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A 30-day cyclic program of application may be specified as two consecutive 15-day periods:
"Overexpression of TRF2 causes telomere shortening in both telomerase-positive and -negative cells. Recent studies also showed that TRF2 also activates telomere degradation." (Cong, Wright, and Shay, 2002). This is discouraging for TRF2-based telomere loop closure therapy programs to lengthen life spans by using Zocor or other TRF2-enhancing drugs such as Pravastatin. See Robert Haas, MS, Lower Cholesterol Safely, Life Extension Magazine, March 2010. Brown WV (2008), Safety of statins, Current Opinion in Lipidology 2008;19:558-62. Ahn SC (2008), Neuromuscular complications of statins, Physical Medicine and Rehabilitation Clinics of North America 2008; 19:47-59, vi.
Pregnenolone [Telomerase Activators/Pregnenolone, Smart-DrugsPregnenolone, a memory improver , Memory Enhancing Nutraceuticals; Wikipedia/Pregnenolone, Links/Pregnenolone, Images, Papers, Patents, Books, LifeExtension LibCong; toxicity, dosage, sources], . Pregnenolone is a precursor for testosterone and DHEA, which increases levels of IGF-1. That is, pregnenolone increases testosterone levels, DHEA levels, and IGF-1 levels. Therefore pregnenolone is a telomerase activator (TA/Pregnenolone) via the IGF-1 pathway Pregnenolone -> DHEA -> IGF-1, such that pregnenolone/DHEA/IGF-1/AKT phosphorylates hTERT for import from the cytoplasm into the nucleus via AKT kinase. Furthermore, the pathway Pregnenolone/DHEA/testosterone produces testosterone, an androgen which increases levels of hTERT mRNA in androgen-dependent cells such as muscle cells and brain cells, though not in androgen-independent cells. .
 Mayo W, Lemaire V, Malaterre J, et al. (2005),
Pregnenolone sulfate enhances neurogenesis and PSA-NCAM in young and aged hippocampus,
Neurobiol Aging 2005 Jan;26(1):103-14.
pRB pathway [Wikipedia/pRB, Links/pRB pathway, Images, Video, Papers, Patents, Books, Amazon, LifeExtension]. pRB refers to the Retinoblastoma Protein [Images, Video, Papers, Patents, Books, LifeExtension]. See Index/Senescence, Index/Senescence Pathway and Index/Replicative Senescence for the role of pRB in senescence [Images, Video, Papers, Patents, Books, LEF]. "Senescence requires activation of the Rb (retinoblastoma) protein and/or p53 tumor suppressor protein and expression of their regulators such as p16INK4a [Wikipedia, Links] and p15ARF.... Three tumor suppressor genes [Wikipedia, Links] are encoded in a common 40 kb stretch of human chromosome 9b21: 2 highly related CDK inhibitor proteins (p16INK4a and p15INK4b) and ARF, a regulator of p53 stability. Expression of p16INK4a and p15INK4b inhibits CDK4/6 activity [Links], leading to hyperphosphorylation of Rb-family proteins (Rb, p107, p130) and growth arrest [Links]. Expression of ARF inhibits the ubiquitin ligase activity of MDM2, thereby stabilizing p53. DNA damage inhibits p53 degradation by MDM2 in an ARF-dependent manner and can promote senescence independent of INK4a/ARF activation. DNA damage also likely activates p16INK4a." - N.E.Sharpless, "A Telomere-Independent Process", from Telomeres and Telomerase in Ageing, Disease, and Cancer, p188.
Preventive Medicine [Wikipedia/Preventive medicine, Links/Preventive Medicine, Images, Video, Papers, Patents, Books, Amazon, LifeExtension, LibCong].
Proantocyanidine [Links/Proantocyanidine, Images, Video, Papers, Patents, Books, Amazon, LifeExtension]. See Govinda Organic Grape Seed Flour [Images; Images/Grape Seed Flour]. 2,100 mg is recommended (3x700 mg) is recommended in Tristan Trefoil's recent proposal for an Immortality Diet.
Proanthocyanins and Proanthocyanidins [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension, Amazon; Wikipedia, Links/Proanthocyanidins, Images, Video, Papers, Patents, Books]. See also Index/Anthocyanins. Note that the anthocyanidins [Wikipedia, Links, Images, Video, Papers, Patents, Books] are the sugar-free counterparts of anthocyanins based on the benzopyrylium (chromenylium) ion.
Probiotics [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon, LifeExtension, Dental]. Oral Probiotics [Links, Images, Video, Papers, Patents, LifeExtension, Dental]. Probiotics may be used to replace bacteria in the mouth responsible for gingivitis and periodontal disease with friendly bacteria such as S. Salivarius, reducing tooth decay [Dental] and lowering the overall level of inflammatory cytokines in the body, which tends to reduce atherosclerosis and thereby heart attack and stroke. Inflammation from periodontal disease may also contribute to Alzheimer's Disease and other disorders associated with an inflammatory environment for cells.
Progenitor Cells [Links/Progenitor cells, Images, Video, Papers, Patents, Books, LifeExtension; Links/Endothelial progenitor cells, Images, Video, Papers, Patents, Books, LifeExtension; Index/Stem Cell Technology; Index/Tissue Engineering, Index/Regenerative Medicine; iPS cells (induced Pluripotent Stem Cells)]. Progenitor cells and stem cells such as iPS cells may both be injected at sites requiring repair to reconstruct tissue. Endothelial progenitor cells are a rare fraction of the blood that is used to repair the vascular endothelium.
Progeria [Ben Best, Links, Images, Video, Papers, Patents, Books, LibCong, LifeExtension], .
Progesterone [Telomerase Activator List/Progesterone, Links, Images, Video, Papers, Patents, Books, Amazon, LibCong; Images/Progesterone Skin Cream, Links/Medroxyprogesterone]. There are sites on the hTERT promoter that interact with signal molecules generated by cell surface receptors for progesterone as well as by cell surface receptors for estrogen, according to some authors. It is usually maintained that progesterone acts on the hTERT promoter otherwise, via the MAP kinase pathway. "If progesterone is applied, hTERT mRNA is induced within 3 hours but decreases after 12 hours." (Cong, Wright, and Shay, 2002). Today one speaks of nutraceuticals containing ligands of the progesterone receptor acting on the progesterone receptor [Images, Papers, Patents, Books].
Progesterone Cream [Links, Images, Video, Papers, Patents, Books]. See also Hormone Skin Creams [Links, Images, Video, Papers, Patents, Books]. The telomerase activator progesterone is often applied in skin creams for soft, smooth, feminine skin. According to some authors, there are sites on the hTERT promoter that interact with signal molecules generated by cell surface receptors for progesterone as well as for estrogen. However, it is usually maintained that progesterone acts on the hTERT promoter otherwise, via the MAP kinase pathway. "If progesterone is applied, hTERT mRNA is induced within 3 hours but decreases after 12 hours." (Cong, Wright, and Shay, 2002).
