Index to Anti-Aging Medicine
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P: Pa - Pq
p16 gene (p16INK4A) [Wikipedia/P16 (gene), Links/p16 gene, Images, Video, Papers, Patents, Books, LibCong, Amazon, LifeExtension; Ref]. "Increased expression of the p16 gene as organisms age reduces the proliferation of stem cells. This reduction in the division and production of stem cells protects against cancer while increasing the risks associated with cellular senescence.... Concentrations of p16INK4A increase dramatically as tissue ages. Therefore p16INK4A could potentially be used as a blood test that measures how fast the body's tissues are aging at the molecular level." - Wikipedia. Note that most cells never become senescent in typical aging specimens (ref) and that our procedure for lengthening telomeres with telomerase activators prevents, but does not necessarily reverse, cellular senescence. See Christian M. Beausejour, Judith Campisi,, (2003), Reversal of Human Cellular Senescence: roles of p53 and p16 pathways, The EMBO Journal, 2003, 4212-4222. Irreversible growth arrest in replicative senescence is established by p53 (P53 gene) and pRb (retinoblastoma) tumor suppressor proteins. Replicative senescence is reversible or not depending on the expression of pRb regulator p16. Cells with low levels of p16 resumed growth when p53 was inactivated, but cells with high levels of p16 at senescence failed to recover and proliferate after p53 inactivation, re-entering the cell cycle without growth after pRb inactivation. Thus the senescence response to telomere dysfunction is reversible and maintained mainly by p53, although p16 provides a 2nd barrier to the unlimited growth of human cells after they have entered the state of replicative senescence. (See also bupleurum extract and p16, Saikosaponin A activates Gene P16 and RevGenetics MasterGene-P16. At this time I disrecommend producing extra p16INK4A for your cells, although this is an element in cancer defense. Promoting tumor suppressor genes has been associated with premature senescence, an observation that applies to p53, below.) I note that senescent cells gradually aquire more p16INK4A, so that replicative senescence itself is more difficult to reverse as p16INK4A accumulates [Papers, Books]. See the accumulation of p16INK4A [Images, Papers, Books] and reducing levels of P16INK4A with exercise, Id-1 from nerve growth factor, resveratrol, retinoic acid from carrots, and by cutting smoking. Also see Tohru Kiyono, Scott A. Foster, Jenn I. Koop, James K. McDougall, Denise A. Galloway and Aloysius J. Klingelhutz (1998), Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells and associated papers, Nature 396, 84-88 (5 November 1998). See also Molovsky AV et al. (2006) Increasing p16INK4A expression decreases forebrain progenitors and neurogenesis during aging. Nature 443 : 448-52. See also Krishnamurthy et al. 2006, p16INK4A induces age-dependent decline in islet regenerative potential, Nature 443: 453-57 and Krishnamurthy et al. 2004, Ink4a/ARF expression is a biomarker of aging, Journal of Clinical Investigation, 114(9): 1299-3107. p16INK4A deficiency inhibits the replicative failure of pancreatic beta cells with aging. Beta cell replication requires cdk4, the biochemical target p16INK4A uses to interfere with the cell cycle (Norman E. Sharpless, 2008). "The p16INK4A protein inhibits cell cycle progression and induces cellular senescence, and its expression increases with age in many tissues (Collins and Sedivy 2003, Campisi 2006, Bracken AP et al. 2007)... Knocking out p16INK4A reduces HSC repopulating effects and apoptosis associated with an improved stess tolerance and survival in cells (Janzen et al. 2006, after S. Zimmerman and U.M. Martens in K. Lenhard Rudolf, 2008)." Id-1 helix-loop-helix protein, which can be induced with Nerve Growth Factor, downregulates p16INK4A. Nerve growth factor can be upregulated with acetyl L-carnitine, carnosic acid, rosemary extract, or Huperzine A. See also (Alcorta DA et al. 1996). Note that p16 can be activated by replicative senescence, somewhat like p53, which is activated in reponse to DNA damage signals caused by an open telomere loop. High concentrations of either protein can induce premature senescence.
"...Results demonstrate that the p16-mediated growth arrest of at least two different epithelial cell types (skin keratinocytes and HMECs or human mammary epithelial cells) is a consequence of the particular tissue culture conditions used, and can be prevented by growing cells on appropriate feeder layers.... When the cells are maintained in a culture environment that does not exceed the threshold for growth arrest until telomeres become too short, then introduction of hTERT can maintain the cells below this growth arrest threshold resulting in cell immortalization." - Jerry W. Shay and Woodring E. Wright, Are Telomeres and Telomerase the Connection? from Mark P. Mattson, Telomerase, Aging, and Disease, 2001, p.5. "Most senescent cells seem to express P16INK4A, a cyclin-dependent kinase inhibitor and tumour suppressor that enforces growth arrest by activating Rb." (Darren J. Baker, et al, (2011)). See also (Lily I. Huschtsha and Roger R. Reddel, 1999).
Retinoic acid reduces p16INK4A expression
Retinoic acid [Images], a telomerase inhibitor on our list, extends cellular lifetimes by reducing p16INK4A expression. Retinoic acid is a dietary metabolite of retinal [Wikipedia/Retinal (sources)], one of the compounds of vitamin A. Vitamin A is usually converted into retinal and retinoic acid. ("Retinol (sources) is produced in the body from the hydrolysis of retinyl esters, and from the reduction of retinal." - Wikipedia/Retinol.) 23,000 IU of vitamin A are contained in 1/2 cup serving of canned carrots. Retinal can be synthesized in the body from beta-carotene and other carotenes to serve as precursor for retinoic acid. Vitamin A may be convered to retinol in the small intestine. Once retinol has been taken up by a cell, it can be oxidized to retinal and then retinal can be oxidized to retinoic acid. The conversion of retinal to retinoic acid is irreversible, such that the production of retinoic acid is tightly regulated, due to its activity as a ligand for nuclear receptors. Vegetables rich in retinoic acid and vitamin A include dark leafy greens such as spinach, kale, collard greens and broccoli. See Yong-Ouk You, Gene Lee and Byung-Moo Min, (2000), Retinoic Acid Extends the in Vitro Life Span of Normal Human Oral Keratinocytes by Decreasing p16INK4A Expression and Maintaining Telomerase Activity, Biochemical and Biophysical Research Communications, Volume 268, Issue 2, 16 February 2000, Pages 268-274. Maurelli, Zambruno, et al. (2006), Inactivation of p16INK4A (inhibitor of cyclin-dependent kinase 4A) Immortalizes Primary Human Keratinocytes By Maintaining Cells in the Stem Cell Compartment, The FASEB Journal, 2006;20:1516-1518. p16INK4A is a ubiquitinated protein (the rate of ubiquitination depending on p16INK4A density), so that reducing its expression really reduces p16INK4A levels in the cell. See (Ronen Ben-Saadon, Ifat Fajerman, Tamar Ziv, et al, 2004).
Other Inhibitors of p16INK4A
Other inhibitors of p16INK4A exist besides the telomerase inhibitor retinoic acid from, say, carrots. Id-1 helix-loop-helix protein (produced by stimulation with nerve growth factor from acetyl L-carnitine, huperzine A, PQQ, carnosic acid, or rosemary) is another inhibitor of p16INK4A expression that can prevent the onset of cellular senescence from high levels of p16INK4A. Resveratrol's heightened SIRT1 expression downregulates P16INK4A expression, retarding the onset of irreversible replicative senescence. Also note that exercise can bring p16INK4A expression down by 2 binary orders of magnitude. High p16INK4A levels are often associated with aging, smoking, and physical inactivity. See inhibitors of p16INK4A expression [Links, Images, Papers, Patents, Books] and supplements that inhibit the expression of p16INK4A [Links, Images, Papers, Patents, Books]. Finally, note that p16INK4A is a ubiquitinated protein that may be eliminated. Then, with reduction in caveolin-1 (CAV1) levels and cellular stimulation from EGF and PDGF boosted by exercise or supplements such as colostrum, one may recover from cellular senescence.
Humor: p16INK4A and the Revolution.
p38 (p38 and cancer) [Wikipedia/P38, Links/p38, Images, Video, Papers, Patents, Books, LibCong, Amazon, LifeExtension; Links/Gene p38; Links/p38 and cancer, Images, Video, Papers, Patents, Books, LifeExtension; Links/stress signaling pathways, Images, Video, Papers, Patents, Books, LifeExtension; Index/Cancer]. Cells with dysfunctional telomeres show activation of stress signaling pathways (p38 pathway). The secretory phenotype of senescent cells features pro-inflammatory cytokines (tumor promoters), growth factors supportive of tumor development, and (in dermal fibroblasts) matrix metalloproteinases that attack the extracellular matrix. If the cell cycle checkpoint for replicative senescence due to an opened telomere loop can be overcome by interference with senescent cell cycle arrest, say by interference with p53 or Rb producing cell cycle checkpoint abrogation, cell division may continue until the telomeres begin to fuse at the critical length. Then fused chromosomes [Images] lead to fusion-bridge breakage [Images], non-reciprocal translocations from fusion-bridge breakage [Images] and aneuploidy [Images] supportive of tumor initiation and characteristic of chromosomal instability [Images]. Accelerated senescence seems to be premature stress-related senescence in Werner Syndrome (WS), as low oxygen conditions and antioxidant treatment reduce WS senescence and associated genomic instability. Oxidative stress and consequent genetic instability from DNA damage activate stress kinases such as p38, so that the p38 inhibitor SB2035880 prevents the premature stress-induced senescence seen in WS fibroblasts. More p38 inhibitors [Images, Video, Papers, Patents, Books] have been developed, including BIRB796, VX702, VX745, R1487, and SCIO-469, and other stress kinase inhibitors [Papers, Patents, Books] have been developed for JNK and the HSP27 kinase MK2. (Terence Davis and David Kipling, Werner Syndrome, Telomeres and Stress Signaling: Implications for Future Therapies? in K.Lenhard Rudolph, 2008, p.285).
p53 from 'About PhosphositePLUS'.
p53 - The Guardian of the Genome, from PhosphositePLUS.
