-9 years/year), although I now (Jan 2010) seem to witness a rejuvenation rate of about -5.2 years/year. Another alternative is Herbal Remedies Astragalus 1.25 mg astragalosides per 250 mg cap, via Nature's Way, ( Standardized 0.5% Astragalosides ), 60 VCapsules per bottle, incuding Astragalus, dried extract 250mg (root) 0.5% astragalosides, with Astragalus Membranaceus (root) 250mg. Four capsules yield 5 mg astragalosides plus 1 gram of astragalus membranaceus root, which improves bioavailability of astragalosides.] This seems to be the genunine article, the telomere-reconstructing, telomerase-activating immortality brew that not only reconstructs telemeres (7) at the end of the chromosome, but which also promotes stem cell proliferation in bone marrow [article, Links, Books] and accelerates wound healing. For best results, take about 25 drops at a of Extra Strength Astragalus Extract at a time in a glass of water 3 times a day well between meals, and use for the first two weeks of each month. It also works well taken 5 mg of astragalosides at a time just before bedtime on an empty stomach. Actually, we are still fretting about the absolutely optimal dosage. I've been using 5 mg/day 2 weeks out of 4 in my approach to telomere remodeling with cyclic telomerase activation. The cost is now about 50 to 60 dollars/month, depending on whether or not Chitosan is purchased to improve astragaloside bioavailability. Eventually, the telomere position effect should manifest itself, so that rejuvenation becomes evident. Human cells that have been telomerase-activated with small molecule telomerase activators like the astragalosides in this brew have been observed to divide more than 400 times in vitro, corresponding to a human lifetime of more than 600 years in vivo. Other experiments have shown > 500 times cell division in vitro. Only time will time will tell how well we can do with off-the-shelf ethanolic astragalus extracts. Telomerase inhibitors to avoid while using astragalus extract to produce telomerase activation include garlic, turmeric (curcumin), resveratrol, vitamin E, green tea, melatonin, silymarin (or silibinin), and fish oil EPA. These may be used during the 2nd two weeks of each month to freeze the telomerase activation process like a cancer screen. However, astragalus extract is not a carcinogen, and telomerase is not associated with an oncogene. After rejuvenation is achieved, stop stretching your telomeres until age begins to creep up again, so that they will not be so long that you experience mouse-like problems with cancer rejection. It may take a year or two before rejuvenation effects become evident. "Cells with sufficiently elongated telomeres energetically produce, in high levels, proteins like catalase, superoxide dismutase, glutathione, Ku, collagen, elastin and many other proteins important in tissue formation, cell repair, and antioxidation, that become scarce as telomeres shorten." - (Defunct) Telomolecular Corporation/case studies Also see TA Sciences, which originally announced small molecule telomerase activators like astragaloside IV [RevGenetics Astragaloside IV (Astral Fruit)] and cycloastragenol (RevGenetics Astral Fruit C, possibly TA-65) from astragalus extract, and the associated Geron European patent (or see A' alternate-source version Compositions and Methods for Increasing Telomerase Activity, or A'') and the Hong Kong University patent. Also, check out the Immortality Institute on Small Molecule Telomerase Activators and LifeExtension/'Turning on' Telomerase To Stop Cell Aging: The Quest for Immortality, an interview with Dr. Michael Fossel. Note that astragaloside IV is more bioavailable when taken in astragalus root extract, which is typically used to boost the immune system. The bioavailability of astragaloside IV [Article, Papers, Revgenetics Astragaloside IV (Astral Fruit)], can also be increased by chitosan [Wiki/chitosan, Links/chitosan] or sodium deoxycholate [Links, Books]. The astragalosides are the safest and most readily available small-molecule telomerase activators for telomere remodeling with cyclic telomerase activation that I know of. GAIA astragalus extract is delicious in glycerin, and may be taken like cough syrup, about 5 droppers full per application, although it should be premixed in a wine glass of water. To improve bioavailability I formerly took 150 drops of GAIA Herbs astragalus extract in glycerin (5 droppers, 150 drops at 1 mg astragalosides per 30 drops) from a wineglass of water into which I premixed 1000 mg of Natural Balance Chitosan extracted from 4x250 mg capsules. However, the resulting mixture seems to be somewhat lumpy, so these days I just take the 4 capsules orally before mixing and drinking my Herb Pharm astragalus extract solution and my Solary astragalus extract pills separately.
The Geron patent on Compositions and Methods for Telomerase Activation and the corresponding Hong Kong University & Geron patent on astragalus extracts published about the same time in 2005 suggest that 50-100 mg of astragaloside IV is optimal for rejuvenation applications, which is 10-20 times as many molecules of the astragaloside family as a 5 mg/day astragalosides approach. However, TA Sciences presently uses just 5 mg/day of TA-65. It is unclear whether it is safe to take 10-20 times as much astragalus extract as corresponds to 5 mg of astragalosides, which was treated above, without further chemical separations and refinements.


