Index to Anti-Aging Medicine
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G
GABA (gamma-aminobutryic acid) [Wikipedia/Gamma-Aminobutryric_acid, Links/Gamma-aminobutyric acid, Images, Video, Papers, Patents, Books, LifeExtension; Links/GABA, Images, Video, Papers, Patents, Books, LifeExtension, Ray_Sahelian/GABA]. GABA calms the patient. "Drugs that.. increase the available amount of GABA typically have relaxing, anti-anxiety, and anti-convulsive effects." - Wikipedia/Gamma-Aminobutryric_acid. GABA is an amino acid and an inhibitory neurotransmitter which substantially elevates HGH when 3 grams are taken prior to lifting weights, when GABA can improve HGH levels by a factor of 4 to 5. GABA may seem to activate the transcription of hTERT via HGH as measured by Gomez and Garcia, based on their count of an increased number of hTERT mRNA transcripts after exitation with HGH. CHECK: GABA activates hTERT transcription; GABA activates telomerase. It has been determined that GABA decreases telomerase activity in HeLa cancer cells. (See The Effect of Malate and Gamma-Aminobutyric Acid on the Activity of Telomerase in Hela Cells from the Tumor Research Center.) "GABA regulates the proliferation of neural progenitor cells, their migration and differentiation, the elongation of neurites, and the formation of synapses. GABA also regulates the growth of embryonic and neural stem cells. GABA can influence the development of neural progenitor cells via brain-derived neurotrophic factor [Images] expression. GABA activates the GABAA receptor, causing cell cycle arrest in the S-phase, limiting growth." - Wikipedia/Gamma-Aminobutryric_acid. "GABA does not cross the blood-brain barrier...(although) at least one study suggests that orally administered GABA increases the amount of HGH."
Galectin-3 and Modified Citrus Pectin (Encyclopedia).
Gallic Acid [Links, Images, Video, Papers, Patents, Books, LifeExtension; Phytochemicals/Gallic Acid, Measurement Ref]. Gallic acid is an antioxidant and an angiogenesis inhibitor found in gallnuts, grapes, grape seed extract, tea, sumac, witch hazel, hops, oak bark, and acacia bark extract. Gallic acid is promoted as an anticancer nutraceutical. Gallic acid from grape seed extract [Links] is thought to be anti-proliferative, pro-apoptotic, and anti-angiogenic in acting against prostate cancer.
Gallstones (Cholelithiasis) [Wikipedia/Cholelithiasis, Links, Images, Video, Papers, Patents, Books, LifeExtension; Wikipedia/Gallbladder, Links, Images, Video, Papers, Patents, Books, LifeExtension, WebMD; Signs and Symptoms of Gallbladder Problems]. "Cholecystectomy (gallbladder removal) has a 99% chance of eliminating the recurrence of cholelithiasis. Surgery is only indicated in symptomatic patients. The lack of a gallbladder may have no negative consequences in many people. However, there is a portion of the population — between 10 and 15% — who develop a condition called postcholecystectomy syndrome which may cause gastrointestinal distress and persistent pain in the upper-right abdomen (due to Sphincter of Oddi dysfunction), as well as a 10% risk of developing chronic diarrhea." - Wikipedia/Cholelithiasis. Gallstones are more prevelant in females before menopause and over-40 people, and in North and South Amerindians... Melatonin tends to prevent gallstones, as does a low-cholesterol and high-fiber diet, whole-grained bread, folate (folic acid), magnesium, calcium, and vitamin C. Gallstones may be promoted by excessive consumption of alcohol. See Mi LJ, Mak KM, Lieber CS (2002), Attenuation of alcohol-induced apoptosis of hepatocytes in rat livers by polyenylphosphatidylcholine (PPC) [LEF abstract], Alcohol Clin Exp Res 2000 Feb;24(2):207-12. See also polyenylphosphatidylcholine [Links, Images, Papers, Patents, Books], gallstone therapy [Links, Images, Papers, Patents, Books], LEF Liver Cirrhosis Abstracts, and G. Paumgartner, J. Pauletzki and M. Sackmann (1994), Ursodeoxycholic Acid Treatment of Cholesterol Gallstone Disease [Abstract], Scandinavian Journal of Gastroenterology, 1994, Vol. 29, No. s204 , Pages 27-31. [Links/Ursodeoxycholic Acid (Ursodiol dissolves certain kinds of gallstones in the body)].
Gamma Tocopherol (pron: Gamma Tow-Cougher-All) [Links, Images, Video, Papers, Patents, Books, LifeExtension], a form of Vitamin E. Unlike alpha tocopherol [Links, Images, Video, Papers, Patents, Books, LifeExtension] alone (the usual Vitamin E supplied), gamma tocopherol quenches peroxynitrite [Wikipedia, Links, Images, Video, Papers, Patents, Books, LEF], which plays a major role in age-related decline. Take at least 200 mg/day. It works even betterwith sesame lignans, which make it up to 25% more effective. Take at least 20 mg/day. See Foods Highest in Gamma Tocopherol. "Gamma tocopherol is abundant in nuts such as walnuts and pecans, and in peanuts (actually a legume, not a nut). Seed oils such as corn oil, soybean oil and sesame oil, are also rich sources of gamma tocopherol....Sesame oil...(also) contains sesamin, a sesame lignan." - LEF/Newly Discovered Benefits of Gamma Tocopherol, LEF, Oct. 2002. Lesser sources of gamma tocopherol include oregano, green peppers, red peppers, yellow onions, ground cinnamon, and wild raspberries. See Index/Vitamin E. Note that walnuts also contain the essential fatty acids linoleic acid (a precursor of elastase-inhibiting ceramides promoting skin elasticity) and alpha linolenic acid in addition to gamma tocopherol. Note that gamma tocopherol blocks the expression of heat shock proteins such as HSP90, so that it should not be taken while trying to upregulate hTERT transcription to activate telomerase.
Gamma Tocotrienol [Index/Tocotrienols; Wikipedia/Gamma Tocotrienol, Telomerase Activators/Gamma Tocotrienol (123), LifeExtension, Links/Gamma Tocotrienol, Images, Video, Papers, Patents, Books; Gamma Tocotrienol Supplements, Gamma Tocotrienol Skin Creams; Images/Tocotrienol-rich fraction supplements with alpha-tocopherol from palm oil; Images/Tocotrienol-rich fraction skin cream with alpha-tocopherol from palm oil; Sources of Gamma Tocotrienol; Preparation of Gamma Tocotrienol (Papers, Patents)]. Annatto is an excellent source of delta- and gamma tocotrienol without interfering tocopherols. See, for instance, Solaray Annatto Tocotrienols and Annatto Tocotrienol supplements [Images]. See Suzana Makpol, Azrina Zainal Abidin, Khalilah Sairin, Musalmah Mazlan, Gapor Md Top, and Wan Zurinah Wan Ngah (2010), Gamma-Tocotrienol prevents oxidative stress-induced telomere shortening in human fibroblasts derived from different aged individuals, Oxidative Medicine and Cellular Longevity, 3(1); Jan-Feb 2010. "Tocotrienols are concentrated in cereal grains such as oat, barley, and rye, rice bran, with the highest level found in crude palm oil." - Wikipedia/tocotrienol. See Suzana Makpol, Azalina Zainuddin, Kien Hui Chua, Yasmin Anum Mohd Yusof, and Wan Zurinah Wan Ngah (2012), Gamma-tocotrienol modulation of senescence-associated gene expression prevents cellular aging in human diploid fibroblasts [NCBI DOC], Clinics (Sao Paulo) 2012 February; 67(2): 135–143, and also Makpol S, Durani LW, Chua KH, Mohd Yusof YA, Ngah WZ (2011), Tocotrienol-rich fraction prevents cell cycle arrest and elongates telomere length in senescent human diploid fibroblasts, [NCBI DOC], Journal of Biomedicine and Biotechnology 2011 Mar 30. Gamma tocotrienol [List] reduces expression of collagenase from senescent fibroblasts, protecting the extracellular matrix, and has favorable impact on gene expression in both senescent and normal fibroblasts, tending to oppose aging. Tocotrienol-rich fraction containing alpha-tocopherol and tocotrienols alpha, beta, gamma, and delta from rice bran, palm oil, oat, or barley, tends to produce telomerase activity in senescent fibroblasts, lengthen telomeres, restore fibroblast morphology, and restart the cell cycle. [Images/Tocotrienol-rich fraction supplements with alpha-tocopherol from palm oil; Images/Tocotrienol-rich fraction skin cream with alpha-tocopherol from palm oil]. Gamma tocotrienol has lengthened animal lifetimes up to 18%.
Garlic [Garlic as telomerase activator (178), Wikipedia, WebMD/Garlic, LifeExtension, Garlic Central, Links/Garlic, Images, Video, Papers, Patents, Books; Links/anticancer garlic, Images, Video, Papers, Patents, Books, Papers/garlic and telomere lengthening; Genital Warts; toxicity, dosage; Recipes/Garlic]. Garlic behaves like a Hayflick-Limit extending telomerase inducer (178) for normal cells, evidently by promoting hTERT mRNA transcription with the HDAC inhibitors diallyl disulfide and allyl mercaptan from crushed garlic allicin, as measured in 1994 for normal, non-cancerous human fibroblasts by Suresh I. Rattan and his European school [3]. This is is probably true for all non-cancerous human cells. Furthermore, garlic improves AMPK signaling to stimulate autophagy that consumes cellular junk and reduces triglycerides and glucose in the blood. Allicin from crushed garlic can inhibit telomerase activity and induce apoptosis of gastric cancer cells. Garlic is an anticancer telomerase inhibitor via allicin and is listed as anti-inflammatory. Garlic seems to be an anticancer telomerase activator. Garlic should improve telomerase activation in normal cells from telomerase activators such as TA-65, astragalus, and cycloastragenol working through the MAP kinase pathway or as hTERT mRNA transcriptional activators from exercise, such as HIF-1, by improving transcription of normal cell proteins. Garlic increases the activity of Natural Killer cells of the immune system [2]. See Stomach Cancer. [25c]. Increased intake of garlic reduced risk of certain cancers according to population studies, including cancers of the stomach, colon, esophagus, pancreas, and breast. The higher the amount of raw and cooked garlic consumed, the lower the risk of stomach and colorectal cancer. In another study, higher intakes of onion and garlic were associated with a reduced risk of intestinal cancer. Garlic (with its allicin) is a small molecule telomerase inhibitor [List] for cancer cells. Garlic as an antibiotic (Allicin): Adult dosage: take 3-5 cloves 3x per day after meals, chop up, mix with honey, mustard, or barbeque sauce, add artificial sweetener, and chew; take on soda crackers and wash down with water or juice. A peppercorn salad dressing with extra sweetener mixed with the garlic and taken on soda crackers makes it a treat. Most infections go away after several days of treatment, including facial infections from bad teeth. Note that cancer and Alzheimer's disease can eventually be triggered by TNF-alpha and NF-KB from inflammation associated with such infections, so that garlic is a real life-saver. Garlic is effective against a wide range of bacteria and viruses, including the HIV virus and the HPV virus. There are current 2014 reports that allicin from crushed garlic has been used effectively against all bacteria and viruses that it has been tested on. For effective treatment against HPV genital warts, use apple cider vinegar in cotton applied to the warty tissue for six days, however, and never mind the garlic. This kills the HPV virion and prevents recurrence of the HPV warts. Garlic can kill all friendly bacteria in the intestinal tract when taken orally, including the bacteria that make vitamin K2, which returns calcium to the bones and prevents aortic stenosis. The bacteria must be replaced with probiotics or acidophilus, to avoid yeast infections. Swiss cheese may be a good source for vitamin K2-producing bacteria, as it is a fine source of vitamin K2. (Swiss cheese is traditionally raw, but may be pasteurized. Aging is used to destroy undesired microbial species in Swiss cheese.) A probiotic "active culture" yogurt is often used to replace friendly intestinal tract bacteria. Note that rubber gloves should be worn when cutting and skinning garlic cloves, as otherwise fingertip skin may peel where fresh garlic was handled. Alternatively, dip your fingers in water. Always take garlic raw, since cooking can destroy garlic allicin.
Can garlic cure appendicitis? Garlic is an effective cure for early-stage appendicitis.
Can garlic cure sepsis? "The list of microbes that garlic can slay includes botulism (not necessarily), tuberculosis, diarrhea, staph, dysentery, pneumonia, sepsis and typhoid." from Garlic Infection Fighter and Virus Killer. See also Garlic Treats Cancer [Books] and Garlic Treats Viral Diseases [Books]. It is suspected that garlic is useful against every prokaryotic bacterial infection, including syphylis, gonorrhea, chlamydia, and anthrax. It is not certain that garlic is safe for babies and toddlers.
