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Echinacoside [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Echinacoside is a phenylethanoid isolated from the stems of Cistances salsa, [Images, Papers, Patents, Books] a traditional Chinese herbal medicine. Echinacoside retards senescence [Images, Papers, Patents, Books]. Furthermore, echinacoside seems to improve DNA damage protection [Images, Papers, Patents, Books]. Cistanche (which promotes NK cell activity boosts naive T-cells) contains echinacoside, which stimulates the creation of T-cells, reduces apoptosis, and suppresses premature conversion of naïve T-cells into activated memory T-cells.
Effros, Rita [UCLA Faculty Site, Links/Rita Effros, Images, Video, Papers, Patents, Books]. See Rita Effros' UCLA Site for links to published papers on telomeres and telomerase in immunology and gerontology. See, for instance, Telomerase-based approaches to enhance immunity to viruses during ageing, August 29, 2007, from TA Sciences' Telomere Science Library.
EGCG (epigallocatechin-3 gallate) [Links/EGCG (epigallocatechin-3 gallate), Links/EGCG, Images, Video, Papers, Patents, Books, LibCong, LifeExtension; Wikipedia/Flavonoid, green tea; polyphenols, Links/green tea polyphenols, Images, Video, Papers, Patents, Books], [25b]. EGCG (epigallocatechin-3 gallate molecule) is an antioxidant and also a telomerase inhibitor for cancer cells found in green tea. Green tea extract (141) containing EGCG behaves like a telomerase activator for normal dermal fibroblasts, possibly because antioxidants tend to confine hTERT to the nucleus. Epigallocatechin gallate represses glucose production in the liver, limiting blood sugar levels and glycation damage. EGCG also increases the number of regulatory T-cells, which suppresses autoimmune disease associated with immunosenescence. - LifeExtension, September 2011; Immunology Letters, 2011 May 20. EGCG is a NF-kB inhibitor effective in blockading many cancers by halting NF-kB transcription factor from promoting TNF-alpha mRNA transcription in the nucleus, reducing iNOS production, and counteracting NF-kB driven pathways promoting cancer cell proliferation, invasion, tumor blood vessel development, and metastasis. EGCG promotes (NF-kB inhibited) apoptosis in prostate cancer cells. EGCG inhibits HMGB1 (High Mobility Group Box-1), which triggers higher levels of inflammatory cytokines. Furthermore, EGCG activates AMP-activated protein kinase (AMPK) (like many other AMPK-activating nutraceuticals), to inhibit fat storage, reduce cholesterol-triglyceride synthesis, and increase glucose uptake into muscle while improving autophagy of cellular junk in senescent cells and supplying ATP for the elimination of pro-inflammatory senescent cells via apoptosis, while regulating mitochondrial biogenesis.
Elderberries [Links/Elderberries, Images, Video, Papers, Patents, Books; Virology].
Black Elderberries [Images] are effective against orthomyxoviruses, including influenza A virus (flu), a 14 kbp virus with an RNA genome that causes all flu pandemics.
See Tiffany Corkern, Elderberry: The Definitive Guide.
Electrophilic Stress and Aging [Links/Electrophilic stress and aging, Images, Video, Papers, Patents, Books; Links/electrophilic stress, Images, Video, Papers, Patents, Books; Links/electrophilic substances, Images, Video, Papers, Patents, Books]. Electrophilic stress can result from lipid peroxidation [Index] due to oxidative stress [Index] and is thought to contribute to aging in C. Elegans, for instance. All electrophilic substances are Lewis acids [Links]. Glutathione and the glutathione S-transferase system work to eliminate problems due to electrophilic substances in phase II reactions [Wikipedia], so electrophilic stress due to lipid peroxidation or the action of metabolizing enzymes producing both xenobiotics and electrophilic substances may probably be treated by using drugs that increase glutathione peroxidase levels, such as ashwagandha, which increases levels of endogenous antioxidants generally, as does bacopa. Other boosters of glutathione include alpha lipoic acid, NAC (N-Acetyl Cysteine), SAMe, whey protein, asparagus, broccoli, avocado spinach, and Changkil saponins (CKS) from the roots of Platycodon grandiflorum A. DC (Campanulaceae), called Balloon Flower Root (Jie Geng). Curcumin increases expression of glutathione S-transferase. Glutathione peroxidase activity is enhanced by vitamin C. Silymarin (milk thistle extract) prevents glutathione depletion. Note that glutathione incorporates selenium, which may be obtained from popular multivitamin pills such as Centrum, for instance, to promote glutathione synthesis. See Links/glutathione, Wikipedia/Glutathione, Books/glutathione, Links/increase glutathione peroxidase levels, Books/glutathione peroxidase levels.
Ellagic acid [Wikipedia, Links, Images/Ellagic acid supplements, Video, Papers, Patents, Books, LifeExtension]. Ellagic acid is an anti-cancer nutraceutical found in walnuts, pecans, strawberries, cranberries, pomegranates and red raspberry seeds, [25e].
Elastase, Elastase Inhibitors, and Elastin
Elastin [Wikipedia, LibCong, Links/Elastin, Images, Video, Papers, Patents, Books, LifeExtension;
Links/Elastase, Images, Video, Papers, Patents, Books, LifeExtension;
Links/Elastase inhibitors, Video, Papers, Patents, Books; Phytoceramides, (5); Anti-Elastase, Anti-Collagenase Nutraceuticals]. Elastin is a component of elastic fibers [Wikipedia, Links, Images, Video, Papers, Patents, Books]. Elastic fibers are primarily composed of the amino acids glycine, valine, alanine and proline. Note that elastin is cross-linked into a network by covalent bonds formed between side chains of lysine residues similar to lysine residues found in collagen. Perhaps supplementing lysine can improve elastin and collagen cross-linking into an elastic network. See Rejuvenation of Elastin [LifeExtension, Links, Images, Papers, Patents, Books] and Repair of Elastin [Links, Images, Papers, Patents, Books, LifeExtension]. Elastin, hyaluronic acid, and collagen can be restored by applying FGF-1 skin cream (FGF). Transforming growth factor beta (TGF-beta), which is found in telomerase-activating colostrum skin creams [Images] and in telomerase-inhibiting TGF-beta skin creams [Images], restores both collagen and elastin in the extracellular matrix. I have gotten good results for elastin restoration by applying soy milk to facial skin and to bags under the eyes. "Topical soy has been shown to improve hyperpigmentation, elasticity, and moisture in the skin. In laboratory studies, soy has been shown to stimulate collagen synthesis and initiate the skin’s process of repairing elastin." - See Gary Goldfaden, MD and Robert Goldfaden (2011), Reverse Skin Aging Around Your Eyes, Life Extension Magazine, June 2011. Music: Dr. Robert.
See Robert Visse, Hideaki Nagase (2003), Matrix Metalloproteinases and Tissue Inhibitors of Matrix Metalloproteinases, Circulation Research, 2003;92:827.) One of the matrix metalloproteinases, Metalloelastase (MMP-12), attacks elastin. See metalloelastase inhibitors and supplements inhibiting metalloelastase. Other matrix metalloproteinases exist for attacking collagens [MMP-1, MMP-8, MMP-13, and MMP-18 (Xenopus)] and gelatin [Gelatinase A (MMP-2) and Gelatinase B (MMP-9)]. TIMP1 and TIMP3 are tissue inhibitors of matrix metalloproteinases. See
(1) Robert Goldfaden and Gary Goldfaden (2014),
Target Wrinkle Formation with Novel Peptides, Life Extension Magazine, April 2014.
Advanced Triple-Peptide Serum.
___See acetyl hexapeptide-51 [Images, Papers, Patents, Books],
___acetyl-tetrapeptide-2 [Images, Papers, Patents, Books; Youth Serum], and
___palmitoyl tripeptide-5 [Images, Papers, Patents, Books; Tripeptide-5].
"One of the main reasons elastin production decreases as we age is due to diminishing levels of the enzymes lysyl oxidase-like 1 (LOXL1) and glycoprotein fibulin-5 (FBLN5)."
(2) Rossetti D, Kielmanowicz MG, Vigodman S, et al. (2011),
A novel anti-ageing mechanism for retinol: induction of dermal elastin synthesis and elastin fibre formation,
Int J Cosmet Sci 2011 Feb;33(1):62-9. Retinol [Images, Papers, Patents, Books].