The alpha helices shown feature 3.6 amino acid residues per helical turn of just 0.54 nm.
The above p53 molecule fits into a rectangle 7.56 nm wide x 5.708 nm high.
p53 pathway [Biocarta, Wikipedia/P53, Links/p53, Images, Video, Papers, Patents, Books, LibCong, Amazon, LifeExtension; Links/Gene TP53; Index/Cancer]. The transcription factor p53 protein from the tumor suppressor gene p53 is involved in detection of DNA damage and halting the cell cycle, and thereby in the transition to the senescent state of the cell. A DNA damage signal can be generated when a telomere t-loop is uncapped as the telomere shortens as a consequence of mitosis [Images]. Also see the pRB (Retinoblastoma) pathway [Wikipedia/pRB, Links, Images, Papers, Patents, Books, Amazon, LifeExtension]. p53 and pRb can lead to senescence arrest often associated with replicative senescence, or p53 can also lead to apoptosis if certain kinds of damage are detected. If neither pathway is activated in a DNA damage scenario (10), attempted gene repair may lead to genomic instability [Index] possibly resulting in cancer. If a person inherits only one functional copy of p53 from their parents, they are predisposed to cancer in early adulthood. Some carcinogens work by allowing cell division to progress beyond the M1 cell senescence checkpoint, when the telomere is about 4000 base pairs long, which is the typical telomere length when the telomere t-loop opens due to telomere shortening associated with cell division, about 50-200 base pairs per cell division. (The number of base pairs lost per cell division may depend on the ROS level and homocysteine levels in the cell's microenvironment. Human adults typically loose about 50 bp of telomere length per year in dermal fibroblasts, endothelial cells, and mitotically competent non-stem cells that do not accompany cell division with telomerase activation.) Cell division past the M1 senescence checkpoint may be done by interfering with the cell cycle arrest controlled by p53, which is activated when the telomere t-loop opens, showing a double-strand DNA break recognized by p53. See carcinogens interfering with the tumor suppressor p53 [Papers, Patents, Books]. Note that:
(1) "More than 50% of human cancers contain inactivating mutations of the p53 gene."
(2) "In the regions with dietary exposure to the fungal aflatoxin B1 (AFB1) a specific mutation at codon-249 of the p53 gene is detected from the cell-free plasma of 30-47% of patients with Hepatocellular Carcinoma (HCC, Liver Cancer).
(3) "Several extrinsic factors, such as aflatoxin, HBV, nutrition, alcohol, and trace elements, are thought to initiate or promote the hepatocarcinogenesis."
- Yong-Song Guan, Qing He, and Zi La, 2006, Roles of p53 in Carcinogenesis, Diagnosis and Treatment of Hepatocellular Carcinoma, Journal of Cancer Molecules 2(5): 191-197, 2006. See also Links/p53 and resveratrol and RevGenetics on resveratrol and p53. "p53 transcriptionally represses hTERT." (Cong, Wright, and Shay, 2002).
(4) P53 and p21 can be lowered by reducing caveolin-1 (gene CAV1) levels, enabling restart of the cell cycle and recovery from cellular senescence, for which p16INK4A should also be reduced with exercise, retinol, or by other means.
P53 and Cancer Suppression Pathways (Tumor Suppression via Cell-Cycle Arrest)
[Links, Images, Papers, Patents, Books, LEF; (Links/Tumor Suppression via Cell-Cycle Arrest, Images, Papers, Patents, Books, LEF)].
(1) Telomere dysfunction typically induces p53-dependent cell cycle checkpoints limiting cellular proliferation via p21 and perhaps also activation of target genes supporting apoptosis including PUMA and Bax.
(2) p53-independent checkpoints may also be induced by telomere dysfunction involving perhaps mitotic checkpoints or ploidy checkpoints.
(3) Chromatin modification can be induced by telomere dysfunction and checkpoint responses activating the Rb-checkpoint producing cell cycle arrest.
p66shc gene knockout [Books, LifeExtension] extends the lifetime of mice 30%!, [51s].
Paclitaxel [Links, Images] essentially slices off telomeres from chromosomes, has been used with telomerase inhibitors like AZT in anticancer therapy. [Patents]. Paclitaxel therapy [Links, Images, Books] looks like one designed by a rod to screw the patient around with slow poison, however, unless applied directly to cells to be destroyed in targeted fashion. Avoid quaffing a test tube full of this one, as it looks like a killing brew, and best scamper from an injection into a vein.
Pain medicine [Links/Pain Medicine, Images, Video, Papers, Patents, Books, Amazon, LifeExtension, LibCong], [93]. See Dental. [OTC: Links/Ibuprofen, Wikipedia/Ibuprofen; MedlinePlus/Pain Relievers: acetaminophen (Tylenol), NSAIDs: Aspirin, naproxen, Aleve]. See also
Anesthesia [Images, Video, Papers, Patents, Books];
Local Anesthesia [Images, Video, Papers, Patents, Books]. See also
Oral Local Anesthetic Injection [Images, Video, Papers, Books],
Local Anesthetic [Wikipedia, Images, Video, Papers, Patents, Books],
Sedation Dentistry [Images, Video, Papers, Patents, Books].
Dental Anesthesiology [Links, Images, Video, Papers, Patents, Books, Amazon];
Dental Anesthesia [Links, Images, Video, Papers, Patents Books].
US Brands: Topical Anesthetics:
Benzocaine [Links, Images, Papers, Patents, Books].
Anesthetics for Injection,
Novocaine [Links, Images, Papers, Patents, Books],
Lidocaine (Xylocaine) [Wikipedia, Images, Papers, Patents, Books]. See
How to give an injection [Images, Video, Papers, Patents, Books].
How to give a dental injection [Images, Video, Papers, Patents, Books]. See also
[Wikipedia/Pain, Links/Pain, Images, Video, Papers, Patents, Books, Amazon, LifeExtension] and
Pain Management
[Wikipedia/Pain, Links/Pain Management, Images, Video, Papers, Patents, Books, Amazon, LEF].
Panax Ginseng [Index/Ginseng, Wikipedia/Ginseng, Links/Panax Ginseng, Images, Video, Papers, Patents, Books, Amazon, LifeExtension; Product B/Asian Ginseng Root Extract (Panax Ginseng)]. See also Ginsenosides [Links/Ginsenosides, Images, Video, Papers, Patents, Books, LifeExtension]. Some ginsenosides are telomerase activators [List], others are telomerase inhibitors [List]. Ginsenoside Rh2 (a protopanaxadiol) is a telomerase inhibitor, ginsenoside Rh1 (a protopanaxatriol) is a telomerase activator, and Ginsenoside Rg1 may also be a telomerase activator. According to Product B literature, panax ginseng behaves like a telomerase activator for normal, non-cancerous fibroblasts. Panax Ginseng ginsenosides increase nitric oxide synthase activity, assisting in the conversion of arginine to nitric oxide, improving blood flow. Panax Ginseng is an antioxidant, decreases inflammation, boosts the immune system, and is used as an adaptogen that improves the ability to handle stress.
Pancreas [Wikipedia/Pancreas, Links/Pancreas, Images, Video, Papers, Patents, Books, Amazon, LifeExtension; Images/Pancreas cells; Index/Diabetes, Type II Diabetes]. Telomerase activation in pancreatic islet cells [Images] is a special problem in longevity research. Failure of insulin-producing cells in the pancreas is characteristic of diabetes, which is associated with more rapid aging. Nattokinase is able to prevent and dissolve a broad spectrum of amyloidosis amyloid fibrils, including transthyretin amyloid fibrils, amyloid beta amyloid fibrils, prion amyloid fibrils, insulin amyloid fibrils, and beta-microglobulin fibrils, including the insulin amyloid fibrils based on the precursor protein amylin that cause apoptosis of pancreatic beta cells in type 2 diabetes. That is, amyloidosis from insulin amyloid fibrils produced by pancreatic islet beta cells from cosecreted insulin and amylin that kills the pancreatic islet beta cells that produce insulin can be treated successfully with nattokinase [Index, US Patent 8137666 B2]. "Fully understanding how to successfully immortalize some cell types is an active area of research. Transfection with hTERT alone appears to be fully capable of immortalizing many cell types. Some cell types require additional cellular intervention to become fully immortalized. This process often involves suppressing the activities of the p16/INK4A, pRB, and p53 cell cycle checkpoints. This is often accomplished by transfecting cells with hTERT and a viral transformation agent, such as HPV E6/E7 or SV40." - ATCC/hTERT Immortalized Cells. The pancreas resembles a tongue beneath the stomach in many drawings.