Note that garlic contains the HDAC inhibitor diallyl disulfide producing the better HDAC inhibitor allyl mercaptan, and seems to be a telomerase inhibitor for cancer cells only, functioning as a telomerase activator (178) for normal cells. Diallyl disulfide increases histone H3 and H4 acetylation in K652 human leukemia cells (a human myeloid leukemia cell line). It may be that crushed garlic (which contains diallyl disulfide) can markedly improve the transcription of hTERT mRNA. See longevityscratchpadlog.html for the associated searches. We find that garlic increases the Hayflick Limit [Images, Papers, Patents, Books, LEF] from 49 cell divisions to more than 55 for normal fibroblasts [3]. Garlic use must be cycled as garlic cannot be taken every day, to avoid yeast infections and to restock vitamin K2-producing bacteria with probiotic cheese and yogurt. Without a greenhouse, garlic is usually planted on the shortest day (Winter Solstice) and harvested around the longest day (Summer Solstice).
Garlic is a supplement that improves Natural Killer cell (NK cell) activity, improving immune system defense.
Garlic Odor Repulsive
Finally, garlic is a "therapeutic" substance that can make you smell bad, and its fumes are a sex repellant that can get you shown out of a study hall, whether you smell it or not. It is best as a stay-at-home remedy for an infection to be cured in 3 days. Chronic use to equip you with youthful, expanded euchromatin to improve transcription of hTERT requires masking garlic odor with a selection or two from parsley, green tea, peppermint tea, mint, fennel, cloves, anise seeds, oral breath sprays, milk, coffee beans, and cologne.
References
[1] Butt MS, Sultan MT, Butt MS, Iqbal J. (2009),
Garlic: nature’s protection against physiological threats,
Crit Rev Food Sci Nutr 2009 Jun;49(6):538-51. [Papers/Garlic protection, Books]
[2] Ishikawa H, Saeki T, Otani T, et al. (2006),
Aged garlic extract prevents a decline of NK cell number and activity in patients with advanced cancer,
J Nutr 2006 Mar; 136(3 Suppl):816S-20S.
[3] Svendsen, L., Rattan, S.I., Clark, B.F. (1994), Testing garlic for possible anti-ageing effects on long-term growth characteristics, morphology and macromolecular synthesis of human fibroblasts in culture,
Journal of Ethnopharmacology, (1994 July 8) 43(2):125-33. Reference by [4].
[4] Garlic, Nature's Perfect Prescription, by C. G. Hullquist, page 69.
Gastric Cancer (Gastrointestinal Cancer) [Wikipedia, Links/Gastric Cancer, Images, Video, Papers, Patents, Books, LifeExtension; Links/Gastrointestinal Cancer, Images, Video, Papers, Patents, Books, LifeExtension; Cancer; Carcinogens; Anticancer Nutraceuticals, Apoptosis, Telomerase Inhibitors; Anticancer Telomerase Activators; Metastasis, NFkB, NFkB Inhibitors, Angiogenesis Inhibitors]. Gastric cancer is the 2nd leading cause of cancer death worldwide. It is linked to the pathogen Heliobacter pylori [Images], which causes stomach ulcers. N-Acetyl Cysteine (NAC) is useful in defending the body against H. pylori. Garlic can be used to induce apoptosis in gastric cancer cells. Overconsumption of alcohol can lead to liver cancer, pancreatic cancer, colorectal cancer, gastrointestinal cancer, and breast cancer. See Stomach Cancer and Carcinogens.
GC-Mass (Gas Chromatography/Mass Spectrometry) [Links, Images, Video, Papers, Patents, Books, Amazon]. See Instrumental Analysis.
GDF11 (Encyclopedia).
Gene [Wikipedia/Gene, Links/Genes, Images, Video, Papers, Patents, Books, Amazon/Genes; Links/Gene Design, Images, Video, Papers, Patents, Books; Gene Design at DNA2.0; Index/Cancer Genes, Links/Proto-oncogenes, Images, Video, Papers, Patents, Books; Index/SNPs, Index/Gene Therapy, Index/Zinc Finger Nucleases; Links/Oncogenes; Images, Video, Papers, Patents, Books; Wikipedia/Chromosome, Links/Chromosomes, Images, Video, Papers, Patents, Books, Amazon; Wikipedia/Cytogenetics, Links/Cytogenetics, Images, Papers, Patents, Books, Amazon; Wikipedia/Chromosome microdissection, Links, Images, Papers, Patents, Books, Amazon; Glossary of Gene Expression Terms]. See also OMIM (External Links), Genatlas, GeneCards, GOpubmed, H-InvDB, QuickGO, Reactome, iHOP, Wikigenes, Affymetrix, SABiosciences, Biocarta Pathways/Genes, PharmGKB - Pharmacogenomics [Index] Databases, Biocompare/Genes by Signaling Pathway, Nature/Human Genome, NIH/Genes and Disease, NCBI/Human Genome Resources, and the HUGO Gene Nomenclature Committee (HGNC) with
Gene Families(B = HUGO Gene Families with Supplemental Links: GHR/Browser).
Human Chromosome 1 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 2 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 3 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 4 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 5 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 6 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 7 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 8 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 9 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 10 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 11 [Ornl, GHR, Wiki, Links, Images, Patents, Books, Amazon, Nature, HUGOv].
Human Chromosome 12 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 13 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 14 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 15 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 16 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 17 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 18 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 19 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 20 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 21 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome 22 [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, Nature, HUGOv].
Human Chromosome X [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, HUGOv].
Human Chromosome Y [Ornl, GHR, Wiki, Links, Images, Papers, Books, Amazon, HUGOv].
See also Bibliography/The Genome of Homo Sapiens, Index/The Human Genome, and Wikipedia/Category: Molecular Genetics. For DNA plasmid applications, see Wikipedia/Plasmid, Links/Plasmids, The Plasmid Genome Database, Invitrogen, Links/Plasmid Design. Transfection, Targeted Genome Editing and Protein Targeting. The average human gene contains 9 exons coding for the gene protein and 8 introns that are spliced out from the mRNA transcript before the gene is translated into the protein or protein subunit. The gene is typically distributed over 30,000 base pairs, with introns comprising more than 90% of the base pairs in the original genomic code for the gene. Note that about 2600 proteins have DNA-binding domains [Images] and are transcription factors (activators or repressors) constituting about 10% of the genes in the human genome. Transcription factors act by binding to gene promoters. See gene promoter architecture [Images, Video, Papers, Books]. See Gene Synthesis Software [Links, Images, Video, Papers, Patents, Books; Links/Gene Synthesis, Images, Video, Papers, Books]: DNA2.0 (Free).
See International Human Genome Sequencing Consortium, Initial sequencing and analysis of the human genome. Nature 409: 860-921, and Venter, J.C. and 273 others (2001), HUGO. The sequence of the human genome. Science 291: 1304-1351. Note that genes span 25% of human genomic DNA, although only 1.5% of it codes for exons describing protein domains. Genes are isolated in cDNA obtained by reverse transcription from messenger RNA used by ribosomes to produce proteins. That is, 23.5% of human genomic DNA codes for introns removed by RNA splicing. Introns are excised from the transcribed messenger RNA (mRNA) used to make proteins for the cell or cDNA by reverse transcription using reverse transciptase (RNA-dependent DNA polymerase) used by RNA retroviruses. 75% of human genomic DNA is intergenic noncoding DNA. The introns (which end at their 5' end with a short consensus sequence [CAG|GUAAGU]) are removed by a two-step process of sequential trans-esterification reactions which expells an RNA intron as an excised intron lariat. 20% of the human genome is composed of "gene deserts" of 500,000 or more nucleotides without genes. Note that to be expressed, a gene in a designer plasmid transfected into a cell usually requires a species-specific promoter sequence and a consensus sequence at the translation start site termed the Kozak sequence (GCCACCATGG) including the ATG initiation sequence. See the DNA triplet code for amino acids (RNA triplet code for amino acids) determined in 1966 featuring the STOP codons UAA, UAG, and UGA that terminate translation. (David A. Micklos, Greg A.Freyer, with David A.Crotty, DNA Science, 2nd edition, Cold Spring Harbor Press, 2003).
Gene Ontology [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon].
Genes and Senescence [Longevity Genes, Cellular Senescence, Replicative Senescence, Senescence, Telomere Loop Control Proteins, Mammalian Telomere Protein Factors, The Telomere Interactome; HUGO Gene Families, Refs_7.8].
Genes associated with the senescent state [Links, Images, Video, Papers, Patents, Books].
(1) Cell cycle inhibitors and cellular senescence [Links, Images, Video, Papers, Patents, Books].
___The CIP-KIP family of kinase inhibitors [Links, Images, Video, Papers, Patents, Books].
______p21 [Links, Images, Video, Papers, Patents, Books].
______p16INK4a [Links, Images, Video, Papers, Patents, Books].
_______P16INK4a is a senescence biomarker.
(2) SAG (senescence-associated gene) [Links, Images, Video, Papers, Patents, Books].
___SAG is a biomarker of cellular senescence.
(3) ECM (extracellular matrix) degrading matrix metalloproteinases.
___[Index/matrix metalloproteinases, Links, Images, Video, Papers, Patents, Books].
___Collegenase [Index/Collagenase, Links, Images, Video, Papers, Patents, Books].
______Attacks collagen.
___Stromelysin [Links, Images, Video, Papers, Patents, Books]. Attacks elastin.
___Tissue plasminogen activator (t-PA)
_____[Links, Images, Video, Papers, Patents, Books; GeneCards].
(4) Promyelocytic leukemia-associated protein (PML) [Links, Images, Video, Papers, Books].
(5) Senescence-associated beta galactosidase (SA-beta-gal).
____[Links, Images, Video, Papers, Patents, Books].
___Senescence-associated beta galactosidase is a biomarker of cellular senescence.
(6) Plasminogen activator inhibitor-1 (PA-1) [Links, Images, Video, Papers, Patents, Books].
___PA-1 is a downstream target of p53 necessary to maintain cell cycle arrest in
___Human Diploid Fibroblasts (HDFs, [Images]).
(7) hTERT, the catalytic component of telomerase
___[hTERT, hTERT promoter, hTERT phosphorylation;
___Telomerase activators (List, Notes), Telomerase Inhibitors (List), (7)].
___hTERT gene [Links, Images, Video, Papers, Patents, Books].
(8) hTR, the RNA component of telomerase.
___Codes for 5'-GGTTAG-3' hex repeats in the telomerase holoenzyme.
___hTR RNA [Links, Images, Video, Papers, Patents, Books].
(9) Dyskerin [Index, Links, Images, Video, Papers, Patents, Books].
___The telomerase complex includes hTERT, hTR RNA, and Dyskerin.
(10) Tumor suppressor genes [Links, Images, Video, Papers, Patents, Books].
___p53 [Index, Links, Images, Video, Papers, Patents, Books] and
___Rb (retinoblastoma) [Links, Images, Video, Papers, Patents, Books].
(11) The caveolin genes for caveolin-1, -2, and -3 establish the senescent phenotype.
___11.1. CAV1 [OMIM/CAV1, Links, Images, Papers, Patents, Books; Therapy].
___4.1. CAV1 [OMIM/CAV1, Links, Images, Papers, Patents, Books; Therapy, Refs9].
_____Caveolin-1 expression is upregulated by FOXO transcription factors (Refs10),
_____and results in cell membrane modifications producing the senescent phenotype,
_____the hyporeactivity of the senescent cell, and its insensitivity to growth factors.
_____Folic acid (vitamin B9) stimulates the PI3K/AKT pathway to down-regulate
_____caveolin-1 by sequestering FOXO factors away from the nucleus.
_____Downregulation of caveolin-1 using IGF-1, insulin, exercise, or cAMP from forskolin,
_____exercise, glycyrrhiza, epinephrine, or schizandra, or via caveolin-1 inhibitors such as
_____N-[2-(Cyclohexy-Loxyl)-4-Nitrophenyl]-Methanesulfonamide can restore the
_____youthful cellular phenotype
and properties of non-senescent cells. Pantethine
_____(vitamin B5), lowers LDL cholesterol to reduce caveolin-1 levels. See caveolae.
___11.2. CAV2 [OMIM/CAV2, Links, Images, Papers, Patents, Books].
___11.3. CAV3 [OMIM/CAV3, Links, Images, Papers, Patents, Books].
(12) FOXO genes upregulate caveolin-1, tending to produce cellular senescence.
_______[Wikipedia/FOX_proteins, Links, Images, Papers, Patents, Books].
_______(A. Pieter J. van den Heuvel, Almut Schulze, and Boudewijn M. T. Burgering, 2005).
___12.1 FOXO3a upregulates caveolin-1, finally producing senescent cells.
______[OMIM/FOXO3a, Links, Images, Papers, Patents, Books].
___12.2 FOXO4 upregulates caveolin-1, finally producing senescent cells.
______[OMIM/FOXO4, Links, Images, Papers, Patents, Books].
(13) Homeobox transcription factors.
___13.1 NANOG overexpression decreases caveolin-1 and FOXO3a mRNA expression.
______[OMIM/NANOG, Links, Images, Papers, Patents, Books].
(14) Cyclin-Dependent Kinase Inhibitors
___14.1 p16INK4A induced G1 cell cycle arrest can increase caveolin-1 expression.
______[OMIM/P16INK4a, Wiki, Links, Images, Papers, Patents, Books].
(15) AKT kinase genes.