(3) Cenizo V, Andre V, Reymermier C, et al. (2006),
LOXL as a target to increase the elastin content in adult skin: a dill extract induces the LOXL gene expression, Exp Dermatol 2006;15:574-81. Dill extract [Links, Images, Papers, Patents, Books].
(4) Braverman IM. (1986),
Elastic fiber and microvascular abnormalities in aging skin, Dermatol Clin 1986 Jul;4(3):391-405.
(5) Downey, Michael (2014),
Phytoceramides Skin Rejuvenation From The Inside Out [OnLine],
Life Extension Magazine, November 2014. Oral phytoceramides such as oral wheat phytoceramides are elastase inhibitors and replenish aging skin's dimenishing ceramides over 4-5 weeks at 350 mg/day to implement facial rejuvenation.
(6) 1.Thring et al. (2009),
Anti-collagenase, anti-elastase and anti-oxidant activities of extracts from 21 plants,
BMC Complement Altern Med 2009, 9:27. See Anti-Elastase, Anti-Collagenase Nutraceuticals. White Tea had the highest anti-elastase and anti-collagenase activity of any extract tested.
ELSD (Evaporative Light Scattering Detection) [Links, Images, Video, Papers, Patents, Books]. ELSD is used by Terraternal for astragaloside testing, along with HPLC [Links, Images, Video, Papers, Patents, Books], High Pressure Liquid Chromatography.
Endometrial Cancer [Links/endometrial cancer, Images, Video, Papers, Patents, Books, Amazon, LifeExtension; Cancer, Carcinogens, Breast Cancer, Ovarian Cancer, Prostate Cancer; Anticancer Nutraceuticals; Apoptosis, Telomerase Inhibitors; Anticancer Telomerase Activators; Metastasis, NFkB, NFkB Inhibitors, Angiogenesis Inhibitors]. Progesterone reduces the likelihood of endometrial cancer due to stimulation with excess estrogen. However, application of combinations of progesterone and estrogen for birth control applications or hormone therapy still increase the liklihood of breast cancer. Genistein, a soy isoflavone, upregulates ER-beta receptors which seem to oppose carcinogenic factors promoted by ER-alpha receptors in breast cancer, ovarian cancer, and endometrial cancer.
Endogenous Antioxidants [Links/endogenous antioxidants, Images, Video, Papers, Patents, Books, LifeExtension]. Antioxidants are either native to the organism (endogenous) or come from the outside (exogenous). Endogenous antioxidants are primary in cellular metabolism and include:
___Alpha Lipoic Acid (Lipoic Acid).
___COQ10 (ubiquinol, ubiquinone),
___Glutathione (GSH), including the oxidized form
______Glutathione disulphide (GSSG),
______Glutathione Reductase (GSR or GR), and
______Glutathione Peroxidases (GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, GPX8),
___SOD (Superoxide Dismutase), including
____(1) CuZnSOD (SOD1) - Cytoplasmic SOD [Links/CuZnSOD, Wiki/SOD1].
____(2) MnSOD (SOD2) - Mitochondrial SOD [Links/MnSOD, Wiki/SOD2].
____(3) Extracellular SOD (SOD3) [Links, Wiki/SOD3]. Selenium and copper SOD.
_______Intracellular SOD (SOD3) [Links]. Selenium & Copper SOD (SeCuSOD).
Levels of SOD, catalase, and glutathione (GSH) can be elevated with supplements such as Ashwagandha, Bacopa, Huperzine A, and Shilajit. SOD levels are elevated by GliSODin, SODzyme, and Chinese Wolfberry (Goji Berries). See Links/supplements elevating endogenous antioxidant levels. Mitochondrially targeted antioxidants such as CoQ10 (ubiquinol, ubiquinone) and alpha lipoic acid are important in the mitochondrial theory of aging as pictured by Aubrey de Grey and Michael Rae in their book Ending Aging. Catalase is presently available directly in hair treatment preparations. Lack of catalase is thought to lead to internal bleaching and grey hair. It is also true that extra catalase can be mitochondrially targeted by gene therapy techniques. Catalase, a protein enzyme, is mitochondrially targeted from its assembly site in the endoplasmic reticulum by a stretch of 20-80 amino acids in which positively charged side chains stick out on one side of a helix and hydrophobic side chains stick on the other, forming an amphipathic helix. Specific receptors in the cytosol guide catalase to the mitochondria using the appropriate cytosolic translocation machinery, which selects proteins for transport destinations based on a targeting sequence (localization sequence) of 3-80 amino acids. - Bolsolver, Hyams, Shephard, White, and Wiedemann, Cell Biology A Short Course, 2nd edition, John Wiley & Sons, 2004, pp. 215. For gene design technique to place targeting sequences and related material, see orf.clone technology from Invitrogen and other firms.
Endogenous antioxidants and antioxidants in general tend to confine hTERT to the nucleus, tending to elevate telomerase activity. "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 usual method of upregulating glutathione is to take alpha lipoic acid. Other glutathione boosters include N-Acetyl-Cysteine (NAC), 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. Note that glutathione incorporates selenium, which may be obtained from popular multivitamin pills such as Centrum, for instance, to promote glutathione synthesis.
Endogenous Telomerase Activators [Index/Telomerase Activators; List/Telomerase Activators, Links/Endogenous Telomerase Activators, Images, Video, Papers, Patents, Books].
Endogenous telomerase activators include:
(1) Transcription factors that activate hTERT transcription via hTERT promoter interactions,
___including c-Myc (List, Index), c-Myc dimerized with Max, Sp1 (List), HIF-1 (List),
___Id-1 helix-loop-helix protein (List), Ets, Ap-1, and estrogen receptor complex (List).
___Note that Survivin (encoded by the BIRC5 gene) phosphorylates transcription factors
___ to upregulate telomerase, including c-Myc and Sp1, and also inhibits apoptosis.
___Histone Acetyl Transferase (hALP) activates telomerase, perhaps by helping
___to construct the estrogen receptor complex from estrogen, estrogen receptor, and hALP.
(2) hTERT protein phosphorylating kinases enabling hTERT protein transport into the nucleus
___from the cytoplasm, including AKT1 kinase (List) and Protein Kinase Cα (List).
(3) Growth Factors and Growth Hormones that activate hTERT transcription,
___including HGH, Epidermal Growth Factor (EGF), which increases expression of c-Myc,
___Platelet-Derived Growth Factor (PDGF), which also increases expression of c-Myc,
___Fibroblast Growth Factor 1 (FGF1), Fibroblast Growth Factor 2 (FGF2),
___Epiregulin (EGF family), ?Transforming Growth Factor alpha? (TGF-alpha).
___Most other human growth factors also activate telomerase. See Growth Factor Skin Creams.
___Vascular Endothelial Growth Factor 2 and Keratinocyte Growth Factor (FGF7)
___have been evaluated as telomerase activators and are used in skin creams.
___According to several scientists, EGF works through the Map Kinase Pathway (Index),
___which can express the hTERT promoter transcription factors c-Myc, AP-1, and Ets.
___Granulocyte Colony-Stimulating Factor is a telomerase activator in hemopoietic stem cells.
___Hepatocyte Growth Factor (HGF) activates telomerase.
___Epithelial Growth Factor activates telomerase via MAP kinase, AKT, and Protein kinase C.
___FGFR-2 - rejuvenates fibroblast cells to produce new collagen, hyaluronic acid and elastin.
___KGFR (Keratinocyte Growth Factor Receptor) - rejuvenates the epidermal cells.
___FGF-7 (Keratinocyte Growth Factor) rejuvenates hair follicle to produce new hair.
___Epiregulin (from the EGF family) probably activates telomerase.
___TGF-alpha interacts with the EGF receptor and probably activates telomerase.
(4) Growth factors and Growth Hormones that phosphorylate hTERT protein for nuclear import,
___such as IGF-1 (PI3/AKT1 pathway).
(5) Exercise-induced telomerase activators (fifteen),
___including HGH (List), IGF-1 (List), PDGF, HIF-1, epiregulin, testosterone (List),
___estrogen (List) (from testosterone via aromatase), HSP90, TFG-alpha, interleukin-2 (List),
___IL-6, amphiregulin, VEGF, TNF-alpha (List), and Nitric Oxide (NO) (List),
(6) Sex hormones including estrogen (List), progesterone (List), and testosterone (List).