Proinflammatory Cytokines [Wikipedia/Proinflammatory cytokine, Index/Inflammatory Cytokines, Links, Images, Video, Papers, Patents, Books, LifeExtension, Amazon]. "A proinflammatory cytokine is a cytokine which promotes systemic inflammation. Examples include IL-1 and TNF alpha." - Wikipedia/Proinflammatory cytokine. NF-kB may be activated by ROS and opposed by NF-kB inhibitors. The expression of proinflammatory target genes of NF-kB (TNF-alpha, COX-2, iNOS, and IL-1beta) increases with age in the mouse. NF-kB expression can cause senescence in human keratinocytes. The expression of proinflammatory genes COX-2, IL-1beta, and others increases in senescent human fibroblasts. A specific COX-2 inhibitor inhibits senescence, and decreases expression of caveolin-1 in the cell membranes of senescent cells, enabling recovery from cellular senescence when the cell is stimulated with telomerase-activating growth factors such as EGF or PDGF. The use of selective Cox-2 inhibitor N-[2-(Cyclohexy-Loxyl)-4-Nitrophenyl-Methanesulfonamide has been patented for this application by S.C.Park and J.A.Han (2008-2012). This substance is believed to transcriptionally inhibit caveolin-1 (gene CAV1) expression. Side effects are still in question. See Restoring Senescent Cells and Therapy for Recovering from Cellular Senescence.
Anti Cytokine Therapy [Links, Images, Video, Papers, Patents, Books, LifeExtension, Amazon], Pro-inflammatory Chemicals [Links, Images, Video, Papers, Patents, Books, LifeExtension], Index/Anti-Inflammatory Nutraceuticals, and Index/Inflammation.
Propolis [Wikipedia/Propolis, Links/Propolis, Images, Papers, Patents, Books]. Propolis may disinfect bees on their way in and out of their hives, as well as the hive itself, and has antifungual, antibacterial, and antiviral properties. "Greeks have used propolis for abscesses; Assyrians have used it for healing wounds and tumors; and Egyptians have used it for mummification." - WebMD/../Propolis.
Promoters (Gene Promoters and Transcription Factors) [Gene Regulation in Eucaryotes, Wikipedia/Promoter, Links/Gene Promoters, Images, Papers, Patents, Books; Links/Gene Promoter structure, Images, Papers, Patents, Books; Links/hTERT Promoter structure, PatentLens/promoters; Links/Drug Interactions with Gene Promoters, Images, Papers, Patents, Books; Links/Transcription Factors, Images, Papers, Patents, Books; Links/Drugs and Transcription Factors, Images, Papers, Patents, Books; Links/Transcription Factor Pathways, Images, Papers, Patents, Books].
See the index entry for the hTERT promoter for the catalytic component of telomerase.
hTR (hTERC) Promoter
Also see the index entry for the hTR (hTERC) promoter controlling the RNA template part of the telomerase holoenzyme.
CAV1 Promoter for caveolin-1
See also Bist A., Fielding P. E., Fielding C. J. (1997), Two sterol regulatory element-like sequences mediate up-regulation of caveolin gene transcription in response to low density lipoprotein free cholesterol, Proc. Natl. Acad. Sci. U.S.A. 1997;94:10693–10698. This article defines the CAV1 promoter [Papers, Patents, Books]. High caveolin-1 levels (gene CAV1) can produce cellular senescence, while lowering caveolin-1 levels can restore the immortal phenotype and the membrane caveolae though which growth factors such as EGF and PDGF communicate with receptors to lengthen telomeres in the cell.
Prostate Cancer [E_Medicine_Health/Prostate Cancer, Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension, LibCong/Prostate Cancer; Benign Prostatic Hyperplasia (BPH); Cancer, Carcinogens, Anticancer Nutraceuticals; Watercress; Apoptosis; Telomerase Inhibitors; Anticancer Telomerase Activators; Metastasis, NFkB, NFkB Inhibitors, Angiogenesis Inhibitors, (71), (49)].
Recently, "We found that men who ate more than 1.5 servings of pan-fried red meat per week increased their risk of advanced prostate cancer by 30%. In addition, men who ate more than 2.5 servings of red meat cooked at high temperatures with 40% more likely to have advanced prostate cancer." . Eggs (which are high in arachidonic acid) increase the likelihood of the most lethal form of prostate cancer. Men who at 2.5 eggs/week had an 81% higher risk of prostate cancer than those who consumed < 0.5 eggs/week. A high intake of arachidonic acid promotes the expression of 5-LOX and COX-2 enzymes establishing tumor formation and progression.
The Life Extension Foundation recommends curcumin, fish oil, and boswellia extract "to impede conversion of arachidonic acid to leukotriene B4 via 5-LOX." Gamma tocopherol and aspirin impede COX-2. - (LEF News, Jan 2012 and Cancer Prevention Research (Phila), 2011 Sep 19). Note that arachidonic acid is more useful during growth and development. See prostate cancer and cruciferious vegetables, prostate cancer causes, prostate cancer prevention. About 50% of males eventually suffer from BPH (Benign Prostatic Hyperplasia, or prostate enlargement), which causes problems with urine flow or the urinary tract. BPH may be treated and prostate cancer prevented by applying saw palmetto [Images], nettle root extract [Images], flax lignans [Images], Norway spruce lignans [Images], boswellia extract [Images], Pygeum Africanum extract [Images], cernitin [Images], boron [Images], lycopene [Images], or Equol [Images], in combination or singly. Saw Palmetto, which includes beta-sitosterol and inhibits the production of dihydrotestosterone (DHT) from testosterone by inhibiting the enzyme 5-alpha-reductase, also interferes with DHT cell surface receptors. Equol binds to 5-alpha dihydrotestosterone (DHT). Green tea inhibits DHT (Jerry Brainum, Iron Man, March 2010). Saw Palmetto is often combined with nettle root extract and Pygeum Africanum to protect the prostate. Other 5-alpha-reductase inhibitors reducing the expression of DHT competitive with saw palmetto include Finasteride and Dutasteride, which are also used to prevent the falling out of hair. One in six men will eventually develop prostate cancer, a leading disease of old age. Eating meat rich in arachidonic acid, or saturated fats, or omega-6 fatty acids (converted by the body into arachidonic acid), tends to the production of the enzyme 5-Lipoxygenase (5-LOX [Links]), which stimulates prostate cancer cell proliferation. 