Pancreatic Cancer [Alcohol; Wikipedia/Pancreatic Cancer, Links/Pancreatic Cancer, Images, Video, Papers, Patents, Books, Amazon, LifeExtension; Cancer; Carcinogens; Anticancer Nutraceuticals; Apoptosis; Telomerase Inhibitors; Anticancer Telomerase Activators; Metastasis, NFkB, NFkB Inhibitors, Angiogenesis Inhibitors; Links/Nutraceuticals treating Pancreatic Cancer, Images, Video, Papers, Patents, Books, LifeExtension; Links/Preventing Pancreatic Cancer, Images, Video, Papers, Patents, Books, LifeExtension]. See Ding, X.Z., et al. (2002), Resveratrol inhibits proliferation and induces apoptosis in human pancreatic cancer cells, Pancreas 2002;25:e71-e76. Note that NF-kB inhibitors block inflammation in the pancreas due to alcohol that can lead to pancreatic cancer. Resveratrol is an NF-kB inhibitor. NF-kB expression is elevated in 95% of human cancers. See David Hoffnung (2011), The Inflammatory Factor Underlying Most Cancers, Life Extension Magazine, November 2011. Gamma tocotrienol down-regulates NF-kB in pancreatic tumor cells (op.cit.). Delta-tocotrienol also prolongs pancreatic cancer survival (Husain K, et al, (2012)). Treatment of pancreatic cancer with gemcitabine and tocotrienols combined produced a 90% survival rate in mice (Husain K, et al, (2012); Thomas Rosenthal, 2014, LEF). Pancreatic cancer may be treated with curcumin, one of the more powerful NF-kB inhibitors and an inducer of apoptosis in cancer cells. See Gukovsky I, Reyes CN, Vaquero EC, Gukovskaya AS, Pandol SJ (2003), Curcumin ameliorates ethanol and nonethanol experimental pancreatitis, Am J Physiol Gastrointest Liver Physiol, 2003 Jan; 284(1):G85-95. "In September 2006, a long-term study concluded that taking vitamin D can substantially cut the risk of pancreatic cancer (as well as other cancers) by up to 50%." - Wiki/Pancreatic cancer. Vitamin D is anti-inflammatory and a telomerase inhibitor. Chronic pancreatitis [Images, Papers, Books] features inflammation of the pancreas and can lead to pancreatic cancer or diabetes. See Eckel F, Schneider G, Schmid RM (2006), Pancreatic cancer: a review of recent advances, Expert Opin Investig Drugs 2006 Nov; 15(11):1395-410. Also see Malafa MP (2008), New insights and gains in pancreatic cancer, Cancer Control 2008 Oct;15(4):276-7. Furthermore, crocetin from saffron is promising in treating pancreatic cancer.
[1] Dhar A, Mehta S, Dhar G, et al. (2009), Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model, Mol Cancer Ther 2009 Feb;8(2):315-23.
[2] Jennifer Provos (2015),
Anticancer Properties Of Saffron, Life Extension Magazine, March 2015.
[3] Shida T, Kamei N, Takeda-Morishita M, Isowa K, Takayama K. (2013),
Colonic delivery of docosahexaenoic acid improves impaired glucose tolerance via GLP-1 secretion and suppresses pancreatic islet hyperplasia in diabetic KK-A(y) mice,
Int J Pharm 2013 Jun 25;450(1-2):63-9.
Pantethine [Links, Images, Video, Papers, Patents, Books, LifeExtension, active-form vitamin B5, Index/Vitamin B5]. Pantethine is pantothenic acid. It may enhance cognitive abilities and energy levels, [36s] (h). Pantethine also reduces cholesterol levels, LDL levels, and LDL/HDL ratios. Note that high LDL levels can activate the transcription of caveolin-1, producing cellular senescence. Thus pantethine has application in a program for recovering from cellular senescence by lowering caveolin-1.
Park, Sang Chul [Links, Images, Video, Papers, Patents, Books; Restoring Senescent Cells].
Professor Sang Chul Park.
Prof. Sang Chul Park
"Sang Chul Park is Professor in the Department of Biochemistry at the Seoul National University Medical School [Maps], South Korea. His research expertise resides in biochemistry, metabolism, and aging. Since 1997, he is the Director of the Institute on Aging at the University. From 2002, he is also the Director of the Aging and Apoptosis Research Centre of Excellence [Link1, Link2], Ministry of Education, Science and Technology. Throughout his career he has held influential scientific positions including Dean of Research Affairs, Seoul National University, President, Korean Society of Gerontology, President, Korean Society of Molecular Biology and Medical Biochemistry, President, Federation of Korean Gerontological Societies, President, International Association of Biomedical Gerontology, and President, Korean Society of Molecular and Cellular Biology." See Cho KA, Ryu SJ, Park JS, Jang IS, Ahn JS, Kim KT, Park SC (2003), Senescent phenotype can be reversed by reduction of caveolin status [Papers, Patents, Books], Journal of Biological Chemistry, 2003 Jul 25;278(30):27789-95. Professor Sang Chul Park has worked extensively on mechanisms of senescence involving signaling from the cell membrane via endocytosis, and has developed numerous papers and patents on therapies for recovering from cellular senescence. See Refs 9 and Refs10.
Parkinson's Disease [Wikipedia/Parkinson's_disease, Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension]. Oxidative stress, mitochondrial dysfunction, and inflammation seem to be the Dementias. causes of Parkinson's Disease. Early warning signs of Parkinson's Disease include slowed movement, tremors, difficulty standing up, and mild cognitive impairment, leading to further symptoms of Parkinson's Disease including more severe tremors and loss of motion control, as Parkinson's irreversibly destroys movement-controlling nerve cells. Aging is the most important risk factor for developing Parkinson's Disease, with incidence beginning at 50 and rising steeply at 60. Parkinson's Disease is associated with destruction of dopaminergic neurons in the substantia nigra that produce dopamine, so that sometimes levodopa is used to provide dopamine after internal conversion in treatment. Note that the "brain food" DHA improves dopamine levels, as does Mucuna Pruriens. Reuptake of dopamine, serotonin, and norepinephrine may be inhibited using St. John's Wort with antidepressive effect. Phenylanaline, a precursor to dopamine formation, is used to treat rigidity in Parkinson's Disease at 250 to 1000 mg/dose 3 times per day. Phenylanaline is also a precursor to thyroid hormones. Phenylanaline has been shown to relieve symptoms of depression, rigidity in Parkinson's Disease, vitiligo and chronic pain. Tyrosine is also a precursor of dopamine and a precursor to other neurotransmitters including norepinephrine and epinephrine. Parkinson's Disease may be treated using creatine, omega-3 fatty acids, CoQ10 (ubiquinol, effectively given with levodopa in treatment), B vitmains such as vitamin B6 (given with the decarboxylase inhibitor carbidopa if levodopa is taken, to prevent early conversion of levodopa into dopamine before reaching the brain), pyridoxal-5'-phosphate, acetyl L-carnitine or Carnitine, alpha lipoic acid, green tea extract, and resveratrol. "Vitamin B6 may help reduce Parkinson's Disease risk by decreasing serum homocysteine, an amino acid that is potentially toxic to dopaminergic nerve cells." Inadequate dietary intake of vitamin B6 may increase the incidence of Parkinson's Disease by 50%. See sources of vitamin B6 and Vitamin B6 supplements. Note that pre-treatment of monkeys with acetyl-L-carnitine prevents artificially induced Parkinson's Disease. (See Julius Goepp, MD, Halt the Stealth Threat of Parkinson's Disease, LEF, July 2010.) Recently Vitamin D deficiency has been linked to cognitive decline (Archives of Internal Medicine 2010;170(13):1135-41) and Parkinson's Disease (Archives of Neurology, 20;67(7):808-11). See Lin TK, Liou CW, Chen SD, et al. (2009), Mitochondrial dysfunction and biogenesis in the pathogenesis of Parkinson's disease, Chang Gung Med Journal, 2009 Nov-Dec; 32(6)589-99. A high prevalence of vitamin D insufficiency in patients with recent onset of Parkinson's Disease was noted in LEF News, June 2011. Vitamin D has an anti-inflammatory effect that may tend to blockade Parkinson's Disease. See also on genetic factors in Parkinson's Disease [Papers, Patents, Books]. Lewis body formation (characteristic of Parkinson's Disease) is promoted by insoluble fibrils of alpha synuclein [Images, Papers, Patents, Books, LifeExtension]. The expression of alpha synuclein can be blocked with NF-kB inhibitors, preventing Parkinson's Disease. Ashwagandha (Withania Somnifera) reverses Parkinsonian neurodegeneration.
Parsley, Sage, Rosemary, and Thyme
Parsley [Links, Images, Papers, Patents, Books, LifeExtension],
Sage [Links, Images, Papers, Patents, Books, LifeExtension],
Rosemary [Index, List, Links, Images, Papers, Patents, Books, LifeExtension],
Thyme [Index, List, Links, Images, Papers, Patents, Books, LifeExtension].
Parsley and Sage provide anti-inflammatory, anticancer luteolin, a TNF-α inhibitor used to inhibit inflammation in diseases such as Alzheimer's Disease. Dietary sources of luteolin include celery, green pepper, parsley, sage, rosemary, thyme, perilla, camomile tea, green pepper, dandelion, perilla, carrots, olive oil, peppermint, navel oranges, and oregano. Luteolin also inhibits muscle catabolism. (Enbrel is perhaps the most effective choice for a TNF-α inhibitor in Alzheimer's Disease.)
Parsley (Petroselinum sativum) contains the highly bioactive anticancer or antibiotic volitile oils myristicin, apiol, and eugenol, which help neutralize carcinogenic benzopyrenes from smoking and charboiling [1], [2]. Myristicin inhibits lung tumor formation, preventing oxidative damage by activating glutathione S-transferase, which detoxifies oxidized molecules via production of glutathione. Myristicin is anti-inflammatory and antibacterial. Parsley also contains small amounts of macular degeneration-preventing zeaxanthin, lutein, which also protect against cataracts [1], and cryptoxanthin. Diuretic properties of parsley reduce edema and improve definition.
Sage activates AMPK via its high internal carnosic acid content, which promotes high levels of the thyroid hormone T3. This helps reduce abdominal fat, improves autophagy in senescent cells, and enables apoptosis of senescent cells.
Rosemary may be taken as an antioxidant, and aroma therapy based on Essential Oil of Rosemary activates Nerve Growth Factor via carnosic acid, improving memory. Nerve Growth Factor also enhances production of Id-1 helix-loop-helix protein transcription factor, which activates telomerase and inhibits p16INK4A, which can accumulate until it causes senescence. Rosemary's carnosic acid is also a lipase inhibitor, slowing the digestion of fatty lipids. Rosemary Extract [Links] contains a high concentration of carnosic acid. Thyme, also a source of anticancer luteolin, is a source of the aniseptic used in Listerine, and was used by the ancient Egyptians in embalming, and by the ancient Greeks (who believed it was a source of courage) it was burnt as incense in their temples. Thyme also supplies a ligand of the progesterone receptor able to induce progesterone-type transformations and is furthermore a telomerase activator [Index].