____AKT phosphorylates FOXO transcription factors, sequestering them away from
____the cellular nucleus, inhibiting caveolin-1 transcription to inhibit senescence.
____"In the absence of growth factor signaling and Akt activity, FOXO is released from
____14-3-3 and translocates to the nucleus, stimulating transcription of genes that
____inhibit cell proliferation and induce cell death.
" - Geoffrey M. Cooper and
____Robert E. Hausman, The Cell: A Molecular Approach, 4th edition (2007), p. 624.
____15.1 AKT1 [OMIM/AKT1, Wiki, Links, Images, Papers, Patents, Books].
____15.2 AKT2 [OMIM/AKT2, Wiki, Links, Images, Papers, Patents, Books].
____15.3 AKT3 [OMIM/AKT3, Wiki, Links, Images, Papers, Patents, Books].
(16) Mammalian Telomere Protein Factor Genes
[Links, Images, Video, Papers, Books, LifeExtension, Amazon;
Links/Telomere plus Telomeric Proteins, Images, Video, Papers, Books, LifeExtension, Amazon;
hTERT promoter, hTERT protein phosphorylation].
_(A) The Shelterin Complex (The Telosome [Index])
___TRF1 [Index, Links, Images, Video, Papers, Books],
______TRF1 is a telomere loop closure protein. TRF1 poly(ADP-ribosylation) by Tankrase 1
______on a NAD substrate opens the t-loop for access by telomerase,
______freeing TRF1 from the opened telomere loop. TRF1 is then ubiquitinated by a proteasome.
______Note that niacinamide (nicotinamide) elevates NAD substrate levels.
______Eventually, more TRF1 is expressed, resealing the telomere loop.
___TRF2 [Index, Links, Images, Video, Papers, Books],
___TIN2 [Index, Links, Images, Video, Papers, Patents, Books],
___RAP1 [Index, Links, Images, Video, Papers, Patents, Books],
___TPP1 [Index, Links, Images, Video, Papers, Patents, Books],
___POT1 [Index, Links, Images, Video, Papers, Patents, Books],
_(B) Other Telomere Management Proteins.
___Tankyrase 1 [Index, Links, Images, Video, Papers, Patents, Books],
_____Tankyrase 1 is more highly expressed after treatment with Nicotinamide (Niacinamide),
_____which elevates NAD substrate levels for poly(ADP-ribosylation) of TRF1 by tankyrase 1.
_____Phosphorylation of Tankyrase 1 by insulin equips Tankyrase 1, a telomeric PARP,
_____to remove TRF1 from telomere loops, opening the t-loops for telomerase access.
_____Continuous overexpression of Tankyrase 1 enlongates telomeres.
___Tankyrase 2 [Index, Links, Images, Video, Papers, Patents, Books],
___PARP [Index, Links, Images, Video, Papers, Patents, Books],
___the MRN complex [Index, Links, Images, Video, Papers, Patents, Books],
___the RecQ helicase WRN [Index, Links, Images, Video, Papers, Patents, Books],
___the RecQ helicase BLM [Index, Links, Images, Video, Papers, Patents, Books],
___KU70 [Index, Links, Images, Video, Papers, Patents, Books],
___KU86 [Index, Links, Images, Video, Papers, Patents, Books],
___DNA-PK [Index, Links, Images, Video, Papers, Patents, Books],
___ATM [Index, Links, Images, Video, Papers, Patents, Books],
___ERCC1 [Index, Links, Images, Video, Papers, Patents, Books],
___XPF [Index, Links, Images, Video, Papers, Patents, Books],
___RAD51D [Index, Links, Images, Video, Papers, Patents, Books].
_(C) Telomere Docking Protein Genes
___hEST1A [Index, Links, Images, Video, Papers, Patents, Books].
____Binds to hTERT, recuits telomerase holoenzyme.
___RP1A Replication Protein A gene [Index, Links, Images, Video, Papers, Patents, Books].
____Provides hEST1A access to chromosome ends.
Gene Silencing [Wikipedia/Resveratrol, Links/Gene Silencing, Images, Video, Papers, Patents, Books, LibCong, Wikipedia, LifeExtension, Amazon; HDACs, HDAC Inhibitors]. Gene silencing sometimes involves activation of SIRT1 (or SIR2 in animal models) with resveratrol, (0). See Ben Best/Gene silencing in aging [Links, Images, Video, Papers, Patents, Books, LifeExtension]. "Experiments in which Drosophila Sir2 expression was quadrupled led to a 57% extension of life span", (0). It was found in the year 2000 that SIR2 deacetylates lysines 9 and 16 of histones H3 and H4, respectively, and that the sirtuins in general require NAD+ (nicotinamide adenine dinucleotide) as a co-substrate for their reactions, motivating supplementation with NAD+. See NAD+, nicotinamide (niacinamide), and Vitamin B3 (niacin). (Interestingly, the SIR2-like sirtuins are not inhibited by the HDAC inhibitor Tricostatin A.) The human homolog of yeast SIR2 is SIRT1. Gene silencing is implemented with resveratrol and/or quercetin, or with a histone deacetylase (HDAC) that condenses chromatin, discouraging transcription from chromatin DNA. Thus gene silencing may be implemented as a therapeutic strategy using drugs that hypoacetylate (deacetylate) chromatin, causing it to condense. Gene silencing in general is done by action on specific amino acids in histone tails to establish (condensed) heterochromatin by modifications involving deacetylation, methylation, phosphorylation, poly(ADP ribosylation) and ubiquitylation, of which deacetylation and methylation are the best studied. Developmental transcriptional silencing [Links/Transcriptional Silencing, Images, Video, Papers, Patents, Books, Wikipedia, LifeExtension] is correlated with DNA methylation of CpG islands [Images], which may be supported and maintained by supplements supporting DNA methylation such as SAMe. The process is controlled by methyltransferases. "Gene silencing by methylation is associated with the formation of condensed chromatin that is enriched by hypo-acetylated histones (deacetylated histones). Furthermore, it was shown that methylated genes were initially transcriptionally active but after a few hours were packed into less accessible chromatin structures." (Petra Boukamp, Biological Clocks in the Aging Cell, from Aging at the Molecular Level, Kluwer, 2003.) Note that methylation is responsible for transcriptional silencing after the role of a gene is played out in the development of the organism from a zygote. "In higher eucaryotes most genes are "silent", meaning that they are transcriptionally inert and that this state is hertiable." Undesirable gene de-methylation is associated with aging and may be treated with drugs like SAMe [Images] or folic acid that tend to maintain proper methylation of genes that have no further role in development. For aging, the cell cycle inhibitor p16 needs to be inactivated for cells to overcome senescence, which is obtained in many immortal and tumor cells by methylation of the p16 promoter. The role of p16INK4a accumulation from p16 as a biological clock for stopping the cell cycle may require some further attention. Nerve Growth Factor, vitamin A or retinol from carrots, resveratrol, and exercise are are useful in limiting levels of p16INK4A which can eventually make senescence irrecoverable. Also note that p21 levels are increased by the inhibition of methytransferases in aging cells.
Otherwise, gene silencing is implemented in the body using RNA interference (RNAi) controlled by the Argonaute/Piwi familiy of genes. "Argonaute proteins are the catalytic components of the RNA-induced silencing complex (RISC), the protein complex responsible for the gene silencing phenomenon known as RNA interference (RNAi)." - Wikipedia/Argonaute. See the video RNA interference.
According to Prof. Vladimir Khavinson, cells display progressively more silenced dark heterochromatin as they age, and less light euchromatin from which transciption may occur. Perhaps HDAC inhibitors such as diallyl disulfide and allyl mercaptan from garlic's allicin can be used to counteract this age-progressive gene silencing. Note that gene silencing reduces hTERT transcription.
Genetic Engineering [GEN (Genetic Engineering News), Links, Images, Video, Papers, Patents, Books, Amazon, Wikipedia/Genetic Engineering Topics, LibCong]. See Bioinformatics, Gene Therapy, Genomics, Longevity Genes, Organism Design, Plasmids, DNA Sequencing Technology, SNPs (Single Nucleotide Polymorphisms), Transfection, Targeted Genome Editing, and Zinc Finger Nucleases. Genetic engineering modifies the nuclear genomes of viral organisms, bacteria, plants, and animals for desired characteristics or designs DNA plasmids for therapeutic applications. Genetic engineering is often used to produce proteins. See Protein Production Methods.
Genetic Theories of Aging [Links, Images, Video, Papers, Patents, Books, LifeExtension] (0). See Breeding for Longevity and Introduction to Longevity Genes including SIRT1, activated by resveratrol, (7). Shortening of chromosomal telomeres changes patterns of gene expression and eventually produces replicative senescence; hTERT is the primary longevity gene for preventing cellular senescence and returning cells to their youthful patterns of gene expression by lengthening telomeres, (10). See also DNA repair in aging, including DNA repair of open telomeric t-loops producing cells with the senescent phenotype, whose closure via the DNA repair enzyme telomerase or the TRF1 telomere loop binding protein restores the youthful phenotype of the cell without lengthening the telomere, a stopgap solution. Telomerase activators repair open telomere t-loops by extending chromosome tip-end telomeres with telomerase until they can close, or TRF1 is transcribed to close open telomere t-loops with TRF1 telomere binding protein.
Recovery from cellular senescence may be achieved when P16INK4A is low enough by downregulating caveolin-1 (gene CAV1) with folic acid or cAMP from exercise or forskolin, maintaining high cAMP levels with phosphodiesterase inhibitors, and stimulating the cell with EGF and/or PDGF from exercise or other sources such as colostrum.
Gene Therapy [Wikipedia, Links/Gene Therapy, Images, Video, Papers, Patents, Books, LibCong, LifeExtension; mRNA in gene therapy, nucleoside-modified mRNA gene therapy vectors; Fast Telomere Extension; New Approaches; Retroviral vectors]. Adenovirus transfection - hTERT or other genes such as C-myc for hTERT activation may be transfected using adenovirus vectors or extra hTERT may be built into the genome with targeted genome editing using zinc finger nucleases. See also mRNA gene delivery [Images, Papers, Patents, Books]. [QbioGene/Adenovirus for gene therapy applications, Books/adenoviral transfections, Links/Adenoviral Transfections, Invitrogen/adenoviral transfections, Amaxa Biosystems, Amazon/adenoviral transfections]. See also Index/Adenovirus Transfection and Index/Transfection. See also [Links/Gene Therapy Safety Issues, Links/Safety Issues in Adenovirus Transfection for Gene Therapy Applications]. Transfection using the Associated Adenovirus (AAV, 4.8 kilobase genome) is painless, safer, and always to the same site AAVS1 in the genome on chromosome 19. However, only a small amount of DNA code < 4.8 kilobases can be transfected using AAV viruses. Gene therapy is very useful for experiments on in vitro cell cultures, and many experimenters have survived it, although not all patients have recovered from gene therapy. Gene therapy safety is improving and varies somewhat between gene therapy techniques. Also see Transfection, Longevity Genes, Organism Design, Plasmids, Gene, Targeted Genome Editing, and Zinc Finger Nucleases. Related topics also include Transposons in Gene Therapy and Transposable Elements in Gene Therapy. Fast Telomere Extension with hTERT mRNA nucleoside-modified and HPLC purified (to mask immune system response and improve hTERT expression) and programmed to provide long mRNA lifetimes then finally transfected via endocytosis in liposomes has also been described as gene therapy.
Genistein [Telomerase Inhibitor List/Genistein, Links/Genistein, Images, Video, Papers, Patents, Books, LifeExtension; hTERT methylation; Index/anticancer diet; Index/Metastasis]. Genistein is a telomerase inhibitor, so soy products containing genistein should not be taken while attempting to activate telomerase. Genistein is useful in treating prostate cancer, breast cancer, and colon cancer. Note that genistein has methylating effect, and can methylate DNA, which leads to gene silencing. Genistein combined with indole-3-carbinol from cruciferous vegetables strongly enhances apoptosis of colon cancer cells. Anticarcinogenic flavonoids apigenin, biochanin A, chrysin, genistein, kaempferol, hesperetin, naringenin, and silymarin (for breast cancer resistance protein (BCRP) inhibition) have been used to treat breast cancer together with additive effect. See Zhang S, Yang X, Morris ME (2004), Combined effects of multiple flavonoids on breast cancer resistance protein (ABCG2)-mediated transport, Pharmaceutical Research 2004 Jul;21(7):1263-73. Furthermore, genistein is a NF-kB inhibitor that is effective against cancer metastasis and other phases of cancer cell proliferation. See Pavese JM, Farmer RL, Bergan RC (2010), Inhibition of cancer cell invasion and metastasis by genistein, Cancer Metastasis Review 2010 September; 29(3):465-82. Banerjee S, Li Y, Wang Z, Sarkar FH (2008), Multi-targeted therapy of cancer by genistein, Cancer Letters 2008 Oct 8; 269(2):226-42.