___Estrogen acts on the hTERT promoter via estrogen receptor.
___Progesterone acts on the hTERT promoter via the MAP Kinase pathway (Index),
___and possibly also through crosstalk with estrogen receptor.
___Testosterone (List) may activate hTERT transcription after conversion to estrogen
___by aromatase. It is still unknown whether or not the effect is direct.
(7) Inflammatory Cytokines IL-2 (List), IL-6, TNF-alpha (List), and NFkB (List).
___"Telomerase is expressed in hemopoietic stem cells via cytokine stimulation." (M.Fossel).
(8) Anabolic cytokines IL-7 (Links) and IL-15 (Links) activate telomerase in T-lymphocytes.
___The cytokine IL-3 activates telomerase in hematopoeitic stem cells.
(9) Ca ionophore activates telomerase in T-lymphocytes.
(10) Surface Ig or CD40 upregulate telomerase expression in B-lymphocyte memory cells.
(11) IRF4 and IRF8 interferon regulatory factors activate telomerase in immune system cells.
(12) The endogenous HDAC inhibitor Sphingosine-1-Phosphate (S1P) activates telomerase.
(13) Epithalon peptide (Ala-Glu-Asp-Gly) [Index], a pineal gland peptide bioregulator.
___Orally bioavailable medicines may discovered to control the expression of epithalon peptide.
___Peptide bioregulators of interest include Livagen (Lys-Glu-Asp-Ala) and Vilon (Lys-Glu).
(14) Specific telomere nucleoprotein complex elements (shelterin components) and their inhibitors,
___For instance, the negative regulator of telomere lengthening TRF1 can be inhibited by
___tankyrase 1, which strips TRF1 from the telomere, allowing the loop to open for
___access by the telomerase holoenzyme.
___RAP1 overexpression causes telomere enlongation.
(15) Specific Mammalian Telomere Protein Factors and their inhibitors.
___Tankyrase 1 poly(ADP-ribo)sylates TRF1 using a NADH substrate, stripping it
______and enabling the t-loop to open for telomerase access. Insulin phosphorylates tankyrase 1
______for the reaction, so that insulin-boosters may be used to improve telomerase activation.
___hEST1A (List) may also be used to open telomere loops to boost telomerase activity.
___Replication Protein A upregulates telomerase activity.
___Mre11 protein lengthens telomeres in both plant and animal cells.
In each case, supplemental medicines to improve expression of the endogenous telomerase activators are important in defining telomere therapy to be applied in cycles with periods of telomerase activation to lengthen telomeres followed by periods of telomerase inhibition with anticancer therapy to ensure genomic stability. For instance, c-Myc is upregulated by Epidermal Growth Factor (EGF) or Platelet-Derived Growth Factor (PDGF), which are sometimes supplied in skin creams. EGF is found in colostrum. Note that PDGF is also upregulated by exercise. Transcription factor Sp1 (List) is upregulated by sodium butyrate. The transcription factor HIF-1 (List) is upregulated by exercise, hypoxia, and by diosgenin from Fenugreek seed, ginkgo biloba and certain ginkgolides. HIF-1 interacts with the hTERT promoter to produce hTERT mRNA in every cell in the body. Similarly IGF-1 may interact with every cell in the body to promote phosphorylation of cytoplasmic hTERT for import into the cellular nucleus. The ID-1 transcription factor for hTERT transcriptional activation can be upregulated by nerve growth factor (NGF), which may itself be upregulated by acetyl-L-carnitine, huperzine A, carnosic acid, rosemary, rosemary tea, PQQ, and reishi mushroom. Histone Deacetylase Inhibitors (HDAC inhibitors) such as lactates from pumping up with weights or L-carnitine enable or promote telomerase activity by expanding chromatin for transcription of hTERT mRNA, while histone deacetylases (HDACs) condense chromatin to halt hTERT mRNA transcription.
With regard to activation via hTERT phosphorylation, AKT1 kinase is upregulated by resveratrol, folic acid, ginkgo biloba extract, Shingosine-1-Phosphate and by IGF-1 via the PI3/AKT1 pathway. Among the inflammatory cytokines known to activate telomerase, IL-2 acts through the PI3/AKT1 pathway, so that it phosphorylates hTERT protein with AKT1 kinase for hTERT transport into the nucleus rather than activating hTERT transcription to produce more hTERT mRNA. That is, IL-2 (List) works like resveratrol on lymphocytes. IL-6 upregulates STAT3 to upregulate telomerase in human fibroblasts and smooth muscle cells in the aorta. At this time, inflammatory cytokines are not usually applied in treatment to upregulate telomerase, except through exercise. Protein Kinase C, which phosphorylates cytoplasmic hTERT for import into the nucleus like AKT1 kinase, is upregulated in blood mononuclear cells by phorbol myristate acetate, which is still being evaluated for application to cyclic treatment.
As regards to mammalian telomere control proteins, the phosphorylation of tankyrase 1 enhances its poly(ADP-ribo)sylation activity on TRF1 telomere loop closure protein, allowing t-loops to open for access by the telomerase holoenzyme. Tankyrase 1 is phosphorylated on serine residues by MAP kinase upon stimulation with insulin, PDGF, and EGF. MAP kinase signaling cascades can influence hTERT mRNA transcription via direct phosphorylation of Sp1, and via the transcription factors c-Myc, AP-1, and Ets in the core promoter region of the hTERT gene.
I have found one endogenous HDAC inhibitor with telomerase-activating properties, namely sphinogosine-1-phosphate (S1P) (List).
Synthetic and Non-Endogenous Telomerase Activators
On the other hand, small molecule telomerase activators [List, (7)] taken as medicine to stimulate the expression of telomerase activating transcription factors or the expression of hTERT phosphorylating kinases are classed as small molecule non-endogenous telomerase activators. The small molecule telomerase activators also include synthetic, non-endogenous histone deacetylase inhibitors (HDAC inhibitors) such as the injectable Tricostatin A, the orally bioavailable CGK 1026, allyl mercaptan and diallyl disulfide from garlic allicin, and sodium butyrate, which is also orally bioavailable and sold both as a supplement and as chicken feed. They also include small molecules like the astragalosides resembling steroid hormones that penetrate cell membranes quickly. The astragalosides including cycloastragenol and astragaloside IV act through the MAP Kinase pathway to stimulate hTERT transcription via transcription factors such as c-Myc, AP-1, and Ets with direct phosphorylation of Sp1. However, astragalus extract also enhances the expression of IL-2, which phosphorylates hTERT protein in the cytoplasm for nuclear import by acting through the PI3/AKT1 pathway. The astragalosides and similar small molecule telomerase activators can reach every cell in the body and are not dependent on cell-surface receptors. Note that ginsenoside RH1 binds like the steroid hormone estrogen to estrogen receptor and is subsequently probably capped with histone acetyl transferase (HAT) to form the estrogen receptor complex, a transcription factor operating directly on the hTERT promoter to enable hTERT transcription. Ecdysone, an insect hormone, also resembles the steroid hormones testosterone, estrogen, and progesterone and activates telomerase in human cells. 26 deoxyacetin in black cohosh extract is another telomerase-activating progesterone-like synthetic sort of steroid hormone that preserves feminine youthfulness by activating telomerase. It can be used to produce the she male effect, but Fenugreek extracts with the steroid hormone-like telomerase activator diosgenin do better by producing hornier, perkier she males with higher testosterone levels. Diosgenin enhances expression of the transcription factor HIF-1 (List) acting directly on the hTERT promoter. Levels of HSP90 (List), which is required for telomerase activity and improves it, can be boosted with exercise and/or alpha lipoic acid. Silver and certain simple antigens activate telomerase in immune system cells, also bypassing cell surface receptors. 1,5-bis acetyloxy anthraquinones [Links/1,5-bis acetyloxy anthraquinones, Images, Video, Papers, Patents, Books] that are related to the antitumor agent mitoxantrone [Links/mitoxantrone, Images, Video, Papers, Patents, Books] behave like small molecule telomerase activators. Novel tri-phenyl compound telomerase activators were discovered at Ben Gurion University on the Negev and patented in 2008. Geron patented a number of new enhanced-bioavailability small molecule telomerase activators in 2010. Product B is now available from IsAGenix with a mix of telomerase activators. Large synthetic molecules that activate telomerase by promoting hTERT transcription or hTERT protein phosphorylation also exist, but special arrangements may be required to introduce the molecule into the cell, or to promote its transcription from plasmid vectors introduced via liposome endocytosis, gene guns, or additional genes transfected into the genome with viral vector technique or zinc finger nuclease technology. For example, we have ependymin peptide, a telomerase activator obtained from goldfish brains. Also, anti-CD3 monoclonal antibody induces telomerase activation in T-lymphocytes. T-cells can also exhibit telomerase activation as a consequence of treatment with various antigens, including phorbol 12, 13-dibutyrate, which stimulates the T-cell antigen receptor.