[1] Michael Downey (2015),
Parsley, Life Extension Magazine, March 2015.
[2] Zheng GQ, Kenney PM, Zhang J, Lam LK (1992),
Inhibition of benzo[a]pyrene-induced tumorigenesis by myristicin, a volatile aroma constituent of parsley leaf oil, Carcinogenesis 1992 Oct;13(10):1921-3.
Music[2]: Scarborough Fair Canticle from Simon & Garfunkel,
Scarborough Fair (with Botanical Images) from Sarah Brightman.
Patent Laws [LibCong, US Patent & Trademark Office, Wikipedia/Patents, Wikipedia/Biological Patents, United States Code Title 35 - Patents, Google Patent Search, Yahoo/Intellectual Property Law/Patents, Links, Video, Books, Amazon]. "The exclusive right granted to a patentee in most countries is the right to prevent or exclude others from making, using, selling, offering to sell or importing the invention for the term of the patent, which is usually 20 years from the filing date. A patent is, in effect, a limited property right that the government offers to inventors in exchange for their agreement to share the details of their inventions with the public. Like any other property right, it may be sold, licensed, mortgaged, assigned or transferred, given away, or simply abandoned." - Wikipedia/Patents
Pathology [Links, Images, Video, Papers, Books, LibCong, Amazon; Links/Pathology of senescent tissues, Images, Papers, Books, Amazon, Links/Pathology of senescent cells, Images, Papers, Books, Amazon].
Pathophysiology [Links, Video, Papers, Books, LibCong, Amazon].
Pathway Analysis [Wikiomics:Pathway_analysis; Links/Biological Pathway Analysis, Images, Video, Papers, Books, LibCong, Amazon; Links/Pathway Analysis for Drug Discovery, Images, Video, Papers, Books, Amazon; Links/Supplements Pathway Analysis, Images, Video, Papers, Books, Amazon; Index/Pharmacogenomics; Index/Nutrional Genomics; Index/Gene; Links/Pathway Analysis Software, SA Biosciences/Pathway Central, Biocompare/Genes by Signaling Pathway, Biocarta Pathways, Biocarta Pathways/Telomeres, Telomerase, Cellular Aging, and Immortality, Wiki/David_(bioinfomatics_tool)(Links), KEGG Pathway Data Base(Links), Wikipedia/NCI-Nature Pathway Interaction Database(Links)]. See Invitrogen LINNEA Pathways. See also Gene Chips(Wiki/DNA microarray) - Affymetrix/Products & Services, SA Biosciences, Links/Gene Chips, Video/Gene Chips, Links/Transcripomics. See also Wiki/Systems biology, (Links/Systems biology), Links/Protein Microarrays, Links/Cellular Microarrays, Links/Antibody Microarrays, Links/Tissue Microarrays, and Links/Chemical Compound Microarrays.
Patton, Noel [Links, Images, Video, Papers, Patents, Books; TA Sciences]. Noel Patton announced astragalus extracts as telomerase activators in March 2007, before we had read the Geron patents of 2005, and defined the Patton Protocol for cyclic activation of telomerase with TA-65.
Peanut [Wikipedia/Peanut, Links, Images, Video, Papers, Patents, Books]. The peanut is a good source of both gamma tocopherol (combatting the peroxidation of lipids) and arginine (for NO generation by nitric oxide synthase, supporting a healthy vascular endothelium [Index/Endothelium] against atherosclerosis), and also of lysine (for DNA maintenance, with arginine) and niacin (contributing to brain health, brain circulation, blood flow, and DNA repair). Peanuts contain up to 30x as much resveratrol (for SIRT1 activation) as grapes, about 73 micrograms per ounce. Furthermore, peanuts contain high concentrations of antioxidant polyphenols, primarily a compound called p-coumaric acid. Roasting can increase peanuts' p-coumaric acid levels by as much as 22%. (Wikipedia/Peanut). On the negative side, the peanut is 47% fat, including 7% saturated fat, 24 percent mono-unsaturated fat (much of which is fairly helpful oleic acid), and 16 percent poly-unsaturated fat, so that the peanut is high in calories at 166 calories per ounce, 126 calories/ounce of which come from fat.
Peptide Bioregulators [Links, Images, Video, Papers, Patents, Books, Amazon] Peptide bioregulators have been investigated by the Institute for Bioregulation and Gerontology in St. Petersburg, Russia, and include one of the first small-molecule telomerase activator ever discovered, epithalon peptide (Ala-Glu-Asp-Gly) [Telomerase Activators/Epithalon Peptide], which was found in 2003. Today peptide bioregulators and sold and explained by Peptides Store in essays such as Bioregulators from Prof. Vladimir Khavinson and the St. Petersburg Institute of Biogerontology.
Epithalon peptide [Links, Images, Papers, Patents, Books, Amazon; Endoluten] is a regulator of telomere homeostasis [Links, Images, Papers, Patents, Books, Amazon] obtained in the epiphysis extracts (pineal gland extracts) before it was synthesized artificially as a peptide chain (ref). Other peptide biogregulators include Vilon (Lys-Glu) and Livagen (Lys-Glu-Asp-Ala) [Paper]. Simple peptide chains (elementary proteins, sometimes enzymes) of note in anti-aging medicine include carnosine (Ala-His) and ependymin [TA/Ependymin] (Glu-Ser-Cys-Lys-Lys-Glu-Thr-Leu-Gln-Phe-Arg-Lys-His-Leu) a telomerase activator found in goldfish brains. Perhaps these peptide chain compounds are best taken in liposomal sprays [Index], as we now take NOW FOODS IGF-1 Liposomal spray. See Liposomes.
Periodontitus [Wikipedia, Links, Images, Video, Papers, Patents, Books, LibCong, Amazon, Dental]. Gum disease follows the receding gums associated with aging, as do cavities around the roots of teeth. Periodontitis affects approximately 50% of U.S. adults over 30 years of age. See also subgingival antibiotics (Arestin [Links/Arestin, Images]).
Peroxidation of lipids [Index/Lipid Peroxidation, Links/Peroxidation of lipids, Images, Video, Papers, Patents, Books, LifeExtension, LibCong, Amazon, Wikipedia]. Lipid peroxidation is inhibited by resveratrol and antioxidants. See Zs.-Nagy on Lipid Peroxidation, and Peroxidation of Fatty Acids, (0). Gamma Tocopherol [Index, Links, Papers, LifeExtension] is useful in preventing lipid peroxidation from peroxynitrites [Index, Links, LifeExtension] generated by high Nitric Oxide levels that may physiologically useful in antiaging applications. Sesame seed oil is rich in gamma tocopherol and sesame lignans such as sesamin and sesamol that improve gamma tocopherol's antioxidant performance. Peanuts are another good source of gamma tocopherol. See also Reinald Pamplona and Gustavo Barja, Aging Rate, ROS Production, and Fatty Acid Unsaturation in Aging at the Molecular Level edited by Thomas von Zglinicki, 2003. Peroxidation of lipid membranes is prevented when Vitamin E reacts with lipid peroxyl radicals and with lipid alkoxyl radicals. Both tocopherol and selenium-dependent glutathione decrease the production of lipid peroxidation products.
Peroxynitrite [Links/Peroxynitrite in aging; Links/Peroxynitrite, Images, Video, Papers, Patents, Books, LibCong, LifeExtension, Wikipedia/Peroxynitrite]. Peroxynitrite is quenched by the gamma tocopherol form of vitamin E, and also by acai extract, and plays a major role in old age decline in the recent literature on the free radical theory of aging (1). See also Lipid Peroxidation.
Pharmaceutical Analysis [Links/Pharmaceutical analysis, Video, Papers, Books, LibCong, Amazon/Pharmaceutical Analysis, Links/pharmaceutical analysis of astragalus extract, Links/Pharmaceutical analysis services; Wikipedia, Links/Analytical chemistry, Books, Amazon; Links/analytical chemistry of astragalus, Links/analytical chemistry of medicines, Links/analytical chemistry services, Links/analytical chemistry supplies].
Pharmaceutical Engineering [Wikipedia, Links/Pharmaceutical Engineering, Video, Papers, Patents, Books, LibCong, Amazon; Links/Pharmaceutical Processing, Images, Video, Papers, Patents, Books; The INTERPHEX Show;; Links/Biopharmaceutical Manufacturing, Images, Video, Papers, Patents, Books].
___Contract Pharmaceutical Manufacturing [Links, Images, Video, Papers, Patents, Books].
___Pharmaceuticals Handling [Links, Images, Video, Papers, Patents, Books],
___Pharmaceuticals Granulation [Links, Images, Video, Papers, Patents, Books],
___Pharmaceuticals Tableting [Links, Images, Video, Papers, Patents, Books],
___Pharmaceuticals Capsule Filling and Banding [Links, Images, Video, Papers, Patents, Books],
___Pharmaceuticals Weight Checking [Links, Images, Video, Papers, Patents, Books],
___Pharmaceuticals Coating [Links, Images, Video, Papers, Patents, Books],
___Pharmaceuticals Washing [Links, Images, Video, Papers, Patents, Books].
Pharmaceutical Vendors [Longevity Supplement Vendors, Links/Pharmaceutical Vendors, Video, Papers, Books]. Some of anti-aging favorites with good on-line educational write-ups include: GAIA Herbs, Herb Pharm, Life Extension Foundation, Medicinal Nutraceutics, NOW Foods, Ray Sahelion, RevGenetics, Solaray, Terraternal, and Vitamin Research Products.
See also drug companies [Links, Video, Papers, Books, LibCong], for anti-aging.
Pharmaceutical Vendors of Anti-Aging Supplements [Longevity Supplement Vendors], embedded [38s].
