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Hair Dye Mutagenic Carcinogens [PNAS/Hair Dye Mutagenic Carcinogens; Links/Non-carcinogenic hair dyes, Images, Video, Papers, Patents, Books, LifeExtension], . According to Wikipedia, hair dyes have been linked to forms of cancer including leukemia, non-Hodgkin's lymphoma, bladder cancer, blood cancer, and multiple myeloma. Toxic chemical ingredients that should be avoided in conventional hair dyes include:
Hair Greying (Hair Graying) [Wikipedia/Human Hair Color, Links, Images, Video, Papers, Patents, Books, LifeExtension; Melanocytes; Melanocyte Stem Cells; Melanocyte-Stimulating Hormone; Refs6]. See Melancor [Index] to reverse greying of hair, . Also see [74s/GREYING]. Oral admistration of small molecule telomerase activators such as astralagus extract, TA-65, cycloastragenol, or astragaloside IV can restore hair color by rejuvenating the stem cells (hair follicle melanocyte stem cells) that restore hair melanocytes, at a rejuvenation rate of -5 to -9 years per year. Hair has been visibly restored by applying astragalosides directly to the scalp at Artandi Labs. "Here we show that conditional transgenic induction of TERT in mouse skin epithelium causes a rapid transition from telogen (the resting phase of the hair follicle cycle) to anagen (the active phase), thereby facilitating robust hair growth. TERT overexpression promotes this developmental transition by causing proliferation of quiescent, multipotent stem cells in the hair follicle bulge region." - after Sarin KY, Cheung P, Gilison D, Lee E, Tennen RI, Wang E, Artandi MK, Oro AE, Artandi SE (2005), Conditional telomerase induction causes proliferation of hair follicle stem cells, Nature, 2005 Aug 18;436(7053):1048-52 and Sarin KY, Artandi SE (2007), Aging, graying and loss of melanocyte stem cells, Stem Cell Review, 2007 Fall;3(3):212-7. See also Siegl-Cachedenier I, Flores I, Klatt P, Blasco MA (2007), Telomerase reverses epidermal hair follicle stem cell defects and loss of long-term survival associated with critically short telomeres. J Cell Biol, 2007 Oct 22;179(2):277-90. See Telomere Remodeling with Cyclic Telomerase Activation. "...Enhanced TERT expression activates mobilization of quiescent hair follicle stem cells, increases keratinocyte proliferation, stimulates hair growth and augments skin hyperplasia," although TERC expression must be adequate for the complete telomerase holoenzyme to be operative. (Paula Martinez and Maria A. Blasco, 2011). A scalp rub containing a variety of telomerase activators might be most effective, and is perhaps most inexpensively concocted from Fenugreek extract, progesterone, or black cohosh extract, although we have had some luck with the more expensive astragalosides and astragalus extracts, and might like to try EGF with IGF-1 from colostrum. This would be used for two weeks before the subsequent two weeks of the telomerase inhibitor phase of treatment. However, the hair follicle rejuvenation rate is expected be slow, perhaps -5 years per year. See also Wigs. Fo-Ti (He Shou Wu) has also been used to restore black hair color by old Chinese masters such as Li Ching-Yuen, especially when treated with black bean sauce. Constituents of Fo-ti: Chrysophanic acid, chrysophanol, emodin. These exhibit anticancer properties (S. Mohammad Abu-Darwish and A. Mazen Ateyyat, 2008). See also chrysophanic acid in treating Colon Cancer. However, there are indicatons that as Fo-Ti colors your hair black, it has the same blackening effect on the colon from anthraquinones found in herbal laxatives that induce melanosis coli. In addition, Forskolin, which elevates testosterone, also stimulates melanocytes and hair follicles with anagen cycles to restore hair color. "Vitamin D metabolites, retinoids (retinoid creams), melanocyte-stimulating hormone, forskolin, cholera toxin, isobutylmethylxanthine (effect), diacylglycerol analogues (effect), and UV irradiation all trigger melanogenesis (the production of melanin from melanocytes) and in turn, pigmentation." - Wikipedia/Melanocyte [Links/Hair Follicle Melanocytes, Images, Video, Papers, Books; Links/Hair Follicle Melanocyte Stem Cells, Images, Papers, Books]. Note that the medicinal mushroom Chaga contains massive amounts of melanin, and may be useful for reversing greying.
Popular Hair Graying Cures
See also the popular cures:
Hair Loss Treatment [Hair Loss Treatment [74s], Links/Hair Loss Treatment, Images, Video, Papers, Patents, Books, LifeExtension, LibCong; Links/alopecia areata, Images, Papers, Patents, Books, LifeExtension; Alopecia World, Xeljanz (Tofacitnib Citrate): Blog, $33,000/yesr expense; Lysine for Preventing Hair Loss], [74s]. 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 also contains catechins that act as 5-alpha-reductase inhibitors. Saw Palmetto (300 mg) [Images] counteracts dihydrotestosterone in the scalp that makes hair fall out. Saw Palmetto is contained in Gray Hair Rescind with Catalase, for instance, which also contains catalase counteracting internal bleaching from hydrogen peroxide and other factors counteracting hair grayness. Topical application of telomerase activators tends to restore hair, according to research at Artandi Labs using topical application astragaloside IV. I obtained similar results using topical astragalus extract. Black Cohosh, a telomerase activator, is also available for combatting hair loss in women, as explained by Zimbio. See Wigs. See also Revage 670 Hair Rejuvenation Therapy [Links/Laser Hair Rejuvenation, Images, Papers, Patents, Books; Links/Hair Rejuvenation, Images, Papers, Patents, Books; Index/Laser Comb, Links, Images].
Laser Hair Restoration at Studio 519 works by increasing scalp blood flow.
VEGF hair serums such as NANOGEN Serum VEGF, by increasing circulation in the scalp, can restore hair more effectively than minoxidil. "A recent study showed that overexpression of TERT (TERT in mice and probably hTERT in humans) in epidermal stem cells enhances mobilization, proliferation, and hair growth..." (Sarin et al. 2005; Steven E. Artandi, 2008; K. Leonard Rudolf, 2008). This probably means that relatively inexpensive colostrum EGF skin cream would act to restore hair, as would other epidermal growth factor skin creams. Cycloastragenol skin cream or Astragaloside IV skin cream (Terraternal), or astragalus extract may be safer for this application. See also Biotin (see above).
Also, phorbol esters cause keratinocyte proliferation. Enhancing hTERT constituatively in skin enhances the proliferative effect of phorbol esters on quiesent stem cells associated with the hair follicle, inducing an anagen hair follicle cycle. So perhaps hTERT transcription activators such as astragaloside IV in scalp skin cream in combination with phorbol esters will be outstanding in hair rejuvenation and in promoting hair growth. However, phorbol esters are often tumor promoters and sometimes have toxic effects when included in animal feed. - after S.E.Artandi (2008), Telomerase as a Potential Regulator of Tissue Progenitor Cells in Lenhard K. Rudolf, 2008, p.207. According to E'shee research, "FGF-1 peptide [Images, Video, Papers, Patents, Books] can transfer different messages to:
* FGFR-2 - rejuvenates fibroblast cells to produce new collagen, hyaluronic acid and elastin;
* KGFR (Keratinocyte Growth Factor Receptor) - rejuvenates the epidermal cells; and
* FGF-7 (Keratinocyte Growth Factor) - rejuvenates hair follicle to produce new hair". Therefore FGF-1 skin creams [Images] applied to the scalp can produce new hair by stimulating the expression of FGF-7. L-arginine is required to produce nitric oxide, which is used by hair follicles [Images] to maintain and promote new hair growth, so that it is sometimes applied in hair regrowth formulas [74s]. Also see fast hair growth formulas [Images].
Hair Thickeners [Links, Images, Videos, Papers, Patents, Books], [74s]. See Wigs.
Hair Transplants [Medical Hair Restoration All-Stars, Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension]. See Wigs.
Haritaki [Links, Images, Video, Papers, Patents, Books; Telomerase Activators/Haritaki]. Haritaki is the ethanol extract from the fruit of Terminalia chebula (Combretaceae), or Haritaki. Also termed chebulic myrobalan. A telomerase activator (67) from Ayurvedic Medicine [Wikipedia/Ayurveda, Links/Ayurvedic Medicine, Papers, Books]. Said to function as a mild laxative with "alterative" properties. Chebuloside II, a pentacyclic triterpene glucoside also described as a triterpenoid glycoside, is used as a marker for the quality of the ethanolic extract. Principle constituents of Haritaki extract include chebulagic acid, chebulinic acid, and corilagin.
Harley, Calvin B. [Ask the Scientists/Calvin B. Harley, Forbes PhD Profile/Calvin B. Harley, Links, Images, Video, Papers, Patents, Books]. Chief Scientific Officer of Geron Corporation.
A key player in the development of small molecule telomerase activators [Index, Alphabetic_List] for rejuvenation and other applications, including wound healing and the treatment of HIV infections [Index]. Co-author of some of the first papers on telomeres and telomerase (7) in treating replicative senescence.
See Calvin B. Harley, Weimin Liu, Maria Blasco, Elsa Vera, William H. Andrews, Laura A. Briggs, and Joseph M. Raffaele (2010), A Natural Product Telomerase Activator As Part of a Health Maintenance Program, Rejuvenation Research, September 7, 2010.