Endogenous Vasodilators [Index/Vasodilators; Links, Images, Video, Papers, Patents, Books]. Endogenous vasodilators include nitric oxide and histamine produced from histadine.
See also cardiology, heart attack, stroke, and dementia.
Endonucleases [Wikipedia/Restriction_enzyme; Links/Endonuclease Techniques; Links/Endonucleases, Images, Video, Papers, Patents, Books, Amazon; Links/Endonucleases for Recombinant DNA Development, Images, Video, Papers, Books, Amazon; Links/Endonucleases for Genome Development, Images, Video, Papers, Books, Amazon; Links/Endonucleases for Plasmid Development, Images, Video, Papers, Books, Amazon; Plasmids, Links/Plasmid Design Software, Gene Therapy, Transfection, Adenovirus Transfection, Adeno-Associated Viral Transfection, Molecular Biology; Links/DNA, Links/Reverse Transcription of mRNA, Links/Human cDNA, DNA Sequencing, Links/DNA Design Software, Links/DNA Synthesis, Links/DNA Synthesizers; Human Genome, Genomics, Bioinformatics, Pathway Analysis, Protocols; LifexLabs3/Cell Culturing, Virology; Links/Recombinant DNA Development Safety Issues, Links/Recombinant DNA Legal Issues; Cold Spring Harbor Laboratory Press].
Endothelial Cells, Human [Images/human endothelial cells, Images/senescent endothelial cells, Images/immortal endothelial cells, Books/human endothelial cells, LibCong, Amazon/Endothelial Cells; Links/human endothelial cells, Images, Video, Papers, Patents, Books; SenescenceInfo/Cells, Shay/Hayflick, His Limit, and Cellular Aging; Index/Nitric Oxide]. The endothelial cells line veins and arteries, and the senescence of endothelial cells leads to higher adhesion to monocytes and a tendency to form atherosclerotic plaque leading to heart attack and stroke. Senescent endothelial cells such as those found at the bases of atherosclerotic lesions [Images] that express senescence marker β-galactosidase also express the inflammatory cytokine interleukin-1a in upregulated form, and down-regulate thymosin-b-10, which sequesters cytoplasmic G-actin. There is also a marked increase in the cell-specific adhesion molecule I-CAM in senescent endothelial cells [Links]. These changes have been identified at sites of atherosclerotic lesions in elderly tissue donors. Endothelial senescence may be inhibited with nitric oxide and nitric oxide supplements such as arginine (5-10 grams/day), citrulline, and horny goat weed. See Life Extension's Endothelial Defense [Links], with cocoa, pomegranate, and GliSODin.
Conversion of Endothelial Cells into Osteoblasts "Osteoblasts (bone cells) are sometimes discovered in the endothelial lining of patients with arterial disease, perhaps indicating that endothelial cells can turn into osteoblast bone cells, or that bone osteoblasts can migrate into the arterial endothelium. This was discovered in 1993, establishing a link between atherosclerosis (involving calcification of arterial tissue) and osteoporosis (involving the decalcification of bone tissue). Patients with osteoporosis are more likely to observe calcification of atherosclerotic plaque. Patients with arteriosclerosis are likely to have lower bone mass. Perhaps as bones dissolve, osteoblasts drift. Vitamin D and vitamin K (K2) may be used together to oppose osteoporosis and arteriosclerosis (hardening of the arteries) with atherosclerosis. Gla proteins found both in bone tissue and vascular wall require vitamin K to function properly. Vitamin D, which modulates fat-derived inflammatory cytokines and other factors, is also crucial to prevention of osteoporosis and atherosclerosis. Severe vitamin D insufficiency can lead to rickets, because Vitamin D is a cofactor in bone mineralization by promoting the absorption of calcium and phosphorus, a continuing process because bones reconstitute themselves over a period of 10 years or so. Vitamin D reduces the expression of genes involved in endothelial bone cell (osteoblast) formation in experimental animals with kidney disease." See Julius Goepp, MD, Brittle Bones and Hardened Arteries: The Hidden Link, Life Extension Magazine, September 2010.
The Effect of Exercise on Endothelial Progenitor Cells [Links, Images, Video, Papers, Books].
"Before exercise [List, (9)], in vitro function and in vivo reendothelialization capacity of EPCs (endothelial progenitor cells) were significantly reduced in elderly men compared with young men. After exercise intervention, in vitro function and in vivo reendothelialization capacity of EPCs from elderly men were markedly enhanced. Physical exercise increased a higher CXCR4 protein expression and higher JAK-2 phosphorylation levels of EPCs." - See Wen-Hao Xia, Jing Li, Chen Su, Zhen Yang, Long Chen, Fang Wu, Yuan-Yuan Zhang, Bing-Bo Yu, Yan-Xia Qiu, Shen-Ming Wang, Jun Tao (2012), Physical exercise attenuates age-associated reduction in endothelium-reparative capacity of endothelial progenitor cells by increasing CXCR4/JAK-2 signaling in healthy men, Aging Cell, February 2012: 11;(1)111-119. See also Umemura T, Soga J, Hidaka T, Takemoto H, Nakamura S, Jitsuiki D, Nishioka K, Goto C, Teragawa H, Yoshizumi M, Chayama K, Higashi Y (2008), Aging and hypertension are independent risk factors for reduced number of circulating endothelial progenitor cells, Am. J. Hypertension, 21, 1203–1209. Werner C, Fürster T, Widmann T, Poss J, Roggia C, Hanhoun M, Scharhag J, Buchner N, Meyer T, Kindermann W, Haendeler J, Bohm M, Laufs U (2009), Physical exercise prevents cellular senescence in circulating leukocytes and in the vessel wall, Circulation 120, 2438–2447.
Endothelial Dysfunction [Links/treating endothelial dysfunction, Images, Video, Papers, Patents, Books; LibCong, Amazon/Endothelial Dysfunction; Links/Endothelial Defense, Images, Video, Papers, Patents, Books, Amazon/Endothelial Defense]. Atherosclerosis (Plaque deposits in the arteries) and Arteriosclerosis (Hardening of the arteries) are associated with endothelial dysfunction. See Life Extension's Endothelial Defense, with cocoa, pomegranate, and GliSODin. Nitric oxide production via cocoa, and nitric oxide synthase may activate telomerase in endothelial cells [Vasa, et al., 2000, Hayashi, et. al, 2006], preventing their replicative senescence, explaining the long lifetime of Madame Jeanne Louise Calment [Index], who consumed 5 pounds of chocolate every week. Chocolate and cocoa contain arginine, which is processed into the vasodilator Nitric Oxide by nitric oxide synthase. Nitric oxide also has telomerase-activating effect on vascular endothelial cells. Arginine, citrulline, and horny goat weed work to improve and sustain Nitric Oxide levels. The nitric oxide activating properties of the resveratrol [Images/resveratrol supplements] Jeanne Calment consumed in her red wine may similarly have acted to refresh her vascular endothelium. See [Erusalimsky JD, 2009] and [Hong Y, Quintero M, Frakich NM, Trivier E, Erusalimsky JD, 2007] for the argument that SIRT1 is activated in endothelial cells by Nitric Oxide, but not telomerase. Telomerase activation in endothelial cells by nitric oxide has been measured, however. Nobel Prize winner Dr. Louis J. Ignarro recommends 4 to 6 grams of L-arginine per day for physiologically effective NO generation, plus L-citrulline at 200 mg/day to 1000 mg/day to maximize it's effect, together with 4 antioxidants in his book NO More Heart Disease and in his advanced technical books on nitric oxide in physiology and medicine [Books/Louis Ignarro nitric oxide]. Arteriosclerosis can result from too little vitamin K2 to produce osteocalcin to direct calcium in the blood back into bones instead of allowing it to deposit itself into tissues that become calcified. Lack of vitamin K2 (from cheeses or natto) can also produce calcification of the aortic valve associated with aortic stenosis and aortic sclerosis. Arteriosclerosis often piggybacks atherosclerosis, calcifying arterial plaque to form a cap. Uneven hardening of the arteries can result in an arterial anuerysm, a local ballooning of the arterial wall, under exceptional stress conditions such as bodybuilding strain producing a subclavian anuerysm during a bench press. However, exercise is usually beneficial to elderly patients, helping them avoid falls and improving their HDL/LDL lipoprotein profiles. Also see Conversion of Endothelial Cells into Osteoblasts. Note that elastase-inhibiting properties of phytoceramides  may have a beneficial effect on the arterial wall.