Pharmacogenomics [Links/Pharmacogenomics, Images, Video, Papers, Patents, Books; Links/Pharmacogenomics Databases, Images, Video, Papers, Patents, Books; Links/The Pharmacogenomics of Nutritional supplements, Papers, Books; Links/The Pharmacogenomics of Bodybuilding supplements, Papers, Books; Links/Nutritional Genomics, Papers, Books; Links/Pathway Analysis for Drug Discovery, Images, Video, Papers, Books, Amazon; Index/Gene; GeneFamiliesHUGOwithLinks]. See PharmGKB as an example of a pharmacogenomics database. See Young-Joon Surh, Zigang Dong, Enrique Cadenas, Lester Packer (2008), Dietary Modulation of Cell Signaling Pathways [Links, Images, Video, Papers], (Google eBooks) CRC Press, Sep 26, 2008, 504 pages.
Pharmacokinetics and Bioavailability [Index/Bioavailability and Pharmacokinetics, Boomer/Pharmacokinetics and Bioavailability, Wikipedia/Pharmacokinetics, Links/Pharmacokinetics, Images, Video, Papers, Patents, Books, LibCong/Pharmacokinetics; Wikipedia/Bioavailability, Links/Bioavailability, Papers, Patents, Books, LibCong/Bioavailability, LifeExtension, Amazon], [42s].
Pharmacology [Wikipedia, Links, Video, Books, Amazon]. See also medicinal properties: [Wikipedia, Links] of medicines in pharmacology .
Phenylanaline [Links, Images, Papers, Patents, Books, LifeExtension]. Phenylanaline is a precursor to dopamine used in the treatment of Parkinson's Disease, and is also a precursor of norepinephrine. Phenylanaline is also a precursor to thyroid hormones. Phenylanaline has been shown to relieve symptoms of depression, rigidity in Parkinson's Disease, vitiligo and chronic pain. The recommended dose for athletes is 250-1,000 mg three times a day, 30 minutes before meals. - after Dwayne Jackson PhD (2011), Musclemag's Essential Supplement Handbook, Fall, 2011.
Phenylbutylnitrone [Links, Images, Papers, Patents, Books, LifeExtension; Links/nitrones in spin trap technology]. Phenylbutylnitrone is an experimental life-extending antioxidant drug. Reduces rat maze running errors. - Dr. Denham Harman. Also referred to as "spin trap" by Truth in Aging, which points out that it is used in Your Best Face skin cream and in Glo Therapeutics products. N-tert-butylhydroxylamine is a spin-trap drug useful for treating mitochondrial aging that is pictured as a mitochondrially targeted anti-senescence drug. See Spin Trap compounds in anti-aging therapy [Links, Images, Papers, Books, LifeExtension].
Phenylethylamine (Beta Phenylethylamine) [Links, Images, Papers, Patents, Books, LifeExtension]. Phenylethylamine, a metabolite of the amino acid phenylalanine, improves the expression of norepinephrine to promote fat burning. By increasing brain levels of dopamine and serotonin, this substance also produces mild euphoria and reduces sensations of pain.
Phlebitis [Wikipedia/Phlebitis, Links, Video, Images, Papers, Patents, Books, Amazon, LifeExtension; Wikipedia/Thrombophebitis, Links, Video, Images, Papers, Patents, Books, Amazon, LifeExtension; Links/Thrombolytic Drugs, Video, Images, Papers, Patents, Books, Amazon, LifeExtension; Links/Anticoagulants, Video, Images, Papers, Patents, Books, Amazon, LifeExtension; Index/Varicose Veins].
Phlebotomy [Links/Phlebotomy, Video, Wikipedia/Venipuncture, Links/Venipuncture, Books/Venipuncture, LibCong/Venipuncture, Amazon/Phlebotomy]. See Venipuncture and Biopsy.
Phosphatidylcholine (Lecithin) [Wikipedia/Phosphatidylcholine, Links/Phosphatidylcholine, Images, Papers, Patents, Books, LifeExtension, Wikipedia/Lecithin, Links/Lecithin, Images, Papers, Patents, Books, LifeExtension; Links/Maintaining phosphatidylcholine in the cell membrane, Images, Papers, Patents, Books, LEF; Links/Phosphatidylcholine in membrane-mediated cell signaling, Images, Papers, Patents, Books, LEF; Links/Extraction of phosphatidylcholine, Images, Papers, Patents, Books; Memory Enhancing Nutraceuticals]. Phosphatidylcholine is obtained from from Soy [Links/Soy] or from egg yolks using extraction with hexane or mechanical extraction. [36s] (b). Lecithin (see also soy lecithin and phosphatidylcholine) enhances the bioavailability of polyphenols, including resveratrol and quercetin. Theodore Nicolas Gobley, a French chemist and pharmacist of the mid 19th century, identified egg yolk lecithin as phosphatidylcholine in 1847, completely describing it chemically in 1874. "Phosphatidylcholine is a major constituent of cell membranes, and plays a role in membrane-mediated cell signaling... At birth and throughout infancy, phosphatidlycholine concentrations are high (as high as 90% of the cell membrane), but it is slowly depleted throughout the course of life, and may drop to as low as 10% of the cellular membrane in the elderly." - Wikipedia/Phosphatidylcholine. See phosphatidylcholine deficiency [Images, Papers, Patents, Books, LEF]. See also the phosphatidylcholine content of soy products [Images, Papers, Books, LEF] and the phosphatidylcholine content of soy milk. CDP-choline (Citicoline) "helps make phosphatidylcholine in human brain cell membranes in older individuals; may increase acetylcholine synthesis; improves mental performance in patients with Alzheimer's Disease; and even improves memory in elderly patients with memory deficits." - Ray Sahelian/CPD-Choline. UMP supplementation [Links, Images, LEF] in laboratory animals "dramatically increases the production of vital brain cell membrane structural molecules such as CDP-choline." - LifeExtension, March 2009.
Phosphatidylserine [Wikipedia/Phosphatidylserine, Links/Phosphatidylserine, Images, Video, Papers, Patents, LifeExtension; Links/side effects (from Bovine Cortex phosphatidylserine pathogens); Synthesis from Phosphatidylcholine; Memory Enhancing Nutraceuticals]. Phosphatidylserine repairs mitochondrial membranes. [Links/Mitochondrial Membrane Repair, Images, Patents, Papers, Books, Amazon, LifeExtension]. Phosphatidlyserine comprises up to 10% of a neuron's lipid content. Phosphatidylserine reverses memory loss, and is useful in treating old age cognitive decline. Furthermore, 600 mg/day to 800 mg/day of phosphatidylserine reduces cortisol levels. Cortisol lowers HGH levels, removing a source of telomerase activation, and increases fat storage while opposing muscle growth. Phosphatidylserine increases time to exhaustion in heavy exercise by reducing cortisol. The three major sources for phosphatidylserine are cow brains (illegal in the USA due to mad cow disease), soy lecithin and lamb's kidneys (an excellent source), and cabbages. A therapeutic dose of phosphatidylserine (100 mg) is most easily obtained from a supplement [Images], although prices are high. Cut-rate phosphatidylserine from cabbage exists at Sea Coast Vitamins for < $25.00 per 100 caps of 100 mg/cap. Some studies suggest that animal-source PS may be more effective than PS from soy or the inner leaves of Savoy cabbage. See Savoy cabbages [Images].
DHA regulates the brain’s concentration of phosphatidylserine, and diets low in DHA decrease phosphatidylserine levels in the hippocampal region of the brain associated with memory consolidation [1], [2].
[1] Russell L. Blaylock, MD (2008),
DHA Supports Brain Development and Protects Neurological Function,
Life Extension Magazine January 2008.
[2] Salem N, Jr., Litman B, Kim HY, Gawrisch K. (2001),
Mechanisms of action of docosahexaenoic acid in the nervous system,
Lipids 2001 Sep;36(9):945-59.
Music[2]: Savoy Truffle, from The Beatles White Album.
Phosphodiesterase Inhibitors (Encylopedia).
Phospholipid Exchange Therapy [Infusion Therapies & Phospholipid exchange (phosphatidylcholine), Links, Books/phospholipid exchange therapy, LibCong/phospholipid exchange, Books/Phospholipid exchange, Books/phospholipid therapy, Amazon/Phospholipid exchange, Amazon/Phospholipid therapy, Papers, Patents, LifeExtension/Phospholipid exchange therapy, LifeExtension/phospholipid exchange, LifeExtension/phospholipid therapy, special links]. Phosphatidylcholine (lecithin) is seriously depleted in aging, from 90% of the cell membrane molecular content down to 10%, so that restoring it is useful in treating old age skin problems. I think perhaps phospholipid exchange methods get showy and quick results for rejuvenation applications. Phospholipid exchange treatments are used by Dr. Terry Grossman, co-author of Fantastic Voyage. See Books/Phospholipid exchanges for cell membrane repair & Links. See also Krill Oil [LifeExtension, Links, IAAS, Index/Krill Oil], which contains choline [Images] and phospholipids [Images] in addition to omega-3 oils [Images]. Check the phospholipid content of Krill Oil.
Phytoceramides (Encyclopedia).
Phytochemicals [Phytonutrients, Ben Best/Phytochemicals as Neutraceuticals, INFO/Phytochemicals, Wikipedia, Wiki/List of Phytochemicals and Foods in which they are prominent, LifeExtension, Links, Images, Papers, Patents, Books, LibCong, Amazon, Phytochemistry] - The Phytochemical Collection.
Phytochemical Activators of hTERT transcription [Links/phytochemical activators of hTERT transcription, Images, Papers, Patents, Books; Links/nutraceutical activators of hTERT transcription, Images, Papers, Patents, Books; Index/Telomerase Activators; Alphabetic List of Telomerase Activators, The Product B Explorer]. Phytochemical and nutraceutical activators of hTERT transcription are simpler and more inexpensive to work with than recombinant proteins brewed by culturing plasmids and then transfected to target tissues in liposomes. Note that some cells such as mesenchymal-derived connective tissues including bone and cartilage require the application of histone deactylase inhibitors (HDAC inhibitors) before hTERT mRNA-boosting telomerase activators function properly in them.