Harman, Denham [Harman, Denham, father of the Free Radical Theory of Aging, Links, Images, Video, Papers, Patents, LifeExtension, Books]. Denham Harman was the discoverer of the free radical theory of aging in 1956 and President of The American Aging Association. (1).
Hawthorn (Crataegus oxyacantha) [Product B/Hawthorn extract as a telomerase activator, Links, Images, Video, Papers, Patents, LifeExtension]. Hawthorn extracts at 80 mg - 180 mg twice daily, and Arjuna bark powder at 500 mg every 8 hours are useful in preventing and reversing heart failures. Hawthorn extracts are termed cardiotonic because of their ability to improve heart muscle tone. Hawthorn extracts can improve coronary blood flow up to 70% and prevent ischemia-reperfusion injuries, reducing mortality rate in cardiac ischemia. Hawthorn extract substantially reduces arrhythmias that may follow or accompany ischemia and reperfusion, and pre-treatment prior to ischemia-reperfusion very substantially reduces the prevalence of deadly arrhythmias manifesting themselves as ventricular fillibration and flutter. Arjuna extracts [Index] reduce total and LDL cholesterol, reduce trigycerides, and elevate HDL, limiting atherosclerotic lesions in the aorta and improving endothelial function. See Silas Hoffman (2013), Novel Support for Chronic Heart Failure, Arrhythmia and Coronary Artery Blockage, Life Extension Magazine, Feb 2013. Hawthorn at 400 mg/dose x 3 doses/day has been observed to lower LDL cholesterol from 105 to 93 mg/dL and to reduce levels of neutrophil elastase [Papers, Patents, Books], "an enzyme released from inflammatory cells that weakens connective tissue in heart and lung tissue, and is a major contributor to later heart failure."
Hayflick Limit Theory [Senescence.info/Hayflick Limit Theory of Aging based on Telomeres, Hayflick limit (typically 50 cell divisions for human embryonic tissues), Hayflick, His Limit, and Cellular Aging by Shay & Wright, Links, Images, Video, Papers, Patents, Books, LibCong, LifeExtension, Amazon; References, Swim and Parker]. The Hayflick Limit is improved by carnosine in vitro, by Neygeront , and by telomerase activators [List, Index]. See totse/The Hayflick Limit, Carnosine & Cellular Senescence, Kinetin, (1), (7).
Hayflick, Leonard [InfoAging/Leonard Hayflick, Wikipedia/Leonard Hayflick, Links/Leonard Hayflick, Images, Video, Papers, Patents, Books, LifeExtension, Amazon]. See Hayflick, His Limit, and Cellular Aging by Shay & Wright, How and Why We Age by Leonard Hayflick. .
HDACs (Histone Deacetylases) [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension, LibCong, Amazon; Endogenous Histone Deacetylases; Histone Modifications]. Histone Dacetylases (HDACs) act to condense and silence chromatin via deacetylation of histones. See human deacetylases (human HDACs) and human HDAC genes. See Cong, Y.S., and S. Bacchetti (2000), Histone deacetylation is involved in the transcriptional repression of hTERT in normal human cells, Journal of Biological Chemistry 275: 35665-35668. Histone deacetylase (HDAC) chromatin condensation for gene silencing is often implemented using SIRT1 via sirtuin activators such as apigenin, EGCG, resveratrol, quercetin, NADH, fisetin, piceatannol, and butein.
HDAC Inhibitors (Histone Deacetylase Inhibitors) [Telomerase Activators/HDAC Inhibitors, Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension, BIOMOL/HDAC Inhibitors; Endogenous HDAC inhibitors; HDAC inhibitor classes; Histone Modifications]. HDAC inhibitors work to expand chromatin, making it more available for transcription. [Video]. "HDAC inhibitors display antitumor activity by promoting either tumor cell apoptosis or normal cell differentiation." [Ref]. "Histone deacetylase (HDAC) inhibitors have the potential to derepress epigenetically silenced genes in cancer cells, leading to cell cycle arrest and apoptosis." [Ref]. See:
Certain specific HDAC inhibitors such as CGK 1026 or Tricostatin A activate transcription of hTERT, producing the catalytic component of telomerase. Sodium butyrate [Images] is a readily available and inexpensive HDAC inhibitor that may be useful in improving transcription rates for hTERT and hTR when telomerase activators are used. This is true for mesenchymal-derived cells including connective tissues, cartilage, and bone, which do not muster enough hTR component of telomerase without the HDAC inhibitor. HDAC inhibitors may be required to make telomerase activators work well enough on connective tissues for neck rejuvenation. (At this time I am trying with L-carnitine L-tartrate as an HDAC inhibitor for connective tissues in neck rejuvenation, so that other telomerase activators I take may work better on acetylated chromatin expanded for transcription of hTERT and hTR.) Sodium butyrate or L-carnitine or L-carnitine L-tartrate may improve rejuvenation rates B in years/year measured in life-extension treatment using telomerase activators such as astragalus extract, Product B, cycloastragenol, or astragaloside IV. Sodium butyrate is a component in farm animal feeds used to improve animal characteristics. See also sodium 4-phenylbutyrate, which has been shown to extend the life span of Drosophila. "Alternatively, HDAC inhibitors induce p21WAF1 expression in cancer cells probably through histone-acetylation of the promoter (Sowa et al., 1999; Richon et al., 2000). This may play an important role in the arrest of cell growth or cellular differentiation, leading to indirect inhibition of telomerase activity." - after Satoru Kyo and Masaki Inoue (2002), Complex regulatory mechanisms of telomerase activity in normal and cancer cells: How can we apply them for cancer therapy?, Section (5) Histone Deacetylase Inhibitors, Oncogene, 21 January 2002, Volume 21, Number 4, Pages 688-697. L-carnitine is also an HDAC inhibitor that may be useful. See Telomeric Chromatin for application of HDAC inhibitors to telomere lengthening via acetylation of telomeric histones H3 and H4. Note that sulforaphane acetylates chromatin histones, which may help accelerate hTERT transcription from the hTERT gene.
"Dietary agents such as
Endogenous HDAC Inhibitors [Links, Images, Papers, Patents, Books].
__ L-carnitine (Vitamin C with Methionine (perhaps from fish) + Lysine -> Carnitine)
_____is an endogenous HDAC inhibitor [Ref].
__ D-beta-hydroxybutyrate (Beta-OHB) is an endogenous inhibitor
_____of class I histone deacetylases (HDACs).
__ Valproic acid [Ref].
__ Beta-hydroxybutyrate [Images, Article (Ketogenic Diets)].
__ Lactate, a product of pumping up [Ref], weaker than Tricostatin A or butyrate.
___Lactate accumulates when glycolysis exceeds the cell’s aerobic metabolic capacity.
A pump-up or lactate workout with HIF-1 elevation symptomatic of hypoxia and CAV-1 inhibition via FOXO inhibition with AKT, and with cyclic AMP generation using creatine monohydrate, seems most promising in connection with anti-aging exercise.
HDL (High-Density Lipoprotein) [Links, Images, Video, Papers, Patents, Books].
See Cholesterol and LDL peroxidation.
Heart Attack (Congestive Heart Failure) [Links, Images, Video, Video/What happens; Video/Heart Disease and Heart Attacks; 3D Animation, Papers, Patents, Books, LibCong, LifeExtension, Amazon, The Heart Scan Blog] . See also index entries for Cardiology, Cardiovascular Disease, Atherosclerosis and Atherosclerotic Plaque, Arteriosclerosis, Taurine, Vitamin D, vitamin K2, Hawthorn, and Arjuna. Note that cigarette smoking [Essay/Smoking, Index] is often seen in connection with heart attack. Smoking a pack of cigarettes a day more than doubles the risk of heart attack. The heart attack usually takes place when a blood clot forms in a small cardiac vessel feeding heart muscle narrowed by atherosclerotic plaque, typically after a piece of plaque breaks off in the progressively narrowing artery, jamming it and clotting up with an embolism after floating downstream. Myocardial infarction follows, killing heart cells near the artery deprived of oxygen. Aspirin is recommended immediately to thin the blood and break up the clot. A more effective clot-busting injection may be used. Anticlotting agents and other blood thinners such as nitroglycerin may be taken. Anticoagulants including warfarin, heparins, fondaparinux or dabigatran work by blocking vitamin K1 or inactivating other clotting factors in the blood. Antiplatelet thromboxane blockers such as aspirin, EPA and DHA from fish oil, dipyridamole, ticlopidine and clopidogrel prevent clotting by preventing thromboxane from rounding up clotting cells in the blood. Foods and nutraceuticals with blood-thinning effects include alfalfa, avocado, beer, bilberry, cat's claw, celery, coQ10, cranberries, fish oil, garlic, ginger, ginkgo, ginseng, grapefruit, green tea, horse chestnut, licorice, niacin, onion, papaya, pomegranate, soybean, St. John’s wort, turmeric, and wheatgrass. A cardiac stent may be inserted by a surgeon in the vessel to widen the passage narrowed by atherosclerotic plaque. This is sometimes done to relieve the pain associated with Angina Pectoris from plaque-narrowed vessels. Perhaps ibuprofen may be used to reduce heart attack pain. See Hypertension: For age greater than 50 years, hypertension exists when the systolic blood pressure is greater than 140 mm Hg or when the diastolic blood pressure is greater than 90 mm Hg, that is, when blood pressure is more than 140/90 mmHg. Normal blood pressure is less than 120/80 mmHg. See Wikipedia for standard medical treatments for hypertension and Links/hypertension treatment. Drugs typically used in medicine to treat hypertension include: Thiazide diuretics "water pills" to reduce blood volume, for age 80 or more perhaps indapamide (Lozol); Beta blockers to reduce the workload on the heart and open blood vessels, causing the heart to beat slower and with less force; Angiotensin-converting enzyme (ACE) inhibitors to help relax blood vessels; Angiotensin II receptor blockers to relax blood vessels; Calcium channel blockers to relax the muscles of the blood vessels; Renin inhibitors such as Aliskiren (Tekturna), which slows down the production of renin, a kidney enzyme that increases blood pressure. Medicine for further therapy includes Alpha blockers to reduce nerve impulses to blood vessels, Alpha-beta blockers to slow the heartbeat in order to reduce the amount of blood that must be pumped through the vessels, Central-acting agents that prevent the brain from signaling to increase heart rate and narrow your blood vessels, and Vasodilators [Index]. From the section on Helicases: Hypertension may be alleviated by supplementation with magnesium or taurine.
