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Ibuprofen [Wikipedia, LifeExtension, Links, Video, Images, Papers, Patents, Books, LibCong/Ibuprofen; Dosage, Toxicity]. Ibuprofen is a pain reliever, inhibits COX-2 enzymes, reducing cancer risks, but long-term use is associated with kidney problems, so that curcumin should be used instead for anticancer COX-2 inhibition. Ibuprofen also shows liver toxicity problems. See COX-2 enzymes, COX-2 enzyme inhibitors, and Links/COX-2 enzymes cause cancer. See also Pain Medicine, Anti-Inflammatory Nutraceuticals, Joint Injuries, TNF-alpha, TNF-alpha inhibitors, NFkB, and NFkB Inhibitors.
Id-1 Helix-Loop-Helix Protein [Telomerase Activator/ID-1, Links, Images, Papers, Patents, Books]. Id-1 helix-loop-helix protein activates telomerase [Links] in human keratinocytes [Images]. See Rhoda M. Alani,Jens Hasskarl, Miranda Grace, Maria-Clementia Hernandez, Mark A. Israel, and Karl Münger, (1999), Immortalization of primary human keratinocytes by the helix–loop–helix protein, Id-1, PNAS, August 17, 1999 vol. 96 no. 17 9637-9641. See also The Helix-Loop-Helix Family of Transcription Factors and Activating expression of Id1 helix-loop-helix protein. Id-1 is promoted, for instance, by Nerve Growth Factor, which can be promoted with carnosic acid from Rosemary Extract, from Rosemary [Links] or from Essential Oil of Rosemary [Images] or from acetyl L-carnitine or huperzine A. So perhaps carnosic acid can be used as a telomerase activator [81s, TA/Telomerase Activators] via its activation of Id-1 helix-loop-helix protein transcription, which normally acts to suppress cellular differentiation. Platelet-Activating Factor also enhances the expression [Links] of Nerve Growth Factor, although Platelet Activating Factor can induce bronchial constriction producing fatal asthma and is not used in practice. Acetyl L-Carnitine improves nerve growth factor levels in experimental animals. Acetyl L-carnitine can improve Nerve Growth Factor levels by up to 100 times. Acetyl L-Carnitine, Acteyl L-Carnitine arginate, Uridine, and Gotu Kola are used in medicine to improve nerve growth factors in general [Images]. See Links/Supplements activating Nerve Growth Factor. Note that Nerve Growth Factor [Images] is a secreted protein that circulates throughout the entire body that binds to high-affinity transmembrane tyrosine kinase receptor TrkA, low affinity nerve growth factor receptor p75 LNGFR, and neurotrophin receptor p75(NTR). Note also that Id-1 helix-loop-helix protein downregulates p16INK4a production (Zheng et al. 2004, Ohani et al. 2001). p16INK4a protein can accumulate to high levels, triggering cellular senescence, stunting neurogenesis and inhibiting forbrain progenitors, so that Id-1 is valuable as an inhibitor for p16INK4a. However, p16INK4a is often described as a tumor suppressor, although the inhibition of p53 and Rb is more likely to be associated with cancer. We seek to limit cellular levels of p16INK4a with Id-1 helix-loop-helix protein to avoid triggering senescence.
Idebenone [Wikipedia, IAAS/Idebenone, Links, Images, Papers, Patents, Books, LifeExtension]. (QSA-10),(a synthetic analog of CoQ10, ubiquinone) [61], [39], [59]. Smart Drugs/Idebenone, enhances serotonin levels and nerve growth factor levels, (4). Idebenone protects myelin sheaths in multiple sclerosis, developer Prof. Zs-Nagy, (4). See also Links/Idebenone enhances serotonin levels and Links/Idebenone boosts Nerve Growth Factor levels.
IGF-1 [TelomeraseActivators/IGF-1, Wikipedia/IGF-1, Links/IGF-1, Images, Video, Papers, Patents, Books, LibCong/IGF-1; Images/IGF-1 supplements; Links/IGF-1 and aging, Images, Papers, Patents, Books, LifeExtension/IGF-1 and aging; Images/IGF-1 antiaging supplements; Images/IGF-1 Liposome Sprays; Wikipedia/Growth Factor, Human Growth Factors]. IGF-1 upregulates telomerase [Telomerase Activators/(9), Telomerase Activators/IGF-1, Index, Biocarta Pathways, 67], and may be produced in the liver from HGH (Telomerase Activators/HGH) stemming from, say, whey protein and/or exercise. Casein (cottage cheese) elevates IGF-1 levels, as does orally ingested colostrum. Almost all human cells are affected by IGF-1, an autocrine/paracrine hormone, but it is limited by the presence of a required IGF-1 receptor [Images, Papers, Patents, Books]. Note, however, that IGF-1 is not an endocrine hormone distributed in the blood to distant target cells. Acetyl L-carnitine restores levels of IGF-1 in aging neural tissue. The growth-promoting effect of IGF-1 on brain cells is potentiated by acetyl L-carnitine plus alpha lipoic acid. "IGF-1 strongly promotes the survival of vascular smooth muscle cells, wheras low plasma IGF-1 is associated with many cardiovascular risk factors... IGF-1 increases nitric oxide production via a PI3K-Akt cascade which increases vasodilation and ROS scavenging... Additionally, activation of IGF-1 receptor and Akt stimulates production of cardiomyocytes and stem cells." - The Biology of Human Longevity, Caleb E. Finch, p.8. "IGF-1 rescues human intervertebral annulus cells from in vitro stress-induced premature senescence." - Books/how to manage senescent chondrocyes - from ISpine: Evidence-Based Interventional Spine Care. "Genetic pathways that promote survival and long life include the IGF-1 signaling pathway [Links, Images, Papers, Patents, Books, Amazon], dietary restriction, and the mitochondrial transport chain..." - from Introduction to Telomeres and Telomerase in Ageing, Disease, and Cancer; Molecular Mechanisms of Adult Stem Cell Aging, by Jerry W. Shay and K. Lenhard Rudolph, edited by K. Lenhard Rudolph, 2008. See the IGF-1/PI3K/AKT pathway for activation of hTERT. I believe that I am stimulating the IGF-1 pathway by doing exercises (9) while full of whey protein (from bodybuilding powder or skim milk), which stimulates HGH, thereby activating the IGF-1 pathway. HGH is converted into IGF-1 by the liver. Note that creatine monohydrate also stimulates the production of IGF-1. Animal protein or soy protein at a gram per pound of bodyweight and essential amino acids at 7.5 grams both stimulate IGF-1 expression, according to Muscle and Fitness Magazine (2010). This is probably a key to the long lifetime of 96+ year-old bodybuilder Jack Lalanne (b. Sept 14, 1914, d.2011). Bovine Colostrum (5-10 grams postworkout) also stimulates expression of IGF-1, although IGF-1 is not absorbed directly from colostrum, according to Wikipedia. See IGF-1 for antiaging. "IGF-1 (Insulin-like Growth Factor-1) is a compound produced primarily in the liver through a conversion of HGH (Human Growth Hormone). HGH is secreted by the pituitary gland [Images] and is essential for growth and optimum immune system function. " - See NOW IGF-1 Lozenges for Anti-Aging [Links, NOW], and NOW IGF-1 Lipospray [A1, NOW] for sublingual administration (about $25.00 at Whole Foods), and IGF-1 telomerase activation [Links, Papers, Patents, Books, TA/IGF-1]. See also the IGF-1 receptor [Wikipedia, Links]. IGF-1 is a risk factor in prostate cancer and breast cancer (Wikipedia). However, vitamin D3 (a telomerase inhibitor [List], although associated with longer leukocyte telomere lengths in women) can reduce these risks. Also, according to Jerry Brainum (Iron Man, March 2010), pomegranate prevents IGF-1 from inducing prostate cancer. IGF-1 induces hypertrophy of skeletal muscle and other target tissues. This is fundamental in exercise biochemistry [Links, Images, Papers, Patents, Books]. See the biochemistry of muscular hypertrophy [Images, Papers, Patents, Books]. See also Lawrence A. Wetterau, Malik J. Francis, Liqun Ma and Pinchas Cohen, Insulin-Like Growth Factor I Stimulates Telomerase Activity in Prostate Cancer Cells, The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 7 3354-3359, Copyright 2003. See IGF-1 from deer antler [Links]. Since IGF-1 increases the risk of prostate cancer by about 4x, a Prostate Specific Antigen (PSA) test is recommended in connection with the use of this class of product [LifeExtension/IGF-1 and Aging]. As Dr. Jerry Brainum recently pointed out in Iron Man, DHEA boosts IGF-1 levels [Links, Images, Papers], as does bodybuilding exercise. Vitamin D is thought to make IGF-1 safe enough to use in connection with telomerase activation, preventing any cancers due to IGF-1. Pomegranate also helps suppress IGF-1 problems, according to Brainum. See Vitamin D inhibits IGF-1 associated cancer. Note that Medical Nutraceutics puts 2000 IU of vitamin D into their telomerase activator (7) Maximum Telomere Support, which is based on Astragaloside IV. Vitamin D3 is a telomerase inhibitor, in addition to being an antiinflammatory agent, so I take it only during the final two weeks of my monthly cycle of 2 weeks of telomerase activators followed by two weeks of telomerase inhibitors and anticancer nutraceuticals. See Jacquemin V, Furling D, Bigot A, Butler-Browne GS, Mouly V (2004), IGF-1 induces human mytotube hypertrophy by increasing cell recruitment, Exp Cell Res 299: 148-158, 2004. IGF-1 from muscles induces muscular hypertrophy in an autocrine/paracrine fashion after exercise and is regulated by IGF-binding proteins IGFBP-3, IGFBP-4, IGFBP-5, and IGFBP-6. - After 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.
IGF-2 [Wikipedia/IGF-2, Links, Images, Papers, Patents, Books; Telomerase Activators/IGF-2]. IGF-2 increases the transcription of progesterone [List], a telomerase activator. IGF-2 is found in colostrum [List, Selected Telomerase Activators] and colostrum skin creams [Images].
iGrowHair Telomerase [Site, Links/iGrowHair Telomerase, Links/telomerase expression enhancing acidophilus, Images, Papers, Patents, Books; Wikipedia/acidophilus, Links/acidophilus, Images, Patents, Papers, Books; Links/telomerase expression enhancing probiotics, Images, Papers, Patents, Books, Wikipedia/probiotics, Books/Probiotics]. For $1,999, you can experiment with the TeloGenesis product iGrowHair Telomerase, which is stated to stimulate hair growth via telomerase from live acidophilus and probiotics. Perhaps they have actually discovered a probiotic organism that secretes a telomerase activator.
The telomerase molecule can get through the cell membrane in a cationic liposome fashioned from cationic transfection reagents, due to liposomal endocytosis. This is the simplest way I know of to target telomerase itself to the cell membrane. It may also be convenient to target hTERT and hTR RNA to the cell membrane in a cationic liposome. Proteins, RNA, DNA plasmids, and Zinc Finger Nuclease product ensembles for targeted genome editing have been successfully transferred to cell in such liposomes.