Phytochemical Separations [Index/Instrumental Analysis/Separations, Links, Images, Papers, Patents, Books, Amazon; Links/chemical separations, Books/chemical separations, Amazon, LibCong/chemical separations].
Phytochemical Testing [from Food Product Design, Links, Books, Amazon].
Phytoestrogens [Links, Video, Papers, Patents, Books, LibCong, LifeExtension, Wikipedia]. "Phyto" means "plant", [20s]. Estriol [Wikipedia, Links, LifeExtension], a weaker form of estrogen derived from plants, produces superior skin rejuvenation results with fewer hormonal side effects than estrogen [Index/Estradiol, Index/Estrogen; Index/Estriol]. Lignans [Index] and isoflavones are two classes of phytoestrogens [Index] related to human estradiol and estrogen useful in treating estrogenic cancers, osteoporosis, and cardiovascular diseases.
Phytomedicines [Links, Papers, Patents, Books, LibCong, Amazon, Phytotherapy Research, Phytochemistry, Planta Medica]. See Journals.
Phytonutrients [Phytochemicals, Links, Papers, Books, LifeExtension].
[1] Anu Rahal, Mahima, Amit Kumar Verma, Amit Kumar, Ruchi Tiwari, Sanjay Kapoor, Sandip Chakraborty and Kuldeep Dhama (2014), Phytonutrients and Nutraceuticals in Vegetables and Their Multi-dimensional Medicinal and Health Benefits for Humans and Their Companion Animals: A Review [PDF], Journal of Biological Sciences, 14(1): 1-19, 2014.
PI3K/AKT Pathway [Telomerase Activators/Phosphatidylinositol 3' kinase, Index/AKT, Links, Images, Video, Papers, Patents, Books, Amazon; Links/PI3/AKT1 pathway, Images, Papers, Patents, Books]. See Shuang Liu, Shu Liu, Xinyue Wang, Jiaxi Zhou, Yujing Cao, Fei Wang and Enkui Duan (2011), The PI3K-Akt pathway inhibits senescence and promotes self-renewal of human skin-derived precursors in vitro, Aging Cell (2011), 10, pp661-674. These researchers used PDGF-AA and bpV(pic), a vanadate molecule coordinated to picolinic acid (2- carboxypyridine) and potassium, to stimulate the PI3K/Akt pathway. See Sury MD, Vorlet-Fawer L, Agarinis C, Yousefi S, Grandgirard D, Leib SL, Christen S. (2011), Restoration of Akt activity by the bisperoxovanadium compound bpV(pic) attenuates hippocampal apoptosis in experimental neonatal pneumococcal meningitis, Neurobiological Disorders. 2011 Jan;41(1):201-8. IGF-1 and IL-2 both phosphorylate hTERT protein in the cytoplasm for import into the nucleus via the PI3/AKT1 pathway. The "PI3K/Akt pathway is a major upstream signaling module leading to the phosphorylation of FOXO factors and their exclusion from the nucleus." - from Dominique A Glauser and Werner Schlegel (2007), The emerging role of FOXO transcription factors in pancreatic b cells [Papers], Journal of Endocrinology (2007) 193, 195–207. AKT kinase and the PI3K/AKT pathway are useful for decreasing expression of caveolin-1 (gene CAV1), a key element in recovery from cellular senescence. Note that folic acid (vitamin B9) supplements stimulate the PI3K/AKT signaling cascade.
Pimagedine [Wikipedia/Pimagedine, Links, Images, Papers, Patents, Books, LifeExtension] - An AGE inhibitor from Alteon.
Pine Bark Extract [Links, Images, Video, Papers, Patents, LifeExtension], with properties similar to PycnogenolTM is available from NOW Foods, Source Naturals, and other supplement vendors.
Pine Pollen [Links, Images, Video, Papers, Patents, LifeExtension], another pine supplement, improves testosterone levels.
Pinolenic acid [LEF/Pinolenic acid appetite suppressant & insulin overload, Links/Pinolenic acid, Images, Papers, Patents, Books, LifeExtension, Links/Insulin Overload]. Pinolenic acid supplements [Images] derived from pine nuts stimulate hunger suppression hormones including cholecystokinin and GLP-1 (glucagon-like peptide 1) making caloric restriction easier to bear.
Pinus Massoniana [Links, Images] pine bark extracts similar to Pycnogenol and pine pollen to boost testosterone from this Asian pine are useful supplements.
Piperine [Wikipedia/Piperine, Links/Piperine, Images, Video, Papers, Patents, Books, LifeExtension]. Piperine can improve the bioavailability of curcumin up to 2000% in humans.
Piracetam [, Wikipedia/Piracetam, Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension, IAAS; Links/Piracetam composition, Images/Piracetam Molecule]. Piracetam is used for lipofuscin removal, and is a smart drug, 4s. Also see Aniracetam [IAAS, Links] and Anacervix [IAAS, Links], which contains Piracetam with a vasodilator. A more powerful version of Piracetam (x8) is available from Iron Dragon and other vendors as Pramiracetam [Wikipedia/Pramicetam].
Plasma (Encyclopedia)
Plasmids [Wikipedia/Plasmid, Links/Plasmids, Images, Video, Papers, Patents, Books, Amazon, The Plasmid Genome Database, Invitrogen, Links/Plasmid Design, Links/Plasmid Engineering Technology, Links/Plasmid Transfection Techniques, Links/Plasmid Transfection with Cationic Liposomes, Links/Cationic Transfection Reagents, Links/electroporation of plasmids, Links/NEON plasmid electroporation, Links/plasmid degradation in dividing cells, Links/fluorescent labeling of plasmids]. See also Transfection, Plasmid transfection with liposomal sprays, plasmid transfection by injection, and oral plasmid transfection. One correspondent who wrote in reported taking plasmid DNA by orally downing a brew including liposomes formed from a cationic transfection reagent. Plasmid DNA enters the cell by liposomal endocytosis and may have a half-life on the order of days or weeks measurable using fluorescent protein bioscience techniques [Index]. Plasmid DNA expressing c-Myc activates hTERT nicely, according to Horikawa, I, Cable, P.L., Afshari, C., and Barrett, J.C. (1999) Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene, Cancer Research, Vol 59, Issue 4, 15 February 1999, pp 826-830. Plasmids have been constructed by adding the hTR coding sequence to the hTERT coding sequence that were very effective in producing active human telomerase. The transcription of fragments of hTR in such plasmids has been researched, rather like gene or chromosome knock-out experiments, so that a section spanning hTR nucleotides 10-159 turned out to be sufficient for producing an active form of telomerase (Klapper, Parwaresch, and Krupp, 2001). Plasmids may be engineered for industrial production of recombinant proteins [Images, Video, Papers, Patents, Books] by adding gene expression controls used by cytomegalovirus, or by other enhancers, and by producing the protein in CHO cells or HEK293 cells nourished with peptones. See pPK-CMV Expression Vectors and Vectors for High-Level Gene Expression. Also see transfection techniques for industrial production of recombinant proteins [Images, Video, Papers, Patents, Books].
Plasmid Expression Vectors [Links, Images, Video, Papers, Patents, Books; Wikipedia/Expression vector, Links/Expression vectors, Images, Video, Papers, Patents, Books; Wikipedia/Vector_(molecular_biology)]. See also Plasmids, Transfection and Transfection Reagents. See Biocompare's Vectors for Inducible Control of Gene Expression.
Plastoquinone Derivatives [Links/Plastoquinone Derivatives, Images, Video, Papers, Patents, Books; Links/Mitochondrially Targeted Plastoquinone Derivatives, Images, Video, Papers, Patents, Books]. Mitochondrially targeted plastoquinone derivatives as anti-senescence drugs have extended mouse lifetimes by 30%. This stems from the work of Vladimir Skulachev in Russia on chemicals that target mitochondria when ingested and work as antioxidants to soak up the free radicals that mitochondria produce. Similar results have been achieved in the USA with catalase and genetic engineering, according to a February 2009 analysis in Fight Aging!. See mitochondrially targeted anti-senescence drugs [Index, Links/Mitochondrially targeted anti-senescence drugs, Images, Video, Papers, Patents, Books].
Platelet Aggregation Inhibitors [Links/Platelet aggregation inhibitors, Images, Video, Papers, Patents, Books, LifeExtension; Wikipedia/Antiplatelet_drug; Links/Anticoagulants, Papers, Patents, Books, LifeExtension, Wikipedia/Anticoagulant_drug; Wikipedia/Thrombolytic_drug]. Platelet aggregation inhibitors include:
Aspirin [Aspirin as a platelet aggregation inhibitor],
Fish oil [Fish oil as a platelet aggregation inhibitor],
Forskolin [Forskolin as a platelet aggregation inhibitor],
Garlic [Garlic as a platelet aggregation inhibitor],
Ginkgo biloba [Ginkgo Biloba as a platelet aggregation inhibitor],
PycnogenolTM [Pycnogenol as a platelet aggregation inhibitor],
Quercetin [Quercetin as a platelet aggregation inhibitor],
Rutin [Rutin as a platelet aggregation inhibitor],
Resveratrol [Resveratrol as a platelet aggregation inhibitor].
Platelet aggregation inhibitors are useful in controlling cardiovascular disease, stroke, heart attack, thrombus formation and embolisms. They are often used together with vasodilators, anticoagulant drugs, and thrombolytic drugs. See also Varicose Veins.