Endothelial Senescence [Index/Cellular Senescence, Index/Senescence, Index/Replicative Senescence, Links, Images, Video, Papers, Patents, Books, LifeExtension, Amazon]. See also premature stress-induced senescence and premature stress-induced endothelial senescence.
End Replication Problem [Links/The Telomere End Replication Problem, Images, Video, Papers, Books; Links/Telomere Replication, Images, Video, Papers, Patents, Books]. "The mechanisms of DNA replication in linear chromosomes are different for each of the two strands (called leading and lagging strands). The lagging strand is made as a series of discrete fragments, each requiring a new RNA primer to initiate synthesis. The DNA between the last RNA priming event and the end of the chromosome cannot be replicated because there is no DNA beyond the end of the end to which the next RNA primer can anneal, thus this gap cannot be filled in (this is referred to as the "end replication problem"). Since one strand cannot copy its end, telomere shortening occurs during progressive cell divisions." - Jerry W. Shay and Woodring E. Wright, Are Telomeres and Telomerase the Connection? in Mark P. Mattson (ed.) Telomerase, Aging, and Disease, 2001, p.2. The theory was worked out by James D. Watson and Alexey Olovnikov in the early 1970s.
EnergoTM [IAAS/EnergoTM anti-aging skin care, before & after photos, Links/Energo for skin care, conference note], .
Engineered Negligible Senescence [Cambridge/SENS/Engineered Negligible Senescence Site, Wikipedia, Aubrey de Grey Video, LibCong, Links, Images, Video, Papers, Patents, Books, LifeExtension], [7s]. Also see reversible senescence, a term pioneered by Woodring E. Wright in his 1989 paper on cellular immortalization.
Enterolactone(s) [LifeExtension, Links, Images, Video, Papers, Patents, Books]. Enterolactones are associated with plant lignans [Links, Images, Video, Papers, Patents, Books, Wikipedia, LifeExtension] and may be obtained from flax or Norway Spruce. They are found in fruits, vegetables, and whole grains. Enterolactones help to prevent prostate cancer [Links, Images, Video, Papers, Patents, Books; Index/Prostate Cancer, LifeExtension]. See Lignans Protect Against Prostate Cancer By William Faloon. See the index entry for Prostate Cancer.
Enzymatic free radical scavengers [Links/Enzymatic free radical scavengers, Images, Video, Papers, Patents, Books, LifeExtension]. Melatonin is an enzymatic free radical scavenger, for instance. See [Books/melatonin and aging]), [35s] (b).
Enzymatic glycation inhibitors [Links, Images, Video, Papers, Patents, Books, LifeExtension; Glycation], [35s] (d). Glycation is inhibited by the vitamin B6 vitamers, which are converted in the intestine to the actived form PLP (pyridoxal-5'-phosphate), by carnosine, by vitamin C, by alpha lipoic acid, by benfotiamine (found in onions) and by aminoquanodine.
EPA, eicosapentaenoic acid [Telomerase Inhibitors/EPA, Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension; Heart Attack (Optimal Cardiac Defense)]. EPA, one of the fatty acid components of SQDG and primary component of fish oil, is a small molecule telomerase inhibitor. DHA is the other component of fish oil, a brain food that improves synaptogenesis, improves the expression of dopamine, induces apoptosis in neuroblastoma cells, and protects normal neural cells from apoptosis. EPA tends to raise triglyceride levels, but is useful in the synthesis of prostaglandin-3 (which inhibits platelet aggregation). Fish oil is used to get a favorable LDL/HDL cholesterol ratio to help prevent atherosclerosis.
Epicatechin (pron: epi-cat-e-kin) [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension]. Epicatechin is found in cocoa powder. See catechins [Links, Images, Video, Papers, Patents, Books, LifeExtension]. "Epicatechin [Wiki/Epicatechin, Images] in cocoa improves blood flow and thus seems good for cardiac health. I might add that cocoa contains arginine, which is converted using nitric oxide synthase into the vasodilator Nitric Oxide, also improving blood flow. Cocoa, the major ingredient of dark chocolate, contains relatively high amounts of epicatechin and has been found to have nearly twice the antioxidant content of red wine and up to three times that of green tea in in-vitro tests." - Wikipedia/Flavoids.
Epidermal Basal Cell Carcinoma [Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension; Cancer, Carcinogens, Anticancer Nutraceuticals; Apoptosis, Telomerase Inhibitors; Anticancer Telomerase Activators; Metastasis, NFkB, NFkB Inhibitors, Angiogenesis Inhibitors].
Epigenetic Regulation in Aging [Links/Epigenetic Regulation in Aging, Images, Video, Papers, Patents, Books, LibCong, Amazon, LifeExtension; Links/Epigenetic Dysregulation in Aging, Images, Video, Papers, Patents, Books, Amazon; Index/Methylation; Index/hTERT Methylation; Index/Gene Silencing]. See also Demethylation in Senescent Cells & DNA Demethylation: [Links/DNA methylation, Images, Video, Papers, Patents, Books; Links/Demethylation in senescent cells, Images, Video, Papers, Patents, Books; Books/epigenetic regulation in senescent cells, Links/causes of DNA demethylation, LifeExtension/DNA demethylation, LifeExtension/DNA Methylation]. Methylation of genes is used in the development of placental mammals to silence gene promoters after their developmental role is over, or to switch on genes controlled by an insulator in charge of an enhancer. Life Extension Magazine promotes SAMe [Links, Images] as a cure for undesirable DNA demethylation, noting that "Cellular aging is partially caused by de-methylation". Furthermore, DNA methylation normally silences oncogenes. "Loss of methylation can induce the aberrant expression of oncogenes, leading to cancer pathogenesis.... Classes of medications, known as HDAC inhibitors and DNA methyltransferase inhibitors [LifeExtension], can re-regulate the epigenetic signaling in the cancer cell." - Wikipedia/Cancer. See Jaenisch R., Bird A. (2003), Epigentic regulation of gene expression: how the genome integrates intrinsic and environmental signals, Nature Genetics, 2003 March; 33 Suppl:245-54.
Epinephrine and Norepinephrine [Links/Epinephrine, Images, Video, Papers, Patents, Books; Links/Norepinephrine, Images, Video, Papers, Patents, Books]. Epineprine and norepinephrine are also termed adrenaline and noradrenaline. Capsaicin upregulates epinephrine. This may be done in caloric restriction to burn fatty acids. Green tea inhibits the enzyme catechol-O-methyl transferase (COMT) that breaks down noradrenaline. See supplements upregulating epinephrine and supplements upregulating norepinephrine.
Epithalon Peptide [Links/Epithalon peptide, Images, Video, Papers, Patents, Books, Original Paper, sources, sources2; See also Endoluten for premature aging and Peptides Store]. Epithalon Peptide [Telomerase Activators/Epithalon Peptide, Cryonet/MSGS/Epithalon Peptide, 81s] a small 4-peptide protein (Ala-Glu-Asp-Gly), that activates telomerase and extends telomeres, a small molecule telomerase activator. Epithalon peptide is found in the body in the pineal gland (epiphysis) [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension]. See Custom Peptide Synthesis [Links, Images, Video, Papers, Patents, Books], Peptide Synthesis [Wikipedia, Books], Peptide Synthesizers [Books, Suppliers], Peptide Analyzers [Links]. A synthetic gene for Epithalon peptide may be provided with an hTERT promoter on plasmids enclosed in liposomes fashioned from cationic transfection reagents and incorporated into skin creams or liposome sprays. Alternatively, its small size may make it optimal for transfection using gentle AAV adeno-associated viruses, if it can be permanently built into the genome on chromosome 19 with good effect. These DNA transfection techniques may also be used with other peptide bioregulators such as Livagen (Lys-Glu-Asp-Ala) that can be programmed with a suitable promoter into plasmids.