Optimal Cardiac Defense
EPA (Eicosapentanoic acid) and DHA (Docosahexaenoic acid) found in fish oil suppress key proinflammatory cellular signaling molecules, including:
Hawthorn extracts at 80 mg - 180 mg twice daily, and Arjuna bark powder at 500 mg every 8 hours are useful in preventing and reversing heart failures. Hawthorn extracts are termed cardiotonic because of their ability to improve heart muscle tone. Hawthorn extracts can improve coronary blood flow up to 70% and prevent ischemia-reperfusion injuries, reducing mortality rate in cardiac ischemia. Hawthorn extract substantially reduces arrhythmias that may follow or accompany ischemia and reperfusion, and pre-treatment prior to ischemia-reperfusion very substantially reduces the prevalence of deadly arrhythmias manifesting themselves as ventricular fillibration and flutter. Arjuna extracts [Index] reduce total and LDL cholesterol, reduce trigycerides, and elevate HDL, limiting atherosclerotic lesions in the aorta and improving endothelial function. See Silas Hoffman (2013), Novel Support for Chronic Heart Failure, Arrhythmia and Coronary Artery Blockage, Life Extension Magazine, Feb 2013. Cardiovascular problems may be reduced by taking green coffee bean extract at 350 mg before meals to reduce consequent elevated glucose. See William Falloon (2013), Preparing Your Body to Eat, Life Extension Magazine, Feb 2013.
Taurine Reduces Mortality Due to Congestive Heart Failure [Index/Taurine].
"Congestive heart failure responds favorably to taurine therapy." (Life Extension), [36s] (k). In animal studies, taurine reduced mortality due to heart failure by 80% [Ian Macleavy, 2013, LEF]. Taurine is abundant in fish.
Head Transplant, Life Extension by
See U.S. Funds Efforts to Freeze Human Organs for Long-Term Storage, Scientific American, March 4, 2015.
Heart Disease See Cardiovascular Disease.
Heat Shock Proteins [Refs7, GeneFamilies/Heat Shock Proteins, FASEBJ/Heat Shock Protein Overexpression via Hsp22 extends Drosophila life span 30%.., Books/heat shock proteins, LibCong, Links/aging and heat shock proteins, Images, Video, Papers, Patents, Books, LifeExtension, Wikipedia; Index/HSP90], [24s]. According to the Geron European Patent (A' alternate-source version Compositions and Methods for Increasing Telomerase Activity, or A''), heat shock proteins mediate the assembly of telomerase and can be used to increase telomerase levels in the cell. (White). Note that senescent cells have a decreased ability to express heat shock proteins. Many heat shock proteins, such as HSP60, HSP70, and HSP90, are chaparonins mediating protein folding. Astragalosides seem to be treated like nuclear superfamily transcription factors complexed with the 90 kDa heat shock protein Hsp90 [Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon] before tranfer into the nucleus of the cell. (Perhaps astragalosides are all stripped down to cycloastragenol, the common alglycone of the astragalosides, prior to transport into the nucleus.) It may accelerate matters to improve Hsp90 expression by some means, perhaps by raising Interleukin 6 [List] levels via exercise. We might pump up just before taking our astragalus root extract with Chitosan to facilite its march into the nucleus complexed with Hsp90 elevated by the exercise session. Heat shock proteins are also more expressed after taking alpha lipoic acid. Furthermore, HSP (Heat Shock Protein) expression is stimulated by testosterone and catecholamines (stress hormones) including epinephrine and norepinephrine, which can be released by taking caffeine. HSP90 maintains cellular steroid receptors and transcription factors vital for protein synthesis. [See Iron Man, Sept.2009, for the Jerry Brainum article on heat shock proteins, summarized and expanded below.] "HSP90 is necessary for telomerase activity, as is p23." (Cong, Wright, and Shay, 2002). Gamma tocopherol blocks heat shock protein expression, so that it should not be taken while attempting to activate hTERT transcription to upregulate telomerase activity. Heat shock proteins (stress proteins) maintain proper protein folding and transport proteins across cellular membranes. HSPs were discovered in 1962, when DNP (dinitrophenol) was used to increase body heat in fruit flies. HSPs help maintain protein shapes degraded by stress, including stress from infections, inflammation, toxins like alcohol, trace metals like cadmium or lead, and from UV light. Starvation, too little oxygen, dehydration and exercise all induce HSP release. We will consider HSP20, HSP22, HSP25, HSP60, HSP70, HSP72, and HSP90. Ubiquitin, which helps degrade certain muscle-associated proteins, acts like a small HSP. HSPs may signal immune cells. HSPs may monitor cell proteins, taking them to a place in the cell to make way for newly synthesized proteins. HSP20 prevents aggregation of platelets, clotting, the immediate cause of heart attacks and strokes, and protects against ischemia and reperfusion injuries. HSPs are involved in anticatabolic insulin metabolism. ROS (Reactive Oxygen Species) stimulate HSP release, so HSPs are released better during exercise in the absence of antioxidants which counteract ROS. Antioxidants should be taken well after exercise if HSPs are to be abundantly available from a workout. HSPs boost glutathione, a major endogenous antioxidant. HSPs such as HSP70 blunt the release and activity of TNF-α, a major agent of muscle catabolism. The presence of TNF-α stimulates HSP70 release. HSP70 also inhibits NFκB, an inflammatory mediator partially responsible for muscle atrophy. In addition, HSP70 prevents FOXO3 transcription. HSPs and NO interact, dialating bronchial tubes, dimenishing exercise-induced asthma. High intensity resistance exercises seem to be required to much boost HSP production from exercise. Note that HSP60 is released during contractions not causing much muscle injury, and is concentrated in mitochondria, helping to protect them. HSP60 also helps to maintain IGF-1 cell receptors, which has anti-aging benefits. HSP70 is produced during high-intensity contractions and helps damaged muscle proteins function again via refolding. Higher levels of HSP70 give better cardiovascular protection. HSP72 is boosted by anabolic steroids such as Deca-Durabolin, allowing more high-intensity training. HSP release is also stimulated by testosterone and catecholamines (stress hormones) including epinephrine and norepinephrine, which can be released by taking caffeine. A combination of lipoic acid, carnosine, and zinc may also be used to elevate HSP expression. Caffeine boosts HSP72 production during workouts. Perhaps the most effective HSP blocker during exercise is gamma tocopherol (abundant in peanuts and walnuts), and so perhaps gamma tocopherol should be taken well after workouts if HSP production is to be emphasized. Another activator of HSPs in muscle cells is lipoic acid, and a combination of carnosine and zinc can also activate HSPs. Unfortunately,overexpression of certain HSPs can initiate cancer [Index/Cancer] in some cells by deactivating p53, a tumor-suppressing protein. From an anti-aging point of view, I believe I prefer to keep antioxidant protection high at all times, and rely on HGH, IGF-1, and NO from exercise more than on heat shock proteins from exercise for anti-aging benefits. On the other hand, lipoic acid and a combination of carnosine and zinc to activate HSPs looks attractive. Otherwise, regarding Hsp22, [Hytest/Human Heat Shock Protein Hsp22, Hsp22 extends the life span of Drosophila 30%. (Ben Best, also FASEB Journal, Genevive Morrow, Milanie Samson, et.al.) Also see elevating Hsp22 with Trichostatin A, [Books/heat shock proteins, Links, Wikipedia, LibCong/Heat Shock Proteins, LifeExtension] [24s]. Resveratrol activates SIRT1, which stress-inducibly regulates Heat Shock Factor (HSF1, HSF2, and HSF4), a transcription factor regulating the expression of Heat Shock Proteins. In fact, Heat Shock Factor 1 (HSF1) regulates life span. Tex OE [Links, Papers, Books], an extract of the skin of prickly pear cactus fruit, is taken 2 hours prior to stress exposure such as bodybuilding exercise to raise levels of HSP70 and HSP27, and can increase HSPs by 200%. HSP70 blocks muscle atrophy. TEX OE is also used for hangovers. Supplements [Links/HSP supplements, Links/HSP activators] include HSPactive.
Alpha Lipoic Acid and Curcumin upregulate HSP expression
Note that alpha lipoic acid increases heat shock protein expression, including the expression of HSP90, which transports transcription factors into the cellular nucleus. See Index/Alpha Lipoic Acid. Furthermore, expression of different Heat Shock Protein family members is induced by curcumin. (Teiten, Eifes, Dicato and Diederich, 2010). Note that curcumin is a telomerase inhibitor.
