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Z
Zeatin [News/Zeatin, pronunciation, Links, Images Video, Papers, Patents, Books, LifeExtension; Nutritional Sources; dosage, toxicity] (7).
Zeaxanthin & Lutein [Links/Zeaxanthin & Lutein for Macular Degeneration (Index), in orange juice and egg yolks; Images/Zeaxanthin and Lutein supplements; Links/Zeaxanthin, Images Video, Papers, Patents, Books, LifeExtension, Dosage(Zeaxanthin), Toxicity(Zeaxanthin); Links/Lutein, Images Video, Papers, Patents, Books, LifeExtension, Dosage(Lutein), Toxicity(Lutein)], [101], [25i]. Cataracts increase in frequency as sun exposure goes up. "Scientists found a 40% lower rate of cataracts occuring at the center of the lens for every milligram increase in their daily intake of lutein and zeaxanthin!" - LifeExtension. See Foods Containing Lutein and Zeaxanthin [Links, Images, Papers, Patents, Books, LifeExtension]. Green vegetables such as kale, spinach, turnip greens, collard greens, romaine lettuce, broccoli, zucchini, garden peas and brussel sprouts are the finest sources of lutein and zeaxanthin.
Zeaxanthin [pronunciation, Wikipedia/Zeaxanthin, Links/Zeaxanthin, Images, Video, Papers, Patents, Books, Dosage(Zeaxanthin), Toxicity(Zeaxanthin), LibCong, LifeExtension; Images/Zeaxanthin supplements].
Zerumbone [zerumbone.com, pronunciation, Wikipedia/Zerumbone, Links/Zerumbone, Images, Video, Papers, Patents, Books, Dosage(Zerumbone), Toxicity(Zerumbone), LibCong, LifeExtension; Images/Zerumbone supplements; Anticancer Drugs and Nutraceuticals, Angiogenesis Inhibitors, Apoposis, Apoptosis Inducers]. Zerumbone, a NF-kB inhibitor found in ginger, suppresses NF-kB activation induced by carcinogens, blocking cancer proliferation, invasion, tumor blood vessel development, and metastasis while promoting apoptosis. It is anticancer, antitumor, an angiogenesis inibitor and promotes the apoptosis of tumor cancer cells. Zerumbone is extracted from ginger, which also contains gingerol. Ginger is an antioxidant, antiinflammatory, anti-tumor spice. The maximum daily dose of ginger is about 5 grams. Ethanolic ginger extract [Images] is a telomerase inhibitor that also inhibits c-Myc expression. See also nutraceuticals promoting the apoptosis of tumor cancer cells [Images, Video, Papers, Patents, Books, LifeExtension] and Subash C. Gupta, Ji Hye Kim, Sahdeo Prasad, Bharat B. Aggarwal (2010), Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals [PDF], Cancer Metastasis Review, 2010, 29-405-434.
Zinc (Zinc Homeostasis and Short Telomeres) [Links/Zinc and Telomeres, Images, Papers, Patents, Books; Links/Zinc Fingers and Telomeres, Images, Papers, Patents, Books; Links/Zinc Homeostasis, Images, Papers, Patents, Books; Wikipedia/Zinc(Biological role), Links/Zinc supplements, Images, LifeExtension; Links/Foods rich in Zinc, GovFactSheet/Zinc, LifeExtension, Amazon; Dosage(Zinc), Toxicity(Zinc)]. See Catia Cipriano, Silvia Tesei, Marco Malavolta, Robertina Giacconi, Elisa Muti, Laura Costarelli, Francesco Piacenza, Sara Pierpaoli, Roberta Galeazzi, Maria Blasco, Elsa Vera, Andres Canela, Fabrizia Lattanzio and Eugenio Mocchegiani, (2009), Accumulation of Cells With Short Telomeres Is Associated With Impaired Zinc Homeostasis and Inflammation in Old Hypertensive Participants, The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2009, 64A(7):745-751. Zinc supplements upregulate Bcl-2, a known telomerase activator (75) on my list of telomerase activators. Note that semen, which perpetually contains cells with long telomeres, is rich in zinc, which is sometimes taken to increase the size of a semen load. "Oysters" are the food source richest in zinc. "Zinc deficiency is characterized by... impaired immune function." Zinc "is required for the catalytic activity of approximately 100 enzymes and it plays a role in immune function, protein synthesis, wound healing, DNA synthesis, and cell division." - GovFactSheet/Zinc. In overdose, however, zinc can function as a neurotoxin. Copper deficiency may be induced at intakes of 100300 mg Zinc/day, because too much zinc interferes with the absorption of copper and iron. Higher hospitalizations were observed among elderly men taking 80 mg Zinc/day. The USDA RDA is 15 mg Zinc/day, while the average intake for men was about 14 mg Zinc/day and 9 mg Zinc/day in women. - Wikipedia/Zinc(Biological role). Optimal dosage turned out to be about 45 mg of zinc per day. Spring Valley markets Zinc in 50 mg caplets for immune health. Otherwise, Terraternal notes that "Zinc helps methylate homocysteine, and the enzyme DNA methyltransferase [Wikipedia] also contains zinc." Note that the DNA repair polymerase PARP is enhanced by combined supplementation of nicotinamide, zinc, and carotenoids (10). [Nicoplex, Sheng Y, Pero RW, et al, 1998].