Epithelial Cells, Human [Links/Human Epithelial Cells, Images, Video, Papers, Patents, Books; Images/senescent epithelial cells, Images/immortal human epithelial cells; Links/senescent human epithelial cells, Images, Video, Papers, Patents, Books; Books/epithelial cells, LibCong/epithelial cells, SenescenceInfo/Cells, Shay/Hayflick, His Limit, and Cellular Aging]. Carcinomas and adenocarcinomas [Index/Cancer] (roughly 90% of human cancers) typically begin in epithelial cells as a consequence of telomeric crisis involving telomere shortening, or due to DNA damage (10) originating from a carcinogen. "Senescent human adrenocortical epithelial cells selectively loose the ability to induce 17α-hydroxylase, a key enzyme in cortisol biosynthesis." - Judith Campisi in Physiological Basis of Aging and Geriatrics, 4th edition, 2007. See also HMEC (Human Mammary Epithelial Cells) Home, with An Overview of Growth, Aging, Senescence, and Immortality in our HMEC Culture System. See Replicative Senescence, Senescence, Cancer, Epidermal Basal Cell Carcinoma.
Equol [Links/Equol, Images/Equol supplements, Video, Papers, Patents, Books, LifeExtension; Links/Equol binds 5-alpha dihydrotestosterone, Images, Video, Papers, Patents, Books, LifeExtension; Equol for Prostate and Urinary Health]. Equol binds 5-alpha-dihydrotestosterone making it useful for treating prostate cancer, benign prostatic hyperplasia, and urinary health. Perhaps it has applications in treating hair loss. Check 5-alpha reductase inhibitors and 5-alpha reductase (converts testosterone into dihydrotestosterone) vs. 5-alpha dihydrotestosterone. Both R-equol and S-equol exist. S-equol activates estrogen-beta receptors, which can cause broadening of the hips. (Wikipedia/Equol).
Escin [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Escin is found in horse chestnut [Links/Horse chestnut, Images, Video, Papers, Patents, Books, LifeExtension]. Escin increases the tone of veinous walls, promoting improved circulation and making it a popular oral and topical treatment for varicose veins [Links, Images, Video, Papers, Patents, Books] and veinous insufficiency. In one test, treatment with 50 mg of escin twice daily was equivalent to compression stocking therapy [Links, Images, Video, Papers, Patents, Books]. See non-invasive therapy for varicose veins [Links].
Esophageal Cancer [Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension; Carcinogens, Cancer; Anticancer Nutraceuticals; Apoptosis; Telomerase Inhibitors; Anticancer Telomerase Activators; Metastasis, NFkB, NFkB Inhibitors, Angiogenesis Inhibitors].
See Junji Takano, Alcohol Can Increase the Risk of Esophageal Cancer by 400 Times!?
by: Junji Takano EST1, EST2 [Links/EST1, EST2, Books/yeast telomerase; Links/EST1, Images, Video, Papers, Patents, Books; Links/EST2, Images, Video, Papers, Patents, Books]. EST1 and EST2 have been described as the yeast homologue predecessors of the hTR and hTERT genes in vertebrates. According to this scheme of nomenclature, EST1 produces the RNA part of the yeast telomerase enzyme, EST2 produces the catalytic protein component in yeast telomerase corresponding to hTERT in vertebrates. Yeast cells are an early eucaryotic cell type featuring many genes that have been conserved (with some transformations) throughout evolution. See Links/the yeast genome, Links/the eucaryotic genome.
EST1p (hEST1A in humans, or SMG6) [Links/EST1p, Images, Video, Papers, Patents, Books; Books/yeast telomerase; YeastGenome/Est1, Books; OMIM; GeneCards]. EST1p has been conserved in evolution and is present in humans as hEST1A [Index, List, Links, Images, Video, Papers, Patents, Books]. "Overproduction of hEST1A cooperated with hTERT to lengthen telomeres." - See Snow BE, Erdmann N, Cruickshank J, Goldman H, Gill RM, Robinson MO, Harrington L., (2003), Functional conservation of the telomerase protein Est1p in humans, Current Biology 2003 Apr 15;13(8):698-704. hEST1A recruits telomerase holoenzyme by binding to hTERT. (See Diagram). hSMG6 [Links/hSMG6, Links/SMG6] is identical to hEST1A. (See Lingner Joachim, Senior scientist, Telomerase and chromosome end replication, ISREC.) According to Gene Cards, overexpression of SMG6 (in humans hEST1A) results in telomere uncapping. Therefore perhaps hSMG6 or hEST1A can be used to extend t-loop capped telomeres, opening them so that they can be extended by telomerase. Note, however, that more chromosome end-to-end fusions are seen when SMG6 is overexpressed (GeneCards). (Typically, t-loops are opened by poly(ADP-ribo)sylation of TRF1 t-loop closure protein by tankyrase 1, which may be phosphorylated for the reaction by insulin, EGF, or PDGF). Telomerase does not act on telomeres unless the telomere is uncapped (7). Thus large telomere t-loops corresponding to very youthful cells may be prepared by using hEST1A (hSMG6) together with telomerase, probably by stopping SMG6 towards the end of a treatment period to reseal telomere t-loops. Such cells may have superior staying power, lasting for more cell divisions before uncapping, generating a DNA damage signal, and entering the state of replicative senescence. Note that Replication Protein A on human Chromosome 17 [Index, List, Links, GeneCards/RPA1, (YeastGenome/RPA1, YeastGenome/Telomere Maintenance)], which is present in all eucaryotic cells, has been observed to activate telomerase by providing Est1p (hEST1A in humans) access to chromosome ends. See Vera Schramke, Pierre Luciano, Vanessa Brevet, Sylvine Guillot, Yves Corda, Maria Pia Longhese, Eric Gilson & Vincent Géli, (2003, 2004), RPA regulates telomerase action by providing Est1p access to chromosome ends, Nature Genetics 36, 46 - 54 (2004) Published online: 21 December 2003.
Estradiol, Stroke, & Heart Attack [Wiki/Estradiol, Links/Estradiol, Images, Video, Papers, Patents, Books, LifeExtension/Estradiol; Links/Aromatase inhibitors, Images, Video, Papers, Patents, Books, LifeExtension]. Estradiol levels of > 34.1 pg/mL more than doubled stroke incidence. Life Extension Magazine recommends estradiol levels < 30 pg/mL, claims ideal ranges of estradiol in aging men are between 20 and 30 pg/mL. Excess estrogen contributes to the development of atherosclerosis. On the other hand, if estrogen levels are too low, men are more likely to suffer osteoporosis and bone fractures. Higher levels of estradiol are observed in heart attack victims. Testosterone can be aromatized into estradiol by the enzyme aromatase [Links, Wikipedia/Aromatase], which can be blocked by aromatase inhibitors [Links, Wikipedia/aromatase inhibitor] such as the plant flavonoid Chrysin, lignans from the Norway spruce tree, or Arimidex (taken 0.5 mg twice a week). Low estrogen levels in men (leading to > 300% higher mortality) can be caused by low testosterone (< 15-20 pg/mL of serum), since men make estrogens from aromatase acting on testosterone.
Water-soluble pumpkin seed extract [Images] inhibits aromatase [LifeExtension]. High estradiol levels (leading to > 100% higher mortality) correlate to body fat mass, especially in the belly, so that subcutaneous abdominal fat acts like a secretory gland for high levels of estradiol. Estradiol and dihydrotestosterone (DHT) stimulate prostate enlargement associated with BPH, Benign Prostatic Hyperplasia. Note that men need some estrogen to maintain bone density, cognitive function, and the vascular endothelium. See also Index/Estrogen Protection. See William Faloon [Images], AS WE SEE IT, Why Estrogen Balance is Critical to Aging Men, Life Extension Magazine, May 2010. See also Jeppesen LL, Jorgensen HS, Nakayama H, Raashou HO, Olsen TS, Winther K (1996), Decreased serum testosterone in men with acute ischemic stroke, Arteriosclerosis, Thrombosis, and Vascular Biology, 1996 June; 16(6): 749-54. Abbott RD, Launer LJ, Rodriguez BL, et al. (2007), Serum estradiol and risk of stroke in elderly men, Neurology, 2007 Feb20; 68(8):563-8. It turns out that c-Myc downregulates caveolin-1 expression (tending to reverse senescence), and that c-Myc can be upregulated by EGF, PDGF, colostrum, or estradiol [Ref, (Tsai L.-C., Hung M.W., et al, (1997))].