Heat Shock proteins and the Telomerase Chaparone Complex
[Links, Images, Papers, Patents, Books, Links/Hsps and telomerase assembly, Images, Papers, Patents, Books]. "Recent findings revealed that chaparone proteins, such as hsp90, p23, hsp70, p60, and hsp40/ydj, are also part of the telomerase RNP, at least during part of the cell cycle. In fact, these chaparones are required to obtain a functionally active telomerase RNP in vitro, although their precise role in telomerase assembly remains enigmatic.... In the presence of hsp90 inhibitors, hTERT degraded with a half-life of 15 minutes." (Keppler, Grady, and Jarstfer, 2006). See supplements promoting the expression of HSP90 [Papers, Patents, Books], which include exercise and alpha lipoic acid. According to Geron's patent Compositions and Methods for Increasing Telomerase Activity, heat shock proteins mediate the assembly of telomerase [Papers, Patents] and can be used to increase telomerase levels in the cell [Papers, Patents]. (White). Many heat shock proteins, such as HSP60, HSP70, and HSP90, are chaparonins mediating protein folding. Astragalosides seem to be treated like nuclear superfamily transcription factors complexed with the 90 kDa heat shock protein Hsp90 [Wikipedia, Links, Images, Papers, Books, Amazon] before tranfer into the nucleus of the cell. HSP90 maintains cellular steroid receptors and transcription factors vital for protein synthesis. "HSP90 is necessary for telomerase activity, as is p23." (Cong, Wright, and Shay, 2002). See Forsythe, H.L., J.L. Jarvis, J.W.Turner, L.W.Elmore, and S.E.Holt (2001), Stable association of hsp90 and p23, but Not hsp70, with active human telomerase, Journal of Biol. Chem. 276: 15571-15574. See also Y shi and J O Thomas (1992), The transport of proteins into the nucleus requires the 70-kilodalton heat shock protein or its cytosolic cognate, Mol Cell Biol 1992 May; 12(5): 2186-2192.
Height loss with age [Links, Images, Video, Papers, Patents, Books, LifeExtension] . It is common for women to loose 3" in height between 40 and 80 years of age [Links, Video]. This may be reduced by exercise. See Bone Growth: [Links, Images, Papers, Patents, Books, LifeExtension; Links/bone growth and hormones; Links/bone growth for height, Images, Papers, Patents, Books]. Bone length growth stops in early adulthood, but bones can grow in thickness in response to stress from handling weights later in life. Using small molecule telomerase activators to return to an early stage of development may be possible, to continue growth and development by supplying the proper bone growth factors, including minerals, other nutrients, and hormones such as HGH stimulated by whey protein in milk, buttermilk (with extra vitamin K2 from its bacteria), or yogurt. Consider vitamin D3, vitamin K2, calcium, magnesium, and vitamin C for collagen synthesis important in bone growth. Bone meal from a young animal may support Lincolnesque bone growth during growth and development if great height is desired inland, and some kinds of sea food (perhaps crab claw meat) can support height improvements even after growth and development is complete. Thus sailors home from the sea might seem to have become giants after feasting on crab claws or halibut out in the ocean, though their height may finally return to normal inland.
In the future, man may resemble a crab or lobster that continues to grow in height and weight throughout his life span, unless he modifies his supplements program to prevent further growth. See world's tallest man Leonid Stadnik [Links]. Greater height requires more food per unit time, and finally increasing height can become suboptimal for various reasons, including peer group approval. See also Bone Repair [Links/Bone repair, Images, Papers, Patents, Books, LifeExtension]. Note that CDP-choline can improve HGH levels 4x (LEF, Mar.2009), and that Wheat Germ [Links] may have application to bone growth. Alpha-glycerylphosphocholine (Alpha-GPC) can increase HGH markedly in the presence of exercise that without it elevates HGH x 3. Other HGH secretagogues like L-arginine + L-ornithine or Secretagogue Gold are available. In the presence of exercise L-arginine alone boosts HGH at 5-10 grams/serving, in addition to enhancing levels of Nitric Oxide. See Hodgson Mill Untoasted Wheat Germ. Note also that grape seed extract promotes bone formation, as does dried plum. For additional remarks, see Age Transformation/Reprogramming Height.
Helicases There are 5 RecQ DNA helicase genes [Wikipedia/Helicases, Links/DNA helicases, Images, Video, Papers, Patents, Books, LibCong; Links/RecQ DNA helicase genes, Images, Video, Papers, Patents, Books]. The 5 RecQ DNA helicase genes are used to unwind DNA, some or all requiring Mg+2 as a cofactor [Hu & Ellis, Bloom Syndrome, in Chromosomal Instabilty and Aging, by Hisama, et al, 2003]. Therefore, it may be that deficiencies in dietary magnesium are connected with genomic instabilities in aging cells via the malfunctioning of DNA helicases. The WRNp helicase associated with Werner Syndrome, for instance, is localized to the telomere, and may malfunction if sufficient magnesium is not available as a cofactor [Links, Papers]. Consider magnesium as a supplement. [Links, Papers]. According to Life Extension magazine, low levels of magnesium are chronic in the US population, and magnesium should be supplemented. Otherwise, consequences include hypertension and higher rates of sudden death.
Hemidesmosomes and Integrins (Encyclopedia)
Hemotology [Wikipedia, Links, Images, Video, Papers, Patents, Books, LibCong, Amazon; LifeExtension/Blood Tests; Wikipedia/Blood, Links/Blood, Images, Video, Papers, Patents, Books/; LibCong/Blood, Amazon/Blood]. See RevGenetics and Repeat Diagnostics for measurements of blood granulocyte and blood leukocyte telomere lengths after treatment with telomerase activators, or TA Sciences for their program of blood measurements after treatment with the telomerase activator (7) TA-65, which also involves telomere length measurements [LifexLabs/Telomeasures].
Herbal Medicine [Index/Herbal Supplements, Supplement Science/Herbal Supplements; Links/Herbal Medicine, Images, Video, Papers, Patents, Books, LibCong, Amazon; Herbs Are Special]. See also Phytomedicines.
Herbal Supplements [Supplement Science/Herbal Supplements, Links, Images, Video, Patents, Patents, Books, LibCong, Amazon].
Herbs and Anti-Aging [Links/Herbs and Anti-Aging, LifeExtension, Links/herbs and anti-aging therapy, Images, Video, Papers, Patents, Books, LibCong/anti-aging herbs]. Herbs, Antioxidant with ORAC scale [LifeExtension, Index/ORAC scale, Links/ORAC scale, Images, Video, Papers, Patents, Books, LibCong/Antioxidant Herbs].
Herpes Virus [Wikipedia/Herpes, Links, Images, Video, Papers, Patents, Books, LibCong, Amazon; Acyclovir; Links/Treating Herpes, Images, Papers, Patents, Books]. Herpes infections include Herpes Zoster and gential herpes. Acyclovir and related drugs can be used to cut the probability of infection from a Herpes-infected individual, as can may other antiviral drugs developed for Herpes. "An oil known as eugenol [Index] that comes from the leaves of the cinnamon bush (or from oil of cloves) has been shown to have antiviral properties in vitro, specifically against both the HSV-1 and HSV-2 (Oral and Genital Herpes) viruses according to a study published in the journal, Phytotherapy Research." - Wikipedia/Cinnamon. Also see Eugenol from Molecules 2012. However, according to Wikipedia/Eugenol, "Eugenol is hepatotoxic, meaning it may cause damage to the liver. Overdose is possible, causing a wide range of symptoms from blood in the patient's urine, to convulsions, diarrhea, nausea, unconsciousness, dizziness, or rapid heartbeat. A 2-year old boy nearly died after taking between 5 and 10 ml., according to a published 1993 report." Investigations into the safe and effective dose of eugenol to be treat HSV-1 and HSV-2 are required, along with further data on eugenol toxicity. Note that eugenol is a component of basil. See Herbal remedies for the Herpes virus, which include scinaia [Images, extract], cloves (Eugenol is sometimes described as oil of cloves), and licorice. Garlic is also effective against Herpes, according to Virology. Note that Lemon balm shows antiviral and antiretroviral effects in vitro against herpes simplex virus and also against HIV-1. (Pizzorno and Murray, Textbook of Natural Medicine, Elsevier, 4th edition, 2013). The very widespread cytomegalovirus is a herpes-family virus. See cytomegalovirus-induced telomere shortening. See also Index/Virology and HIV. Viral infections present a stress on the immune system that reduces telomere lengths and shortens lives. Treatment with telomerase activators can compensate for this virus-induced telomere shortening. I suspect Herpes is a provirus already integrated into the human genome that may be conditionally promoted as a consequence of specific sexual behaviors (perhaps after breaking a skin cell), so that eliminating the proviral code with zinc finger nuclease technology may be feasible to eradicate genital herpes. The same may be true of HPV. By 2010, HTLV (which causes T-cell leukemia) and HIV [Index] are known to be associated with endogenous retroviral DNA code associated with latent infections. See virosome vaccine technology, Virology, and Antibiotics.
He Shou Wu (Fo-Ti) See Fo-Ti.