Zinc initiates muscle synthesis by activating the mTOR pathway, a required cell signaling event for muscle growth. Since zinc can restore hormone levels in stressful environments, it has some value as an adaptogen. Weight-training leads to zinc deficiency, and giving a zinc supplement to bodybuilders augments both testosterone and thyroid hormone expression.
Zinc Fingers [HUGO Gene Families/Zinc Fingers, Wikipedia/Zinc Fingers, The Zinc Finger Consortium, Links/Zinc Fingers, Images, Videos, Papers, Patents, Books, Amazon; Zinc Finger Consortium Data Base, Zinc Finger Tools; Index/Zinc Finger Transcription Factors, Index/Zinc Finger Nucleases]. Note that subtelomeric DNA activated by the telomere position effect when telomeres become short contains genes for zinc fingers and olfactory receptors. At the same time, beta galactosidase levels associated with oral malodor (Wikipedia/Halitosis) are enhanced, making old men stink by comparison with infants. Thus lengthening your telomeres will make you smell younger according to women, and improve your breath. Zinc finger proteins found in nature may be very elaborate. Consider, for instance, TFIIIA: A Sophisticated Zinc Finger Protein. Also see Monika Papwortha, Paulina Kolasinska, and Michal Minczuk 2005, Designer Zinc Finger Proteins and their Applications, Gene, Volume 366, Issue 1, 17 January 2006, Pages 27-38.
Zinc Finger Protein Transcription Factors [Wikipedia/Transcription factor, Index/Transcription Factors, Wikipedia/Zinc finger protein transcription factor, Wikipedia/Artificial transcription factor, Links/Zinc Finger transcription factors, Images, Video, Papers, Patents, Books; Zinc Finger Consortium Data Base].
Zinc Finger Transcription Factors include:
(1) Zinc Finger Transcription Activators [Images, Papers, Patents, Books] and
(2) Zinc Finger Transcription Repressors [Images, Papers, Patents, Books]. There are also
(3) Zinc Finger Methylases [Images, Papers, Patents, Books].