Pluripotent Stem Cells (iPS) [Links/Pluripotent stem cells, Images, Video, Papers, Patents, Books, LifeExtension, Amazon, LibCong; Links/Induced Pluripotent stem cells, Images, Video, Papers, Patents, Books, LifeExtension, Amazon, LibCong]. Pluripotent strem cells can be produced by transcription factors taken out of the egg cell in Nuclear Reprogramming [Index, Links, Images, Papers, Patents, Books]. Harvested skin cells may now be reprogrammed as pluripotent stem cells [Papers], so that treatment is autologous: the patient recieves stem cells (8) based on his own DNA. Thus, we may be able to produce human stem cells for life extension applications in this manner (8). These cells may be treated with telomerase activators (7) hTERT plasmids, or zinc finger nucleases for targeted genome editing prior to implantation, so that youthful stem cells will be available for rejuvenation applications. On the other hand, such treatment may be confined to after transplantation. Note that telomerase activators such as ethanol and water astragalus extracts, astragaloside IV, cycloastragenol, TA-65, and others boost adult stem cells and provide them in rejuvenated form for application to less difficult cases. Cell culture telomerase activation may be applied in vivo using viral transfection techniques to stem cell cultures (equipping them with additional hTERT, for instance) before the cells are transplanted into the patient. This is usually done instead of attempting to treat cells in external cultures with small-molecule telomerase activators prior to transplantation. Experiments are done on external cell cultures with lentivirus transfection technique, adenovirus transfection technique, associated adenovirus AAV transfection technique, and new methods based on targeted genome editing with zinc-finger nucleases using liposomal transfection technologies.
PML Bodes [Diagram of PML body proteins, Links, Images, Video, Papers, Patents, Books; Links/Promyelocytic Leukemia Protein, Images, Papers, Patents, Books; Links/Nuclear Dots, Images, Papers, Patents, Books; Index/Cajal Bodies; The Nucleus and Subnuclear Domains (Links, Books)].
The Cellular Nucleus. "The "guardian of the genome," p53, is at work in the PML bodies [Papers, Books], which are often adjacent to the Cajal bodies. In the PML body, the telomeres are being checked, repaired and capped [Papers, Books]." - CrackAging/Aging/telomeres-and-telomerase. Like the Cajal bodies, the PML bodies are located in the cellular nucleus outside the nucleolus. See Cristiano Marinelli (2011), Role of PML in telomere metabolism of normal and cancer cells (online direct), PADIS, Sapienza Universita di Roma, 2011. See also Graham Dellaire and David P. Bazett-Jones (2004), PML nuclear bodies: dynamic sensors of DNA damage and cellular stress, Bioessays, 26:963-977. Emma Langley, Mark Pearson, Mario Faretta, Uta-Maria Bauer, Roy A. Frye, Saverio Minucci, Pier Giuseppe Pelicci and Tony Kouzarides (2002), Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence, The EMBO Journal (2002) 21, 2383 - 2396. Valentina Fogal, Monica Gostissa, Peter Sandy, Paola Zacchi, Thomas Sternsdorf, Kirsten Jensen, Pier Paolo Pandolfi, Hans Will, Claudio Schneider, and Giannino Del Sal (2000), Regulation of p53 activity in nuclear bodies by a specific PML isoform, The EMBO Journal (2000) 19, 6185 - 6195.

Press for Mortality Charts.
Leading Causes of Death in New York State

Pneumonia [Wikipedia/Pneumonia, Links/Pneumonia, Images, Video, Papers, Patents, Books, LifeExtension; Antibiotics, Index/Garlic; Links/Chronic Lower Respiratory Disease, Images, Video, Papers, Patents, Books, LifeExtension; Wikipedia/Asthma, Links/Asthma, Images, Video, Papers, Patents, Books, LifeExtension; Wikipedia/Pollens, Links/Pollens; Images/Pollen Maps; Links/Antihistamines, Links/Decongestants, Links/Bronchodilators]. Many old people die of pneumonia, especially in the spring, when pollen counts are high. Jack Lalanne died at 96 this spring 2011 of pneumonia. My grandfather Green died in the spring of 1973 at age 83 from pneumonia, in a high-pollen region of south Texas. Literature on life extension with astragalosides in China describes life-extended old people finally perishing from whooping cough. Old people are more vulnerable to respiratory diseases. Perhaps breathing a fine inhalant mist of antioxidants, arginine (for nitric oxide), coQ10, PQQ, testosterone, and/or some effective telomerase activator could strengthen old lung tissue against failure. On the other hand, the fault often lies with an immunosenescent immune system, which may have had its white blood cell average telomere lengths reduced by prior infections. Allergic responses to pollens may be a factor. "Cigarette smoke interferes with many of the body's natural defenses against pneumonia." - Wikipedia/Pneumonia. The same may be true of spring pollens [Links, Images, Papers, Patents, Books]. Garlic and other antibiotics provide effective cures for pneumonia [Patents, Books].
Policosanol [Links/Policosanol, Images, Video, Papers, Patents, Books, LibCong, LifeExtension]. Policosanol, found naturally in beeswax and sugar cane, is effective at reducing blood lipid levels [LEF] for people with high cholesterol. Policosanol treatment improves outcomes in ischemic stroke, and can prevent arterial wall thickening [LEF] and endothelial damage [LEF] when given with omega-3 fatty acids.
Poly (ADP-ribose) polymerase (PARP) [Links, Images, Video, Papers, Patents, Books, LibCong/PARP, Amazon, LifeExtension]. PARP is a DNA repair polymerase (10) enhanced by combined supplementation of nicotinamide, zinc, and carotenoids (Nicoplex). See Sheng Y, Pero RW, Olsson AR, Bryngelsson C, Hua J., 1998: DNA repair enhancement by a combined supplement of carotenoids, nicotinamide, and zinc, Cancer Detection and Prevention, 1998;22(4):284-92.
Polygonum Cuspidatum Root [IndexJ/Japanese Knotweed, Japanese_Knotweed/Polygonum Cuspidatum Root, Links, Video, Images, Papers, Patents, Books, Amazon, LifeExtension, Benefits of Resveratrol]. Japanese Knotweed [Links, Images, Video, Papers, Patents, Books, LifeExtension], resveratrol [Wikipedia, Links, Papers, Patents, Books, LifeExtension], (0).
Polyphenols [anti aging polyphenols, Wikipedia, Links/polyphenols and aging, Papers, Patents, Books, LibCong/polyphenols, LifeExtension/polyphenols, LifeExtension/polyphenols and aging]. Dietary Polyphenols [as Telomerase Inhibitors] - tea polyphenols, chocolate polyphenols, apple polyphenols. "Degraded dietary polyphenols are potent telomerase inhibitors". Telomerase inhibitors include not only EGCG (found in green tea), but also epicatechin and quercetin, myricetin, naringin, naringinen, and biochanin A. Cacao is a telomerase inhibitor according to Terraternal, no doubt because of its abundance of polyphenols, the flavonoids and flavinols including catechins, epicatechins, and procyanidins. See Imad Naasani, Fujiko Oh-hashi, et al., (2003), Blocking Telomerase by Dietary Polyphenols is a Major Mechanism for limiting the growth of Human Cancer Cells in Vivo, Cancer Research, Feb 15, 2003, 63: 824. This is impacting to our telomere lengthening program of 30-day cycles of 15 days telomerase activation ON, 15 days telomerase inhibition ON. Polyphenols including cocoa beverages or chocolate presently taken for antioxidant protection should be dropped during the first 15 days to avoid interference with telomerase activation during the first part of the cycle. Polyphenols should be taken only during the 2nd 15-day period, when telomerase inhibitors are applied. This should result in a faster rate of telomere growth to support rejuvenation and more youthful patterns of gene expression. This has some impact on diet during our telomere-lengthening rejuvenation program for 30-day cycles of 15 days of telomerase activation followed by 15 days of telomerase inhibition. See polyphenol-free foods. "The main source of polyphenols is dietary.... For example, most legumes; fruits such as apples, blackberries, blueberries, cantaloupe, cherries, cranberries, grapes, pears, plums, raspberries, and strawberries; and vegetables such as broccoli, cabbage, celery, onion and parsley and honey are rich in polyphenols. Red wine[4], chocolate, green tea, olive oil, bee pollen and many grains are sources. Ingestion of polyphenols occurs by consuming a wide array of plant foods; correspondingly, the role of dietary supplements as a method of realizing these health benefits is the subject of considerable discussion." - Wikipedia/Polyphenol antioxidant See Claudine Manach, Augustin Scalbert, Christine Morand, Christian Rémésy and Liliana Jiménez, (2004), Polyphenols: food sources and bioavailability, American Journal of Clinical Nutrition, Vol. 79, No. 5, 727-747, May 2004. "Fruit and beverages such as tea and red wine constitute the main sources of polyphenols. Certain polyphenols such as quercetin are found in all plant products (fruit, vegetables, cereals, leguminous plants, fruit juices, tea, wine, infusions, etc), whereas others are specific to particular foods (flavanones in citrus fruit, isoflavones in soya, phloridzin in apples)." I get the impression that a low polyphenol diet for a telomerase activation phase might be devised from skim milk, fish and meat. However, very little seems to be available on low polyphenol diets or on plants whose degraded polyphenols are NOT telomerase inhibitors. On the other hand, milk seems to bind EGCG and tea polyphenols, so that milk should not be taken when polyphenols should be high. See Debora MacKenzie, (2007), Milk Wrecks the Health Benefits of Tea, New Scientist, 01/09/2007. See also GeneSmart/List of High Polyphenol Foods and Low Polyphenol Foods and High and Low Polyphenol Food Links. Lecithin (see also soy lecithin) enhances the bioavailability of polyphenols, including resveratrol and quercetin.
Polypodium Leucotomos Extract (Life Extension FERNBLOCK ) [Links, Images, Papers, Patents, Books]. Polypodium Leucotomos Extract is taken as an oral anti-sunburn pill and typically used together with a topical sunscreen. It is thought to inhibit harmful ultraviolet rays, quench free radicals, and to be associated with other anti-sunburn physiological elements. An extract of Polypodium leucotomos "was used as a sunburn remedy by native Indians for centuries." See Scott Newman (2013), Avoiding Cancer Risks of Sun Damage, Life Extension Magazine, July 2013.