Hesperidin [Links/Hesperidin, Images, Papers, Patents, Books; Sources; Extraction; Bioflavonoid Skin Creams - Hesperidin Supplements, Hesperidin Skin Creams; Quercetin, Quercetin Supplements, Quercetin Skin Creams; Rutin, Rutin Supplements; Rutin Skin Creams]. Hesperidin is a vasoprotective and skin-lightening bioflavonoid that reduces old age spots [Images, Papers, Patents, Books]. Hesperidin attacks old age spots by reducing the activity of tyrosinase, the enzyme which produces melanin. The melanin synthesis-blocking tyrosinase inhibitors hesperidin and nobiletin can be extracted from citrus peels [Papers, Patents]. Hesperidin has a structure similar to hydroquinone, which is used to treat hyperpigmentation. A combination of the bioflavonoids quercetin and rutin was shown to rejuvenate drying skin cells that refused to replicate, so that they began to reproduce again. (Chondrogianni, Kapeta, Chinou, Vassilatou, and Papassideri, 2010), referenced in Gary Goldfaden MD and Robert Goldfaden (2012), How Bioflavonoids Create Youthful Skin Tone, Life Extension Magazine, November 2012 [Dr.Robert]. Quercetin also improves the synthesis of collagen in skin. (Ref). Three bioflavonoids for skin creams, quercetin, hesperidin, rutin (a blood-thinning antiplatelet glycoside of quercetin), can be used in topical skin creams to "prevent and reverse wrinkles, reduce the appearance of age spots, and even fight spider veins and varicose veins".
Extraction of Hesperidin [Links, Images, Papers, Patents, Books].
In China, hesperidin is often extracted with boiling water from citrus peels, then taken orally. In other research "crude extracts from citrus peel (C. unshiu Marc.) were extracted with 95% ethanol and fractionated by petroleum ether (PCPE). The ethanol phase (ECPE) was further desorbed from macroporous adsorption resin (FGRE)". Naringin and hesperidin, glycosylated citrus flavonoids, are two major bioflavonoids in tangerine-peel extract and in oranges. Still other research showed that phenolics extracted from grapefruit peels had the highest total antioxidant activity, followed by Yen Ben lemon, mandarin, orange and Meyer lemon peels. See B.B. Lia, B. Smitha, Md. M. Hossain (2006), Extraction of phenolics from citrus peels: II. Enzyme-assisted extraction method, Separation and Purification Technology, vol 48, issue 2, March 2006, pp 189-196.
hEST1A [TA/76, Links/hEST1A, Images, Papers, Patents, Books; Links/SMG6, Images, Papers, Patents, Books; Images/hEST1A molecule; (Images/SMG6 molecule); Links/hEST1A promoter, Images, Papers, Patents, Books; Links/hEST1A promoter binding sites, Images, Papers, Patents, Books; Links/SMG6 promoter, Images, Papers, Patents, Books; Links/SMG6 promoter binding sites, Images, Papers, Patents, Books]. The hEST1A gene is the human form of EST1p in yeast. See the index entry EST1p. hEST1A in humans, or Est1p [YeastGenome/Est1] has been conserved in evolution and is present in humans as hEST1A [Links]. "Overproduction of hEST1A cooperated with hTERT to lengthen telomeres." - See Snow BE, Erdmann N, Cruickshank J, Goldman H, Gill RM, Robinson MO, Harrington L., (2003), Functional conservation of the telomerase protein Est1p in humans, Curr Biol. 2003 Apr 15;13(8):698-704. hEST1A recruits telomerase holoenzyme by binding to hTERT protein (the catalytic component of telomerase) and to the telomere end binding complex (Cdc13p/Stn1p/Ten1p in yeast, shelterin in humans). (See Diagram) and Links/Cdc13p, Links/Stn1p, and Links/Ten1p. hEST1A promotes the ability of existing telomerase to elongate telomeres. hSMG6 [Links/hSMG6, Links/SMG6] is identical to hEST1A. (See Joachim Lingner, Senior scientist, Telomerase and chromosome end replication, ISREC.) According to Gene Cards, overexpression of SMG6 (in humans hEST1A) results in telomere uncapping. Therefore perhaps hSMG6 or hEST1A can be used to extend t-loop capped telomeres, opening them so that they can be extended by telomerase. Telomerase does not act on telomeres unless the telomere is uncapped (7). Thus large telomere t-loops corresponding to very youthful cells may be prepared by using hEST1A (hSMG6) together with telomerase, probably by stopping SMG6 towards the end of a treatment period to reseal telomere t-loops. Such cells may have superior staying power, lasting for more cell divisions before uncapping, generating a DNA damage signal, and entering the state of replicative senescence.
"hEST1A, one of 3 similar proteins hEST1A, hEST1B, and hEST1C, shares a 17.5% identity with yeast Est1p. Overexpression of hEST1A must be accompanied by hTERT coexpression for telomere elongation to be observed. hEST1A#7 overexpression promotes telomere enlongation. Also note that hEST1A negatively regulates telomere-transcribed TERRA RNA association with telomeres. hEST1A interacts with hTR through its RNA interaction domain (RID domain), and also with hTERT, probably through the hTERT EID domain. DNA damage, cell cycle arrest, and loss of telomere length results from hEST1A knockdown." (Sichun Lin (2011), Analysis of the Role of TRF1 and SMG6 in Telomere Length Maintenance, MS Thesis, McMaster University.) Note that
Replication Protein A [Index, List] on human Chromosome 17 [TA/RPA, Links, GeneCards/RPA1, (YeastGenome/RPA1, YeastGenome/Telomere Maintenance)], which is present in all eucaryotic cells, has been observed to activate telomerase by providing Est1p (hEST1A in humans) access to chromosome ends. See Vera Schramke, Pierre Luciano, Vanessa Brevet, Sylvine Guillot, Yves Corda, Maria Pia Longhese, Eric Gilson & Vincent Géli, (2003, 2004), RPA regulates telomerase action by providing Est1p access to chromosome ends, Nature Genetics 36, 46 - 54 (2004) Published online: 21 December 2003. Note that telomeric fusions have been observed in hEST1A-overexpressing cells. - See Joachim Lingner, Telomerase and chromosome end replication, ISREC.
HGH [TelomeraseActivators/HGH, Wikipedia, Links/Human Growth Hormone, James_South/HGH,
Links/HGH and Aging, Images, Video, Papers, Patents, Books, LibCong, LifeExtension;
Wikipedia/Growth Factor, Human Growth Factors, Human cells with HGH receptors,
Human cells without HGH receptors; HGH tissue gene expression; GeneCards/GHR expression in Tissue; GHR; HGH receptor (GHR) tissue gene expression;
Links/HGH secretagogues, Images, Video, Papers, Patents, Books, LibCong, LifeExtension].
"Aging is also accompanied by a gradual decrease in the output of GH, like the drying of an internal fountain, until in the eighth decade of life, it is secreted at less than one-fifth of the "youthful" level."
- [Jason Wolfe, 1998].
"In humans, the calculated daily GH secretion rate falls approximately 50% every 7 years beginning at age 18 to 21..." - [J.D. Veldhuis, 1998].
Human Growth Hormone (first isolated in 1956, structure identified in 1972) upregulates telomerase (article), improving the transcription of hTERT mRNA. [Links/HGH and telomerase activation, Papers, 67]. See L Gomez Garcia, et al., Direct Activation of Telomerase by GH via Phosphatidylinositol 3'-kinase, Journal of Endocrinology, 2005, 185, 425-228. Note that HGH (Telomerase_Activators/HGH) is processed by the liver to produce IGF-1, reviewed as a telomerase activator (Telomerase_Activator/IGF-1). HGH is stimulated by whey protein [Links]. According to Life Extension Magazine (March 2009) CDP-choline [Links, LifeExtension, Index/CDP-Choline] can amplify HGH levels by a factor of 4. Supplementation with L-Arginine and Ornithine (Links/HGH secretagogues, Links/Arginine plus Ornithine for HGH) can produce a large increase in growth hormone secretion lasting many hours. I note that fish contain both arginine and ornithine, stimulating HGH, so that coastal people are usually taller than natives that live inland and do without fish. Bodybuilding exercise (9) also stimulates HGH [Links]. HGH may be used to stimulate greater height development in the years 15-25. Human Growth Hormone (HGH) may activate telomerase directly through the PI3-K signaling pathway employing PhosphatidylInositol 3'-kinase. See the article: L Gomez-Garcia, FM Sanchez, MT Vallejo-Cremades, IA Gomez de Segura and E De Miguel del Campo, Direct activation of Telomerase by GH via phosphatidylinositol 3'-kinase, Journal of Endocrinology, 2005, 185, 421-428. An increase in the number of hTERT mRNA transcripts was observed in Chinese hamster ovary cells when GH was applied. See also Wikipedia/Phosphoinositide 3-kinase, which introduces the family of phosphatidylinositol 3'-kinases. , , (2), [17s].
Human Growth Hormone boosters:
Also see Daniel Rudman, M.D., Axel G. Feller, M.D., et.al, (1990), Effects of Human Growth Hormone in Men over 60 Years Old, The New England Journal of Medicine, Vol 323, No.1, July 5, 1990. Note that "declining HGH levels are associated with poorer cognitive function." Growth hormone is "neuroprotective, increasing survival of damaged nerve cells and promoting regeneration of nerve tissue". Receptors for HGH are "especially dense in brain regions responsible for learning and memory." Joseph Carrington (2012), Using Hormones to Heal Traumatic Brain Injuries, Life Extension Magazine January 2012. Also see Pathipati P, Gorba T, Scheepens A, Goffin V, Sun Y, Fraser M (2011), Growth hormone and prolactin regulate human neural stem cell regenerative capacity, Neuroscience 2011 Sept 8;190:409-27. Sanders EJ, Lin WY, Parker E, Harvey S (2011), Growth hormone promotes the survival of retinal cells in vivo, Gen Comp Endocrinol 2011 May 15; 172(1):140-50. Quick EH, et al. (2010), Cognitive performance in older males is associated with growth hormone secretion, Neurobiol Aging 2010 May 17. HGH is neuroprotective.