Artandi Labs has noted that direct activation of the scalp with conventional astragaloside telomerase activators (7) seems to produce superior results for the rejuvenation of hair, possibly by rejuvenating associated crypts and hollows of the hair follicle microenvironment, based on their experiments with rodents. [74s]. I experimented with astragalus root extract to change my hair color in about 12 months, based on these observations.
iHerb Life Extension Supplements [41].
Immortalism and Life Extension - Aleph/Trans/Immortalism and Life Extension links [44]. - Immortality, Inc. links [19].
Immortality Institute [, Links, Video, Papers, Patents].
Immortal Cellular Phenotype
__immortal cellular phenotype [Amazon, Links, Images, Papers, Patents, Books, Papers].
__youthful fibroblasts vs. senescent fibroblasts [Links, Images, Papers, Patents, Books],
__youthful cellular phenotype [Amazon, Links, Images, Papers, Patents, Books], the
__senescent cellular phenotype [Amazon, Links, Images, Papers, Patents, Books], and the
__cancerous cellular phenotype [Amazon, Links, Images, Papers, Patents, Books]. See also
__lymphoma cells [Amazon, LibCong, Links, Images, Papers, Patents, Books],
__leukemia cells [Amazon, LibCong, Links, Images, Papers, Patents, Books], and
__human cell types [Amazon, LibCong/human cell types, Links, Images, Books, Papers].
Immortalization of Cells [Index/Cellular Immortalization, Links/Immortalization of Cells, Images, Papers, Patents, Books; Links/Cellular Immortalization Protocols, Images, Papers, Patents, Books; The History of Cellular Immortalization, Images, Papers, Patents, Books; Refs/Telomeres and Telomerase, Refs/Telomere Capping Proteins]. See Hayflick, His Limit, and Cellular Aging by Shay & Wright. The DNA sequence of telemere structure was decoded for the protozoan Tetrahymena in 1978 by Elizabeth Blackburn and Joseph G. Gall, soon after Fred Sanger developed Sanger Sequencing technology for DNA sequencing. Telomerase was discovered by Elizabeth Blackburn and Carol W. Greider in 1985, just a few years before the 1989 paper on cellular immortalization or reversible senescence [Images, Papers, Patents, Books] written by Woodring E. Wright, Jerry W. Shay, and Pereira-Smith OM. Subsequently an escalating number of papers connecting telomere shortening with aging (7) appeared by Calvin B. Harley, Jerry W. Shay, Woodring E. Wright, Elizabeth Blackburn, Carol W. Greider, many other leading bioscientists, biochemists, and medical investigators. Suresh I. Rattan and fellow researchers discovered in 1994 that crushed garlic extract [List (178)] can extend the fibroblast cell division limit from 49 to more than 55, closing in on the first telomerase activator. By 1998, plasmid methods for immortalizing human fibroblasts in culture were worked out in Andrea G. Bodnar, Michel Ouellette, Maria Frolkis, Shawn E. Holt, Choy-Pik Chiu, Gregg B. Morin, Calvin B. Harley, Jerry W. Shay, Serge Lichtsteiner, Woodring E. Wright (1998), Extension of life-span by introduction of telomerase into normal human cells, Science 16 January 1998, pp. 349 - 352. Dr. Bill Andrews of Sierra Sciences developed plasmid vectors for the project. Insertion of an extra copy of the hTERT gene into the human genome using viral vectors such as the adenovirus was also pioneered. By the turn of the century, the telomere loop structure had been seen in electron microscopes and was beginning to be understood. The telomere nucleoprotein complex (shelterin, the telosome) was thoroughly investigated in the first decade of the 21st Century by Titia de Lange and leading bioscientists. This was paralleled by the development of telomerase activators between 1994 and the present time (2011) by Suresh I. Rattan and his coworkers, by Geron, and many investigators, along with the application to human life extension and investigations of telomerase inhibitors for controlling cancer. Geron announced small molecule telomerese activators in the spring of 2005 based on astragalosides, black cohosh, astraverrucins, and ginsenosides, and by 2007 TA Sciences was publicly promoting TA-65. Zinc Finger Nuclease technology for inserting additions to the human genome was also under development.
The History of Telomerase Activators - The Countdown.
[Changelog History, Numeric List of Telomerase Activators with Dates]

By the end of 2014, there were 180 telomerase activators on the big list here. Additions included ligands of the progesterone receptor and strong estrogen bioactivity nutraceuticals.
Fast Telomere Extension using purified nucleoside-modified mRNA for hTERT applied via liposomal transfection methods was announced in 2013.
By February of 2012, I had 121 telomerase activators on my big list, including endogenous telomerase activators and 14 telomerase activators upregulated by exercise, together with supplements to boost their levels. Sierra Sciences claimed then to have screened 254,593 compounds and found 858 telomerase inducers from 38 distinct drug families using high-throughput testing techniques. Some of their discoveries must have been incorporated into Product B (announced approximately January 2012), which William H. Andrews has claimed superior to TA-65, as supported by my own calculations.
By one year later in February 2013, there are 153 telomerase activators on the big list, which has grown 1.264 times as large. Most of the increase is due to telomerase inducers incorporated into Product B (Master Formulator John Anderson, Product B patent [Links, Images, Videos, Papers, Patents, Books]) as now identified in The Product B Explorer. Product B analysis seems to indicate that it is superior to TA-65 and useful for rejuvenation at rates that may approach 8.22 years/year. Further experimental work and published scientific papers on telomerase inducers and associated measurement techniques will be required to better characterize these substances.