Furthermore, genistein may be used to treat or prevent senile systemic amyloidosis, and familial forms of amyloidosis from amyloid fibrils formed from transthyretin protein. Genistein is "an excellent transthyretin amyloidogenesis inhibitor".
Genistein stimulates the skin’s production of collagen [LEF] which in turn increases its elasticity [LEF] and a youthful appearance. Note that soy, which contains genistein, also provides phytoceramides that improve skin elasticity by inhibiting elastase. Genistein upregulates estrogen-beta receptor expression.
Finally, genistein activates AMPK.
Genital Warts (Encyclopedia).
Genome Engineering [HUGO, Links, Images, Video, Papers, Patents, Books].
See Genome engineering with modularly assembled nucleases [Papers, Patents, Books]. This is an application of Cell Engineering with Synthetic Messenger RNA.
Genomes of Plants [Links/Plant Genomes, Images, Video, Papers, Patents, Books; Links/Plant Genomes sequenced, Images, Papers, Patents, Books].
Genomics [genomics.energy.gov, Wikipedia, Links, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/genomics of aging, Amazon/genomics of aging, Genomics at Senescence.info]. 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, Index/Gene, Bibliography/The Genome of Homo Sapiens, Nobel Prize Winners, Protein Data Bank, Protein Explorer Front Door, UnitProt/Swiss-Prot, U.S. National Institutes of Health, and WormBase. See also Charles R. Cantor & Cassandra L. Smith, Genomics, The Science and Technology Behind the Human Genome Project, John Wiley & Sons, 1999. Also see The Plasmid Genome Database, Targeted Genome Editing, and HUGO Gene Families
Genomic Stability [Links, Images, Video, Papers, Patents, Books, Amazon]. Of primary concern is tissue genomic stability against cancer [Links, Images, Video, Papers, Patents, Books, Amazon]. See Index/inflammatory factors secreted by senescent cells, Index/Anticancer Diet, Index/Antiinflammatory Nutraceuticals, and Index/Carcinogens. Also see
Genomic Instabilities in Aging Cells [Links, Images, Video, Papers, Patents, Books] and Index/Telomere Fusion. Genetic instabilities are well-described in (Paula Martinez and Maria A. Blasco, 2011). See Lengauer, C., Kinzler, K.W., and Vogelstein, B. (1998), Genetic instabilities in human cancers, Nature 396, 643-649. "Genetic studies in mice have demonstrated that short telomeres rather than average telomere length (TL) are causative of age-related pathologies and that rescue of short telomeres by telomerase is sufficient to restore cell and organismal viability as well as genomic stability." - from Elsa Vera and Maria A. Blasco (2012), Beyond average: potential for measurement of short telomeres, AGING, June 2012, Vol.4, No.6. Note that the age of an elderly individual can be better estimated from his percentage of short telomeres in a given cell type than from his average telomere length in a given cell type. See also Calvin B. Harley, Weimin Liu, Maria Blasco, Elsa Vera, William H. Andrews, Laura A. Briggs, and Josheph Raffaele (2011), A Natural Product Telomerase Activator As Part of a Health Maintenance Program, Rejuvenation Research, 14(1), 2011. In this last paper TA-65 rescues cells by repairing shortest telomeres, but without substantial improvement in average telomere length, which would have been still better news for rejuvenation applications of TA-65 in rescuing genomic stability from replicative senescence.
Geriatric Dermatology
[Links/Geriatric Dermatology, Images, Video, Papers, Patents, Books; Index/Dermatology, Index/Skin, Index/Lesions, Index/Purpura, Index/Senile Purpura, Index/Veil Cells, and Index/Wrinkles and Wrinkle Treatments]. Common conditions in geriatric dermatology include:
Actinic Keratoses [Images, Video, Papers, Patents, Books] (pre-cancer [Images])
Aging Skin [Images, Video, Papers, Patents, Books; Phytoceramides]
Atypical Nevus [Images, Video, Papers, Patents, Papers] (dysplastic nevus [Images])
Atopic Eczema [Images, Video, Papers, Patents, Books] / Dermatitis [Images]
Basal Cell Carcinoma [Images, Video, Papers, Patents, Books]
Contact Dermatitis [Images, Video, Papers, Patents, Books]
Dandruff [Images, Video, Papers, Patents, Books]
Dry Skin [Images, Video, Papers, Patents, Books; Phytoceramides]
Hair Loss [Images, Video, Papers, Patents, Books]
Herpes Zoster [Images, Video, Papers, Patents, Books] (shingles [Images])
Itching [Images, Video, Papers, Patents, Books]
Lichen Planus [Images, Video, Papers, Patents, Books]
Liver Spots [Images, Video, Papers, Patents, Books]
Malignant Melanoma [Images, Video, Papers, Patents, Books]
Moles [Images, Video, Papers, Patents, Books]
Perioral Dermatitis [Images, Video, Papers, Patents, Books]
Photoaging [Images, Video, Papers, Patents, Books]
Photodamage [Images, Video, Papers, Patents, Books]
Pruritus [Images, Video, Papers, Patents, Books] (Itching [Images])
Psoriasis [Images, Video, Papers, Patents, Books]
Psoriatic Arthritis [Images, Video, Papers, Patents, Books]
Ringworm [Images, Video, Papers, Patents, Books] (Fungal Infection [Images])
Rosacea [Images, Video, Papers, Patents, Books]
Scabies [Images, Video, Papers, Patents, Books]
Scars [Images, Video, Papers, Patents, Books]
Seborrheic Dermatitis [Images, Video, Papers, Patents, Books]
Seborrheic Keratoses [Images, Video, Papers, Patents, Books]
Skin Cancer [Images, Video, Papers, Patents, Books]
Squamous Cell Carcinoma [Images, Video, Papers, Patents, Books]
Tinea Capitis [Images, Video, Papers, Patents, Books] (fungal infection of scalp [Images])
Tinea Corporis [Images, Video, Papers, Patents, Books] (fungal infection of body [Images])
Tinea Cruris [Images, Video, Papers, Patents, Books] (fungal infection of groin [Images])
Tinea Faciei [Images, Video, Papers, Patents, Books] (fungal infection of face [Images])
Tinea Pedis [Images, Video, Papers, Patents, Books] (fungal infection of foot [Images])
Urticaria [Images, Video, Papers, Patents, Books] (Hives [Images])
Geriatrics [Wikipedia/Geriatric medicine, Links, Images, Video, Papers, Patents, Books, Amazon, American Geriatrics Society. British Geriatrics Society, Canadian Geriatrics Society].
Geriatrics and Aging Skin [Index/Skin; Links, Images, Video, Papers, Patents, Books, LifeExtension; Index/Growth Factor Skin Creams, Index/Geriatric Dermatology; Phytoceramides], [54].
Geron [Geron Corporation Site, Links, Papers, Patents, Books, LifeExtension, Images] [3]. Geron: Compositions and methods for increasing telomerase activity, A' alternate-source version Compositions and Methods for Increasing Telomerase Activity, A'', Formulations Containing Astragalus Extracts and Uses Thereof [Patents]. See the Geron SEC Report on rewinding the clock of cellular aging with telomerase activation and Immortal Cells on > 8x life extension in telomerase-activated cells. See also Geron subsidiary TA Sciences. [Geron Press Releases, Links], [Geron/patents, European patent/telomerase activation methods, A' alternate-source version Compositions and Methods for Increasing Telomerase Activity, A'', European patent/Astralagus extracts(for Hong Kong Univ.)] ,[3].
Ginger [Ray/Ginger, Wikipedia, Links/ginger, Images, Video, Papers, Books, LifeExtension, Links/ginger and inflammation; Links/ginger and COX-2 inhibitors, Books, LifeExtension], [36s] (f). Ginger is an antioxidant, antiinflammatory, anti-tumor spice. Fresh ginger is preferred over dried ginger to preserve high levels of gingerol content. The maximum daily adult dose of ginger usually totals 5 grams or less. - Amercian Cancer Society. Ethanolic ginger extract [Images] is a telomerase inhibitor that also inhibits c-Myc expression. It contains gingerol and zerumbone.
Gingerol [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Gingerol inhibits NF-kB activity by blocking the entrance of the transcription factor NF-kB into the nucleus, thereby down-regulating TNF-alpha and other inflammatory cytokines such as inducible nitric oxide synthase (iNOS). Gingerol can kill ovarian cancer cells by inducing apoptosis (programmed cell death) and autophagocytosis (self-digestion). Furthermore, gingerol powerfully activates AMPK, supporting catabolism producing ATP for many life-extending processes while reducing triglycerides and glucose in the blood.
Zerumbone [Index, Links, Images, Video, Papers, Patents, Books, LifeExtension]. Zerumbone, a NF-kB inhibitor, suppresses NF-kB activation induced by carcinogens, blocking proliferation, invasion, tumor blood vessel development, and metastasis while promoting apoptosis.
Ginkgo Biloba (Ginkgo) [Wikipedia/Ginkgo Biloba, TelomeraseActivators/Ginkgo Biloba, Links, Images, Video, Papers, Patents, Books, Amazon/Ginkgo Biloba, LifeExtension, Terraternal/Ginkgo Biloba Studies; Anticancer/Ginkgo Biloba, Memory Enhancing Nutraceuticals]. Ginkgo Biloba is believed to promote healthy neurological and circulatory function. It achieves this by reducing the stickiness of platelets via ginkgo biloba glycosides. Ginkgo Biloba thus promotes blood flow to the muscles and the brain. Ginkgo biloba plus vinpocetine speeds processing of short-term memory. Note that ginkgo biloba is a component of the Jim Stoppani Nitric Oxide stack described in the index entry for Horny Goat Weed, which may be useful in applying telomerase activation to the vascular endothelium, as well as for bodybuilding. Note that Ginkgo Biloba [Images] and ginkgolides upregulate HIF-1 expression (Li Z, Ya K, Xiao-Mei W, et.al, 2008). The HIF-1 transcription factor (also upregulated by exercise, diosgenin from Fenugreek or Wild Yam) upregulates hTERT mRNA expression. Also see Boveris AD, Galleano M, Puntarulo S. (2007), In vivo supplementation with Ginkgo biloba protects membranes against lipid peroxidation, Phytotherapy Research 2007 Aug; 21(8):735-40. Chung HS, Harris A, Kristinsson JK, Ciulla TA, Kagemann C, Ritch R. (1999), Ginkgo biloba extract increases ocular blood flow velocity, J Ocul Pharmacol Ther. 1999 Jun;15(3):233-40.
Ginkgolides [Wikipedia/Ginkgolides, Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension]. Ginkgolides from Ginkgo Biloba include:
(1) Ginkgolide B [Wikipedia/Ginkgolide B, Links, Images, Papers, Patents, Books, LEF],
(2) Bilobalide [Wikipedia/Bilobalide, Links, Images, Papers, Patents, Books, LEF],
(3) Ginkgolide C [Wikipedia/Ginkgolide C, Links, Images, Papers, Patents, Books, LEF],
(4) Ginkgolide A [Wikipedia/Ginkgolide A, Links, Images, Papers, Patents, Books, LEF],
(5) Ginkgolide J [Wikipedia/Ginkgolide J, Links, Images, Papers, Patents, Books, LEF],
(6) Ginkgolide M [Wikipedia/Ginkgolide M, Links, Images, Papers, Patents, Books, LEF],
(7) Ginkgolide F [Wikipedia/Ginkgolide F, Links, Images, Papers, Patents, Books, LEF],
(8) Ginkgolide K [Wikipedia/Ginkgolide A, Links, Images, Papers, Patents, Books, LEF],
(9) Ginkgolide L [Wikipedia/Ginkgolide L, Links, Images, Papers, Patents, Books, LEF],
(10) adrenotransferrin [Wikipedia, Links, Images, Papers, Patents, Books, LEF].
Ginseng [Telomerase Activators/(135) Asian Ginseng Root Extract, Wikipedia/ginseng, Ray Sahelian/Ginseng, Links/Ginseng, Images, Video, Papers, Patents, Books; Links/Ginsenosides]. Ginsenoside Rh1 was investigated as a small molecule telomerase activator by Geron [81s/6b]. Ginsenoside Rh2 is a small molecule telomerase inhibitor [article]. Perhaps a telomerase-activation procedure based on ginsenosides could be specified using Solaray Korean Ginseng Extract, 535 mg extract/capsule, 26 mg ginsensides/capsule, Rg1/Rg2 ratio = 0.5. However, Korean Red Ginseng Extract is a telomerase inhibitor that decreases telomerase activity in leukemia cells. Perhaps Korean Red Ginseng Extract activates telomerase in normal, healthy cells, since it is an antioxidant which tends to confine hTERT to the cellular nucleus. Ginseng is sometimes tagged as an adaptogen. Note that Panax Ginseng extract has an anticancer effect [Index/Anticancer] on cancers induced with benzopyrene, as in smoking [essay]. According to (Susan Machado, 2012), Ginseng is an anti-inflammatory antioxidant that improves mitochondrial function, helps to overcome insulin resistance, and that supports membrane integrity. See also Kim HG, Yoo SR, Park HJ, et al. (2011), Antioxidant effects of Panax ginseng C.A. Meyer in healthy subjects: a randomized, placebo-controlled clinical trial, Food Chemistry and Toxicology 2011 Sep; 49(9):2229-35. Jung HL, Kwak HE, Kim SS, et al. (2011), Effects of Panax ginseng supplementation on muscle damage and inflammation after uphill treadmill running in humans, American Journal of Chinese Medicine 2011; 39(3):441-50. Luo JZ, Luo L (2009), Ginseng on hyperglycemia: effects and mechanisms, Evidence Based Complementary Alternative Medicine, 2009 Dec; 6(4):423-7. Luo JZ, Luo L (2006), American ginseng stimulates insulin production and prevents apoptosis through regulation of uncoupling protein-2 in cultured beta cells, Evidence Based Complementary Alternative Medicine, 2006 Sep; 3(3):365-72. Voces J, Cabral de Oliveira AC, Prieto JG, et al. (2004), Ginseng administration protects skeletal muscle from oxidative stress induced by acute exercise in rats, Brazilian Journal of Medical and Biological Research 2004 Dec; 37(12):1863-71.