5-LOX also metabolizes arachidonic acid to leukotriene B5 [Links], a pro-inflammatory agent. Fish oil lowers 5-LOX activity in the body, and 5-LOX is also suppressed by lycopene [Links], saw palmetto extract [Links], and Boswellia extract (See 5-LOXIN) [Links/Boswellia extract]. Lycopene reduces PSA (prostate-specific antigen), decreases cancer risk, and induces apoptosis in prostate cancer cells [Images] and their metastases away from the primary tumor. Loss of glutathione S-transferase [Index] precedes prostate cancer [Links], so Ashwagandha, which elevates endogenous antioxidants, might help with this. "Curcumin (turmeric) has been found to increase expression of the glutathione S-transferase." Otherwise, sulforaphane [Wikipedia, Images] from broccoli sprouts typically does a good job of preventing prostate cancer [Books, Papers]. Partial proteasome inhibition in human fibroblasts triggers accelerated M1 senescence or M2 crisis depending on p53 and Rb status . Enterolactone(s) [LifeExtension, Links, Books] from plant lignans [Links, Wikipedia, LifeExtension] are also useful in preventing prostate cancer and may be obtained from flax or Norway Spruce . It is good to avoid most salad dressings [Index/Oils] and omega-6 oils. Note that "diets high in omega-6 fats [LEF] and saturated fats [LEF] are associated with greater prostate cancer risk, whereas increased intake of omega-3 fats from fish has been shown to reduce risk." , (76). Also, according to Jerry Brainum (Iron Man, March 2010), pomegranate prevents IGF-1 from inducing prostate cancer. Vitamin D also inhibits IGF-1 from causing cancer. Obese men, those with a BMI higher than 30, were 1.6 times more likely to die from their disease, according to a recent report in the journal Cancer. Note that prostate cancer is one of the scourges of she males, who in the future will be protected against them by medicines and nutraceuticals that have preventative effect. The blockage of the urinary tract might cause a psuedo-pregnancy associated with Episcopalian bladders. (Note that relatively harmless BPH [Benign Prostatic Hyperplasia] can also cause temporary urinary tract blockage and a state of alarm.) Another she male scourge is breast cancer, probably preventable by treatment with telomere-lengthening astagalosides (telomerase activators) to prevent telomere fusion in breast epithelial tissue responsible for carcinomas. (Carcinomas and adenocarcinomas in glandular tissue include 90% of human cancers. More than 50% of human cancers contain inactivating mutations of the p53 gene. In these cases cell division may continue past the M1 senescence checkpoint at a telomere length of about 4000 bp until telomeres are so short that they fuse.) One in 8 women suffers from breast cancer. Esophageal cancer can result from tissue rejection phenomenae associated with the flow of semen through the esophagus, and might be prevented by a glass of water.
Experiments with Vitamin D binding protein (Gc macrophage activating factor, or Gc-MAF) have resulted in complete remission of breast cancer and prostate cancer in initial studies. A clinical study of Gc-MAF will be described in a future issue of Life Extension Magazine. Vitamin D improves cancer immunity, as do other drugs and nutraceuticals that strengthen the immune system. Men with higher levels of vitamin D have a 52% reduced incidence of prostate cancer. Vitamin D is anti-inflammatory and a telomerase inhibitor.
NF-kB inhibitors work to make prostate cancer cells more vulnerable to apoptosis, and disable NF-kB support for metastasis .
Also see Metastasis of Cancer. The highest vitamin K2 intake group in a recent cancer study of prostate cancer and lung cancer victims had a 28% lower risk of dying from cancer, the reduction occuring mainly in men , . Vitamin K2 is useful in treating many kinds of cancer, as is a combination of vitamin C and vitamin K3 .
Note that silibinin, the primary constituent of silymarin in milk thistle, is a telomerase inhibitor that works well as an anticancer agent against human prostate adenocarcinoma cells, breast cancer carcinoma cells, ectocervical cancer cells, colon cancer cells, and both small and large lung carcinoma cells. Silibinin from milk thistle is effective against many malignancies, including those of the liver, colon, skin, and prostate, and inhibits cancer metastasis , , , . Gallic acid from grape seed extract [Index] is thought to be anti-proliferative, pro-apoptotic, and anti-angiogenic in acting against prostate cancer.
 Rettig MB, Heber D, An J, et al (2008),
Pomegranate extract inhibits androgen-independent prostate cancer growth through a nuclear factor-kappaB-dependent mechanism, Molecular Cancer Therapy, 2008 September; 7(9):2662-71.
 Deep G, Oberlies NH, Kroll DJ, Agarwal R (2007),
Isosilybin B and Isosilybin A inhibit growth, induce G1 arrest and cause apoptosis in human prostate cancer LNCap and 22Rv1 cells, Carcinogenesis, 2007 July 28(7):1533-42.
 P. Thelen, Wuttke W, Jarry H, Grzmil M, Ringert RH (2004),
Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells,
The Journal of Urology, 171(5);1934-1938.
 Thelen P, Jarry H, Ringert RH, Wuttke W (2004),
Silibinin down-regulates prostate epithelium-derived Ets transcription factor in LNCaP prostate cancer cells, Planta Medica 2004 May;70(5):397-400.
 Mokhtari MJ, Motamed N, Shokrgozar MA (2008),
Evaluation of silibinin on the viability, migration and adhesion of the human prostate adenocarcinoma (PC-3) cell line, Cell Biology International 32 (8): 888–92.
 Wu YD, Lou YJ (2007),
Brassinolide, a plant sterol from pollen of Brassica napus L., induces apoptosis in human prostate cancer PC-3 cells, Pharmazie 2007 May;62(5):392-5. See Brassinolide [Images, Papers, Patents, Books].
 Wu YD, Lou YJ. (2007),
A steroid fraction of chloroform extract from bee pollen of Brassica campestris induces apoptosis in human prostate cancer PC-3 cells, Phytother Res 2007 Nov;21(11):1087-91.
 Han HY, Shan S, Zhang X, Wang NL, Lu XP, Yao XS (2007),
Down-regulation of prostate specific antigen in LNCaP cells by flavonoids from the pollen of Brassica napus L, Phytomedicine 2007 May;14(5):338-43.
 Zhang X, Habib FK, Ross M, et al (1995),
Isolation and characterization of a cyclic hydroxamic acid from a pollen extract, which inhibits cancerous cell growth in vitro, J Med Chem 1995 Feb 17;38(4):735-8.
 Taper HS, Jamison JM, Gilloteaux J, Gwin CA, Gordon T, Summers JL (2001),
In vivo reactivation of DNases in implanted human prostate tumors after administration of a vitamin C/K(3) combination, Journal of Histochemistry and Cytochemistry (2001) Jan;49(1):109-20.
 American Journal of Clinical Nutrition, 2010, March 24;
 Dayna Dye (2010),
Reduced Vitamin K Intake Associated with Greater Cancer Mortality, Life Extension Magazine, July 2010.
 Annamaria Biroccio and Carlo Leonetti, (2004),
Telomerase as a new target for the treatment of hormone-refractory prostate cancer,
Endocrine-Related Cancer, 11(3), pp. 407-421.
 David Hoffnung (2011), The Inflammatory Factor Underlying Most Cancers,
Life Extension Magazine, November 2011.