High Blood Pressure (Hypertension) [Index/Hypertension, Wikipedia/Hypertension, Links/Hypertension, Images, Video, Papers, Patents, Books, LibCong, LifeExtension]. (See) Hypertension is high blood pressure. Atherosclerosis elevates blood pressure by narrowing arterial passageways, but high blood pressure may also be due to high sodium. Nicotine may aggravate high blood pressure and atherosclerosis by constricting arterial passageway dimensions. Also see treating hypertensive emergencies [Links, Images, Video, Papers, Patents, Books] and antihypertensive drugs [Links, Images, Video, Papers, Patents, Books].
High Throughput Screening (High Throughput Testing) [Labs2/High Throughput Screening, Wikipedia, Links/High Throughput Screening, Images, Video, Papers, Patents, Books, LibCong, Amazon; Sierra Sciences; Links/Assay development for high-throughput screening, Images, Video, Papers, Patents, Books; Links/Bioscience Assay development, Images, Video, Papers, Patents, Books; Index/Protocols]. High throughput screening is supported by US grants, as described in Assay Development for High Throughput Molecular Screening (R21). Also see the ebook A Practical Guide to Assay Development and High-Throughput Screening in Drug Discovery by Taosheng Chen. See also High Throughput Quantitative Fluorescent In Situ Hybridization telomere measurement (HT Q-FISH [Links, Images, Video, Papers, Patents, Books]) in Ref1b 7.11 Telomere Measurement. Also see High Throughput Telomerase Activity Assays [Links, Images, Video, Papers, Patents, Books; Sierra Sciences] and High Throughput Telomere Measurement Assays [Links, Images, Video, Papers, Patents, Books].
HT-qFISH with automated confocal microscopy
High-throughput screening technique has also been applied to quantitative fluorescence in situ hybridization [Images, Papers, Books; qFISH] to yield HT-qFISH [Images, Papers, Books] based on automated confocal microscopy [Images, Papers, Books], which can be obtained at this time through CNIO, in Madrid, Spain, for internuclear [Images, Papers] and intranuclear telomere length distributions [Images, Papers]. See also Life Length with Dr. Maria A. Blasco. For application, see Calvin B. Harley, Weimin Liu, Maria Blasco, Elsa Vera, William H. Andrews, Laura A. Briggs, and Joseph M. Raffaele (2010), A Natural Product Telomerase Activator As Part of a Health Maintenance Program, Rejuvenation Research, September 7, 2010. For a 2012 overview of telomere measurement including HT Q-FISH, see Elsa Vera and Maria A. Blasco (2012), Beyond average: potential for measurement of short telomeres, Aging, June 2012, Vol.4, No.6., http://www.impactaging.com.
Histidine [Wikipedia/Histadine, Links/Histidine, Images, Video, Papers, Patents, Books, LifeExtension]. Histidine (the amino acid forming carnosine in combination with beta-alanine) forms histamine, which enhances Nitric Oxide expression by promoting the activity of nitric-oxide synthase (NOS), which synthesizes NO from arginine. (Histamine also plays a role in immune response.) A practical dose to boost NO is 1-2 grams of L-Histidine or Histidine Alpha-Ketoglutarate.
Histology [Wikipedia, Links, Images, Video, Papers, Books, LibCong, Amazon].
Histology of the Aging Brain [Index/Aging Brain, Links/Histology of the Aging Brain, Links/the cells of the aging brain, Books/the cells of the aging brain, LibCong, LifeExtension/Aging Brain Cells, Papers/the cells of the aging brain, Papers/microphotographs of aging brain cells, Papers/histology of the aging brain, Books/histology of the aging brain], [59s]. See Prolla TA (2002), DNA Microarray Analysis of the Aging Brain [Links, Images, Video, Papers, Patents, Books], Chem Senses, 27:299-306.
Histology of Senescent Cells [Links, Images, Papers, Books; Links/senescent cells, Images, Papers, Books, LibCong/senescent cells, Books/cellular senescence, Links/senescent cells, Wikipedia, Links/microphotographs of senescent cells, Papers/microphotographs of senescent cells, and photos of senescent fibroblasts from Hayflick, His Limit, and Cellular Aging by Jerry W. Shay & Woodring E. Wright]. See Senescence.info.
Histone Deacetylases (HDACs) [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension, LibCong, Amazon]. Histone Deacetylases (HDACS) act to condense and silence chromatin via deacetylation of histones. Methylation of DNA, incidentally, is also often associated with deacetylation and hypoacetylation of DNA for gene silencing via chromatin compaction. Yeast SIR2 (a sirtuin) is the founding member of the Class III histone deacetylases, and has the human homologue SIRT1, a gene turned on by caloric restriction and by CR-mimetics like resveratrol. See Index/Sirtuin Activators and histone deacetylase classes. When calories are too restricted, protein synthesis is blocked by SIRT1 hypoacetylation of chromatin, so that input materials can be combusted for energy, rather than used up in protein construction, it seems.
Histone Deacetylase Inhibitors (HDAC Inhibitors) [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension, Amazon, BIOMOL/HDAC Inhibitors]. HDAC inhibitors work to expand chromatin, making it more available for transcription. [Video]. Certain specific HDAC inhibitors such as Tricostatin A activate transcription of hTERT, producing the catalytic component of telomerase. Sodium butyrate, another histone deacetylase inhibitor, also hyperacetylates chromatin to expand it for accelerated transciptional activity. Sodium butyrate is thought to improve the transcription of both hTERT and hTR, which may be important for rejuvenation of mesenchymal-derived tissues with poor hTR expression, such as connective tissues. cartilage, and bone. "Alternatively, HDAC inhibitors induce p21WAF1 expression in cancer cells probably through histone-acetylation of the promoter (Sowa et al., 1999; Richon et al., 2000). This may play an important role in the arrest of cell growth or cellular differentiation, leading to indirect inhibition of telomerase activity." - after Satoru Kyo and Masaki Inoue (2002), Complex regulatory mechanisms of telomerase activity in normal and cancer cells: How can we apply them for cancer therapy?, Section (5) Histone Deacetylase Inhibitors, Oncogene, 21 January 2002, Volume 21, Number 4, Pages 688-697.
___History of Telomeres & Telomerase
[Links, Video, Papers, Books, Hayflick, His Limit, and Cellular Aging by Shay & Wright]. See also the 2009 Nobel Prize Winner's essay Telomeres and Telomerase: the path from maize, Tetrahymena, and yeast to human cancer and aging by Elizabeth H. Blackburn, Carol W. Greider, and Jack W. Szostak. See also
___History of Telomerase Activators
[Immortalization of Cells: History of Telomerase Activators, Change Log 2/History of Telomerase Activators, Index Change Log, Links, Video, Papers, Books; Index/Telomerase Activators, Numeric List with Dates].