The VIDA Institute in Cambodia measures the relative performance of astragalus root, astragalus root extract, cycloastragenol, and astragaloside IV in lengthening telomeres with tests including granulocytes, leukocytes, and NK cells. VIDA Institute determined that astragalus root at 15 to 30 grams/day is superior to cycloastragenol and astragaloside IV at conventional dosages for lengthening telomeres, and explained how to enhance its performance with gotu kola and ginkgo biloba to improve circulation and access of astragalus telomerase activators to tissue. This was consistent with measurements done by other firms, including by TA Sciences on astragalus extract TA-41, on TA-65 (mostly cycloastragenol) in measurements done by Calvin B. Harley, et al, 2011, and other measurements done by Terraternal on astragaloside IV, which did not perform as well as cycloastragenol. (Video Jim63).
Spring 2011
Most recently in the Spring of 2011 Terraternal has offered Terraternal cycloastragenol at 25 mg/cap, following a paper by Calvin B. Harley, et. al, 2011 that recommends 20-30 mg as the optimal dose for TA-65, which is primarily cycloastragenol according to independent lab analysis. See also US Patent 7,846,904 B2, Dec.7,2010., Compositions and Methods for Increasing Telomerase Activity, Geron Corporation. See also Compositions and Methods for Increasing Telomerase Activity by Calvin B. Harley, et al., US Patent 2010/0292197, Nov.18, 2010.
I note that recent work (Calvin B. Harley, et al. 2010, In vitro intestinal absorption and first-pass intestinal and hepatic metabolism of cycloastragenol, a potent small molecule telomerase activator) shows that cycloastragenol is highly bioavailable orally, much more so than astragaloside IV. Thus TA-65 shows < 6 mg cycloastragenol in chemical analyses prepared by industrial investigators, commercial vendors of cycloastragenol (Iron-Dragon, Biologix Peptide) offer cycloastragenol in 10 mg/dose formulations, while astragaloside IV may be taken 50 mg per tablet or 2x50 = 100 mg per dose per day from vendors such as Terraternal.
Leptin from CLA (conjugated linoleic acid) was understood to activate telomerase via the STAT3 activation pathway used by some Human Growth Factors such as EGF, PDGF, and IL-6.
Enhanced-bioavailability telomerase activators from Geron (2010).
See (WO/2010/135247) COMPOSITIONS AND METHODS FOR INCREASING TELOMERASE ACTIVITY [Links, Images, Papers, Patents, Books]. Exemplary compounds from the new Geron patent for more bioavailable telomerase activators include
(1) 2-(L)-amino-3-methyl-butyric acid 6-alpha.
___[Images, Papers, Patents, Books; molecule, sources, toxicity],
(2) 2-(L)-Amino-3-methyl-butyric acid.
___[Images, Papers, Patents, Books; molecule, sources, toxicity;
____Wikipedia/Valine, Links/L-Valine, Images, Papers, Patents, Books;
____molecule, supplements, sources].
____L-Valine is a branched-chain amino acid that must be ingested, as it is not produced by the body. L-Valine promotes muscle growth and tissue repair, stimulating protein synthesis and boosting the immune system. It appears by Nov 18, 2010 as a component molecule of a class of Geron exemplary telomerase activators. L-Valine = 2-(L)-Amino-3-methyl-butyric acid.
(3) 4 C3-(L)-valyl-cycloastragenol
[Images, Papers, Patents, Books; molecule, sources, toxicity].
____4 C3-(L)-valyl-cycloastragenol refers to an L-Valine attatched by an ester bond to carbon 3 of the usual cycloastragenol structure in the lower left hexagonal ring, numbering 1,2,3 counterclockwise from carbon 1 at the topmost vertex of that hexagonal ring left of the triangular cyclopropane ring. One wonders about the benefits of taking a mix of L-Valine and cycloastragenol together, as separate molecules. Combining them into one molecule may have largely the same result, if the ester bond is metabolized. However, the bioavailability may be improved by the bound molecule.
(4) C3-(L)-isoleucyl-cycloastragenol was the most bioavailable compound tested, and more bioavailable than cycloastragenol. Note that L-valine, L-leucine, and L-isoleucine are branched-chain amino acids that turn on muscle synthesis. See lifexnotes5.html for other enhanced-bioavailability telomerase activators and relevant synonyms.

The invention includes many related chemicals and pharmaceutically acceptable salts including simple hydrochloride salts. To improve bioavailability, some of the former star compounds, such as astragaloside IV, were modified. For instance, astragaloside IV was converted to 17-[5-(l -Hydroxy- 1 -methyl-ethyl)-2- methyl-tetrahydi'O-furan-2-yl]-4,4J3J4-tetramethyl-tetradecahydro- cyclopropar9, 1 Olcvclopentaraiphenanthrene-3 ß,6a, 16ß-triol f cycloastragenol].

Nicotine turned out to be a telomerase activator, though probably not useful for our application. See Zhu JunHui; He XiaoJing; Zhou BinQuan; Xie XuDong; Chen JunZhu; Fu GuoSheng, (2009), Nicotine-reduced endothelial progenitor cell senescence through augmentation of telomerase activity via the PI3K/Akt pathway, Cytotherapy, Volume 11, Issue 4 July 2009 , pages 485 - 491.
Tri-Phenyl Compound Telomerase Activators developed at Ben Gurion University on the Negev [Links, Images, Papers, Books; toxicity]. See Aviv Gazit et al, TELOMERASE ACTIVATING COMPOUNDS AND METHODS OF USE THEREOF, US Patent, US Patent App. 12/602,956, 2008, WO Patent WO/2008/149, 353, 2008. (See PDF version.) Many of these molecules resemble 9-legged web spiders.