 M.Richmond (2012),
Improperly Cooked Red Meat May Affect Cancer Risk, Life Extension Magazine, In the News. Nov 2012.
 Lignans Protect Against Prostate Cancer By William Faloon, and Julius Goepp MD (2010),
Optimal Prostate Defense requires a Multi-Modal Strategy, Life Extension Magazine, Feb 2010.
 Niki Chondrogianni, Ioannis P. Trougakos, Dimitris Kletsas, Qin M. Chen and Efstathios S. Gonos,
Partial proteasome inhibition in human fibroblasts triggers accelerated M1 senescence or M2 crisis depending on p53 and Rb status, (Abstract), Aging Cell, Volume 7 Issue 5, 717 - 732.
 William Falloon (2007),
Eating Your Way to Prostate Cancer, Life Extension Magazine, February 2007.
 John Reeves (2015),
Safely Reduce Annoying Prostate Symptoms, Life Extension Magazine March 2015.
Prosthetic Restoration [Links, Images, Video, Papers, Patents, Books, LifeExtension]. See Medical Art Resources and Clinical Anaplastology [Links, Video, Images, Papers, Patents, Books, LifeExtension].
For a technical introduction, see:
Buckwheat Protein [Links, Video, Images, Papers, Patents, Books, LifeExtension; ]
___Reduces bodyfat, cholesterol absorption, total blood cholesterol; heart-healthy, 90% of egg.
Casein Protein [Index, Links, Video, Images, Papers, Patents, Books, LEF]
___Slow: digestion time of 7 hours opposes muscle catabolism.
___See calcium caseinate, micellar casein, potassium caseinate, sodium caseinate.
___Casein Protein is slow-digesting, useful for supporting muscle synthesis and preventing
___catabolic destruction of muscle tissue overnight.
Egg-White Protein (Egg Albumin) [Links, Video, Images, Papers, Patents, Books, LEF]
___High Branched Chain Amino Acid content, rich in arginine, high sulphur-protein content.
___Some bodybuilders may take 8-12 egg whites at a meal.
Goat-Milk Protein [Links, Video, Images, Papers, Patents, Books, LifeExtension]
___Enhances protein and mineral utilization, casein & whey content; organic-fed goats.
Milk Protein [Links, Video, Images, Papers, Patents, Books, LEF]
___Contains casein & whey; whey/casein = 20/80 in cow's milk, = 60/40 in human milk.
Soy Protein [Index, Links, Video, Images, Papers, Patents, Books, LifeExtension]
___Rich in arginine and BCAAs, anticancer isoflavones, boosts HGH & nitric oxide.
___Soy was superior to whey, more antioxidant, more anticancer.
Whey Protein [Index, Links, Video, Images, Papers, Patents, Books, LifeExtension].
___High in BCAAs. See whey concentrates (70-80% protein),
___whey isolates (95% protein), and whey hydrolysates (fast-digesting).
___Whey protein elevates HGH (Human Growth Hormone) levels.
___Pre-digested fast whey hydrolysates or whey isolates taken with dextrose from corn (actually glucose, perhaps alternatively supplied as honey, as honey on rice cakes, or honey on white bagels) may be optimal with or in a post-workout shake, to peak up the expression of insulin, the body's most anabolic hormone via the simple sugar and oppose cortisol's tendency to rebuild glycogen stores from enzymatically processed protein obtained catabolically from muscle fibers. Note that fruit fructose is processed more slowly through the liver, and will not spike insulin like fast carbs including glucose (dextrose or maltodextrin). On the other hand, complex carbs from whole grains and vegetables are better taken pre-workout.
An Insider's Guide to Protein by Dwayne N. Jackson, PhD, (from a bodybuilding supplement magazine, July, 2010) communicated figures of merit for various proteins that seem very instructive:
Digestibility is given here as the relative digestiblity of the protein realtive to casein protein, measured by tests of feces.
Protein Efficiency Ratio is proportional to the weight gain per gram of protein ingested after measurements on rodent body weight, for instance.
Net Protein Utilization is the nitrogen retention per unit of nitrogen ingested.
Hidden Dangers of Foods
Note that eggs increase the probability of prostate cancer in adults, since they are high in arachidonic acid that is more useful to developing children. Meats often contain fats promoting the development of artherosclerosis leading to stroke or heart attack, while fish is high in omega-3 fatty acids that are safer and anti-inflammatory. Casein has been associated with neuropathy in some scientific studies.
 Michael Downey (2015),
Buckwheat: A Complete Protein, Life Extension Magazine May 2015.
Protein Carbonyls [Links/Protein Carbonyls, Images, Papers, Patents, Books, LifeExtension].
Protein carbonyls arise from protein carbonylation associated with glycation and from subsequent oxidation. See Dkhar P, Sharma R. (2011), Amelioration of age-dependent increase in protein carbonyls of cerebral hemispheres of mice by melatonin and ascorbic acid, Neurochemistry International 2011 December 59(7):996-1002.
Protein Damage and Maintenance in Aging [Ben Best/Protein Damage and Maintenance in Aging, Links/Protein Damage in Aging, Images, Papers, Patents, Books, LifeExtension, LibCong/Protein Damage in Aging, Books/protein maintenance in aging; Glycation, Protein Cabonyls, Alkylation, Arachidonic Acid, Proteasome, Protein Turnover; Links/Protein Damage Resistant to Proteolysis, Images, Papers, Patents, Books, LifeExtension].
Arachidonic Acid Damage from Eggs
The worst protein damage problems happen when damaged proteins cannot be removed by proteolysis and replaced. See proteolysis of damaged proteins [Links, Images, Papers, Patents, Books].
"Free radical mediated arachidonic acid oxidation can produce a mixture of gamma-isoketals capable of reacting with proteins to produce structures that are not only resistant to proteolysis but inhibit proteasome function." (After Hipkiss in Aging at the Molecular Level, ed. T. Zglinicki, p.160.) This protein damage resistant to proteolysis poisons the cell, so adults typically consume fewer eggs, which are rich in arachidonic acid, to avoid prostate cancer. Arachidonic acid is found in meat, poultry, and eggs, so fish such as salmon is a wise replacement for older people, although youth needs it for growth and development.
Glycation Damage from Sugar (Carbonylation of Proteins)
Glycation damage to proteins from sugar (carbonylation of proteins) treatable with anti-glycating drugs produces AGEs (Advanced Glycation End-Products) that produce ROS and inflammation leading to disorders such as Alzheimer's Disease. Antioxidants and anti-inflammatory nutraceuticals help treat these results.
Oxidative Damage to Proteins from ROS [Links, Images, Papers, Patents, Books, LifeExtension].
This may be indirect, via oxidative stress damage to DNA from ROS, when we speak of mutations and DNA damage (10) leading to cancer. Oxidation of lipoproteins is a factor in atherosclerosis. See lipoprotein phospholipase A2 (Lp-PLA2) tests and therapy for inflamed atherosclerotic plaque in which LDL peroxidation is taking place.