Ginsenosides [Links, Images, Video, Papers, Patents, Books].
Ginsenosides from Ginseng are divided into two classes:
(1) 20(S)-Propanaxadiols (Rb1, Rb2, Rb3, Rc, Rd, Rg3, Rh2, Rs1) and the
(2) 20(S)-Propanaxatriols (Re, Rf, Rg1, Rg2, Rh1).
It seems that some propanaxadiols are telomerase inhibitors for cancer cells, while some propanaxatriols such as ginsenoside Rh1 are telomerase activators for normal, healthy cells. (Check.) Emerging ginsenosides Ra1, Ra2, Ra3, Rf2, Rg4, Rg5, Rg6, Rk1, Rs1 and Rs2 are obtained following the steam heating of ginseng to produce red ginseng. The major anti-tumor ginsenosides are Rh2 (a telomerase inhibitor), Rg3, Rg5, and Rk1, where the last two are obtained after 2-4 hours of steaming regular ginseng at 100 degrees Centigrade to make red ginseng. See Kar Wah Leung and Alice Sze-Tsai Wong (2010), Pharmacology of ginsenosides: a literature review, Chinese Medicine, 2010, 5:20.
Ginsenoside Rh1 [C36H62O9, molecular weight 638.87208, Images/Molecule; TA/Ginsenoside Rh1, Links, Images, Papers, Books, Amazon; sources; bioavailability; toxicity]. See Papers/Ginsenoside Rh1 activates telomerase. A telomerase activator appearing in Geron patent specifications, such as Compositions and Methods for Increasing Telomerase Activity, or A' alternate-source version Compositions and Methods for Increasing Telomerase Activity, or A''. The minimum effective concentration of ginsenoside Rh1 used in vitro is approximately 1000 times the concentration used for astragaloside IV or cycloastragenol, 10 μM vs. 0.01 μM. The telomerase-activating ginsenoside Rh1 is a functional ligand of the estrogen receptor (Kar Wah Leung and Alice Sze-Tsai Wong, 2010). Ginsenoside Rh1 is a component of Korean Ginseng extract, which also contains telomerase inhibitors. Korean Red Ginseng Extract is a telomerase inhibitor that decreases telomerase activity in leukemia cells. See Lee Y, Jin Y, Lim W, Ji S, Choi S, Jang S, Lee S (2003), A ginsenoside-Rh1, a component of ginseng saponin, activates estrogen receptor in human breast carcinoma MCF-7 cells., The Journal of Steroid Biochemistry and Molecular Biology, 2003 March;84(4):463-8.
Gla Proteins [Links/Gla proteins, Images, Papers, Patents, Books, Amazon, LifeExtension]. Gla proteins are modified by vitamin K2 to protect against arterial calcification. Low vitamin D can cause rickets and is associated with both arterial disease and bone loss. Vitamin K is a cofactor for the conversion of glutamate into gamma-carboxyglutamate, or Gla proteins. Vitamin K2 stimulates bone formation. Both vitamin D and vitamin K2 work together with calcium supplements to prevent osteoporosis and arteriosclerosis. The Gla proteins must be modified by vitamin K before the matrix can be properly formed that incorporates calcium and phosphorus into new bone. The Gla proteins regulate physiological processes controlled by calcium (such as blood coagulation and bone mineralization) and include osteocalcin and matrix Gla-protein. Osteocalcin is ordinarily found in bone, but is found in calcified atherosclerotic plaque and is upregulated in patients with atherosclerosis. See Julius Goepp, MD, Brittle Bones and Hardened Arteries: The Hidden Link, Life Extension Magazine, September 2010. It was found in 1993 that endothelial cells lining arteries can turn into osteoblasts when vitamin D and vitamin K2 are insufficient. This leads to calcification of tissue and hardening of the arteries due to systemic calcification. Other causes of arterial hardening include glycation and the development of atherosclerotic plaque. Calcium supplements also help prevent systemic calcification.
Glaucoma [Wikipedia/Glaucoma, Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension]. Glaucoma is a painless disease often associated with elevated interocular eye pressure (IOP) leading to blindness in old people. Low levels of vitamin C and high levels of uric acid (associated with gout) were found in glaucoma. Vitamin C may be protective against glaucoma. (LEF, June 2010). See Eye Problems of Old Age. Recently, LEF publishes that Glaucoma can be prevented with French maritime pine bark [Images] and bilberry [Index, Images]. These medicines reduce interocular pressure (IOP) in the eyes, a primary cause of glaucoma. Latanoprost eye drops (XalatanTM), may also be used. See Matilde Parente, MD (2011), Nutrient Intervention for Glaucoma, Life Extension Magazine, June 2011.
Glioma [Index/Brain Cancer, Index/Brain Cancer/Glioma, Wikipedia/Glioma, Links, Images, Video, Papers, Patents, Books; Images/glial cells, Images/glioma cancer cells, Images/glioblastoma; Links/Glioblastoma multiforme pathway, Images, Video, Qiagen/Glioblastoma multiforme pathway]. Note that Sodium 4-Phenylbutyrate has been used to induce apoptosis in glioma cancer cells. See Index/Brain Cancer and Index/Brain Cancer/Glioma for more details. See Lisa Antone (2014), Common Virus Links to Deadly Brain Cancer with preamble by William Faloon, Life Extension Magazine, February 2014. According the the article, gliomablastoma multiforme is associated with CMV, or cytomegalovirus. Note from Virology that CMV may be treated with garlic or glycyrrhizin or prescription drugs. Researchers have suggested the relatively expensive valganciclovir for CMV treatment.
GliSODinTM [LEF/GliSODinTM , Links, Images, Video, Papers, Patents, Books, LifeExtension]. GliSODin is long-shelf-life cantaloupe-derived bioavailable SOD [52] from the Life Extension Foundation, [64s].
Glossaries of anti-aging terms [81].
Glucomannan [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Glucomannan (derived from the Asian konjac root), expands to up to 50 times its original volume when mixed with water, curbing hunger by filling the stomach. It delays digestion of carbohydrates and all other nutrients, and binds to bile acids, carrying them out of the body in feces, promping the body to convert more cholesterol into bile acids and thus lowering cholesterol and other fats. One or two grams are taken before meals. - (after Muscle and Fitness Magazine, 2010).
Glucoregulatory Agents [Links, Images, Video, Papers, Patents, Books, LifeExtension; see also Caloric Restriction]. Glucoregulatory agents include cinnamon [Images], 2-Deoxyglucose [Images], Phenformin [Images], Metformin [Images], Chromium Picolinate [Images], and also DHEA [Images]. Enzyme inhibitors (functioning as carbohydrate blockers) block the action of sucrase, amylase, and glucosidase, which are digestive enzymes that process carbohydrates. See
Sucrase Inhibitors [Links, Images, Video, Papers, Patents, Books, LifeExtension],
___L-arabinose.
Amylase Inhibitors [Links, Images, Video, Papers, Patents, Books, LifeExtension],
___White Kidney Bean Extract [Index], acarbose [Images],
___seaweeds [Images] (InSea), and Irvingia [Images].
Glucosidase Inhibitors [Links, Images, Video, Papers, Patents, Books, LifeExtension].
___Acarbose, Kelp seaweed supplements, and pomegranate flower extracts.
Sucrose (composed of glucose and fructose) is very prevalent in our diet and processed into glucose and fructose by sucrase, which can be blocked by L-arabinose [Images]. This is a simple indigestible plant sugar which is never absorbed, but finally excreted from the digestive system. It lowers measures of glycation. White bean extract [Images, Index] from the white kidney bean is used to block alpha-amylase, inhibiting the absorption of starches and slowing the rate at which free sugars are absorbed. Red kidney bean also works. Green tea extracts [Images] burn excess calories by raising the basal metabolic rate (by inhibiting the enzymatic degradation of norepinephrine) and inhibit the absorption of fat into the bloodstream by inhibiting the enzyme lipase.
Glucoregulatory Herbs [Links, Images, Video, Papers, Patents, Books, LifeExtension, Amazon/glucoregulators] include:
Banaba leaf extract [Links, Images, Video, Papers, Patents, Books, LifeExtension],
Bittermellon extract [Links, Images, Video, Papers, Patents, Books, LifeExtension],
Blueberry leaf extract [Links, Images, Video, Papers, Patents, Books, LifeExtension].
Gymnema sylvestre [Index, Links, Images, Video, Papers, Patents, Books, LifeExtension],
High galactomannan [Links, Images, Video, Papers, Patents, Books, LifeExtension],
Fenugreek extract [Index, Links, Images, Video, Papers, Patents, Books, LifeExtension],
Konjac mannan [Links, Images, Video, Papers, Patents, Books, LifeExtension],
Nopal cactus [Links, Images, Video, Papers, Patents, Books, LifeExtension],
[See tip source: Anti-Aging, a Jon Barron Report].
Glucoregulatory Mechanisms [Links, Images, Video, Papers, Patents, Books, LifeExtension].
Glucosamine Sulfate [Wikipedia/Glucosamine_Sulfate, Links, Images, Video, Papers, Patents, Books, LifeExtension; Toxicity; Side Effects]. Glucosamine is a structural component of cartilage involved in joint flexibility and mobility. Glucosamine (500 mg x 3) can treat elderly stiff back problems that have old men describing themselves as "stiffs". Glucosamine supplements slow cartilage degeneration, repair connective tissue, and boost the synovial fluid that lubricates joints. Glucosamine sulfate is often given with chondroitin sulfate [Index, Images] at 400 mg x 3, a primary structural component of joint cartilage often combined with glucosamine and used to treat osteoarthritis and joint inflammation that helps in treating and avoiding joint problems [Index]. Other elements of a joint treatment program include collagen hydrolysate [Images] at 1.5 g x 3 to help regenerate cartilage and hyaluronic acid (150 mg x 2) [Images, Index] (a glycosaminoglycan like glucosamine) to enhance cartilage repair [Index] and promote the expression of synovial fluid. For treating a stiff back, medical specialists also sometimes prescribe ENBREL, a TNF-alpha inhibitor like luteolin from celery or the TNF-alpha inhibitor in pomegrante flower extracts.
Glucose [Wikipedia/Glucose, Links, Images, Video, Papers, Patents, Books, LifeExtension; Links/Glucose level control, Images, Video, Papers, Patents, Books, LifeExtension]. Men and women with high glucose, high triglycerides, high C-reactive protein high LDL, and low HDL, have "sharply higher vascular disease risks". Higher glucose and insulin levels raise cancer risks. High glucose levels are associated with poorer outcomes and elevated risk of death in cancer cases. Ingestion of glucose inhibits the release of neuroprotective HGH by the pituitary via inhibitory receptors in the hypothalamus, according to Vladimir Dilman. Careful diet and green coffee bean extract is recommended to lower glucose levels. Cinnamon may be used to reduce blood sugar levels. See William Falloon, As We See It, Dangerous Misconceptions, Life Extension Magazine, June 2013. Also see Caloric Restriction.
Glucosinolates [Wikipedia/Glucosinolate, Links, Images, Video, Papers, Patents, Books, LifeExtension]. Glucosinolates derived from cruciferous vegetables (broccoli, Brussels sprouts, mustard greens, cabbage family) are antimutagenic and anticancer.
Glutamine [Wikipedia/Glutamine, Links, Images, Video, Papers, Patents, Books, LifeExtension]. Glutamine is the primary amino acid in skeletal muscle, is depleted during heavy exercise (9), and is considered crucial for muscle synthesis, boosting muscle growth, enhancing muscle cell volumization, and reducing muscle catabolism. Glutamine increases bicarbonate levels in muscles, dampening acidity and allowing better muscle performance. Jim Stoppani recommends 5-10 grams within 30 minutes prior to training as a part of his pre-workout stack for strength and endurance, which also includes beta alanine (2-3 grams) and caffeine (200-400 mg). According to Muscle & Fitness Magazine, glutamine promotes muscle growth by enhancing concentrations of the branched-chain amino acid leucine, and also by elevating HGH levels. Research has also shown that glutamine increases metabolic rate and improves fat-burning. Glutamine is also believed to increase HGH secretions and enlarge muscle cell volume. Glutamine is believed to help maintain a positive nitrogen balance in skeletal muscle and to boost steroid production. Some authors recommend 5 grams immediately after workouts to boost muscle growth and reduce catabolism during caloric restriction, which may be mandatory to obtain good muscular definition. Other sources recommend 5 grams before a workout and 5 grams after the workout.