Zinc finger methylases turn off gene expression by methylation, typically methylation of a region in the gene promoter, to implement gene silencing. Zinc finger-targeted transcription factors can be designed for applications such as transcriptional repression in cases involving undesirable gene activation in cancer. Perhaps it will be useful to design such artificial transcription factors for hTERT activation, or to upregulate SOD or other endogenous antioxidants, and transport these several at a time into the cell in the same package. We may devise supplemental genes to be installed for life extension applications and zinc finger transcription factor supplements for longevity. Sangamo Biosciences designs and sells zinc finger protein (ZFP) transcription factors. See Engineered anti-angiogenic zinc finger protein in Molecular Therapy, 2007, (Nature). Also see Shuxin Ren, 2003, Telomerase Activator 1: A Zinc-Finger Protein That Acts Synergistically with Auxin to Control Telomerase Expression in Arabidopsis Thaliana, 2003, PhD thesis, Texas A&M University. Also see Ren S, Johnston JS, Shippen DE, McKnight TD., 2004, TELOMERASE ACTIVATOR1 induces telomerase activity and potentiates responses to auxin in Arabidopsis, Plant Cell 2004 Nov;16(11):2910-22, and S. Ciftci-Yilmaz and R. Mittler, 2008, The Zinc Finger Network of Plants, Cellular and Molecular Life Sciences, Issue Volume 65, Numbers 7-8 / April, 2008. Note that Cys(2)His(2) Zinc Finger protein transcription factors [Wiki] are the most common DNA-binding motif found in humans and animals. The motif features a 23- to 26-residue sequence containing 2 cysteine residues and 2 histidine residues that bind one Zn2+ ion. The binding of the Zn2+ ion folds the short polypeptide into a compact domain that can insert its alpha helix into the major groove of DNA. There are many transcription factors in the human genome that contain multiple Cys(2)His(2) zinc fingers interacting with successive groups of base pairs as the protein wraps around the double helix of DNA. It is the zinc finger class that is strung together to support the formation of zinc finger nucleases targeting unique sites in the human genome for targeted genome editing supporting gene therapy. However, there is another class of Cys(4) zinc fingers in which 4 cysteine residues bind one Zn2+ ion, in which 2 groups of 4 cysteine residues occur at opposite ends of a 55- or 56-residue domain. The Cys(4) class of zinc fingers includes the steroid receptor superfamily [Images, Papers, Patents, Books] and altogether about 50 human transcription factors. (After Molecular Cell Biology By Harvey F. Lodish and Arnold Berk, page 291, 6th edition, St. Martin's Press, 2008, 973 pages.) In addition, Cys(6) transcription factors bind two Zn+2 ions per zinc finger.
Zinc Finger Nucleases [Refs5, Wikipedia/Zinc Finger Nuclease, Links/Zinc Finger Nucleases, Images, Videos, Papers, Patents, Books, Amazon; Sigma-Aldrich ZFN References; Zinc Finger Consortium Data Base, Zinc Finger Tools; Targeted Genome Editing; Longevity Genes; HUGO's Human Genome; Model Organism Genomes]. Zinc finger nucleases (ZFN) are used in genetic engineering and gene therapy to target a unique sequence within a complex genome. Zinc Finger Nuclease Technology for Targeted Genome Editing is ready to go from Sigma Aldrich/Zinc Finger Nuclease Technology. Zinc fingers can be assembled from Sigma Aldrich standard components to fit gene patterns. See Sigma Life Science CompoZr ZFN technology. A zinc finger nuclease consists of a gene targeting zinc finger complex and a FokI restriction endonuclease [Links, Images, Papers, Patents, Books] forming one side of a pair of "scissors" for cutting DNA at the target site. (The FokI endonuclease usually binds to duplex DNA via its DNA-binding domain at its palindromic 5'-GGATG-3': 5'-CATCC-3' recognition site, before the DNA cleavage domain is activated and cleaves non-specifically between nine and 13 nucleotides downstream of the recognition site. A pair of FokI restriction endonucleases [Images, Video, Papers, Papers, Books] may dimerize, however, to cut at a specific site specified by the genome-targeting zinc fingers [Images, Video] in the zinc finger nucease pair at a non-palidromic site.) A pair of zinc finger nucleases making up a catalytically active FokI dimer [Images] that functions like scissors at a specific site in the mouse, rat, or human genome can be packaged with a DNA repair template insert (with two overlapping DNA end sections to match DNA on either side of the break) including a desired gene sequence and delivered to the cell by electroporation or transfection with liposomes made with cationic transfection reagents. This strips the genetic sequence one specifies