Damage from Alkylation due to Aldehydes produced by Lipid Peroxidation
Free radicals containing one or more unpaired electrons may ultimately produce [Video, Papers, Patents] aldehydes [Images, Video, Papers, Patents, Books] from lipid peroxidation that are impacting to the process of aging, generating protein and DNA damage (10). See alkylation and aging [Images, Papers, Patents, Books, LifeExtension]. Also see protein damage due to aldehydes [Images, Papers, Patents, Books] and DNA damage due to aldehydes [Images, Papers, Patents, Books]. For instance MDA (Malondialdehyde) can produce damage to proteins or DNA via alkylation reactions [Links, Papers, Books, LifeExtension]. "Aldehydes such as malondialdehyde (causes DNA adducts) and hydroxynonenal, arising from the free radical degradation of polyunsaturated fatty acids, can cause cross-links in lipids, proteins, and nucleic acids." (L.J.Machlin and Adrianne Bendich, 1987). See defense against alkylation damage [Papers, Patents, Books, LifeExtension] and treatment of alkylation damage [Papers, Patents, Books, LifeExtension]. Note that alcohol produces poisonous aldehydes using endogenous alcohol dehydrogenases, which are converted to harmless carboxylic acids by endogenous aldehyde dehydrogenases and alkylation repair homologs if the load is not too high. Ethanol toxicity (which may be reduced by N-acetylcysteine and vitamin B1) is primarily due to its metabolites acetylaldehyde and acetic acid. Acetylaldehyde binds to proteins to form DNA adducts linked to cancer and organ disease. Also see Steven Clarke (2003), Aging as war between chemical and biochemical processes: Protein methylation and the recognition of age-damaged proteins for repair [PDF], Ageing Research Reviews 2 (2003) 263–285; Department of Chemistry and Biochemistry, the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569, USA.
Protein Kinase C Pathway [Links/Protein Kinase C, Images, Video, Papers, Patents, Books, LifeExtension; Links/Protein Kinase C Pathway, Images, Video, Papers, Patents, Books, LifeExtension, Amazon; Links/Nutraceuticals promoting expression of Protein Kinase C, Images, Video, Papers, Patents, Books, LifeExtension].
Protein Production Methods for Recombinant Proteins (Large Scale)
[Links, Images, Papers, Patents, Books; Index/Protein Protocols]. Proteins are often produced in small quantities using recombinant DNA technology from E. Coli transfected with appropriate plasmids, perhaps from cell-free extracts featuring cell-free in vitro extraction. For large-scale methods, see commercial large-scale recombinant protein production [Images]. OriGene now offers >5,000 full length human proteins expressed in HEK293 cells and purified with affinity column. GeneArt produces proteins from from transient transfected HEK293 or CHO cells with protein purification by affinity tag chromatography, Protein G/A chromatography, or ion exchange chromatography, using SDS PAGE or general gel filtration for quality control. Eukaryotic proteins can usually not be folded correctly in prokaryotic bacterial cells, so that eukaryotic HEK293 cells and CHO cells are used. Several transfection techniques may be used. See transfection techniques for industrial production of recombinant proteins [Images, Video, Papers, Patents, Books]. Plasmids are engineered with an EBNA1 expression vector (5- to 8-fold increase) to increase the protein production. Using the promoter from a cytomegalovirus DNA (a cytomegalovirus expression cassette) can drive the protein production up by a factor of 10. See pPK-CMV Expression Vectors and Vectors for High-Level Gene Expression. The epi-CHO cell line was developed to increase protein production by adding peptones such as GPN3 and TN1 (Tryptone N1, a casein peptone). See Industrial choices for protein production by large-scale cell culture [Images, Papers, Books]. See Chris Wenstrom (2006), Advances in large-scale recombinant protein production, Basic Biotechnology eJournal, 2006 2:20-25.
[Links/Protein structure, Images, Video, Papers, Patents, Books, Amazon].
Alpha Helix: Alpha helices feature 3.6 amino acid residues per helical turn of 0.54 nm.
Beta Sheets. Beta sheet strands are separated by about 0.5 nm between opposite carbon atoms.
DNA-binding domains [Wikipedia].
____Types of DNA-binding domains
_______Helix-turn-helix [Links, Images, Video, Papers, Patents, Books].
_______Zinc finger [Links, Images, Video, Papers, Patents, Books].
_______Leucine zipper [Links, Images, Video, Papers, Patents, Books].
_______Winged helix [Links, Images, Video, Papers, Patents, Books].
_______Winged helix turn helix [Links, Images, Video, Papers, Patents, Books].
_______Helix-loop-helix [Links, Images, Video, Papers, Patents, Books].
_______HMG-box [Links, Images, Video, Papers, Patents, Books].
_______Wor3 domain [Links, Images, Video, Papers, Patents, Books].
____Unusual DNA binding domains
_______Immunoglobulin fold [Links, Images, Video, Papers, Patents, Books].
_______B3 domain [Links, Images, Video, Papers, Patents, Books].
_______TAL effector DNA-binding domain [Links, Images, Video, Papers, Patents, Books].
_______RNA-guided DNA-binding domain [Links, Images, Video, Papers, Patents, Books].
N-terminal regulatory domain.
PH domains [Images, Video, Papers, Patents, Books, Amazon].
Protein domains [Images, Video, Papers, Patents, Books, Amazon].
Protein-protein interaction motifs [Images, Video, Papers, Patents, Books, Amazon].
Short linear motifs [Images, Video, Papers, Patents, Books].
Zinc Finger Domains.
One full turn of the DNA double helix spans 10 base pairs and 3.4 nm distance.
The p53 molecule fits into a rectangle 7.56 nm wide x 5.708 nm high.
Hydrogen nuclei are separated by 0.074 nm in the H2 molecule.
The Bohr radius of the hydrogen atom is 0.053 nm.
Spacing between silicon atoms is 0.543 nm in silicon chips.
The visible spectrum is centered at 555 nm wavelength.