___History of Molecular Biology [Wikipedia, Links, Video, Papers, Books, LibCong],
___History of Medicine [Wikipedia, Links, Video, Papers, Books, Wiki/Timeline],
___History of Science [Wikipedia, Links, Papers, Books, Timeline of Scientific Discoveries].
HIV [Index/Virology, Wikipedia/HIV, Wikipedia/HIV/AIDS, Links/HIV, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/HIV virus, Images, Video, Papers, Patents, Books, Books/early senescence of CD8+ cells in HIV, HIV genes, Links; Links/antiretroviral drugs, Images, Video, Papers, Patents, Books, Amazon, LEF; Links/antiretroviral drugs for HIV, Images, Video, Papers, Patents, Books, Amazon, LEF; Wiki/Management of HIV/AIDS, Hots/Medical and Cautionary]. HIV-1 is the more virulent HIV type that troubles the USA, HIV-2 is found almost entirely in Africa. Difficult strains of HIV-1 evolve. Astragaloside IV and other anti-senescence drugs such as cycloastragenol or astragalus extract may be used to treat HIV infections, which exhaust CD8+ cytotoxic T-cells with premature stress-induced or replicative senescence. See CD8+ cytotoxic T-cells [Wikipedia, Links, Images, Video, Papers, Patents, Books]. See also Geron's TAT2 (TAT0002). Garlic at 3-5 cloves 3 times per day (flavored with mustard or BBQ sauce) is useful against many bacterial and viral pathogens, including tooth abcess pathogens and HIV virus. Antioxidants can prevent apoptosis due to oxidative stress from HIV infection. Hyssop [Images], Olive Leaf Extract [Images], EGCG [Images] from Green Tea [Images], Theaflavin [Images], Rooibos Tea [Images], Self-heal [Images], Tannic acid [Images], Gallic acid [Supplements], and Catuaba [Images] show anti-HIV activity. Mint family Lemon Balm extract [Images], Sage [Images], and Peppermint extracts [Images] were also effective against HIV-1. "In a 2000 study published in The Indian Journal of Medical Research, it was shown that of the 69 plant species screened, 16 were effective against HIV-1 and 4 were against both HIV-1 and HIV-2. The most effective extracts against HIV-1 and HIV-2 were respectively Cinnamomum cassia (bark) and Cardiospermum helicacabum (shoot + fruit)." - Wikipedia/Cinnamon. Finally, note that alpha-lipoic acid or its reduced form dihydrolipoic acid are used to inhibit replication of the HIV virus via inhibition of reverse transcriptase and of NF-kB. The recommended therapeutic dose of alpha-lipoic acid is 600-1800 mg daily. See Baur A, Harrer T, Peukert M, et al. (1991), Alpha-lipoic acid is an effective inhibitor of human immuno-deficiency virus (HIV-1) replication, Klin Wochenschr 1991; 69:722-724. For T-cells in culture, "an over 90% reduction of reverse transcriptase activity could be achieved with 70 micrograms of alpha-lipoic acid/ml. Trypan blue staining revealed no toxic effects of alpha-lipoic acids on peripheral blood mononuclear cells and T-cell lines even in concentrations of > 70 micrograms/ml." There are 70 mL/kg in the human body per male and there are 65 mL/kg in the human body per female. A 200 lb male weighs 90.718474 kg and carries 70 mL x 90.71 = 6349.7 ml of blood. Then 70 micrograms alpha-lipoic acid/ml x 6349.7 ml blood = 444479 micrograms = 444 mg of alpha-lipoic acid. Thus for perfect absorption into the blood, one should take about 450 mg of alpha-lipoic acid to achieve better than 90% blockade of HIV-1 reverse transcriptase activity. Doses of 400 mg x 4 per day of alpha lipoic acid are standard in life extension therapy. See Geronova Bioenhanced Alpha Lipoic Acid for high bioavailability alpha-lipoic acid. See also sodium-R-lipoic acid [Images, LEF], high bioavailability alpha-lipoic acid [Images], and alpha-lipoic acid plasma levels as a function of time [Links, Images]. Note that curcumin inhibits HIV-1 integrase, inhibits HIV-1 protease and HIV-2 protease, restrains gene expression of chronically infected HIV-1 cells, and inhibits the release of factors promoting HIV-1 replication. See Cohly HHP, Asad S, Das SK, Angel MF, Rao M. (2003), Effect of antioxidant (turmeric, turmerin, and curcumin) on human immunodeficiency virus, Int J. Mol. Sci, 2003 Jan; 4(2): 22-33.
Virosomes for HIV-1 vaccines [Links/Virosomes, Images, Papers, Patents, Books; Links/HIV vaccines, Images, Papers, Patents, Books]. Virosomes are lipid membranes modeled after envelope viruses that fuse with target cells. They may be engineered with gp41 antigen or other antigens on their surfaces for applications such as HIV-1 preventive vaccines or other preventive antiviral vaccines for Herpes simplex, RSV, malaria, or influenza. Certain virosomes have been developed around spherical empty influenza virus envelopes that may be used to port proteins, or perhaps engineered plasmid DNA, for transfection applications. See Mymetics. The Mymetics HIV-1 vaccine is designed to block early transmission of the HIV virus at mucosal surfaces by inducing IgA antibodies on mucosa to block viral entry, as well as IgG antibodies that circulate in the blood. Perhaps colostrum could be a useful source of such antibodies.
Music: The Theme from DR. ZHIVAGO.
HMGB-1 (High Mobility Group Box-1) (encyclopedia).
Holy Basil [Index/Basil, Links, Images, Video, Papers, Patents, Books, LifeExtension; Images/Holy Basil Extract supplements]. Holy basil lowers COX-2 and cortisol levels. See William Gamonski (2012), Basil: A Potent One-Two Punch of Robust Flavor and Medicinal Advantages, Life Extension Magazine, May 2012.
Homocysteine [Wiki, Links, Images, Video, Papers, Patents, Books, Amazon, LibCong, LEF].
32% more heart attack victims had homocysteine levels > 10 mmol/L.
500% more heart attack victims had homocysteine levels > 15 mmol/L."
- William Falloon, As We See It, Life Extension Magazine, September 2010.
Recent research suggests high homocysteine levels lead to Alzheimer's Disease [Papers, Patents, Books]. See LuYa-Qin, LuoYu, HeZhong-Fang, ChenJun, YanBo-ling, WangYing, and YuQin (2013), Hydroxysafflor Yellow A Ameliorates Homocysteine-Induced Alzheimer-Like Pathologic Dysfunction and Memory/Synaptic Disorder, Rejuvenation Research, December 2013. See Hydroxysafflor Yellow A [Papers, Patents, Books].
Furthermore, Tocotrienols reduce homocysteine levels , .
 Norsidah KZ, Asmadi AY, Azizi A, Faizah O, Kamisah Y. (2013),
Palm tocotrienol-rich fraction reduced plasma homocysteine and heart oxidative stress in rats fed with a high-methionine diet, J Physiol Biochem 2013 Sep;69(3):441-9.
 Thomas Rosenthal (2014), The Little-Known Benefits Of Tocotrienols, Life Extension Magazine, August 2014.
 William Faloon (2015), Newly Identified Risks Of Excess Homocysteine, Life Extension Magazine May 2015.
 Greenberg JA, Bell SJ, Guan Y, Yu YH (2011),
Folic Acid supplementation and pregnancy: more than just neural tube defect prevention,
Rev Obstet Gynecol 2011 Summer;4(2):52-9.
Homocysteine Blocker [Index/Homocysteine, Links/Homocysteine Blocker, Images, Papers, Patents, Books, Amazon, brand BIOCHEM; Images/Homocysteine Shield]. A homocysteine blocker (homocysteine shield) prevents atherosclerosis, and typically includes TMG (trimethylglycine), folic acid, vitamin B6, vitamin B12, and additives. Atherosclerotic plaque has been implicated in heart attacks, strokes, and macular degeneration.
Honey [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension; Links/Composition of Honey, Images]. Post-workout shakes are typically made with plenty of extra glucose (dextrose, maltodextrose) to spike insulin in the presence of BCAAs, whey isolates, or whey hydrolysates. Average honey is 82.4 % carbohydrates, containing 31.0% fast-digesting glucose and 38.5% slower-digesting fructose (routed through the liver), along with 7.2% Maltose and 1.5 % Sucrose. Note, however, that extra glucose inhibits the production of neuroprotective HGH. Furthermore, "declining HGH levels are associated with poorer cognitive function." Growth hormone is "neuroprotective, increasing survival of damaged nerve cells and promoting regeneration of nerve tissue". Receptors for HGH are "especially dense in brain regions responsible for learning and memory." Joseph Carrington (2012), Using Hormones to Heal Traumatic Brain Injuries, Life Extension Magazine January 2012.
Hoodia [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Hoodia is an extract from the South African plant hoodia gordonii [Images], and contains P57, which seems to trick the brain into thinking the stomach is full. Hoodia is recommended 300-500 mg/dose one or two times per day on an empty stomach. - (after Muscle and Fitness Magazine, 2010).
Hormesis [Links, Images, Papers, Patents, Books, LibCong, LifeExtension/Hormesis, Wikipedia/Hormesis] (9), [5s]. Small doses of radiation make mice and insects live longer, although large doses reduce life span. The same "hormesis" effect applies to heat treatments and exercise. Dieting might be pictured as a mild stress resulting in life span prolongation, whereas starvation results in death, so that the "hormesis" approach is to diet, not to starve, for longevity and slenderizing restructuring. Heat shock protein levels may become elevated as a result of hormesis when the stress is due to elevated temperature or exercise. Application of low-grade stresses such as exercise or sauna may upgrade biomolecule levels such as heat shock protein levels to improve defenses against aging. See M Natarajan, S Mohan, R Konopinski, R A Otto, and T S Herman (2008), Induced telomerase activity in primary aortic endothelial cells by low-LET gamma-radiation is mediated through NF-kappa-B activation, British Journal of Radiology, (2008) 81, 711-720. Also see Suresh I. S. Rattan, Rehab E. Ali (2007), Hormetic Prevention of Molecular Damage during Cellular Aging of Human Skin Fibroblasts and Keratinocytes, Annals of the New York Academy of Sciences, 18 APR 2007. Abstract: "Our studies have shown that repeated mild heat stress (RMHS) has antiaging effects on growth and various other cellular and biochemical characteristics of normal human skin fibroblasts undergoing aging in vitro. RMHS at 41°C, for 1 h twice a week (105.8 degrees F), increased the basal levels of various chaperones, reduced the accumulation of oxidatively and glycoxidatively damaged proteins, stimulated proteasomal activities for the degradation of abnormal proteins, improved cellular resistance to ethanol, hydrogen peroxide, and UV-B rays, enhanced the levels of various antioxidant enzymes, and increased the phosphorylation-mediated activities of various stress kinases. RMHS-exposed human fibroblasts are also better protected against glucose- and glyoxal-induced growth inhibition and apoptosis. We have also observed various hormetic effects of RMHS on normal human epidermal keratinocytes, which include increased replicative life span, increased proteasomal activity, and enhanced levels of Na/K-ATPase pump. We are also testing the above effects of RMHS in combination with potential hormetic molecules, such as curcumin, on aging, longevity, and differentiation of human cells in culture."