Glutamine required for Telomerase Function
Recently, it has been pointed out by Al Sears MD that some glutamine (perhaps from fish or meat) is required for telomerase to function properly in lengthening telomeres: "Recently I was looking through the Public Library of Science’s open access journal PLOS One, scouring it for any new studies I could use for my lectures in Malaysia. I found a link to a study published back in 2009 titled “Human Telomerase Reverse Transcriptase (hTERT) Q169 Is Essential for Telomerase Function In Vitro and In Vivo.” The title interested me because the words “in vivo” mean that the researches were looking at how telomerase acts in a live organism, not just in a lab-created culture. When I started reading I realized I had stumbled on something everyone missed, and that no one is talking about... What I found is that in higher animals like humans, there is a tiny bit of the amino acid glutamine that’s necessary for telomerase to work properly. I won’t bore you with the “science-speak” from the study, but in plain English, without glutamine to create a protein called Q169, telomerase won’t have proper structure or function. In other words, if there’s no glutamine, there’s no telomerase." - Al Sears MD, May 10, 2013. See the role of glutamine in telomerase activity and the role of glutamine in telomere maintenance. "Glutamine is the most abundant amino acid in human serum." - Unterluggauer H, et. al. (2008), Premature senescence of human endothelial cells induced by inhibition of glutaminase, Biogerontology August 2008, Volume 9, Issue 4, pp 247-259. [Links/glutaminase]. Also see TrueMD.com/Glutamine.
Glutathione [Ben Best/Glutathione, Wikipedia, Links/Glutathione, Images, Video, Papers, Patents, Books, LifeExtension]. Glutathione (GSH) is an endogenous antioxidant. Glutathione is a large molecule, so that the usual method of supplementing it is to take alpha lipoic acid daily. Glutathione can be boosted in the liver by Schisandra chinensis. The related enzyme Glutathione peroxidase (GPX) activity is enhanced by vitamin C. See Glutathione links, [107], [111], (1). See also Food Sources that Boost Glutathione Naturally [Links]. These include N-Acetyl-Cysteine (NAC), alpha lipoic acid, SAMe, whey protein, asparagus, broccoli, avocado and spinach. N-Acetyl-cysteine is an amino acid precursor of glutathione. "Raw eggs, garlic and fresh unprocessed meats contain high levels of sulphur-containing amino acids and help to maintain optimal glutathione levels." Silymarin from Milk Thistle prevents glutathione depletion.
"Curcumin (turmeric) has been found to increase expression of the glutathione S-transferase." Changkil saponins (CKS) from the roots of Platycodon grandiflorum A. DC (Campanulaceae), called Balloon Flower Root (Jie Geng), have been found to increase intracellular glutathione (GSH) content. Selenium is a co-factor for the enzyme glutathione peroxidase, although too much selenium is harzardous. "Maximum levels of glutathione coincide with a peak of telomerase activity in proliferating 3T3 fibroblasts; glutathione depletion decreases by 60% telomerase activity, and restitution of glutathione levels restores telomerase activity..." - from Maria Dolores Edo and Vicente Andres, 2005, "Aging, Telomeres, and Atherosclerosis", Cariovascular Research, 66 (2005), 213-221. The same paper observes that high glutathione levels keep hTERT in the cell nucleus, while low glutathione levels lead to an exodus of nuclear hTERT into the cytoplasm.
There are a number of important glutathione-related enzymes and variants:
(1) Glutathione (GSH) [Links/Glutathione, Images, Papers, Patents, Books, Wiki/Glutathione]. Glutathione is a tripeptide antioxidant that protects cells from reactive oxygen species (ROS), including free radicals and peroxides. Glutathione (GSH) is nucleophilic (electron-donating) at sulpher. By acting as an electron donor, glutathione (GSH) reduces disulfide bonds formed within cytoplasmic proteins to cysteines.
(2) Glutathione disulphide (GSSG) [Links/Glutathione disulphide, Images, Papers, Patents, Books, Wiki/Glutathione disulphide]. Glutathione disulphide (GSSG) is the oxidized form of glutathione (GSH) seen after donating an electron, called glutathione disulphide, composed of two glutathione molecules linked by a disulphide bond.
(3) Glutathione reductase (GSR or GR) [Wiki/Glutathione reductase, Links/Glutathione reductase, Images, Papers, Patents, Books]. Glutathione reductase (GSR or GR) is an enzyme catalyzing the reduction of glutathione disulphide (GSSG) to 2 molecules of glutathione (GSH), the sulfhydryl form, an important antioxidant. Glutathione reductase activity is used an an indicator for oxidative stress.
(4) Glutathione peroxidase [Wikipedia/Glutathione peroxidase, Links/Glutathione peroxidase, Images, Papers, Patents, Books]. Glutathione peroxidase is the name of an enzyme family (GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, GPX8) that reduces lipid hydroperoxides to their corresponding alcohols and reduces free hydrogen peroxide to water, producing 1 molecule of Glutathione disulphide (GS-SG) from 2 molecules of glutathione (GSH) in reactions that protect the organism from oxidative damage, such as

2GSH + H2O2 -> GS–SG + 2H2O.

The cycle is completed when glutathione reductase reduces the oxidized gluthathione (glutathione disulphide, GS-SG) to two molecules of glutathione (GSH):

GS–SG + NADPH + H+ -> 2 GSH + NADP+.

Glutathione peroxidase activity is enhanced by vitamin C.
(5) Glutathione S-transferase
[Wikipedia/Glutathione S-transferase, Links/Glutathione S-transferase, Images, Papers, Patents, Books]. "Curcumin (turmeric) has been found to increase expression of the glutathione S-transferase." "Prostate cancer is characterized by an early and near universal loss of expression of the phase 2 enzyme glutathione S-transferase." - LifeExtension, Abstracts, Sept.2005.
Glutathione peroxidase [Wikipedia, Links/Glutathione peroxidase, Images, Video, Papers, Patents, Books, LifeExtension]. See (4) Glutathione peroxidase, above. Glutathione peroxidase is a endogenous antioxidant containing selenium, (1). See selenium as a supplement and selenium supplements [Images]. Melatonin increases levels of glutathione peroxidase. - Wikipedia/Glutathione. See supplements that enhance expression of glutathione peroxidase. There exist selenium dependent glutathione peroxidases and selenium independent glutathione peroxidases (GPX5) that reduce hydrogen peroxide and organic hydroperoxides in reactions including glutathione. Glutathione peroxidases are found in the mitochondria (mitochondrial glutathione peroxidases) and in the cellular cytosol (cytosolic glutathione peroxidases). Glutathione peroxidases help prevent lipid peroxidation [Index] to protect biological membranes. See GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, and GPX8.
Glycation (pron: Gly-cay-shun) [Wikipedia/Glycation, Links/Glycation, Images, Video, Papers, Patents, Books, LifeExtension, Terraternal Links/Diseases impacted by glycation; Index/Antiglycating Drugs; Ben Best/Glycation; Carbonylation of Proteins; Caloric Restriction], (5).

Age in Years
Fluorescence of AGEs due to glycation in human tissue VS. Age in years. (Photo from text.)
After Annette T. Lee and Anthony Cerami (2006), The Role of Glycation in Aging [PDF], NY Acad Sci, 17 DEC 2006. "Glycation" is typically used to specify non-enzymatic glycosylation, as in reactions between proteins and sugars to produce carbonylated proteins, or between DNA and sugars. Sugars may react with proteins to form carbonylated proteins that may evolve into advanced glycation end-products (AGES) that elevate free radical levels up to 50x, leading to DNA damage (10), lipid peroxidation, and cross-linking of proteins and DNA. "Carnosine both protects proteins from carbonylation and helps reverse proteasomal decline.", [75s]. Irreversible glycation can happen when sustained blood glucose levels reach 85 mg/dL or more (LEF, Jan.2012). Glycosylation, on the other hand, typically enzymatic glycosylation, adds sugars to proteins as a part of a nuclear program for a cell signaling or cell transport tagging processes. See (Glycosylation [Links, Books, LibCong, LifeExtension]), Sugar Damage [LifeExtension, Links Books], Cross-Linking Theory of Aging [Links, Books, LifeExtension], AGE inhibitors [LifeExtension, Links, Books], (5).
Glycation inhibitors include:
__alpha lipoic acid,
__aminoquanodine,
__benfotiamine (a lipid-soluble form of vitamin B1 found in onions),
__carnosine,
__vitamin B6 vitamers, converted in the intestine to the actived form PLP (pyridoxal-5'-phosphate),
__vitamin C.

Antiglycation Agents include
__benfotiamine (a lipid-soluble form of vitamin B1 found in onions),
__carnosine,
__cinnamon,
__cortisol inhibitors
____(such as ashwagandha, rhodiola rosea, exercise, because cortisol increases sugar levels),
__green tea,
__green coffee bean extract (350 mg, before meals, reduces glucose),
__kidney bean extract (limits sugar from starch).
__L-arabinose (lowers glucose),
__vitamin B1,
__vitamin C.

Damage from glycation and AGEs (5) can often be prevented or reversed with
__acetyl L-carnitine,
__alpha lipoic acid, and
__CoQ10.
Acetyl L-Carnitine [Index, 58, Best] can be used to clean out glycated proteins associated with sugar damage to the cell. An added benefit is that it improves cellular energy in the brain by facilitating fatty acid transport and oxidation in the cell and (especially in combination with alpha lipoic acid, B-vitamins, and CoQ10) reduces mitochondrial aging. Acetyl L-carnitine may be taken with CoQ10, which also cleans AGEs out of the cell and is in addition a powerful antioxidant. See also Glycation and The Aging Brain: What Causes It. The Glycation Theory of Aging by Ben Best [Index]. Glycation, glucose, and aging, [15s], (5). "Eye retinal cells and insulin-producing pancreas beta cells may be damaged by glycation. Furthermore, glycation results in the stiffening of blood vessel wall collagen, leading to high blood pressure. Glycation may also cause weakening of the collagen in the blood vessel walls leading to micro- or macro-aneurisms that may cause strokes. " - Wikipedia/Glycation, paraphrased. AGEs (Advanced Glycation End products) pre-formed in the diet by cooking yielding browned food Maillard reaction products, exogenous AGEs, are implicated in the initiation of retinal dysfunction, cardiovascular diseases, type II diabetes, and many other age-related chronic diseases [103]." - Wikipedia/Glycation. Blood sugar driving glycation can be elevated by high stress producing high cortisol levels, which can be reduced by exercise or Ashwagandha. Note that the glucoregulatory agent L-arbinose reduces glycosylated hemoglobin (hemoglobin A1C), a measure of chronically high blood sugar (hyperglycemia leading to type 2 diabetes) and glycation often associated with low-grade systemic inflammation and elevated levels of C-Reactive protein correlated to obesity. See H.Adachi and N.Ishii (2000), The effects of tocotrienols on life span and protein carbonylation in Caenorhabditis Elegans, The Journals of Gerontology Series A, vol 55, no. 6, pp. B280-B285, 2000. Glycation may be reduced by taking green coffee bean extract at 350 mg before meals to reduce consequent elevated glucose. See William Falloon, Preparing Your Body to Eat, Life Extension Magazine, Feb 2013.
Glycerophosphocholine (GPC) [Links, Images, Video, Papers, Patents, Books, LifeExtension]. GPC (glycerophosphocholine) increases acetylcholine synthesis, and is useful in preserving cognitive function with aging. The similar Alpha-GPC is a component of HGH Secretagogue formulas like Secretagogue Gold, and can elevate HGH remarkably in the presence of exercise, where exercise alone would raise HGH by 3 times. See Alpha-glycerylphosphocholine (Alpha-GPC). Since HGH is a telomerase activator, Alpha-GPC should be useful in therapy to lengthen telomeres in connection with exercise.
Glycine [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Glycine is a neurotransmitter found in meat and fish that improves HGH release and reduces catabolism.
Glycine propionyl-L-carnitine [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Glycine propionyl-L-carnitine improves fat burning by enhancing the moving of fats into mitochondria like ordinary carnitine, but it also improves nitric oxide levels, providing vasodilation and telomerase activation in the vascular endothelium. One takes 1 to 3 grams before meals and before and after workouts. L-carnitine, acetyl L-carnitine, L-carnitine L-tartrate, and Glycine propionyl-L-carnitine are all used to promote fat loss via carnitine.