Protein Targeting [Wikipedia/Protein_targeting, Links, Images, Video, Papers, Patents, Books, Amazon]. See orf.clone technology from Invitrogen and other firms to support protein targeting in gene and protein design. Phoenix Biomolecular announced peptide protein targeting for hTERT to the cell membrane, but their web page on the topic vanished a year or two ago. Protein targeting uses target sequences (localization sequences) to manage directed internal transport of proteins to organelles from the rough endoplasmic reticulum. The protein is synthesized in eucaryotes by the ribosome from mRNA transcribed by RNA polymerase II from DNA in the cell nucleus, where non-coding mRNA introns are removed by the splicosome before mRNA export from the nucleus through the nuclear pore to the rough endoplasmic reticulum. A ribosome moves along the mRNA to synthesize the protein peptide chain from amino acids as directed by the mRNA code [Images]. Protein targeting sequences of 3-80 amino acids are recognized by cytosolic receptors that guide the proteins to the appropriate destination to make contact with organelle translocation machinery. After import of the protein peptide chain, the targeting sequence is stripped from the protein. It may be folded in a process guided by chaparones including the heat shock proteins, then further assembled from individual subunits. There are signal sequences for protein transport into the:
(1) smooth endoplasmic reticulum
___[5-15 mostly hydrophobic amino acids at the N terminus of the protein.],
___[20-80 amino acids making up an amphipathic helix with hydrophobic sides sticking out on one side, and positively charged side chains on the other side],
(3) the nucleus
___[5 positively charged amino acids inside the protein sequence],
(4) the peroxisomes
___[the C-terminal tripeptide Ser-Lys-Leu-COOH].
(5) the proteasomes
___[the ubiquitin molecule for proteasome-directed ubiquitination of proteins].
It is also possible to transport proteins into cells though the cell membrane inside liposomes fashioned from cationic transfection reagents (Debs et al. 1990). These liposomes are absorbed into the cell via liposomal endocytosis. Furthermore, RNA may be transfected into the cell by this technique (Malone et al. 1989; Wilson et al. 1979), as in Fast Telomere Extension. See Promega Applications and Protocols Guide, Chap. 12. Transfection.
Protein Turnover [Links/protein turnover, Images, Papers, Patents, Books, LibCong/Protein turnover, Amazon/protein turnover in aging, LifeExtension]. The turnover rates of molecular species are:
nucDNA < myelin lipids < histone proteins < mtDNA < microsomal lipids < RNAs & proteins,
- from Principles of Neural Aging ed. Dani, Hori, and Walter, 1997. The proteasome digests old proteins tagged with ubiquitin to maintain protein turnover. The pRB regulator P16INK4A is ubiquitinated, so that reducing its expression with retinoic acid (from, say, retinol, retinal, carrots, spinach, or broccoli) reduces its density in senescent cells, simplifying recovery from the senescent state. Proteasomes can become clogged with isoketals from high arachidonic acid levels, a condition which may be treated with oleuropein.
Proteasomes [(14), Wikipedia, LifeExtension, Links, Images, Video, Papers, Patents, Books, LibCong, Amazon/proteasomes in aging, Papers/Oleuropein & proteasome; Links/Preserving proteasome function in aging cells, LifeExtension]. Proteasomes, which digest used proteins tagged with ubiquitin, can be gummed up from isoketals formed from arachidonic acid excess, [3s, 4s]. Proteasomes function in damaged protein garbage collection. "Normal human fibroblasts undergo replicative senescence due to both genetic and environmental factors. Senescence and aging can be further accelerated by exposure of cells to a variety of oxidative agents that contribute among other effects to the accumulation of damaged proteins. The proteasome, a multicatalytic nonlysosomal protease, has impaired function during aging, while its increased expression delays senescence in human fibroblasts. The aim of this study was to identify natural compounds that enhance proteasome activity and exhibit antiaging properties. We demonstrate that oleuropein, the major constituent of Olea europea leaf extract, olive oil and olives, enhances the proteasome activities in vitro stronger than other known chemical activators, possibly through conformational changes of the proteasome. Moreover, continuous treatment of early passage human embryonic fibroblasts with oleuropein decreases the intracellular levels of reactive oxygen species (ROS), reduces the amount of oxidized proteins through increased proteasome-mediated degradation rates and retains proteasome function during replicative senescence. Importantly, oleuropein-treated cultures exhibit a delay in the appearance of senescent morphology [Senescence.info] and their life span is extended by approximately 15%." [article].
"Decreased proteasome activity has been recently associated to a decline of proteasome content in replicative senescence of human fibroblasts and keratinocytes as well as in aging rat myocardiac cells and human epidermis, suggesting that proteasome expression is down-regulated with age." - Geraldine Carrard and Bertrand Friguet, The Proteasome in Aging, from Aging at the Molecular Level, edited by Thomas von Zglinicki, Kluwer, 2003, p.219. This suggests that since replicative senescence is associated with proteasome dysfunction in aging, application of telomerase activators to prevent replicative senescence will help preserve proteasome function.
Quercetin is a Proteasome Activator
"Proteasome activities and function are decreased upon replicative senescence, whereas proteasome activation confers enhanced survival against oxidative stress, lifespan extension and maintenance of the young morphology longer in human primary fibroblasts. Several natural compounds possess anti-ageing/anti-oxidant properties. In this study, we have identified quercetin (QUER) and its derivative, namely quercetin caprylate (QU-CAP) as a proteasome activator [Patents, Books] with anti-oxidant properties that consequently influence cellular lifespan, survival and viability of HFL-1 primary human fibroblasts. Moreover, when these compounds are supplemented to already senescent fibroblasts, a rejuvenating effect is observed." after Niki Chondrogiannia, Suzanne Kapetaa, Ioanna Chinoub, Katerina Vassilatouc, Issidora Papassiderid, Efstathios S. Gonosa (2010), Anti-ageing and rejuvenating effects of quercetin, Experimental Gerontology, Volume 45, Issue 10, October 2010, Pages 763–771.
Protein Damage [Ben Best/Protein damage other than glycosation, LifeExtension/protein damage, Amazon/protein damage in aging, LibCong, Links/protein damage in aging, Images, Video, Papers, Patents, Books; Books/protein damage; Index/Glycation].
Protein glycation [Index/Glycation; Links, Images, Video, Papers, Patents, Books, LibCong, Amazon/protein glycation and aging LifeExtension, Glycation of Proteins], (5)
Protein glycosylation [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon]. Protein glycosylation enzymatically adds a sugar to a protein as part of a cell signaling process. On the other hand, protein glycation [Index] results in carbonylation of proteins, a form of protein damage, and is not controlled by an enzyme.
Proteoglycans [Links/Proteoglycans, Images, Papers, Patents, Books, LibCong, LifeExtension; Books/proteoglycans and repair].
Proteomics [Wikipedia, LibCong, Links, Video, Papers, Patents, Books, LibCong, Amazon]. See Biomolecular Interaction Network Data Base (BIND), Dolan DNA Learning Center of Cold Spring Harbor Laboratory, Ensembl!, ExPASy (Expert Protein Analysis System) Proteomics Server, FlyBase, Howard Hughes Medical Institute/Biointeractive, Kyoto Encyclopedia of Genes and Genomes, National Center for Biotechnology Information (NCBI), NCBI Blast!, NCBI Online Medelian Inheritance in Man, Nobel Prize Winners, Protein Data Bank, Protein Explorer Front Door, UnitProt/Swiss-Prot, U.S. National Institutes of Health, and WormBase. Also see the National Cancer Institute proteomics site, the Korean site Seoulin Virtual Biology, and the genetics and proteomics applications at Gene Families (HUGO).