[79s] Rejuvenation [Wikipedia, Wikipedia/Facial Rejuvenation, Google links, Books, Papers/Rejuvenation and aging in humans, LifeExtension]. See the Aubrey de Grey interview with Ben Best from Life Extension magazine. Dr. de Grey is the editor of the journal Rejuvenation Research. Rejuvenation should produce an anti-aging transformation [Links, Books, Papers, LifeExtension] rapidly. For such a demonstation see Dr. Terry Grossman with a patient example. Dr. Grossman is co-author with Ray Kurzweil of Fantastic Voyage. See also Ray & Terry's Longevity Products. I note that rejuvenation as we conceive of it may involve exercise and cosmetic anti-aging therapies [Books, Links, Papers, LifeExtension] in addition to biogerontological procedures in order to achieve the 35-forever effect. Melancor [Links, clinical reports] promotes hairline and hair color rejuvenation effects. See also neck firming treatments [Links, Books, LifeExtension, Rejuvenex with DMAE]. I note that CoQ10 and Centrophenoxine (DMAE + Auxin) help remove cellular debris (lipofuscin) from tissues that turns your heart black as time goes on, and that sometimes quite high doses of CoQ10 > 1000 mg/day are prescribed for a time until age spots and heart-blackening lipofuscin deposits are cleared up. This is sometimes done prior to surgery. I also get the impression that phospholipid exchanges [Books, LifeExtension] and other intravenous therapies [Books, LifeExtension] are very useful in this regard, and am still struggling to get at the facts in this domain involving the membrane theory of aging [LifeExtension, Books]. See cosmetic anti-aging therapies [LifeExtension, Books, Google links, Papers]. I note that carnosine extends available cell divisions for cells in vitro, and is now available in Carnosine Skin Creams [Books, Links, LifeExtension], which may be particularly effective anti-wrinkle creams. For instance, see Resilience Rescue skin cream.
CoQ10 skin creams [Books, Links, Papers, LifeExtension] like Energo can seem to be very effective at wrinkle removal.
I personally got a big 1-dollar bottle of Vitamin E skin cream (lasts about a month) [Books, Links] promoted as "age defying" [Links, Books, LifeExtension] from a Dollar Tree, and sometimes rub Extra Virgin Olive Oil [Links, Books] into my skin, like Jean Calment did. For a more recent approach, see Life Extension's New Face Solution [LifeExtension].
Restoring the Bloom of Youth [Links, Books, Papers].

[80s] The Anti-Aging Solution by Giampappa, Pero, and Zimmerman, John Wiley & Sons, 2004.
Hyperlinked Synopsis - A selection of interesting high points.
Chap.1 - Finding Your Personal Aging Equation.
"By enhancing DNA repair, skin fibroblasts produce healthier, more youthful cells." - pg.10.
The authors later recommend cat's claw extract [Books, Links, Papers, LifeExtension] and topical application of cat's claw extract creams [LifeExtension, Books, Links] for DNA repair (10).
(By this time, we also recommend astragaloside IV skin cream, available from Terraternal, to rejuvenate the scalp hair follicle microenvironment [74s] and skin.)

Tests of skin elasticity, reaction time, static balance, visual accommodation, body composition, BMI, WHR are objective measures of aging that can be done at home. (See Index/Markers of Aging, Index/Markers of Longevity, and Index/Biomarkers of Longevity.)

"Ideal body fat content for men is 15 to 17 percent; for women it is 18 to 22 percent." - pg.11. This can be measured with calipers with about 5% error, otherwise hydrostatic or bioimpedance analysis is available for more accurate measurements of body fat.

Body Mass Index = [weight in pounds/(height in inches)2] x 703. [Images/Body Mass Index].
20 - 25 BMI = ideal, 26-30 BMI = overweight, 31-34 BMI = obese, 35 or higher BMI = morbidly obese.

WHR = waist girth to hip girth ratio. 0.85 or below looks good. [Images/Waist girth to hip girth ratio].