into the genome where one wants it to go. You just order it up from Sigma Aldrich, and they will send you the package to do the job. They also supply gene knockout packages and other gene-task packages. For instance, they have one that integrates a plasmid from a liposome into the AAVS1 [Wikigenes] site where the AAV adeno associated virus integrates into the genome on chromosome 19. There are indications that the genome can be painlessly modified using liposomes prepared with Invitrogen transfection reagents. On the other hand, electroporation would be used to prepare genetically modified cell cultures or modified blood fractions, for instance. Using Zinc Finger Nuclease technology you might strip in genes for more glutathione peroxidase (gene GPX1), SOD or MnSOD, or get yourself extra copies of the telomerase component genes hTERT and hTR for lasting youth someday soon. Human superoxide dismutases include SOD1 (cytoplasmic SOD, CuZnSOD), SOD2 (mitochondrial SOD, MnSOD), and SOD3 (extracellular SOD). However, this is still new and being tested and companies offering ZFN Targeted Genome Editing technology for sale as therapy to patients are obscure. Sigma Aldrich sells primarily to scientists doing research leading to the development of therapies. Also see Targeted Genome Editing, Plasmids, Protein Targeting, Gene, and Gene Therapy. ZFN HIV therapy may be available now from Sangamo Biosciences (Press Release) to be applied by transfection or electroporation and subsequent transfusions or stem cell transplants. Diseases based on Single Nucleotide Polymorphisms (SNPs) such as sickle cell anemia are correctable with Zinc Finger Nuclease technique. Most cases (70%) of cystic fibrosis are due to single-nucleotide polymorphism at phenylanaline 508 in the CFTR gene for a membrane clorine ion transporter that might be fixed with Zinc Finger Nuclease technique. It may also be possible to knock out DNA code for proviruses in the genome (endogenous retroviruses) that can cause diseases like genital herpes, HPV causing genital warts, HTLV causing T-cell leukemia, and HIV. Today (2010), HTLV and HIV are known to manifest themselves as endogenous retroviruses associated with proviral code in the human genome associated with latent infections. Fast, inexpensive whole-genome DNA sequencing may be required to implement such cures reliably. Also see Nucleofection, Sangamo Biosciences, and the early article Qiang Liu, David J. Segal, Jayant B. Ghiara, and Carlos F. Barbas III, 1997, Design of polydactyl zinc-finger proteins for unique addressing within complex genomes, PNAS May 27, 1997 vol. 94 no. 11 5525-5530. By 2005 the early genome-targeting (Cys2His2) ZFPs of the late 1990s were combined with FokI endonucleases [Images] for Targeted Genome Editing [Links, Images, Video, Papers, Patents, Books]. See also Polydactyl Zinc Finger Gene Switches as a New Software for the Genome from The Barbas Laboratory at The Scripps Research Institute and David A Wright, Stacey Thibodeau-Beganny, et.al, 2006, Standardized reagents and protocols for engineering zinc finger nucleases by modular assembly, Nature Protocols, 1, - 1637 - 1652 (2006) and associated Papers [Papers/Engineering Zinc Finger Nucleases]. Check out constructing zinc finger nucleases [Images, Video, Papers, Patents, Books, Amazon].
Zinc Finger Nucleases for Cancer Therapy [Links, Images, Video, Papers, Patents, Books]. Zinc Finger Nucleases may be used for targeted treatment of certain cancers. For instance, when the cancer is due to p53 mutations or mutation of Rb, the tumor suppressor genes, new copies of the tumor suppressor genes may be inserted in place of mutated ones, or a splice may be inserted to produce apoptosis. It may be feasible to develop ZFNs to produce targeted apoptosis in cancer cells characterized by specific oncogenes, as the ZFNs can recognize and replace a specific oncogene with a substitute designed to produce apoptosis or repair of the cell. In some cases, multiple mutations may lead to cancerous cells that can be targeted for apoptosis by a suitable Zinc Finger Nuclease engineered to produce an apoptotic splice. ZFNs may be devised to recognize characteristic telomere fusions or karyotype abnormalities and insert a sequence leading to apoptosis to treat certain carcinomas arising through chomosomal fusion.
Zinc Finger Nuclease References [Refs]
[1] Stephen Alwin, Maja B. Gere, Eva Guhl, Karin Effertz, Carlos F. Barbas III, David J. Segal, Matthew D. Weitzman, and Toni Cathomen (2005), Custom Zinc-Finger Nucleases for Use in Human Cells, Molecular Therapy Vol. 12, No. 4, Oct. 2005.
[2] Matthew H. Porteus and Dana Carroll (2005), Gene targeting using zinc finger nucleases, Nature Biotechnology Vol. 23, No.8, August 2005.