February 2007
See Dong, Xie Xu, PhD; et al., (2007), Ginkgo Biloba reduces endothelial progenitor cell senescence through augmentation of Telomerase Activity, Journal of Cardiovascular Pharmacology, Feb 2007, vol.49, issue 2, pp. 111-115. "Ginkgo biloba extract significantly increased telomerase activity and phosphorylation of the serine/threonine protein kinase Akt, a downstream effector of phosphoinositide 3-kinase (PI3K). Moreover, pretreatment with PI3K inhibitor, LY294002, significantly attenuated the Ginkgo biloba extract-induced telomerase activity. Taken together, the results indicated that Ginkgo biloba extract delayed the onset of Endothelial Progenitor Cell senescence, which may be related to activation of telomerase through the PI3k/Akt signaling pathway."
March, 2007
TA Sciences announces TA-65, based on a molecule from astragalus extract.
I became aware that astragalus extracts might be used to lengthen telomeres. Until this time I did not begin to intensively research small molecule telomerase activators. Greta Blackburn of TA Sciences reported experimental telomere growth rate results (230 bp of telomere growth in 3 months of steady appliction of astragalus extract TA-41) to me in the email.
"Growth factors such as epithelial growth factor (EGF) elicit cellular signaling including MAP kinase [Links], Akt [Links] and protein kinase C [Links]." - 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. Many growth factors and growth hormones are upregulated by exercise.
May 2005
Geron announces astragalosides including cycloastragenol (TAT2) for rejuvenation applications in its patent Compositions and Methods for Increasing Telomerase Activity, which includes other small-molecule telomerase activators including Ginsenoside Rh1 and Black Cohosh (C. Racemosa). The 2005 Hong Kong University and Geron patent Formulations Containing Astragalus Extracts and Uses Thereof for astragalus extracts and applications appeared about the same time.
Jim Green (age 56) more intensively researched his web pages in anti-aging medicine that he began in June, 2000. The Geron and Hong Kong University patents escaped my attention until 2007, when the Immortality Institute in Cambridge supplied links to the patents online.
CGK 1026 (TA/CKG1026, a Telomerase Activator and HDAC inhibitor) was discovered in Korea as part of a high-throughput screening of 20,000 or so promising biochemicals. See Won J, Chang C, Oh S, and Kim T, Small-molecule-based identification of dynamic assembly of E2F-pocket protein-histone deacetylase complex for telomerase regulation in human cells, PNAS, 2004, and related articles on CGK1026. There are indications that CGK1026 is orally bioavailable, relatively non-toxic, and penetrates the cell membrane directly. CGK 1026 was used to replace Tricostatin A (TA/Tricostatin A) in some programs of treatment.
New Symmetrical Bis-Substituted Derivatives of the Anthraquinone [Links/Anthraquinone; Links/Symmetrical Bis-Substituted Derivatives of the Anthraquinone; toxicity]. See Hsu-Shan Huang, Jeng-Fong Chiou, Yaou Fong, Ching-Cheng Hou, Yu-Cheng Lu, Jen-Yi Wang, Jing-Wen Shih, Yen-Ru Pan, and Jing-Jer Lin (2003), Activation of Human Telomerase Reverse Transcriptase Expression by Some New Symmetrical Bis-Substituted Derivatives of the Anthraquinone, Journal of Medicinal Chemistry, 2003, 46, 3300-3307.
The St. Petersburg Institute for Bioregulation and Biogerontology in Russia announces Epithalon Peptide (Ala-Glu-Asp-Gly), a telomerase activator [Index, (7)] first isolated from the pineal gland.
Dr. William H. Andrews and colleagues file a 2002 patent based on hTERT repressor proteins binding to region(s) in and around the hTERT promoter. They also specify an inhibitor for the repressor that functions as a telomerase activator that can produce massive or minor hTERT transcriptional activity, depending on the dose. This is subsequently backed up by another related patent in 2007. Finally, Sierra Sciences promotes the telomerase activator C0057684.
Masahiro Takakura,, Telomerase activation by histone deacetylase inhibitor in normal cells, Nucleic Acids Research, 2001, Vol. 29, No. 14 3006-3011. More investigation of HDAC inhibitor Tricostatin A's promotion of hTERT mRNA transcription to produce enhanced telomerase activity.
Trichostatin A induced a significant activation of hTERT mRNA and telomerase activity in telomerase-negative cells (Cong & Bacchetti 2000). Vasa [Vasa, et al., 2000, Hayashi, et. al, 2006, Haendeler, 2006] discovers telomerase activation via nitric oxide.
Jim Green (51, b.1949) starts his longevity web pages in June, 2000 after reading a special issue of Scientific American on anti-aging and began to read more in medicine and the life sciences. I became more keenly aware of The Hayflick Limit (7), telomeres, telomerase, and a search for techniques to lengthen telomeres as part of anti-aging therapy. I became vaguely aware of these points earlier during the 1990s from news reports and books on aging at the Wichita Public Library.
A plasmid was developed by Bill Andrews and R. Adams to activate telomerase in cultured cells, proving life extension feasible based on improved production of hTERT mRNA in the historic paper Extension of Life-Span by Introduction of Telomerase into Normal Human Cells.
Astraverrucins Astraverrucin I and Astraverrucin II, obtained from the aerial parts of Astragalus verrucosus (cultivated in Arbus, Sardinia), being cycloastragenol glycosides, were extracted, later being identified as telomerase activators in 2005 by Geron.
Crushed garlic extract [List (178)] was observed to modify the Hayflick Limit for fibroblast cell division from 49 to more than 55 by Suresh I. Rattan and researchers from his school of anti-aging medicine. It may be that crushed garlic (which contains allicin yielding the chromatin-expanding HDAC inhibitors diallyl disulfide and allyl mercaptan) can markedly improve the transcription of hTERT mRNA. See 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.