The authors state that "Aging is characterized by a decline in the body's immune responsiveness... As we age, the immune functions [of B and T immune cells] decline, particularly that of T cells." T-cell ratios change, with overproduction of pro-inflammatory cells and a decrease in anti-inflammatory cells. T cells are less active in defense against invading organisms, and increasingly lax in regulating B-cells (which produce antibodies). Therefore, autoimmunity against one's own tissues increases. "Scientists estimate that 10 to 15 percent of seemingly healthy older individuals have increased levels of antibodies against their own tissues". "The thymus gland produces stem cells that can be programmed into different kinds of immune cells, and it actively communicates with the hypothalamus and pituitary glands in the brain. As we age, the thymus shrinks in size with decreased production of stem cells." The authors believe that "most aging conditions have a basis in immune dysfunction" [LifeExtension]. The brain influences the immune system via cytokines. Psychological stress can activate adrenaline and cortisol output so that cytokines "promote inflammation and accelerate aging by increasing damage to cells and genes." Inflammation is a primary cause of atherosclerosis characterized by soft plaque that spews forth C-reactive protein, an inflammation marker and predictor for cardiovascular disease.

Prior infections with "Chlamydia pneumoniae, Helicobacter pylori (gastric and peptic ulcers, risk factor for stomach cancer), herpes simplex virus, Streptococcus, or cytomegalovirus (CMV) lead to chronic inflammation with high CRP levels."
A primary author-stated goal is to reduce chronic inflammation marked by high CRP levels.

Chap.2 - How Aging Occurs
"Nearly 1.5 million SNPs [Books/single-nucleotide polymorphisms, Links, Papers, Index/SNPS, LifeExtension] have been identified" in the human genome. Designer therapeutics deals with individual polymorphisms in designing therapies for individuals. However, only 30,000 genes exist in the human genome. (Actually, < 21,500.) A typical cell can divide 70 times or less. The authors emphasize DNA repair improvements associated with errors that occur primarily when DNA is duplicating in cellular mitosis.

"Fine-tuning of genetic expression" involves turning genes on and off with methyl groups CH3 connected to the cytosine bases. As aging takes place, growth genes are switched off and body-repair genes are switched on. "Approximately 4 percent of cytosine bases in DNA are normally methylated or switched off..." Aging switches more and more genes off, "contributing to the development of cancer and certain brain and nerve disorders." However, proper nutrition safeguards gene switching and can overcome faulty gene switching.

Post-transcriptional modifications occur that express genetic instructions after transcription to RNA with a wide variety of protein products.

12% of 1 billion proteins/cell are enzymes, of which 3,870 have been cataloged for the human genome, most requiring a vitamin coenzyme, and many needing a mineral cofactor for activation. So use a vitamin and mineral supplement.

Tests are available to measure DNA damage "and to identify its enhanced repair".

Free radicals accelerate damage to DNA, certain proteins, carbohydrates, lipids, and lipid membranes composed of PUFAs (polyunsaturated fatty acids), beginning "early in life and eventually exceeding the body's self-repair capabilities".

An ATP molecule is cycled inside a mitochondrion about 1,000 times per day.

Free radicals activate NFκB, leading to an increase in the cytokine TNFα, which supplies the signal leading to apoptosis. NFκB promotes aging by attaching to genes promoting inflammatory conditions and tumor growth, and blocking genes that destroy tumors. (See the index entries for Cancer, Carcinogens, Anticancer Diet, Nuclear Factor kappa Beta, and Tumor Necrosis Factor alpha). Carboxyl Alkyl Esters (CAEs, article) from water-soluble extract of cat's claw can block NFκB to modify these aging problems. NFκB "causes TNFα to increase inflammation, depress immune cell function, and increase free radicals ....[it] also increases DNA damage (10) and alters gene expression".

The authors recommend combating free radicals with acetyl L-carnitine with alpha lipoic acid, in capsules or topically applied, together with vitamin E, vitamin C, lipoic acid, Coenzyme Q10, nicotinic acid, and glutathione.