[3] Sudar Durai, Mala Mani, Karthikeyan Kandavelou, Joy Wu, Matthew H. Porteus and Srinivasan Chandrasegaran (2005), Zinc finger nucleases: custom-designed molecular scissors for genome engineering of plant and molecular cells, Nucleic Acids Research, 2005, vol. 33, No. 18.
[4] Urnov F.D., J.C. Miller, Y.L. Lee, C.M. Beausejour, J.M. Rock, S. Augustus, A.C. Jamieson, M.H. Porteus, P.D. Gregory and M.C. Holmes (2005), Highly efficient endogenous human gene correction using zinc-finger nucleases, Nature 435(7042): 646-651.
[5] Moehle E. A., J.M. Rock, Y.L. Lee, Y. Jouvenot, R. C. DeKelver, P.D. Gregory, F.D. Urnov and M.C. Holmes (2007). Targeted gene addition into a specified location in the human genome using designed zinc finger nucleases, Proceedings of the National Academy of Sciences USA 104(9): 3055-3060.
[6] Angelo Lombardo, Pietro Genovese, Christian M. Beausejour, Silvia Colleoni, Ya-Li Lee, Kenneth A. Kim, Dale Ando, Fyodor D. Urnov, Cesare Galli, Philip D. Gregory, Michael C. Holmes, and Luigi Naldini (2007), Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery, Nature Biotechnology 2007.
[7] Jeffry C. Miller, Michael C. Holmes, Jianbin Wang, Dmitry Y. Gushin, Ya-Li Lee, Igor Rupniewski, Christian M. Beausejour, Adam J. Waite, Nathaniel S. Wang, Kenneth A. Kim, Phillip D. Gregory, Carl O Pabo and Edward J. Rebar (2007), An improved zinc-finger nuclease architecture for highly specific genome editing, Nature Biotechnology, Vol.25, No.7, July 2007.
[8] Meng X, M.B. Noyes, L.J. Zhu, N.D. Lawson and S.A. Wolfe (2008). Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases, Nature Biotechnology 26(6): 702-708.
[9] Elena E. Perez, Jianbin Wang, Jeffrey C. Miller, et al. (2008), Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases, Nature Biotechnology, Vol. 26, No.7, July 2008.
Zocor (Simvastatin) [Links/Simvastatin, Images, Video, Papers, Patents, Books; Links/Zocor, Images, Video, Papers, Patents, Index/Simvastatin, Index/Statin Drugs]. Simvastatin (Zocor) is a statin drug used primarily for the control of cholesterol LDL/HDL ratio that also activates the telomere loop control protein TRF2 [Shelterin/TRF2], which it made it theoretically capable of closing open telomere t-loops to eliminate the senescent state of the cell by removing the DNA damage signal associated with an open t-loop. Atorvastatin is another statin drug expected to be useful in producing temporary synthetic youth (for perhaps > 200 years) by this technique. However, this turned out not to be possible. Telomerase activators which actually extend and repair the telomere provide a relatively open-ended solution to cellular rejuvenation [Images, Papers, Patents, Books] featuring possibly infinite lifetimes. Simvastatin (Zocor) upregulates Bcl-2 (75), a telomerase activator [List].
Simvastatin is usually prescribed with CoQ10 or ubiquinol to oppose its side effects, because statin drugs lower internal CoQ10 levels. Note that CoQ10 is a life-extending drug and endogenous metabolic factor that helps mitchondria process fatty acids into ATP for energy. Therefore, taking Zocor without supplemental CoQ10 subtracts a life-extending substance and precious stores of energy, so that side effects including tired muscles and weak memory become evident, as muscular and mental energy fail due to lack of CoQ10. In addition, Zocor without CoQ10 would produce a shorter lifespan, as supplemental CoQ10 produces longer lifespans. See Zocor Side-Effects and Statin Drug Side Effects.
TRF2 Overexpression
"Overexpression of TRF2 causes telomere shortening in both telomerase-positive and -negative cells. Recent studies also showed that TRF2 also activates telomere degradation." (Cong, Wright, and Shay, 2002). This is discouraging for TRF2-based telomere loop closure therapy programs to lengthen life spans by using Zocor or other TRF2-enhancing drugs.

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