Estriol [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension]. Estriol is a weaker form of estrogen derived from plants producing superior skin rejuvenation results with fewer hormonal side effects than estrogen (estradiol).
Estrogen [Telomerase Activators/Estrogen, Wikipedia/Estrogen, Index/Estradiol, TA/Estrogen, Links/Estrogen, Images, Video, Papers, Patents, Books, LibCong/Estrogen, LifeExtension]. Estrogen [List] is a telomerase activator , prevents skin aging, and is associated with an increase in the synthesis of collagen, maintaining a youthful plump skin appearance. The usual method of delivery for women's skin rejuvenation is in a topical cream. Note that Fo-ti (He Shou Wu) from the sexually suggestive Polygonum multiflorum root boosts estrogen levels. See Karen Oerter Klein, Mona Janfaza, Jeffrey A. Wong and R. Jeffrey Chang (2003), Estrogen Bioactivity in Fo-Ti and Other Herbs Used for Their Estrogen-Like Effects as Determined by a Recombinant Cell Bioassay, The Journal of Clinical Endocrinology and Metabolism Vol. 88, No. 9 4077-4079. "Soy, clover, licorice, and hops have a large amount of measurable estrogen bioactivity." The telomerase-activating ginsenoside Rh1 is a functional ligand of the estrogen receptor (Kar Wah Leung and Alice Sze-Tsai Wong, 2010). The minimum effective concentration of ginsenoside Rh1 [List] used in vitro is approximately 1000 times the concentration used for astragaloside IV or cycloastragenol, 10 μM vs. 0.01 μM.
The hormone estriol [Index, Wikipedia, Links, Images, LifeExtension], a weaker form of estrogen derived from plants, produces superior skin rejuvenation results with fewer hormonal side effects than estrogen. Black cohosh is also associated with rejuvenating effects, and produces breast tissue more stable against breast cancer. Undesirable cellular proliferation [Images] may occur when using estrogen, leading to endometrial cancer [Images], but estrogen patches are safer than oral estrogen, producing less CRP (C-reactive protein) in the liver. - Caleb E. Finch, p. 166. See also Index/Estrogen Protection.
Strong Estrogen Bioactivity nutraceuticals are ligands of the estrogen receptor and have telomerase-activating effect like estrogen. They include estrogen, fo-ti (he shou wu), soy, clover, licorice and hops, and can be used to restructure the pelvis via the estrogen beta receptor.
Estrogen Protection DIM anti-estrogen caps (Diindolylmethane, or 3,3'-Diindolylmethane) are used for protection against high estrogen levels, and are described as normalizing estrogen levels. DIM is anticancer, and is derived from the digestion of indole-3-carbinol [Images] found in broccoli, cauliflower, and collard greens.
Eugenol [Links, Images, Video, Papers, Patents, Books, LifeExtension; Virology]. Eugenol, an antiviral antibiotic, is found in cinnamon and basil. Eugenol reduces blood sugar and may be used in diabetes treatment, and perhaps for reducing glycation.
 Srinivasan S, Sathish G, Jayanthi M, et al. (2014),
Ameliorating effect of eugenol on hyperglycemia by attenuating the key enzymes of glucose metabolism in streptozotocin-induced diabetic rats, Mol Cell Biochem 2014 Jan;385(1-2):159-68.
Evodiamine [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Evodiamine is an extract [Images] from the evodia rutaecarpa fruit [Images] that boosts metabolic rate by stimulating central nervous system receptors. It is taken 30-50 mg 2-3 times/day prior to meals. - (after Muscle and Fitness Magazine, 2010).
Exercise Theory of Aging [Telomerase Activators/(81) Exercise, WorldHealth/Exercise Theory of Aging, Theory, article, Links, Images, Video, Papers, Patents, Books, LibCong, LifeExtension, Papers/exercise and telomere extension, Papers/Growth Hormone and telomere extension, Books/growth hormone and telomere extension, Books/growth hormone and telomerase activation, Links/growth hormone and telomerase activation; Index/Bodybuilding], (9), . See Exercise Boosts Telomerase, Reduces Erosion of Telomeres at Fighting Aging. Exercise can elevate telomerase activating HGH growth hormone x 3 on a normal diet, and by a larger factor if one takes an HGH secrectagogue like alpha-glycerylphosphocholine (a component of Secretagogue Gold) before working out. The HGH is finally converted to IGF-1 in the liver, and that is another telomerase activator. Toxic estrogen metabolites such as 16-alpha-hydroxyestrone can be defended against with cruciferous vegetable substances such as indole-3-carbinol and sulforaphane. Genistein and daidzein from soy also act against toxic estrogen metabolites. See Estradiol for the effect of estrogens on heart attack and stroke. On the cautionary side, heavy bodybuilding in an old man with arteriosclerosis can cause a subclavian anuerysm in the arteries around the heart. Vitamin K2 can be used to return calcium from hardened arteries to the bones, via enhanced expression of osteocalcin. On the other hand, hardening of the arteries may actually be due to glycation acting on proteins, finally yielding cross-links with stiffened arterial collagen. Note that exercise improves the reendotheliazation capacity of endothelial progenitor cells. Avoid beef fat while working out in old age, as it seems to induce high triglycerides, cardiovasular disease, and strokes. Eat fatty fish like salmon instead that produce elevated HGH and dopamine from DHA, and drink HGH-elevating whey protein with creatine monohydrate.
Genes Up- and Down- Regulated with Exercise
[Links/Genes Upregulated by Exercise, Images, Video, Papers, Patents, Books;
Links/Genes down regulated by Exercise, Images, Video, Papers, Patents, Books;
Links/Exercise and Gene Expression, Images, Video, Papers, Patents, Books].
Exercise activates AMPK (AMP-activated protein kinase) to obtain ATP by a weight-reducing catabolic process and improves autophagy in senescent cells, accelerating the removal of cellular junk and also reducing triglycerides and glucose in the blood. AMPK activity also allows pro-inflammatory senescent cells to have enough ATP to self-destruct via apoptosis, and regulates mitochondrial biogenesis and other life-extending cellular processes. Thirty minutes of exercise upregulates PDGF (1.55-fold), and also HIF-1 (hypoxia-inducible factor-I) (2.40-fold). Both are telomerase activators. Epiregulin is also upregulated by 30 minutes of exercise (3.50-fold). VEGF (vascular endothelial growth factor) is simultaneously upregulated by 1.36-fold. Epiregulin is a candidate telomerase activator that is a member of the EGF (epidermal growth factor) family. See Peter H. Connolly, Vincent J. Caiozzo, Frank Zaldivar, Dan Nemet, Jennifer Larson, She-pin Hung, J. Denis Heck, G. Wesley Hatfield and Dan M. Cooper (2004), Effects of exercise on gene expression in human peripheral blood mononuclear cells, Journal of Applied Physiology, October 2004, vol. 97 no. 4 1461-1469. Note that anti-apoptotic genes are up-regulated and proapoptotic genes are down-regulated in skeletal and cardiac muscles in response to prolonged endurance exercise. See PM Siu, RW Bryner, JK Martyn, et.al. (2004), Apoptotic adaptations from exercise training in skeletal and cardiac muscles, The FASEB Journal, 2004. Exercise and vitamin D both improve the expression of Klotho [gene KL], which increases intelligence, improves life span, and deflects coronary artery disease.