CAE extract is considered sacred by indians in Peru, who use it to treat inflammation, infections, and cancer. Ron Pero, one of the authors, duplicated CAE extraction methods used by Peruvian shamans, christening it C-Med 100, 100 standing for the 100 percent bioavailability engineered for this proprietary CAE extract. (See index entries for AC-11 and Cat's Claw Extract.) (Also see Suracell cat's claw facial cream, Solaray Cat's Claw Extract, Cat's Claw Extract Supplements.) Pero isolated the carboxyl alkyl esters or CAEs at his lab in Lund, Sweden, showing how the work by inhibiting NFκB and boosting immune cell activity, also by stimulating natural DNA repair enzymes. The CAEs are the only known natural substances to stimulate DNA repair enzymes. The effectiveness of CAE extract is improved by the cofactors B vitamin nicotinamide, zinc, and natural carotenes, since these are cofactors for the DNA repair enzymes. Ron Pero's C-MED-100 CAE extract is the first nutraceutical having FDA permission to claim natural DNA repair activity. (By this time, astragalus extract might be added, since it not only stimulates the production of the telomeric DNA repair enzyme telomerase by activating the hTERT gene, but also somewhat improves DNA repair in general, according to recent studies of hTERT activation.)

The authors recommend eliminating foods triggering inflammation, including sugar (via glycation) and free radicals from AGEs), alcohol, caffeine, and in some people nightshade family vegetables such as tomatoes, peppers, and potatoes.

Chap.3 - Reduce Stress. Reviews neural receptors of hormones and peptides, cortisol, and elements of the neuroendocrine theory of aging as related to stress. Carbohydrate intake raises levels of the stress hormone cortisol.
(Note that ashwagandha reduces high cortisol levels associated with stress, and that exercise (9) reduces stress.)
Chap.4 - Nourish your Genes. Avoid foods feeding obesity, emphasize micronutrient-rich vegetables and fruits featuring brightly colored foods and whole grains containing a variety of vitamins, minerals, and phytochemicals. Smoking plus being overweight decreases life expectancy 13 years, and "90% of aging conditions stem from being overweight." Avoid too much sugar: "Oxidized glucose coats the surface of proteins such as collagen, hemoglobin, and albumin, preventing them from functioning." This is glycation, leading to ills including: memory loss from sugar coating of neurons, disruption of neurotransmitter function, damaged cortisol receptors reducing stress adaptation, hormone imbalances from unbound free cortisol, skin wrinkling from collagen glycation, and damage to the thymus, lymphatic tissue, and immune cells leading to impaired immune function. Glycation can cause cross-links making normally flexible protein stiff and unyielding. Eventually, irreversible advanced glycation end products (AGEs) form.

The pancreatic hormones insulin (anabolic hormone) and glucagon (catabolic hormone) are antagonistic to each other. Insulin locks on to cellular membrane receptors that store proteins, carbohydrates, and fats, and insulin interacts with cortisol, DHEA, and insulin-like growth factor IGF-1, which also mediates fat storage. (See insulin interations with cellular membrane receptors, cortisol, DHEA, and IGF-1.) Decreased sensitivity of insulin receptors is called insulin resistance, which increases glycation, leading to sugar-coating of insulin, glucagon, DHEA, growth hormone, and IGF-1 molecules, reducing their effective function. Insulin resistance is aggravated by obesity and causes the release of too much insulin, which is linked to diabetes and premature aging. A high level of testosterone from bodybuilding will lower insulin resistance in men. "...Overweight people have elevated levels of monoamine oxidase [Links, Images], lowering levels of serotonin and increasing the desire to eat." Monoamine oxidase also lowers the levels of epinephrine and norepinephrine, adversely impacting happiness. High levels of insulin resistance, hyperinsulinemia, and increased IGF-1 levels increase the risk of breast cancer, which is worsened with high levels of free estradiol and free testosterone. When obese subjects lost 26% of their weight, TNFα and TNFα mRNA levels decreased 42%, and TNF protein dropped 52%. Since TNFα inhibits uptake of triglycerides into cells, high TNFα levels are associated with greater risk of cardiovascular disease.

For fat servings, the authors recommend canola, olive, macadamia, flaxseed, sesame, and walnut oils. Flaxseed oil, however, breaks down in high heat and should not be used for cooking; canola, walnut, and macadamia oils are rich in omega-3 fatty acids.

Gene repair foods include cruciferous vegetables, mustard vegetables, the onion family, and the garlic family. They include sulphur, an essential component of DNA repair enzymes. (Sulphur is also a component of the endogenous antioxidant glutathione peroxidase.) Broccoli sprouts are a powerful inducer of superoxide dismutase and glutathione peroxidase and other phase 2 detoxifying enzymes. Isothiocyanates inhibit enzymes promoting glycation and formation of AGEs. "Scottish researchers reported that indoles and isothiocyanates from cruciferous vegetables protect DNA from damage (10) and stimulate apoptosis in cancer cells." (See Anticancer Nutraceuticals.)