Glyconutrients [Wikipedia, Links/Glyconutrients, Images, Video, Papers, Patents, Books, LifeExtension; Links/Glyconutrients scam, Ray Sahelian/glyconutrients]. At this time, "glyconutrients" are a bit controversial. See Ambrotose [Links] as an immune support polysaccharide supplement from Mannatech, a popular example. Manntech's "claims of scientific links to cellular glycobiology [Papers, Patents, Books] have been long disputed by the relevant individual Nobel prize winners." - Wikipedia/Glyconutrients. Mannatech has been hit with a Securities Exchange Act class-action lawsuit for material misrepresentation of the value of its products.
Glycosylation [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension]. Glycosylation typically refers to the enzymatic glycosylation used in a cell signaling or cell transport processes, rather than to sugar damage glycation producing carbonylated proteins. See Glycation, above, inhibitor drugs, (3). See also Carbonylation of Proteins [Index, Links, Images, Video, Papers, Patents, Books, LifeExtension] "Carnosine that both protects proteins from carbonylation and helps reverse proteasomal decline.", [75s]. Antiglycating substances found to protect against glycation include aspirin, ibuprofen, aminoquanidine, vitamin C, vitamin B1 (thiamine), vitamin B6, benfotiamine, and green tea. See Antiglycating Drugs.
Glycotoxins [Links, Images, Video, Papers, Patents, Books, LifeExtension/glycotoxins]. Glycotoxins (Advanced Glycation End products [LEF], or AGEs that can elevate proinflammatory Reactive Oxygen Species [ROS] levels) often arise in foods from cooking foods with sugar and/or fat content. As glycotoxins accumulate and sugar-damaged or carbonylated proteins appear with AGEs to elevate ROS levels, signals are generated that produce pro-inflammatory cytokines such as tumor necrosis factor-alpha [List], interleukin-6 [List], interleukin-1(b) and/or interleukin-8.
Glycyrrhiza (source of licorice, glycyrrhizin, pron: glis-sir-eye-za, glis-sir-eye-zin) [Wikipedia/Glycyrrhiza, Links, Images, Video, Papers, Patents, Books; LifeExtension; Links/Licorice]. Glycyrrhiza has been found to activate immune system cells [Links, Video, Papers, Patents, Books, LifeExtension] as quantified by CD69 expression in manner similar to echinacea and astragalus root. Glycyrrizin is effective against many viruses, exceeded by garlic, however. Glycyrrhiza extract also promotes cyclic AMP, and inhibits cAMP phosphodiesterase, which degrades cAMP. Cyclic AMP (cAMP) lowers caveolin-l levels, which can recover cells from the senescent state. Thus licorice (glycyrrhiza) plus exercise with creatine monohydrate (acting to boost c-AMP from boosing ATP) is useful for treating senescence, especially with carrots for retinol to suppress p16INK4A, which makes recovery from senescence difficult, plus a suitable choice of telomerase activators. Glycyrrhiza is also an anti-inflammatory HMGB1 inhibitor [Zhu S, Li W, Ward MF, Sama AE, Wang H (2010)]. Finally, licorice is a strong estrogen bioactivity nutraceutical that activates the estrogen-beta receptor in hip bones, causing hip broadening. The strong estrogen bioactivity means that licorice is a telomerase activator.
GMP Compliant Production Facilities Good Manufacturing Practices [Links; Links/GMP Compliance; Links/Good Manufacturing Practices].
Goji Berries (Wolfberries) Shangri-la's Chinese Wolfberry (Links/GoJi Berries, Images, Video, Papers, Patents, Books, Ray) [LifeExtension/Wolfberry; Links/Wolfberries, Images, Video, Papers, Patents, Books, Wikipedia/Wolfberry, Index/Wolfberry]. Goji Berries (Wolf Berries) are said to "elevate SOD". Li-Ching Yuen, said to have lived to the age of 252 years (1678-1930), consumed Goji berries daily. See SOD and supplements improving the expression of SOD, such as Chaga, Xango, Noni, Ashwagandha, Bacopa, SODzyme, and GliSODin. Supplements elevating endogenous antioxidants often elevate SOD.
Good Manufacturing Practices (GMP) [Wikipedia, Links, Video, Papers, Patents, Books, LibCong].
Gotu Kola (Centella Asiatica) [Links/Gotu Kola, Images, Video, Papers, Patents, Books; Telomerase Activator Candidates/Gotu Kola; Links/Centella Asiatica, Images, Papers, Patents, Books]. Gotu Kola (Centella Asiatica) stimulates collagen synthesis, and is found in LifeExtension's Cellulite Suppress formula. It has also been used as an Aryurvedic nerve tonic to improve mental clarity, and is a component in several of Ray Sahelian's mind-power formulations. Vitamin Research promotes Gotu Kola as a nerve growth regeneration component of a product for brain regeneration. Gotu Kola is also used to accelerate wound healing and is applied to varicose veins. Gotu Kola was used by the Li Ching-Yuen in his prior research on Immortality Diet. VIDA Institute recommends taking astragalus extract with ginkgo biloba (to improve circulation) and gotu kola (to improve vision and fine circulation). "Centella Asiatica (gotu kola) has been shown clinically to improve circulation in the fine capillary vessels of human tissue."
GPC - Glycerophosphocholine [Links, Images, Video, Papers, Patents, Books, LifeExtension]. GPC (glycerophosphocholine) increases acetylcholine synthesis, and is useful in preserving cognitive function with aging. It is also an HGH secretagogue that can elevate HGH by a substantial factor in the presence of exercise that would otherwise elevate HGH by a factor of perhaps 3. HGH is a telomerase activator [List/HGH], useful in lengthening telomeres in the presence of exercise [Index]. See Alpha-glycerylphosphocholine (Alpha-GPC).
Grape Seed extract [Links, Images, Video, Papers, Patents, Books, LifeExtension], [36], (0). Grape Seed Extract (bodybuilding site), (0). Grape seed extract with calcium promotes bone formation and defeats osteoporosis. Gallic acid from grape seed extract is thought to be anti-proliferative, pro-apoptotic, and anti-angiogenic in acting against prostate cancer. See angiogenesis inhibitors, which include gallic acid. Grape seed extract also contains resveratrol. Grape seed extract (140) is a telomerase inducer promoting telomere growth in dermal fibroblasts according to Product B literature.
Grape Seed Polyphenols [Links, Images, Video, Papers, Patents, Books, LifeExtension]. "Phosphatides from soy lecithin [Index/Lecithin, Index/Phosphatidylcholine] enhance the uptake of grape seed polyphenols to targeted brain tissues." Hydroxyl free radicals that peroxidize lipids and oxidize DNA are thereby neutralized. This combination can "improve age-related cognitive oxidative damage and cerebral amyloid deposition while improving blood circulation to the brain." - [LifeExtension, October 2009, Robert Haas, Are You Safe from Alzheimer's Disease and Cognitive Decline?]. Also see Life Extension Cognitex, [Links/soy lecithin phosphatides with grape seed extract, Images, Papers, Books; Links/soy lecithin, Images, Video, Papers, Patents, Books].
Grape Varieties [Wikipedia/Grape Varieties, Links/grape varieties, Images, Video, Papers, Patents, Books], (0).
Green Coffee Bean Extract [Links/Green coffee bean extract, Images, Video, Papers, Patents, Books]. Green coffee bean extract can be taken at 350 mg before meals to help with fat loss in a diet program. By lowering postprandial glucose levels with chlorogenic acids, green coffee bean extract is believed to lower heart attack risks. "Green coffee bean extract lowers blood glucose by inhibiting carbohydrate digestive enzymes (similar to the drug acarbose) and suppressing creation of glucose in the liver (like metformin)." See William Falloon (2013), Preparing Your Body to Eat, Life Extension Magazine, Feb 2013.
Green Fluorescent Protein (GFP) [Wikipedia, Prospec rGFP from E.Coli/Amino Acid sequence, Links/GFP, Images, Video, Papers, Patents, Books, Amazon; Wiki/Yellow Fluorescent Protein; Introduction to Fluorescent Proteins, Fluorescence Microscopy (Links); Index/Luciferase].
Press for 'Knockout Rats the Easy Way' in Chemical and Engineering News. Green Fluorescent Protein, discovered in the early 1960s, is produced by the jellyfish Aequorea Victoria, which produces green bioluminescence. The GFP gene was cloned in 1992. The GFP gene encoded by the l GFP2 genomic clone is comprised of at least three exons spread over 2.6 kb. Green Fluorescent Protein is a useful and ubiquitous instrument for producing chimeric proteins, where it functions as a fluorescent protein tag. It is associated with a useful class of biosensor fluorophores called fluorescent proteins. Note that modern Zinc Finger Nuclease Technology for Targeted Genome Editing can insert the genetic code for the 238 amino acid green fluorescent protein [Images] anywhere in the mammalian genome. Thus we now have rats with tails that glow green in the dark, for instance. Then we test our gene deletion capabilities by using ZFN technique to delete the green fluorescent protein gene, and the rat's tail gets back to normal. The AAV virus 4.8 kilobase genome << 3x238 + 6 = 720 bp required for minimal representation of GFP and also smaller than the 2.6 kb GFP2 genomic clone. A sizable promoter might even be included to register the effect of various cofactors on the expression of designer GFP in various experiments. On the other hand, hTERT has an estimated size of about 40kb, far too much to include in an AAV virus targeted to AAVS1 [Wikigenes] on human chromosome 19, although still small enough to insert into the cell in a plasmid via a cationic liposome endocytosis, with or without a zinc finger nuclease dimer with FokI endonucleases for insertion of the plasmid into the host genome. The adenovirus genome, which always integrates into the same site in the host genome like an AAV virus, is composed of between 26 and 45 Kbp of nonsegmented, linear, double stranded DNA. See Fluorogenic Probes and Primers from Biosearch Technologies. Green Fluorescent Protein driven by the hTERT promoter installable with adenovirus serotype 35 tropism-based vectors is described in Anna Edqvist, Johnan Rebetz, Marcus Jaras, Anna Rydelius, Gunner Skagerberg, Leif G. Salford, Bengt Widegren, and Xialong Fan, (2006), Detection of cell and differentiation stage-dependent human telomerase reverse transcriptase expression in single living cells, Molecular Therapy, 2006, 14:139-148. See also In Vivo internal tumor illumination by telomerase-dependent adenoviral GFP for precise surgical navigation, PNAS, August 2009, vol 106, no 34, 14514-14517. See also Chalfie, M. (1995), Green Fluorescent protein, Photochemistry and Photobiology 62:651-656.
Luciferase [Index/Luciferase, Links, Images, Video, Papers, Patents, Books; Links/Luciferase assays, Images, Videos, Papers, Patents, Books]. Note that many bioscience fluorescent assays have been developed around luciferase, firefly luciferase or renilla luciferase, by incorporating a gene for luciferase in an engineered test plasmid, for instance. See also the related themes cell staining, and cell staining reagents, fluorescence microscopy and flow cytometry.
Green, Jim [Home Page] All-time best lifts [26].
Green Tea [Index/Tea Polyphenols, Index/(Black Tea) Theaflavins, LEF/Green tea, Green tea polyphenols, LifeExtension/green tea polyphenols, Links/Green tea, Images, Video, Papers, Patents, Books; Black Tea, White Tea, Tea Polyphenols, Theaflavins; Coffee]. Green tea is an antioxidant and protects against sunlight UV damage. Note that green tea inhibits collagenase. "Topical application of green tea extract reduces protein glycation in the skin by up to 75%." (LE), [25b]. Green tea is a small molecule telomerase inhibitor for cancer cells, but behaves like a telomerase activator (141) for normal cells, possibly because antioxidants tend to confine hTERT to the cellular nucleus. Green tea extract catechins get through to eye tissues and lower oxidative stress marker 8-epi-isoprostane throughout the eye. (Chi Pui Pang, et. al, J. Agric Food Chem, 2010 Feb 10;58(3):1523-34.) On the bodybuilding side, according to Jim Stoppani PhD of Muscle and Fitness magazine (Fall 2009) in Elements of a Stack, green tea is an effective component of a program for fat burning, and EGCG in green tea is itself an effective fat burner, boosting fat release from cells. (See caloric restriction.) Green tea also inhibits the enzyme lipase, preventing fat absorption into the blood. To increase basic metabolic rate, green tea inhibits the enzyme catechol-O-methyl transferase (COMT) that breaks down noradrenaline. Stoppani recommends 500-1000 mg of green tea extract standardized to 50% EGCG taken 30-60 minutes before a workout. Components of an effective bodybuilding fat burning program include the primary component
L-carnitine (1-3 grams with meals and pre- and post-workout shakes), with
CLA (1-3 grams),
Forskolin (20-50 mg 30-60 min before each workout and before meals), and
Green Tea extract (500-1000 mg taken 30-60 min before each workout and before meals).