Polyunsaturated fats (PUFAs) [Anne Collins/Polyunsaturated fats, Wikipedia, Links, Images, Papers, Patents, Books, LibCong, LifeExtension; Links/Foods high in polyunsaturated fats; Links/Oils high in polyunsaturated fats; Links/Foods high in monounsaturated fats; Links/Oils high in monounsaturated fats], [55]. Polyunsaturated fats increase the risk of Age-related Macular Degeneration, while monounsaturated fats [Wikipedia, Books] in meat and milk decrease the risk of macular degeneration (LEF, June 2010; Arch Opthamol. 2009 Nov;127(11)1483-93). High levels of polyunsaturated fats double the rate of macular degeneration in women. (LEF, Diets High in Fat Increase Risk of Macular Degeneration, June 2010; after Arch Opthamol 2009 Nov;127(11):1483-93.)
Pomegranate [Links/Pomegranate, Images, Video, Papers, Patents, LifeExtension; Telomerase Activators/Product B/(148) Pomegranate Fruit Extract]. Pomegranates are rich in punicalagins [Links/Punicalagins, Images, Video, Papers, Patents, Books, Patents/Pomegranate, Wikipedia/Punicalagins]. Punicalagins are powerful antioxidants. Pomegranate increases synthesis of nitric oxide (NO), inhibits oxidation of LDL cholesterol, when applied topically, promotes youthfulness in skin, slows PSA (prostate-specific antigen) doubling time (anti-prostate cancer), speeds wound healing when applied topically, inhibits cyclooxygenase(s) and lipoxygenase when applied to skin, increases collagen synthesis by skin fibroblasts, which also synthesize elastin. [LifeExtension, Wikipedia, Links, Books, Books/Pomegranate in NO synthesis, Papers, Links]. Dr. Shiuan Chen at the Division of Tumor Cell Biology at the City of Hope found 10 ellagitannins in pomegranate that can potentially prevent estrogen-responsive breast cancer, and a metabolite of ellagic acid termed urolithin B inhibiting associated breast cancer cell growth. Pomegranates are anticancer. (Dayna Dye, Pomegranate Inhibits Hormone-dependent Breast Cancer Cell Growth, Life Extension Magazine, April 2010.) Note that Pomegranate contains the powerful antioxidant ellagitannin. Pomegranate also upregulates PON-1 (paraoxonase-1, HUGO), an enzyme required for optimal function of artery-cleansing HDL, and down-regulates nuclear factor kappa beta. (See the Julius Goepp article, below, LEF, May 2010.) Recently, Life Extension Magazine (May 2010) has also been heralding Pomegranate Seed Oil [Index] and Pomegranate Flower Extracts [Index]. Pomegranate extracts chelate iron. Pomegranate has the ability to "reverse clinical measurements of systemic atherosclerosis (in both carotid and coronary arteries)." - William Falloon (2013), Misconceptions about Atherosclerosis, Life Extension Magazine, April 2013.
Pomegranate Flower Extracts
[Links/Pomegranate Flower Extracts, Images, Video, Papers, Patents, LifeExtension]. In 2009, studies showed that pomegranate flower extract was 70% effective in reducing hardening of the arteries, while pomegranate fruit extract was 40% effective. (See Julius Goepp, MD, Is Conventional Pomegranate Extract Enough?, Life Extension Magazine, May 2010, p.39). Pomegranate flower extracts were also found to markedly decrease blood lipid and blood glucose levels, and provide "unparalleled protection against type 2 diabetes and many metabolic consequences of obesity". Pomegranate flower extract is useful in the treatment of fatty liver disease. Pomegranate flower extracts improve insulin sensitivity by upregulating the transcription factor PPAR-gamma, and reduce cardiac muscle triglyceride content. Pomegranate flower extract also inhibits the digestive enzyme alpha-glucosidase, which breaks complex carbohydrates down into simple sugars, making it useful in caloric restriction. Furthermore, punicanolic acid in pomegranate flower extracts inhibits the production of TNF-alpha.
Pomegranate Seed Oil
[Links/Pomegranate Seed Oil, Images, Video, Papers, Patents, Books, LifeExtension]. "Pomegranate seed oil offers potent chemoprevention against breast cancer, prostate cancer, and other common human cancers." Pomegranate seed oil inhibits aromatase, which produces estrogen from testosterone. It also inhibits 17-beta-hydroxysteroid dehydrogenase type 1, which converts estrone to estradiol. Pomegrate seed oil facilitates repair of aging skin, modulates immune function, and reduces inflammation.
Postmitotic Cells [Links, Video, Images, Papers, Books, LibCong, Amazon]. For the converse, see mitotically competent cells, above. Postmitotic cells include many varieties of nerve and muscle cell. Mitotically competent cells [Links, Images] include dermal fibroblasts [Index], microglial cells, ect.
Post-Translational Protein Modifications [Links, Images, Papers, Patents, Books; Links/Post-translational protein modifications, Images, Papers, Patents, Books].
Post-translational protein modifications are signals for the accumulation of specific proteins at telomeres during various stages of the cell cycle. These protein modifications include:
(1) Phosphorylation [Links, Images, Video, Papers, Patents, Books; Kinases],
(2) Dephosphorylation [Links, Images, Video, Papers, Patents, Books; Kinase Inhibitors],
(3) Poly-ADP ribosylation [Links, Images, Video, Papers, Patents, Books].
(4) Deribosylation [Links, Images, Video, Papers, Patents, Books].
(5) Acetylation [Links, Images, Video, Papers, Patents, Books; HDAC Inhibitors].
(6) Deacetylation [Links, Images, Video, Papers, Patents, Books; HDACs].
(7) Ubiquitination [Links, Images, Video, Papers, Patents, Books], and
(8) Sumoylation [Links, Images, Video, Papers, Patents, Books].
POT1 [Shelterin/POT1, Science Daily article, Links, Images, Papers, Books, Video; Links/POT1 and the telomere, Images, Papers, Books/POT1 and the telomere]. A protein that protects the single-stranded end of the telomere. See index entries for Telomere T-Loops and the Telosome (Telomere Loop Control Proteins).
PQQ - Pyrroloquinoline Quinone [Links, Images, Video, Papers, Patents, Books, LifeExtension; Images/PQQ molecule; Images/PQQ Supplements; Links/PQQ synthesis, Images, Papers, Patents, Books; Links/PQQ extraction, Images, Papers, Patents, Books; Links/PQQ solubilities; Links/Producing PQQ by natural bacterial fermentation, Images, Papers, Patents, Books; Index/Mitochondrial Biogenesis; Index/Mitochondrial Theory of Aging]. Pyrroloquinoline Quinone, a dark chocolate antioxidant found in cocoa powder at 800 ng/kg, possibly a key factor in the 122-year lifespan of Jeanne Calment, who devoured 5 pounds of chocolate per week. Today Life Extension Foundation markets 20 mg PQQ supplement pills to promote mitochondrial biogenesis [LEF; PQQ Food Concentrations, PQQ Supplements]. [25k]. Cocoa contains a high level of flavonoids [Links], such as catechins [Links] and epicatechin [Index, Links], which have beneficial effect on cardiovascular health [Links]. 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). See Chowanadisai W, Bauerly KA, Tchaparian E, Wong A, Cortopassi GA, Rucker RB (2010), Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression, Journal of Biological Chemistry, 2010 Jan 1; 285(1):142-52. PQQ is a redox cycler [Images, Papers, Patents, Books, LifeExtension]. Quercetin, green tea extracts, and vitamin C are redox cyclers. Redox cyclers blunt the impact of ROS on brain tissue. Note also that PQQ promotes the expression of nerve growth factor (NGF). Pyrrolo-quinoline quinone has the power "to stimulate nerve growth factor, combat stroke, Alzheimer's, and Parkinson's, and speed regeneration of damaged nerve cells". - Michelle Flag (2011), Reverse Brain Cell Death by Growing New Mitochondria, Life Extension Magazine, November, 2011. PQQ protects brain cells from the toxic proteins beta amyloid [Links, Images, Papers, Patents, Books] and alpha synuclein [Images, Papers, Patents, Books] that promote Alzheimer's and Parkinson's. PQQ also improves cardioprotection and provides enhanced immune function, in addition to slowing mitochondrial aging in mammals. PQQ is found in mammalian tissue like an endogenous vitamin for slowing mitochondrial aging in various tissues. See Yamaguchi K, Sasano A, Urakami T, Tsuji T, Kondo K (1993), Stimulation of nerve growth factor production by pyrrolquinoline quinone and its derivatives in vitro and in vivo, Biosci Biotechnol Biochem, 1993 July; 57(7):1231-3. See also Jensen FE, Gardner GJ, Williams AP, Gallop PM, Aizenman E, Rosenberg PA (1994), The putative essential nutrient pyrroloquinoline quinone is neuroprotective in a rodent model of hypoxic/ischemic brain injury, Neuroscience, 1994 September; 62(2):399-406. Zhang Y, Rosenberg PA (2002), The essential nutrient pyrroloquinoline quinone may act as a neuroprotectant by suppressing peroxynitrite formation, European Journal of Neuroscience 2002 September; 16(6):1015-24. Urakami T, Tanaka A, Yamaguchi K, Tsuji T, Niki E (1995-1996), Synthesis of esters of coenzyme PQQ and IPQ, and stimulation of nerve growth factor production, Biofactors, 1995-1996; 5(3):139-46. Adachi O, Moonmangmee D, Shinagawa E, Toyama H, Yamada M, Matsushita K (2003), New quinoproteins in oxidative fermentation, Biochim Biophys Acta 2003 April 11; 1647 (1-2):10-7. See also Michael Downey (2012), Powerful Protection Against Cellular Aging, Life Extension Magazine, October 2012.

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