Dr. Andreas Constantinou discovered that DNA topoisomerase I and II, which cause one- or two-strand breaks in DNA and assist in DNA replication, are inhibited by ellagic acid, preventing DNA damage. However, these enzymes must work properly during mitosis and meiosis, or serious problems arise, since Topoisomerase II inhibition prevents anaphase chromatid segregation in mammalian cells.

"Red meat should be eaten infrequently, if at all."

Vegetable juices, except carrot juice, are more slowly converted to glucose because they contain protein and are a better choice for meals than other juices.

"Aspartame (e.g.,Equal) contains phenylalanine, which can reduce serotonin." Wine and aged cheeses contain tyramines elevating monoamine oxidase, reducing serotonin, which can cause pain in some individuals.

Chap.5 - Exercise (9) your genes. - Get plenty of exercise.

Chap.6 - Supplement your genes. A few of the high points:
DNA Damage (10) and Micronutrients with Anti-Aging Dosage level and Deficiency Problems

Folic acid (400-1000 mcg) - Deficiency leads to chromosome breaks and base substitutions. Folic acid is required for cytosine and thymidine synthesis. (See foods rich in folic acid.) Deficiency leads to colon cancer [Index/Colon Cancer, Index/Cancer], cardiovascular disease, brain dysfunction, and birth defects.

Vitamin B12 (400-600 mcg) - Same as for folic acid, but required for all four bases (thymidine, adenine, guanine, cytosine). Deficiency leads to nerve damage, breast cancer, plus same as above for folic acid (cardiovascular disease, brain dysfunction, and birth defects).

Vitamin B6 (50-100 mg) - Same as for folic acid, required for thymidine synthesis. Deficiency problems same as for folic acid (cardiovascular disease, brain dysfunction, and birth defects) and B12.

Vitamin C (750-1000 mg) - Deficiency leads to DNA oxidation damage similar to that from radiation, but due to free radicals. Deficiency leads to 4 x cataract risk, cancer, and cardiovascular disease.

Vitamin E (200-800 IU) - DNA oxidation damage similar to radiation due to free radicals. Deficiency leads to 2 x risk of colon cancer, 1.5 x risk of cardiovascular disease, and immune dysfunction.

Iron (9-18 mg) - Too little leads to DNA breaks, brain dysfunction, immune dysfunction, and cancer. Too much leads to iron deposits in the hippocampal region of the brain, causing old age cognitive decline effects.

Zinc (10-25 mg) - Too little leads to chromosome breaks, mimicking radiation damage, and to brain dysfunction, immune dysfunction, and cancer.

Niacin (100-500 mg) - Deficiency disables DNA repair enzymes (polyADP-ribose), and leads to neurological symptoms and memory loss.

CoQ10 (30-280 mg/day) and alpha lipoic acid (500-1000 mg/day) protect mitochondrial DNA best.
CoQ10 must be supplemented when statin drugs are used.
Lipoic acid is an antioxidant for protecting lipids and aqueous cellular components, blocks NFκB binding to DNA, improves carbohydrate metabolism, reduces insulin resistance in muscles, protects red blood cell membranes from diabetic effects, may reverse memory loss by reducing DNA/RNA oxidation, increases brain energy and skeletal muscle performance.
L-carnitine or acetyl-L-carnitine (50-1000 mg/day) provides anti-aging benefits and antioxidant protection.

DNA REPAIR with CAE EXtract, including cofactors:
Cat's Claw Extract - 350 mg/day
Niacinamide - 100-300 mg/day
Zinc (amino acid chelated) -- (10-25 mg/day)

Medicinal Mushrooms
The authors claim that medicinal mushrooms [Links, Images] contain phytochemicals that reduce stress and support immune functions, and belong to the class of adaptogenic nutraceuticals. The only medicinal mushroom at the grocery store is the "shiitake" mushroom [Links, Images]. Note that:
"Mushroom polysaccharides have remarkable anti-tumor activity.
Mushrooms have anti-hyperlipidemic, hypotensive, and hypoglycemic actions.
Beta-glucan from maitake mushrooms [Links, Images] may induce apoptosis in prostate cancer cells.
Shiitake extracts [Images] have reduced cholesterol and have anti-viral effects.
Medicinal mushrooms are high fiber and function as prebiotics, antioxidants, and antibiotics.
The authors prescribe CAE extract (700 mg/day) plus medicinal mushroom extracts (500-1000 mg/day) for reducing inflammation and boosting immunity.