Protocols [Links/Bioscience Protocols, Images, Video, Papers, Patents, Books, LibCong, Amazon]. Experimental protocols determine Bioinformatics information. See below:
Protocols, Antioxidant [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon].
Protocols, Biomedical [Links/biomedical protocols, Images, Video, Papers, Patents, Books; Books/bio method protocols, Amazon/Biomedical Protocols] John M. Walker Series, Humana Press.
Protocols, Biotechnological [BioProtocol, LibCong, LibCong2, Links, Images, Video, Papers, Patents, Books] | Nature/Methods and Nature Protocols; [Links/Bioscience Protocols, Images, Video, Papers, Patents, Books, Amazon]. See also Biowww.net, and SA Biosciences.
Protocols, Chromosome [Links, Images, Video, Papers, Patents, Books, Amazon, LibCong].
Protocols, Cold Spring Harbor Laboratory [Sigma Aldrich Selection from Cold Spring Harbor Protocols, Links, Images, Video, Papers, Patents, Books, Amazon, LibCong].
Protocols, Drug Receptor Assays [Links, Images, Video, Papers, Patents, Books].
Protocols, Gene Transfection [Chapter 12: Promega Gene Transfection Protocols, Links, Images, Video, Papers, Patents, Books, Amazon, LibCong].
Protocols Guide [Links/Guides to Biotechnology Protocols, Books, Biotechniques/Protocols Guide, on-line, from Biotechniques].
Protocols, Human Cell Membrane [Links, Images, Video, Papers, Patents, Books, Amazon, LibCong].
Protocols, Lipid Membrane [Links/lipid membrane protocols, Images, Video, Papers, Patents, Books, LibCong, Amazon].
Protocols, Mitochondrial [Index/Mitochondrial Measurements; Links/mitochondrial protocols, Images, Video, Papers, Patents, Books, LibCong, Amazon]. See
Measuring mitochondrial aging [Links, Images, Video, Papers, Patents, Books],
Measuring mitochondrial biogenesis [Links, Images, Video, Papers, Patents, Books],
Blood tests for mitochondrial aging [Links, Images, Video, Papers, Patents, Books],
Protocols for mitochondrial dysfunction [Links, Images, Video, Papers, Patents, Books].
See Courtagen clinical mitochondrial genome sequencing, Courtagen clinical sequencing of nuclear mitochondrial genes, and the GeneDx list of diseases associated with SNPs in genes programming the 1,100 protein mitochondrial proteome.
Protocols, Molecular Biology [Molecular Station, Links/molecular biology protocols, Images, Video, Papers, Patents, Books, LibCong, Amazon].
Protocols, Nucleic Acid [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon].
Protocols, PCR [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon].
Protocols, Peptide [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon].
Promega Protocols [Promega, Links/Promega Protocols, Chapter 12: Promega Gene Transfection Protocols].
Protocols, Protein [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon; Index/Protein Production - Large Scale for Recombinant Proteins].
Protocols, Shay-Wright [Shay-Wright Laboratory Methods].
Protocols, Telomere and Telomerase [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon].
Protocols, Transcription Factor [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon]. For for measurements to associate gene promoters with their transcription factors [Index], see Analysis of gene promoter occupancy in vivo using chromatin immunoprecipitation assays, chromatin immunoprecipitation assays, Wikipedia/Chromatin Immunoprecipitation (ChIP) [Links, Images, Video, Papers, Patents, Books], and Wikipedia/ChIP-on-chip [Links, Images, Video, Papers, Patents, Books, Publications].
PTB (N-Phenacyl Thiazolium Bromide) [Links, Images, Papers, Patents, Books, LifeExtension]. PTB (N-Phenacyl Thiazolium Bromide) - Breaks cross-links a little less effectively than ALT-711 [LifeExtension, Links, Books], or Alagebrium [Books, Amazon, Links, Images, LifeExtension].
Pterostilbene [Links, Images, Video, Papers, Patents, Books, LifeExtension; Nutritional Sources]. Pterostilbene is found in blueberries. A polyphenol closely related to resveratrol, it favorably regulates gene expression (LEF) to mimic caloric restriction and inhibits Nuclear Factor Kappa Beta. Trans-pterostilbene is the medicinally preferred form. It suppresses tumor metastasis and promotes cancer cell apoptosis, (possibly by being a telomerase inhibitor (7) like resveratrol). Pterostilbene found in blueberries reduces the multiplicity of colon cancer adenocarcinomas, lowers proliferating cell nuclear antigen, and downregulates the expression of beta-catenin and cyclin D1 , .
Pterostilbene effect on Stem Cells
Pterostilbene supports normal mesenchymal cell growth, migration, and proliferation, as does Vitamin C .
Pterostilbene effect on Nrf2 [Links, Images, Video, Papers, Patents, Books, LifeExtension; Links/Nrf2, Images, Video, Papers, Patents, Books, LifeExtension].
 Jon Finkel (2010),
Pterostilbene Aids in Colon Cancer Prevention, Life Extension Magazine, April 2010.
 Carcinogenesis, 2010, Jan 8.
 Bickford PC, et al. (2006),
Nutraceuticals synergystically promote proliferation of human stem cells, Stem Cells Dev. 2006 Feb;15(1):118-23.
 Chang J, Rimando A, Pallas M, et al (2012),
Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer’s disease,
Neurobiol Aging 2012 Sep;33(9):2062-71.
 McCormack D, McFadden D (2012),
Pterostilbene and cancer: current review, J Surg Res 2012 82. Apr;173(2):e53-61.
Pumpkin Seed Extract [Links, Images, Video, Papers, Patents, LifeExtension]. Water-soluble pumpkin seed extract decreases urinary tract incontinence by increasing nitric oxide levels, helping to relax bladder muscles. In addition, it inhibits aromatase, making testosterone available to strengthen the muscles of the pelvic floor. In addition, it inhibits 5-alpha-reductase contributing to prostate enlargement [LEF] in Benign Prostatic Hyperplasia (BPH) [Index] with aromatase.