Cyclic AMP from exercise or forskolin represses the expression of caveolin-1 (gene CAV1), allowing recovery from cellular senescence. Check cyclic AMP, cyclic AMP signal, adenyl cyclase, cyclic AMP in bodybuilding cyclic AMP from exercise, and plasma levels of cyclic AMP from exercise. "The effect of one bout of intense swimming caused significant increases in the cyclic AMP content of fast-twitch white skeletal muscle, liver, and heart. Further investigation of the exercise-induced increase in myocardial cyclic AMP indicates that the nucleotide content remained elevated long after (24 h) termination of exercise. This increase in cyclic AMP was time dependent, with the level increasing gradually throughout the work bout. The increase in cardiac cyclic AMP seemed to be independent of work intensity, provided that work time was of sufficient duration (greater than or equal to 30 min)." - After Palmer WK (1988), Effect of exercise on cardiac cyclic AMP, Medicine and Science in Sports and Exercise 1988 Dec;20(6):525-30. Also see Bodybuilding and Anabolics, and Vassilis Mougios, Exercise Biochemistry, Human Kinetics, 2006. Note that after exercise causes a return to the youthful phenotype from the senescent state by the action of cyclic AMP to inhibit the expression of caveolin-1 (gene CAV1), PDGF and EGF-family growth factor telomerase activators such as epiregulin (also from exercise) lengthen cellular telomeres and restart the cell cycle.
Furthermore, exercise increases the number of dopamine receptors in the brain.
A Good Hard Pumping Up - Don't Leave Home Without It.
Lactic acid from pumping up is an HDAC inhibitor expanding chromatin for protein transcription, producing more euchromatin and reducing dark condensed heterochromatin, producing a more youthful pattern of gene expression. Also see Fabio Demontis, Rosanna Piccirillo, Alfred L. Goldberg and Norbert Perrimon (2013), The influence of skeletal muscle on systemic aging and lifespan, Aging Cell (2013) 12, pp943–949. Note that exercise increases the expression of Klotho (gene KL), a longevity gene (Index/KL) most highly expressed in the kidneys. See also Sutoo D, Akiyama K. (2003), Regulation of brain function by exercise, Neurobiol Dis 2003 Jun;13(1):1-14.
Exercise and Rejuvenation (encyclopedia).
Exercise and Hormesis [Links, Images, Video, Papers, Patents, Books; LifeExtension/Hormesis, LifeExtension/Exercise, Wikipedia/Hormesis] [5s].
Exercise Physiology [Links/Exercise physiology, Images, Video, Papers, Patents, Books, LibCong; Links/Exercise biochemistry, Images, Video, Papers, Patents, Books].
Experimental Aging Research on-line [Books, Links].
Experimental Gerontology, The Journal of, [Links, LibCong], .
Extension of Life Span by introduction of telomerase into human cells article by Andrea G. Bodnar, Michel Ouellette, Maria Frolkis, Shawn E. Holt, Choy-Pik Chiu, Gregg B. Morin, Calvin B. Harley, Jerry W. Shay, Serge Lichtsteiner, and Woodring E. Wright, (Science 16 January 1998) . [Links, Images, Video, Papers, Patents, Books, LibCong, LifeExtension, Geron, Geron/Telomerase Activation]. This was the first paper (1998) to demonstrate the extension of life span in human cells by introducing extra telomerase using a viral vector to transfect additional copies of hTERT into cellular DNA. In the year 2000, Tricostatin A was shown to activate hTERT to produce more telomerase, followed in 2003 by epithalon peptide (Ala-Glu-Asp-Gly) by the St. Petersburg Institute for Biogerontology. Both the histone deacetylase inhibitor Tricostatin A and epithalon peptide were administered by injection, however. The first orally bioavailable telomerase activators were defined by Geron Corporation in 2005, including astragaloside IV, cycloastragenol, other compounds derived from astragalus membranaceus, and ginsenoside Rh1 from ginseng. Excipients to improve their bioavailability were identified later. TA Sciences began marketing TA-65 with telomere measurement services in the Spring of 2007, about the time I started experimenting with astragalus extracts myself. Today, 7.1 years later in the Summer of 2014, I have 175 telomerase activators on my search-the-web list, perhaps 1/4 of which are potentially useful for life extension. Sierra Sciences is uncovering more telomerase activators by applying high-throughput testing technology and theoretical analysis. In addition, I have 72 telomerase inhibitors on another list, which helps avoid mixing telomerase inhibitors with telomerase activators in therapy to lengthen telomeres. However, some telomerase inducers for fibroblasts seem to behave like telomerase inhibitors when applied to cancer cells.
Extra-chromosomal circular DNA [Links/Extra-chromosomal circular DNA (eccDNA), Images, Video, Papers, Patents, Books]. Note eccDNA levels are increased by exposure to carcinogens and inhibition of eccDNA formation by resveratrol, probably due to chromatin compaction associated with the histone deacetylse property of SIRT1. (0), [14s]. See DNA Nanocircles.
Extracellular Matrix [Wikipedia, Links, Images, Video, Papers, Patents, Books, LibCong, Amazon; Index/Skin; Index/Growth Factor Skin Creams; Index/Matrix Metalloproteinases; Index/Collagen; Index/Elastin]. The extracellular matrix turns over slowly, thus collagen and elastin in the matrix are only slowly replaced [Links, Images, Video, Papers, Patents, Books] by rejuvenated fibroblasts with telomerase-enlongated telomeres after gene expression is reset to the expression characteristic of the youthful phenotype. After the replicative senescence of dermal fibroblasts, matrix metalloproteinases may attack components of the extracellular matrix, especially collagen (with collagenase), elastin (with stromelysin), and gelatin.
Molecular components of the extracellular matrix include:
__Proteoglycans: Heparan sulfate, Chondroitin sulfate, and Keratan sulfate;
__Non-proteoglycan polysaccharide: Hyaluronic acid;
__Ceramide components of sphingolipids that can be upgraded with oral phytoceramides;
__Fibers: Collagen fibers, elastin fibers;
__Other: Fibronectin, Laminin, Human growth factors, Matrix metalloproteinases. Also see
Hynes RO (2009), The extracellular matrix: not just pretty fibrils, Science 326, 1216-1219. "Both Ku and SIRT1 are induced during restoration and are required for senescent cells to return to a youthful phenotype." - Choi HR, Cho KA, Kang HT, Lee JB, Kaeberlein M, Suh Y, Chung IK, Park SC. (2011), Restoration of senescent human diploid fibroblasts by modulation of the extracellular matrix, Aging Cell 2011 Feb;10(1):148-57. Young extracellular matrix can restore senescent dermal fibroblasts, so perhaps young extracellular matrix can function as a rejuvenating skin cream component [Papers, Patents]. Orally bioavailable phytoceramides inhibiting elastase and making up for lost skin ceramide production as aging proceeds are associated with dramatic facial rejuvenations.
Extraction Methods (for Phytomedicines) [Links, Video, Papers, Patents, Books, LibCong, Amazon, Wikipedia Topic Selection]. See
[LEF/Overexposure of eyes to sunlight, Links, Images, Video, Papers, Books, LibCong, LifeExtension;
CoQ10 and Retinal Protection];
DHA and Macular Degeneration [Links, Images, Video, Papers, Patents, Books]. DHA is associated with dendrite formation and complexity, brain synaptogenesis, and corneal nerve regeneration in experimental animals, making it useful for treating cataract surgery problems. See DHA with Epithelial Growth Factor Enhances Nerve Regeneration After Corneal Surgery, PUFA Newsletter, Issue 79. Recently human embryonic stem cells [Images] have been used to restore the retina in cases of macular degeneration. See Michelle Roberts (2012), Advanced Cell Technology: Stem cell retinal implants safe, BBC News, Jan 23, 2012. See Human Embryonic Stem Cells used to Cure Macular Degeneration [Images, Video, Papers, Patents, Books].
Taurine provides retinal protection [Links, Images/Taurine Supplements]
Taurine, abundant in fish, is found at high concentrations in the retina that decline with age. Taurine defends against age-related vision loss, retinal ganglion degeneration, retinal dysfunction, and macular degeneration [Index], and taurine deficiencies can induce vision problems.
 Ian Macleavy (2013),
The Forgotten Longevity Benefits of Taurine,
Life Extension Magazine, June 2013.
 Froger N, Cadetti L, Lorach H, et al. (2012),
Taurine provides neuroprotection against retinal ganglion cell degeneration,
PLOS One, 2012;7(10):e42017.
 Zeng K, Xu H, Mi M, et al. (2009),
Dietary taurine supplementation prevents glial alterations in retina of diabetic rats,
Neurochemical Research, 2009 Feb;34(2):244-54.
 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.
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