Hormones [Cope/Hormones, Ben Best/Hormones and Aging, Links/Hormones, Images, Papers, Patents, Books; Links/Endocrine Hormones, Images, Papers, Patents, Books; Links/Paracrine Hormones, Images, Papers, Patents, Books; Links/Autocrine Hormones, Images, Papers, Patents, Books; Index/HGH, Index/IGF-1, Index/Testosterone, Index/Estradiol, Index/Progesterone].
Hormone Replacement Therapy [Links, Images, Video, Papers, Patents, Books, LibCong, LifeExtension, Wikipedia, Ben Best/Hormones] (2). See also Sex Hormone Replacement in Older Adults by Ben Best.
Hormone Skin Creams [Links, Images, Video, Papers, Patents, Books, LEF]. See Skin and Growth Factor Skin Creams.
Horny Goat Weed [Telomerase Activators/(144) Horny Goat Weed; Links, Images, Video, Papers, Patents, Books, LibCong, LEF, Wikipedia; Thymus Gland]. Horny goat weed (epimedium) inhibits the enzyme phosphodiesterase-5 (PDE5) that ordinarily decomposes NO. Jim Stoppani [Images], in his essay "Elements of a Stack", recommends it as a NO amplifier to be taken at about 500 mg when arginine [Images] is taken (3-5 grams in the morning, 30-60 minutes before a workout, and again 30-60 minutes before bedtime). Note that pycnogenol [Images], by increasing the activity of nitric oxide synthase, acts like a catalyst for the production of nitric oxide from arginine, and is also a component of the nitric oxide stack recommended by Jim Stoppani at 50-100 mg. He also recommends Ginkgo Biloba [Images] at 40-80 mg for its glycosides reducing the stickiness of platelets to promote blood flow to the muscles and the brain. The Jim Stoppani arginine stack consists of arginine (3-5 grams), pycnogenol (50-100 mg), horny goat weed (500 mg), and ginkgo biloba (40-80 mg). Since nitric oxide has been observed to upregulate telomerase, this stack may also be quite useful in antiaging medicine, especially when combined with a pump-up sort of exercise session. High NO levels are thought to refresh the vascular endothelium, reducing the senescence of endothelial cells lining central arteries and veins that increases adhesion to monocytes, leading to the buildup of atherosclerotic plaque. Nobel Prize winner Dr. Louis J. Ignarro recommends 4 to 6 grams of L-arginine per day for physiologically effective NO generation, plus L-citrulline at 200 mg/day to 1000 mg/day to maximize it's effect, together with 4 antioxidants including alpha lipoic acid in his book NO More Heart Disease and in his advanced technical books on nitric oxide in physiology and medicine [Books/Louis Ignarro nitric oxide]. Perhaps a souped-up form of the Jim Stoppani Nitric Oxide stack would also include L-Citrulline [Images] and Louis B. Ignarro's antioxidants. Doses of arginine 5-10 gr/day are sometimes prescribed to restore the thymus gland production of thymic hormones [21s] and T-lymphocytes, which strengthens the immune system (11). Since this takes place via the action of nitric oxide synthase on L-arginine to produce Nitric Oxide, horny goat weed should be useful in restoring thymus gland activity [Images, Papers, Patents, Books]. (See Phillip Lee Miller, M.D. with Monica Reinagel, Life Extension Revolution, Life Extension Foundation).
Horse Chestnut [Ray/Horse Chestnut, Links, Images, Videos, Papers, Patents, Books, LEF] - A cure for varicose veins [Index, Links, Images, Video, Papers, Patents, Books, LifeExtension]. Escin [Links, Images, Video, Papers, Patents, Books]. Escin in horse chestnut increases the tone of veinous walls, promoting improved circulation and making it a popular oral and topical treatment for varicose veins and veinous insufficiency. In one test, treatment with 50 mg of escin twice daily was equivalent to compression stocking therapy [Links]. See support hose [Images]. See also non-invasive treatment for varicose veins [Links]. In bodybuilding, horse chestnut [Links] is used to increase vascularity and improve definition. Several pairs of conventional support hose worn 24 hours around-the-clock with shower breaks seem to be more effective than escin in causing varicose vein problems to recede.
Hot Flashes [Wikipedia/Hot flashes, Links/Hot Flashes, Video, Papers, Patents, Books, LibCong, LifeExtension, Amazon]. Women experience hot flashes as a consequence of menopause. Hot flashes may be treated with a combination of estrogen and progesterone applied in skin creams [Images] or in patches [Images].
HPLC (High performance liquid chromatography) [Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon, LibCong]. See also organoleptic HPLC [Links, Images, Video, Papers, Patents, Books, Amazon] and quantitative HPLC [Links, Images, Video, Papers, Patents, Books, Amazon]. See Instrumental Analysis, Separation, and Phytochemical Separation.
HPV Virus [Virology, Wikipedia, Antiviral Drugs, Links/HPV virus, Images, Video, Papers, Patents, Books, Amazon; Links/HPV treatment, Images, Video, Papers, Patents, Books; Links/HPV vaccination, Images, Video, Papers, Patents, Books; Cervical Cancer; Genital Warts; Erotic Hots Study Guide; HIV]. HPV virus is a papovavirus (papilloma virus) with a DNA genome of 5-8 kilobase pairs that causes genital warts and leads to certain forms of cancer such as cervical cancer. A 2004 study of 6,000 anal cancer patients (the majority of whom were women) found that 73 percent of the patients tested positive for the strain HPV-16, one of the four strains of the HPV virus that the Gardasil vaccine protects against. Another popular HPV vaccine is Cervarix. Genital warts may be removed with apple cider vinegar in cotton taped on for about 6 days, or frozen with Compound W Freeze-Off or liquid nitrogen and peeled off after a few days, and the new skin treated over several days with finely grated fresh garlic, allicin from garlic, or Aldara to destroy remaining HPV virions in the skin, perhaps preventing the return of the warts. Carrageenan personal lubricants are believed to be effective inhibitors of HPV. Carrageenan (extracted from Irish Moss) has good adhesiveness to skin. Lubricated prophylactics prevent pregnancy and also blockade flesh against HPV-generating friction and other STDs. See Sutapa Mahata, Alok C Bharti, Shirish Shukla, Abhishek Tyagi, Syed A Husain and Bhudev C Das (2011), Berberine modulates AP-1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells, Molecular Cancer, April 15, 2011 (online edition). Also see (137) Berberine Rhizome Extract in Product B and berberine supplements [Images; Papers, Patents, Books]. Perhaps some transdermal cures for HPV are better applied to the skin after treatment with a skin-pricking Derma Roller to make skin more penetrable.
HSP90 [Refs7, Wikipedia/HSP90, Links/HSP90, Images, Video, Papers, Patents, Books, LifeExtension; Links/the HSP90 promoter, Images, Video, Papers, Patents, Books; Links/upregulating HSP90, Images, Video, Papers, Patents, Books, LifeExtension; Index/Heat Shock Proteins; Links/Heat Shock Protein Supplements; Telomerase Activators/Heat Shock Proteins]. HSP90 assists with the transport of several telomerase activators into the nucleus, including the astragalosides or their metabolites, and also with the transport of testosterone bound with dimerized androgen receptor and cofactors into the nucleus. HSP90 is important for folding and assembly of telomerase, so that it behaves like a telomerase activator. Gamma tocopherol blocks heat shock proteins, so that it should not be taken while attempting to activate hTERT transcription to upregulate telomerase activity. Low HSP90 results in lower telomerase levels, and HSP90 is required for human telomerase activity, as is p23, which forms a HSP90-p23 telomere-associated complex. HSP90 is upregulated by exercise and/or alpha lipoic acid. HSP90 has been upregulated in rat kidneys by a low-sodium diet (Victoria Ramírez, et al., 2004). Furthermore, HSP (Heat Shock Protein) expression is stimulated by testosterone and catecholamines (stress hormones) including epinephrine and norepinephrine, which can be released by taking caffeine. A combination of lipoic acid, carnosine, and zinc may also be used to elevate HSP expression. See supplements that upregulate HSP90 expression and supplements upregulating heat shock protein expression. HSP70, which is upregulated by TEXOE, is also important in transporting proteins and testosterone bound with dimerized androgen receptor and cofactors into the nucleus, where it acts like a transcription factor complex, similar to the estrogen plus dimerized estrogen receptor plus histone acetyl transferase transcription factor complex. HSP90 may be high in cancer cells, so that HSP90 inhibitors like geldanamycin are offered as anticancer drugs, and both geldamycin and novobiocin HSP90 inhibitors also inhibit telomerase activity. It useful to promote HSP90 when using telomerase activators in a program of cyclic telomerase activation, although it is abundant in cells. See Shawn E. Holt, Dara L. Aisner, Joseph Baur, Valerie M. Tesmer, Marife Dy, Michel Oullette, James B. Trager, Gregg B. Morin, David O. Toft, Jerry W. Shay, Woodring E. Wright, and Michael A. White (1999), Functional requirement of p23 and Hsp90 in telomerase complexes, Genes and Development 1999 13: 817-826. (Connolly, et. al, 2004) shows exercise-stimulated upregulation of HSP90 in human blood peripheral mononuclear cells [Images]. Also see Brian R. Keppler, Allen T. Grady, and Michael B. Jarstfer (2006), The Biochemical Role of the Heat Shock Protein 90 Chaparone Complex in Establishing Human Telomerase Activity, The Journal of Biological Chemistry, 281(29), 19840-19848.
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