Prior History
Astragalus membranaceus was observed to delay or even reverse aging effects in China as a consequence of the popularity of astragalus tea. Astragalus was realized effective against lymphoma night sweats in the reign of Shen Nong, who was said to turn green as a result of his experiments with medicinal herbs. Herbal life extension research was extensively pursued by Chinese masters including Li Ching-Yuen. In the West, biochemist Linus Pauling specified vitamin C (which tends to preserve telomeres) for life extension, passing away at 93 in 1993. Jeanne Calment survived to 123.45, relying on exercise, chocolate, and red wine rich in resveratrol.
Immortomouse [Links/Immortomouse, Images, Video, Papers, Patents, Books; Links/mouse genome, Images, Video, Papers, Patents, Books]. Immortomouse is a transgenic mouse [Books/transgenic technology, Links/transgenic mice, Images, Video, Papers, Patents, Books, Amazon] carrying a temperature-sensitive SV40LT gene. A number of tissues from the mouse [Images] give rise to immortal cell lines, including cells from the colonic epithelium [Images], brain [Images], astroglia [Images], muscle [Images], and retinal epithelium [Images]. [Fenton & Hord, 2004; Nobel & Barnett, 1996; Ahmed et al, 2004; Su, et al, 2003].
Immunological Theory of Aging and The Immune System (Immunosenescence) [Links/Immunological theory of aging, Images, Video, Papers, Patents, Books, LibCong, LifeExtension, Amazon; Links/The Immune System, Images, Video, Papers, Patents, Books, LibCong, LifeExtension, Amazon; Ben Best/The Immune System and Aging; Hyperimmune Eggs] (10). Drugs observed to strengthen the immune system often turned out to be telomerase activators [List] that lengthen telomeres, allowing immune system B-lymphocytes and T-cells to divide more times in fighting infection before suffering replicative senescence. For example, astragalus extract lengthens the telomeres of Natural Killer cells to stengthen the body's defenses against infection with viral or bacterial pathogens. The telomerase activators could lengthen telomeres in other cells, too, and often seem to have anti-aging effect. Antioxidants such as vitamin C were observed to strengthen the immune system by conserving telomere length, rather than by lengthening telomeres. The G-rich GGTTAG telomere sequence of hex repeats is more vulnerable to oxidative stress and attack by ROS and free radicals than many other DNA sequences. See also Index/Hyperimmune Eggs and Index/Colostrum, which contains immunoglobins IgA and IgB.
Immunosenescence References [Links, Video, Papers, Patents, Books, LifeExtension].
[1] Aw D, Silva AB, Palmer DB. (2007),
Immunosenescence: emerging challenges for an ageing population,
Immunology 2007 Apr;120(4):435-46.
[2] Martorana A, Bulati M, Buffa S, et al. (2012),
Immunosenescence, inflammation and Alzheimer’s disease,
Longev Healthspan, 2012 Nov 1;1:8. eCollection 2012.
[3] Sidler C, Wóycicki R, Ilnytskyy Y, Metz G, Kovalchuk I, Kovalchuk O. (2013),
Immunosenescence is associated with altered gene expression and epigenetic regulation in primary and secondary immune organs, Front Genet 2013 Oct 18;4:211.
[4] Palmer DB. (2013),
The effect of age on thymic function, Front Immunol 2013 Oct 7;4:316.
[5] Libby P. (2006), Inflammation and cardiovascular disease mechanisms,
Am J Clin Nutr 2006 Feb;83(2):456S-60S.
[6] Swann JB, Smyth MJ. (2007), Immune surveillance of tumors,
J Clin Invest 2007 May;117(5):1137-46.
[7] Castle SC. (2000), Clinical relevance of age-related immune dysfunction,
Clin Infect Dis 2000;31(2):578-85.
[8] Fulop T, Larbi A, et al. (2011),
Aging, immunity, and cancer, Discov Med 2011 Jun;11(61):537-50.
[9] Whiteside TL. (2010), Immune responses to malignancies,
J Allergy Clin Immunol 2010 Feb;125(2 Suppl 2):S272-83.
[10] Salvioli S, Monti D, Lanzarini C, et al. 2013), Immune system, cell senescence, aging and longevity—inflamm-aging reappraised, Curr Pharm Des 2013;19(9):1675-9.
[11] Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E,
De Benedictis G. (2000), Inflamm-aging. An evolutionary perspective on immunosenescence,
Ann N Y Acad Sci 2000 Jun;908:244-54.
[12] Walter Thompson (2014), Fight Immune Decline With Reishi,
Life Extension Magazine August 2014.
[13] Pawelec G, Larbi A, Derhovanessian E. (2010),
Senescence of the human immune system,
J Comp Pathol 2010 Jan;142 Suppl.
[14] William Faloon (2015), How Immune Decline Hastens Aging,
Life Extension Magazine, Jan 2015.
[15] Hakim FT, Gress RE (2007),
Immunosenescence: deficits in adaptive immunity in the elderly,
Tissue Antigens 2007 Sep;70(3):179-89.
[16] Gruver AL, Hudson LL, Sempowski GD (2003),
Immunosenescence of ageing, J Pathol 2007 Jan;211(2):144-56.
[17] Wu J, Lanier LL (2003),
Natural killer cells and cancer, Adv Cancer Res 2003;90:127-56.