Purge-the-Poisons Theory of Rejuvenation (Theoretical Tales of Transformation)
Purpura [Links/Purpura, Images, Papers, Patents, Books/Purpura, LibCong; Links/Senile Purpura, Images, Papers, Patents, Books, Books/Treating Senile Purpura, LifeExtension/purpura, 81bs; Index/Skin Lesions]. Purpura Senilis is characterized by extreme bruising in old people on the hands, arms, and legs that can occur from minor contact and take months to heal. The number of fibroblast-like veil cells surrounding small vessels in the dermis of the skin responsible for depositing basement membrane material around blood vessels in response to vascular damage declines with age. The cellular proliferation of veil cells may probably be improved by the application of telomerase activators and growth factors, as described below. The weakened capillary walls may rupture, allowing blood to leak out. This subcutaneous bleeding may be treated with a vitamin K1 skin cream [Images] activating expression of blood clotting proteins [Images]. "Fat-soluble vitamin K1 skin cream is a valuable topical treatment for all disorders arising from vascular injury." Senile purpura are characteristic lesions of old age due to collagen loss in veinous walls partially originating from replicative senescence in dermal fibroblasts which maintain the extracellular matix. Possible treatments include vitamin C and bilberry, improved with with the addition of bioflavonoids. Astragaloside IV skin cream (Terraternal), astragalus extract, or cycloastragenol skin cream should also help, because the collagen loss is characteristic of replicative senesence. Product B literature has identified numerous telomerase activators providing telomerase-inducer test hits for normal human fibroblasts. Epidermal Growth Factor (EGF) and acidic Fibroblast Growth Factor (FGF1) are also used in cosmetic preparations to treat replicative senescence in skin epidermal keratinocytes and dermal fibroblasts and similar veil cells that maintain extracellular matrix collagen and elastin. Senescent dermal fibroblasts attack the extracellular matrix with collagenase, stromelysin, and reduced expression of TIMP1 and TIMP3 factors that inhibit matrix metalloproteinase degradation of the extracellular matrix. Astragalus Membranaceus Extract dissolved in glycerin might be effective in long-term treatment. See Age Transformation for the associated de-aging rates amounting to -5.2 years per year up to -9 years per year. Old age spots are often treatable with CoQ10 or ubiquinol, which attacks discoloration due to accumulation of lipofuscin. "Vitamin K, Arnica montana extract, oats, and vitamin D have been shown to help speed the recovery time for bruises, accelerate wound healing, reduce swelling and inflammation, combat infection (via Vitamin D), and relieve pain". - Gary Goldfaden, MD, and Robert Goldfaden (2010), Heal Traumatic and Degenerative Skin Lesions Naturally, Life Extension Magazine, Sept. 2010, pp.75-80. I note that Ginkgo Biloba activates telomerase in endothelial progenitor cells, as does 5-10 grams of L-Arginine per day, so that these may be useful in treating veinous conditions such as purpura.
P-value [Wikipedia, Links, Video, Papers, Books].
PycnogenolTM [Links, Images, Video, Papers, Patents, LifeExtension; Memory Enhancing Nutraceuticals]. PycnogenolTM is a Pinus pinaster bark extract [Images, Video, Papers, Patents, Books], often termed French Maritime Pine bark extract. Pycnogenol is an antioxidant and a vasodilator due to its ability to enhance the function of nitric oxide synthase, which produces nitric oxide from arginine. See Peng QL, Buz’Zard AR, Lau BHS (2002), Pycnogenol protects neurons from amyloid-beta peptide-induced apoptosis, Molecular Brain Research 2002, 104(1-2):55-65. Pycnogenol and bacopa are being tested in clinical trials for application to treatment of cognitive decline. (Stough, et al, 2012). Liu FJ, Zhang YX, Lau BHS (1998), Pycnogenol enhances immune and haemopoietic functions in senescence-accelerated mice, Cellular and Molecular Life Sciences 1998, 54(10):1168-1172, and Fujun Liu, Yongxiang Zhang, Benjamin H.S. Lau (1999), Pycnogenol Improves Learning Impairment and Memory Deficit in Senescence-Accelerated Mice, Rejuvenation Research, Winter 1999. See also Janet Sarto (2012), Pycnogenol: Multimodal Defense Against Aging, Life Extension Magazine, August 2012. "Pyconogenol.... rejuvenates skin elasticity, reduces collagen degradation, lowers blood glucose levels, increases nitric oxide to dilate blood vessels, restores capillary health, and normalizes blood pressure". Pycnogenol is described in the article as working against 5 major mechanisms of aging including:
Pine Bark Extract [Index, Links, Images, Video, Papers, Patents, LifeExtension], which is available from NOW Foods, Source Naturals, and other supplement vendors, is similar to Pycnogenol.
Pine pollen [Index, Links, Images, Video, Papers, Patents, LifeExtension], a related supplement, improves testosterone levels.
Pinus Massoniana [Index, Links, Images] pine bark extract and pine pollen from Asia to boost testosterone are similarly useful supplements.
Pygeum Extract [Links, Images, Video, Papers, Patents, LifeExtension]. Pygeum Africanum extract helps suppress prostaglandins [Links, Images, Papers, Patents, LifeExtension] that increase the size of the prostate gland [Links, Images, Video, Papers, Patents, Books, LifeExtension] as men age. The most biologically active constituent of Pygeum extract is beta-sitosterol [Wikipedia, Links, Images, Papers, Patents, Books, LifeExtension], which may also be obtained from other plant sources.
Pyridoxamine [ MoreLife/Pyridoxamine, Links, Images, Video, Papers, Patents, Books, LifeExtension]. Pyridoxamine (a Vitamin B6 vitamer), a glycation inhibitor, inhibits the formation of both Advanced Lipid Oxidation End products (ALEs) [Links, Papers, Books, LifeExtension] and Advanced Glycation End products (AGEs) [Index/AGEs, Books], cross-link inhibitor, (5). See also Preventing AGEs and Cross-linkages: A Comprehensive Approach, 14th Apr 2006 and Index/AGE Inhibitors.
Pyridoxal 5'-phosphate [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension].
Pyridoxal 5'-phosphate is the active co-enzyme form of vitamin B6, [36s] (i). According to LEF, Pyridoxal 5'-phosphate inhibits glycation of both protein and fat. It is effective in reducing blood vessel damage from sugar and in reducing kidney damage from diabetes. (Julius Goepp MD (2010), Reverse Mitochondrial Damage, Life Extension Magazine, Feb. 2010).
Pyritnol [IAAS/Pyritnol, Links, Images, Papers, Patents, Books, LifeExtension; (Cerbon 6 [Links, Images, Papers, Patents, Books, LifeExtension])]. Pyritnol is a life-extending nootropic "smart drug" increasing brain glucose uptake, improving brain memory, vigilance, and concentration, and is also an antioxidant. James South article, [Links, Images, Wikipedia].
Pyrroloquinoline Quinone (PQQ) [Index/PQQ, Links, Images, Video, Papers, Patents, Books, LifeExtension]. Pyrroloquinoline Quinone (PQQ) a dark chocolate antioxidant found in cocoa powder, possibly a key factor in the 122-year lifespan of Jeanne Calment. PQQ promotes mitochondrial biogenesis to defeat mitochondrial aging. (25k). Cocoa contains a high level of flavonoids [Links], such as catechins [Links] and epicatechin [Links], which have beneficial effect on cardiovascular health. Cocoa's epicatechins and polyphenols [Links] are antioxidants. Cocoa powder has roughly twice the antioxidants of red wine, and up to three times the antioxidants found in green tea. Cocoa also contains: magnesium, iron, chromium, vitamin C, zinc and arginine (100 mg/tablespoon).
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