Green tea contains catechins that also inhibit hair loss by inhibiting 5-alpha-reductase, an enzyme which converts testosterone into dihydrotestosterone, which attacks hair and promotes benign prostatic hyperplasia (BPH) and prostate cancer. Green tea reduces the incidence of dementia, Alzheimer's Disease, and Parkinson's Disease, all of which may be induced by inflammation. See Weinreb O, Mandel S, Amit T, Youdim MB (2004), Neurological mechanisms of green tea polyphenols in Alzheimers and Parkinsons diseases, Journal of Nutritional Biochemistry 2004 Sept;15(9):506-16 and Michael Downey (2014), How Green Tea Protects Against Alzheimer’s Disease, Life Extension Magazine, August 2014. See also Xu Y, Zhang JJ, Xiong L, Zhang L, Sun D, Liu H. (2010), Green tea polyphenols inhibit cognitive impairment induced by chronic cerebral hypoperfusion via modulating oxidative stress, J Nutr Biochem 2010 Aug;21(8):741-8. Green tea reduces inflammation by inhibiting the transcription factor NF-kB with EGCG. NF-kB is found in 95% of human cancers and promotes the expression of genes supporting cancer-related pathways. Its normal function may be to promote wound healing and tissue remodeling associated with wound healing, as in the healing of varicose veins, when some inflammation may be observed. The NF-kB inhibitor property of EGCG blocks carcinogenesis at every stage, including proliferation, invasion, tumor blood vessel development, and metastasis, while defending cancer cells (usually obtained via successive mutations induced by carcinogens) from apoptosis. Green tea catechins, shown to kill bacteria associated with dental caries and periodontal disease, strengthen teeth. - after Jon Finkel, Green Tea May Strengthen Teeth, Life Extension Magazine, July 2010. Green tea extract [Images] is also used to protect kidneys against kidney disease. See Nathaniel S.W. Luce, Proprietary Green Tea Extract Protects the Kidneys, Life Extension Magazine, June 2011.
Greider, Carol W. [pron: grader; Wikipedia, Links, Images, Video, Papers, Patents, Books; Carol Greider (Images).Nobel Lecture by Carol Greider (Video); Interview with Elizabeth H. Blackburn, Carol W. Greider, and Jack W. Szostak (Video)]. Carol W. Greider is the codiscoverer of the telomere [Links] sequence in the cilliate Tetrahymena (1978), codiscoverer of the enzyme telomerase (1985). Elizabeth Blackburn, Carol Greider, and Jack Szostak shared the 2009 Nobel Prize in Medicine (Links) for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase. See the Nobel Prize Winner's essay Telomeres and Telomerase: the path from maize, Tetrahymena, and yeast to human cancer and aging by Elizabeth H. Blackburn, Carol W. Greider, and Jack W. Szostak.

G-rich Telomeric Overhangs [Links, Images, Video, Papers, Patents, Books]. G-rich telomeric overhangs (G-tails, G-overhangs) feed back into homologous double-stranded telomeric tracts to form a telomere t-loop (Griffith, et al, 1999). See also Wright WE, Tesmer VM, Huffman KE, Levene SD, Shay JW (1997), Normal human chromosomes have long G-rich telomeric overhangs at one end, Genes and Development 11: 2801-09.
Grey hair [Index/Hair Greying]. See Melancor to reverse greying of hair, [48], [74s]. On the average, 50% of persons have 50% grey hair by age 50 [Hisama, Chromosomal Instability and Aging, p.565]. See Hair Greying: [Index/Hair Greying, Links, Images, Video, Papers, Patents, Books, LifeExtension], Melancor to reverse greying of hair, [48]. Also see [74s/GREYING]. Topical admistration of small molecule telomerase activators such as astralagus extract can restore hair color by rejuvenating the stem cells that restore hair melanocytes, at a rejuvenation rate of about 5 to 9 years per year. Oral administration does not work as well in this case as direct application to the scalp, rubbing astragalus extract in with one's fingers. See Telomere Remodeling with Cyclic Telomerase Activation. Tribulus, an aphrodisiac, may be used to activate the transcription of melanocyte-stimulating hormone, darkening hair. Greying seems to be due in part to lack of the endogenous antioxidant catalase, so that hydrogen peroxide bleaches the hair from the inside out. Ashwagandha, Bacopa, and other medicines can elevate expression of endogenous antioxidants to eliminate internal hydrogen peroxide bleaching.
GRN139951 [Aegis/GRN139951 (probably astragaloside IV), a small molecule telomerase activator from Geron. [Links]. "Geron Corporation, in collaboration with the Biotechnology Research Institute, Hong Kong University of Science and Technology, conducted a screen for telomerase activators [List] (7) using human keratinocytes. The source of material for the screen was natural product extracts. In the course of the screen, several extracts were discovered that reproducibly up-regulated the low, basal level of telomerase in human keratinocytes. With analysis of the extract and further testing, one compound in the extract, named GRN139951, was identified as the key telomerase activator in the extract. It was capable of activating telomerase in keratinocytes and other human cell types (e.g. lymphocyte immune cells) at very low concentrations. GRN140665 (probably cycloastragenol), a derivative of GRN139951 also present in the extract but at lower concentrations, was prepared and found to possess similar telomerase activating properties. (I note that cycloastragenol may be chemically derived from astragaloside IV by a process well-described by Geron patent literature.) These molecules are under development for the treatment of degenerative diseases by TA Therapeutics, Limited." - BioExchange News.
GRN140665 [Aegis/GRN140665 (probably cycloastragenol, and TA Sciences TA-65), a small molecule telomerase activator from Geron. [Links].
Growth Hormone [Index/HGH, Smart-Drugs/Growth Hormone, Links, Images, Video, Papers, Patents, Books, Ben Best, (2)]. Growth hormone HGH and IGF-1 may also be useful in lengthening telomeres, but they must be applied carefully, as telomerase activation does not inhibit proliferation of undesirable cell colonies and interferes with one of the body's cancer-inhibiting mechanisms. See the relatively extensive entry Index/HGH. "Aging is also accompanied by a gradual decrease in the output of GH, like the drying of an internal fountain, until in the eighth decade of life, it is secreted at less than one-fifth of the "youthful" level." - (Jason Wolfe, Rejuvenation Research, 1998). IGF-1 receptors exist in every cell in the body. See the tissue distribution of HGH receptors.
Growth Hormones and Growth Factors [Index/Human Growth Factors, Links/Growth Hormones, Images, Video, Papers, Patents, Books, LifeExtension, Amazon; Links/Growth Factors, Images, Video, Papers, Patents, Books, LifeExtension; Amazon, Index/Growth Factor Skin Creams].
Most growth hormones and growth factors activate hTERT using pathways or activation sites on the hTERT promoter. Some of the activation pathways include:
MAP kinase [Links/MAP Kinase Pathway, Biocarta],
___(activates transcription of hTERT mRNA from the hTERT gene),
Akt [Akt1, Links/Akt1 Pathway, Biocarta],
___(phosphorylates hTERT protein in the cytoplasm for translocation into the nucleus), and/or
Protein kinase C [Links/Protein Kinase C Pathway, Biocarta]
___(phosphorylates hTERT protein in the cytoplasm for translocation into the nucleus).
Epithelial Growth Factor (EGF) [Links, Images, Video, Papers, Patents, Books]. "Growth factors such as epithelial growth factor (EGF) elicit cellular signaling including MAP kinase, Akt and protein kinase C." - Sharyn Baynea and Jun-Ping Liu, (2005) Hormones and growth factors regulate telomerase activity in ageing and cancer, Molecular and Cellular Endocrinology, Volume 240, Issues 1-2, 30 August 2005, Pages 11-22.
Some Growth Hormones and Growth Factors associated with telomerase activation include:
Growth Hormone or FactorNotes
HGH [Index]Human Growth Hormone. Enables hTERT mRNA transcription.
IGF-1 [Index]Insulin-like Growth Factor 1.
Phosphorylates hTERT protein for transfer into the nucleus.
EGF
Epidermal Growth Factor. Enables hTERT mRNA transcription.
EGF
Epithelial growth factor. Enables hTERT mRNA transcription.
PDGFPlatelet-Derived Growth Factor. Enables hTERT mRNA transcription.
FGF1 Fibroblast Growth Factor 1. Activates telomerase.
FGF2 Fibroblast Growth Factor 2. Activates telomerase.
FGF7 Keratinocyte Growth Factor. Activates telomerase.
VEGFAVascular Endothelial Growth Factor A activates telomerase.
VEGF2Vascular Endothelial Growth Factor 2 activates telomerase.
NGF [Index]Nerve Growth Factor.
Immortalizes keratinocytes, enables hTERT mRNA transcription. Limits P16INK4A. Activates hTERT transcription via Id-1 transcription factor.
TGF-alpha
Transforming Growth Factor alpha. Telomerase activator candidate.
and others from our list of Telomerase Activators.
Regulation of FOXO Without growth factor stimulation, the FOXO transcription factor translocates to the nucleus and induces target gene expression in genes such as CAV-1, leading to cellular senescence. Growth factor stimulation leads to activation of Akt kinase, which phosphorylates FOXO. This creates binding sites for the cytosolic chaparone 14-3-3, which sequesters FOXO in inactive form in the cytoplasm outside the nucleus, preventing FOXO-induced expression of CAV1 and caveolin-1 induced senescence. (after G. Cooper and R.E.Housman, p.626).
Guggulsterones [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Guggulsterones are plant sterols extracted from the Indian tree commiphora mukul. E guggulsterones and Z gugglesterones are the most bioactive, enhancing thyroid hormone output and thermogenesis for improved fat burning. Guggulsterones also improve joint recovery and cholesterol levels. Guggulsterones are taken at 20-60 mg/dose 2 or 3 times per day. - (after Muscle and Fitness Magazine, 2010). Check: Guggulsterones promote thyroid hormone T3 expression, "especially through increased conversion of T4 to T3 in the liver..." (Thyromend). Note that thyroid hormone T3 rapidly induces AMPK activation, supplying more ATP via catabolic reactions for improved autophagy of cellular junk in senescent cells and for apoptosis of senescent cells.
Gugulipid [Links/Gugulipid, Images, Video, Papers, Patents, Books, LifeExtension]. Gugulipid lowers LDL, raises HDL, lowers cholesterol & triglycerides. "Guggulipid (Commiphora mukul) has shown an ability to support thyroid function, especially through increased conversion of T4 to T3 in the liver, the principle site of T3 generation." - Thyromend
Gulonolactone oxidase [LewRockwell/Gulonolactone oxidase, Links, Images, Video, Papers, Patents, Books]. See gulonolactone oxidase and Vitamin C metabolism, [29].
Gymnema Sylvestre [Links, Images, Video, Papers, Patents, Books, LifeExtension]. The main constituents of Gymnema Sylvestre are:
(1) gymnemic acid [Links, Images, Video, Papers, Patents, Books, LifeExtension],
(2) tartaric acid [Links, Images, Video, Papers, Patents, Books, LifeExtension],
(3) gumarin [Links, Images, Video, Papers, Patents, Books, LifeExtension],
(4) calcium oxalate [Links, Images, Video, Papers, Patents, Books, LifeExtension],
(5) glucose [Links, Images, Video, Papers, Patents, Books, LifeExtension],
(6) stigmasterol [Links, Images, Video, Papers, Patents, Books, LifeExtension],
(7) betain [Links, Images, Video, Papers, Patents, Books, LifeExtension], and
(8) choline [Links, Images, Video, Papers, Patents, Books, LifeExtension].
Gymnema Sylvestre extract (from the Gymnema Sylvestre rain forest vine) drives up insulin levels when carbs are present. 250-500 mg of Glymnema Sylvestre extract [Images] is recommended in a recovery stack also including whey protein (20-30 grams), Branched-Chain Amino Acids (5-10 grams, emphasizing leucine), and slow-digesting casein protein (10-20 grams). Since Jerry Brainum's observation ("Whey Ahead", Iron Man, July 2010) that myostatin inhibition is better served by taking whey protein before the workout, post-workout shake contents are in question. Whey protein taken after a workout tends to block myostatin inhibitors [Images] that allow muscle size to increase, so perhaps slowly absorbed casein protein, egg protein, tuna, or fertilized hen's eggs containing myostatin inhibitors would be an improvement. See Protein. Gymnema Sylvestre also increases the excretion of cholesterol in feces, so that it is useful for lowering cholesterol. (P.Kanetkar, R. Singhal, and M. Kamat (2007), Gymnema Sylvestre: A Memoir, J. Clin. Biochem Nutr., 41, 77-81, September 2007). Gymnema Sylvestre leaves lower serum cholesterol and triglycerides. Gymnemic acid molecules from Gymnema Sylvestre fill a receptor location in the absoptive layers of the intestine, preventing sugar molecule absorption and lowering blood sugar. Its power to boost insulin secretions causes Gymnema Sylvestre to phosphorylate tankyrase 1, a telomeric PARP which strips telomere binding protein TRF1 from telomeres via poly(ADP-ribosylation), causing them to open and become accessible to the enzyme telomerase, which lengthens the telomere. Therefore, Gymnema Sylvestre may be useful as a tankyrase-activating adjuvant for telomerase activator therapy, making telomeres more accessible to telomerase.

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