Impaired Glucose Tolerance [Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension]. Older people are less likely to properly utilize ingested sugars. According to LEF, impaired glucose tolerance may manifest itself in obesity, metabolic syndrome, or type 2 diabetes. A program to correct impaired glucose tolerance may specify attaining fasting blood glucose levels below 86 mg/dL. Caloric Restriction alone may be sufficient to address the problem. Since carbohydrates are often the culprit, however, glucoregulatory agents such as Irvingia may be applied to inhibit associated digestive enzymes. If fats are the problem, lipase inhibitors such orlistat, green tea extract, black tea, or black tea theaflavins [Index] may be used. Also, green tea or green tea extract may be used to elevate the basal metabolic rate as part of a program to burn off fats or to improve muscle definition. Appetite suppressants such as pinolenic acid from pine nuts may be employed. Thyroid hormone stimulators like 7-Keto DHEA (T3 elevator) and bacopa (T4 elevator), are also useful in burning calories and controlling weight.
Indole-3-carbinol [GettingWell/Indole-3-carbonol, Links, Images, Video, Papers, Patents, Books, LifeExtension, Wikipedia]. Indole-3-carbinol exhibits estrogen-modulating anticancer properties, [25f]. Genistein combined with indole-3-carbinol from cruciferous vegetables strongly enhances apoptosis of colon cancer cells. Indole-3-Carbinol inhibits class I HDAC expression [Ref], and might be useful as an HDAC inhibitor for expanding chromatin to support telomerase activators in stubborn tissues such as mesenchymal cell-derived connective tissues.
Induced Pluripotent Stem Cells (iPS cells) [Refs, Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension; Index/Stem Cells]. Induced pluripotent stem cells (iPS cells) equivalant to embryonic stem cells may be obtained by manipulation of skin cell fibroblasts using a small number of defined factors. See also Thomson J.A., J. Itskovitz-Eldor, S.S. Shapiro, M.A. Waknitz, J.J. Swiergiel, V.S. Marshall and J.M. Jones (1998), Embryonic stem cell lines derived from human blastocysts. Science 282: 1145-1147. See also Jai-Hee Moon, June Seok Heo, Jun Sung Kim,, (2011), Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1, Cell Research (2011) 21:1305–1315. 28 June 2011: "Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by the transcription factors Oct4, Sox2, and Klf4 in combination with c-Myc. Recently, Sox2 plus Oct4 was shown to reprogram fibroblasts and Oct4 alone was able to reprogram mouse and human neural stem cells (NSCs) into iPS cells. Here, we report that Bmi1 leads to the transdifferentiation of mouse fibroblasts into NSC-like cells, and, in combination with Oct4, can replace Sox2, Klf4 and c-Myc during the reprogramming of fibroblasts into iPS cells. Furthermore, activation of sonic hedgehog signaling (by Shh, purmorphamine, or oxysterol) compensates for the effects of Bmi1, and, in combination with Oct4, reprograms mouse embryonic and adult fibroblasts into iPS cells." According to Michael West, iPS cells feature more cell division capacity than aged cells from which they are derived. He has described this as "resetting the cellular telomere clock", although the effect was credibly due to stem cell telomerase activation allowing more cell divisions in the stem cell class, and not due to a sudden reconstruction of the telomere restoring its embryonic length. However, restoration of youthful telomere length was observed. See Michael West (2010), Spontaneous Reversal of the Developmental Aging in Normal Human Cells Following Transciptional Reprogramming, Regenerative Medicine, 2010, (and at the futuremedicine site, announced at Biotime, and ReCyte Therapeutics). Also see West MD, Vazin H. (2010), Back to Immortality: The restoration of embryonic telomere length during induced pluripotency, Regenerative Medicine, 2010; 5(4):485-8. However, some controversy exists: iPS cells may be prematurely old [Images, Papers, Patents, Books]. See Research Funded by Life Extension could lead to Therapies that Reverse Human Aging, Life Extension Magazine, September 2011. "Some studies with iPS cells have shown that they don't work as well as hES (human Embryonic Stem) cells in stimulating the production of telomerase, the enzyme that maintains healthy cells by keeping the length of their telomeres intact." On the other hand, on March 16, 2010, BioTime announced a scientific paper on reversal of developmental aging of iPS cells, and showed new data at the 4th French-American Biotech Symposium supporting it. "Biotime scientists measured the replicative life span of five human cell types derived from aged human cells that had been returned to the embryonic state using transcriptional reprogramming. These life spans...greatly exceeded the normal life expectancy of the original aged cells... Biotime's subsidiary Cell Cure Neurosciences, Ltd., has developed a OpRegenTM retinal cell product for treatment of age-related macular degeneration based on stem cell technology. Also see products from Cell Cure Neurosciences, Ltd., also a BioTime subsidiary, for stem cell-derived products for neural degenerative diseases. See Michael D. West PhD (2013), How Engineered Stem Cells May Enable Youthful Immortality, Life Extension Magazine, February 2013 [Stem Cells]. Also see Gourronc FA, Klingelhutz AJ (2012), Therapeutic opportunities: telomere maintenance in inducible pluripotent stem cells, Mutation Research 2012 Feb 1; 730(1-2):98-105, and Stadtfeld M, Hochedlinger K (2010), Induced pluripotency: history, mechanisms, and applications, Genes and Development 2010 Oct 15; 24(20):2239-63, and West MD, Vazin H. (2010), Back to Immortality: The restoration of embryonic telomere length during induced pluripotency, Regenerative Medicine, 2010; 5(4):485-8 [PDF version]. The Nobel Prize in physiology or medicine was awarded on October 2012 to Dr. John B. Gurdon at the University of Cambridge in England and Dr. Shinya Yamanaka of Kyoto University in Japan for their work on iPS cells.