An active polysaccharide beta-1,3-glucan is isolated from yeast, and has immune-enhancing effect.

"The best supplemental form of minerals to take are those bound to amino acids or small peptides, which escort minerals across the intestinal barrier and into the blood."

Curcumin (take 250 mg 3 times a day) inhibits the pro-inflammatory mediator COX-2.

Methylating agents include vitamin B12, folic acid, alpha-GPC (glycerylphosphocholine, or glycerophosphocholine) or choline [Index/choline] (take up to 1000 mg/day), S-adenosyl methionine (SAMe, take 200-1200 mg/day), trimethylglycine (TMG, [32s] take 100-200 mg/day), and dimethylaminoethanol (DMAE, take 500-1,500 mg/day).
"Overmethylation can silence genes that should be expressed." The above methylating agents can help methylate vital segments of DNA correctly and allow proper gene expression.

Chap.7 - Make over your skin and body.
The authors recommend topical application of CAE extract in creams. Other ingredients for creams might include estrogen, progesterone, DHEA, testosterone, and antioxidants. Liposome creams are recommended. Tests show that UV-induced skin damage may be reduced by using transdermal CAE creams for DNA repair, and in one test sunburned skin cells were reduced 99.5%. Topical CAE creams are typically enhanced with supplements of lipoic acid, vitamin C, ascorbyl palmitate oil-soluble vitamin C, and vitamin E. Zinc, carotenes, and niacinamide are added as cofactors for the CAEs. Dr. Perricone demonstrated that glycolic acid creams [Images] reduced sunburn significantly.

Cortisol breaks down skin collagen and elastin, as well as joint, bone, and muscle tissue, also raising insulin levels, leading to glucose intolerance that increases the bad effects of sugar on the skin and sagging neck. Cortisol reduces levels of youthful hormones and causes deposits of fat around the waistline, while relaxing skin tone in a way that leads to flabbiness.

"Melatonin is nature's anti-stress hormone because it counters the effects of high cortisol. Yet continued stress induces a vicious cycle.... The cycle may be reversed with therapy using melatonin and perhaps tryptophan or its metabolite 5-hydroxytryptophan (5-HTP) plus niacin (vitamin B3) and pyridoxine (vitamin B6).... Many scientists consider melatonin to be the best antioxidant known....it protects mitochondrial DNA."
The immune system and the hematopoietic system are associated with circadian rythms, like melatonin.
Melatonin counteracts the osteoporotic effects of cortisol, preserving bones, and inhibits the synthesis of prostaglandin E, which is also implicated in bone loss. Exercise (9) increases melatonin secretion. Melatonin is sometimes applied in a transdermal cream [Images].

Conclusion
Appendix A: Anti-Aging Home Testing
The authors recommend 3 or 4 tests:
1) Serum thiol test for DNA repair capacity, $65.00 - Draw blood or prick finger and send the test kit to a commercial lab for analysis. When oxidative stress is high, thiol bonds located within DNA folds of DNA repair enzymes are degraded by oxidation, so that the enzyme cannot repair your genes. "The thiol status of serum proteins and DNA repair enzymes has been associated with longevity in many species of mammals." In one study, treatment with CAEs was shown to reverse aging, as indicated by an increase in serum thiols.
2) F2-isoprostane test for oxidative burden, $10.00 - Uses urine dipsticks you purchase and read at home. The F2-isoprostanes are prostaglandin-like compounds that are specific stable products of fatty acid oxidation (formed from oxidized arachidonic acid, a major membrane fatty acid) that are reduced by treatment with antioxidants.
3) Saliva hormone panels for hormonal assessment of endocrine status, $25.00 per panel, test kit costs $10.00 (refundable with submission of a test panel), $30.00 for a single test. Collected at home and sent to a commercial lab. "Analysis determines the free and active hormones that reflect the free and unbound fraction in serum." One selects two panels. There are 2 for men and 2 for women, an anti-aging panel, and a competitive athlete panel. The anti-aging panel covers testosterone, cortisol, IgA, DHEA-S, Aldosterone, Thyroid T3, Thyroid T4, and melatonin.
4) SNP single nucleotide polymorphism screening tests - DNA is collected with a cotton swab rubbed on the inside of the cheek.
Appendix C lists labs providing home test kits and kits for your doctor.

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