Infectious Burdens and Aging [Links, Images, Video, Papers, Patents, Books, Amazon, LibCong/infections and aging, LifeExtension]. "High infectious burdens and poor nutrition attenuate somatic repair and growth." - The Biology of Human Longevity, C.E.Finch, p.4. Cytomegalovirus, related to Herpes, reduces life span in the American population. We found rapid telomere length loss in telomerase activator experimenter Correspondent A, amounting to - 533 bp/year in lymphocytes, and - 1,333 bp/year in granulocytes, in spite of treatment with telomerase activators. This prompted a check for a viral infection, which turned up HSV-1 (Herpes).
Inflammation and Aging [Links, Images, Video, Papers, Patents, Books, Amazon, LibCong, LifeExtension, Ben Best/Inflammation and Aging; Main Essay/Inflammation and Aging]. See [70s], [68s] on NFκB, and [67s] on C-reactive protein [Index] as a marker of inflammation and aging. TNF-alpha is another inflammation-associated factor associated with senescent cells and Alzheimer's Disease. See index entries for Dementia, Antiinflammatory Nutraceuticals, Anticancer Diet with Anticarcinogens, and Carcinogens. Old-age diseases featuring inflammation include:
Alzheimer's Disease [Index, Links, Images, Papers, Patents, Books, LEF, Amazon],
Atheroscelerosis [Encyclopedia, Links, Images, Video, Papers, Patents, Books, LEF, Amazon],
Osteoporosis [Index, Links, Images, Video, Papers, Patents, Books, LEF, Amazon],
Parkinson's Disease [Index, Links, Images, Video, Papers, Patents, Books, LEF, Amazon],
Rheumatoid arthritis [Index, Links, Images, Video, Papers, Patents, Books, LEF, Amazon], and
Ulcerative colitis [Index, Links, Images, Video, Papers, Patents, Books, LEF, Amazon].
See index entries for Anti-inflammatory nutraceuticals, TNF-alpha Inhibitors, NF-kB Inhibitors, Amyloid Inhibitors, Homocysteine, Inflammatory Cytokines, Free Radical Theory of Aging, ROS, Mitochondrial Themes, and Antioxidants.
InfoAging. See InfoAging, [57]
Inflammatory Cytokines [Links, Images, Video, Papers, Patents, Books, LifeExtension, Amazon]. See also Proinflammatory Cytokines [Index, Wikipedia/Proinflammatory cytokine, Links, Images, Video, Papers, Patents, Books, LifeExtension, Amazon]. "A proinflammatory cytokine is a cytokine which promotes systemic inflammation. Examples include IL-1 and TNF alpha." - Wikipedia/Proinflammatory cytokine. See Anti-inflammatory drugs and nutraceuticals. Inflammation is also a factor in cancer, carcinogens, and Alzheimer's Disease. I note that inflammation can produce more blood flow to an inflamed area, and that focal remodeling of tissue in inflammation is sometimes associated with tissue telomere growth to support cell division and differentiation in the healing process with reform and/or repair of distressed tissue and wound healing. TNF-alpha turns out to be a telomerase activator [Notes/TNF-alpha], as does NF-kappa-B [Notes/NF-kappa-B]. Thus gradient compression support hose can induce inflammation in varicose veins. If conventional support hose are applied, the veins sometimes heal back into their non-varicose form. The support hose should be retained, however, as the varicosities may otherwise reappear due to a permanently damaged valve. See Anti-inflammatory nutraceuticals, TNF-alpha Inhibitors, and NF-kB Inhibitors. Also see COPE Cytokines Online Pathfinder Encyclopaedia [Links].
Inflammatory factors secreted by senescent cells [Links, Images, Video, Papers, Patents, Books, LibCong/senescent cells, LifeExtension]. Inflammatory factors secreted by senescent cells "have been implicated in focal remodeling of premalignant cells." - Caleb E. Finch, p.32. That is, inflammatory factors secreted by senescent cells may lead to cancer. Furthermore, inflammatory factors such as TNF-alpha are also associated with dementia and Alzheimer's Disease. Thus, telomerase activation with small molecule telomerase activators [Index] (7) to avoid replicative cellular senescence, reducing inflammatory factors and insuring genomic stability, protects against cancer. See index entries for Anti-Inflammatory Nutraceuticals, TNF-alpha Inhibitors, NF-kB Inhibitors, Anticancer Diet, Alzheimer's Disease, Dementia, Carcinogens, Matrix Metalloproteinases, and the Extracellular Matrix.
Infrared Spectroscopy [Wikipedia, LibCong, Links, Images, Video, Papers, Patents, Books, Amazon]. See Instrumental Analysis.
Inositol [Wikipedia/Inositol, Links, Images, Video, Papers, Patents, Books, Amazon LibCong, LifeExtension].
Instant Face Lift Serum [Links/Instant Face Lift, Images, Video, Papers, Patents, Books, Amazon, LifeExtension]. Some "Instant Face Lift" formulations use hyaluronic acid or hyaluronic acid with retinol to restore hyaluronan as a component of the extracellular matrix for up to 12 hours, after which it slowly vanishes over the next 12 hours. For better results, the pattern of dermal fibroblast gene expression may be gradually rendered more youthful with telomerase activators and HDAC inhibitors, or by other means. See retinol [Links, Images]. Other components of the extracellular matrix may be included in solution. More elaborate Instant Face Lift compositions exist. Note that isopropyl alcohol or glycerin may be used as transporters to enhance skin penetration. Hyaluronic acid solution encapsulated in milk lipid liposomes made with heavy whipping cream may be more effective. An ultrasonic cleaner may be used to produce milk lipid liposomes from mixtures. Milk lipid liposomes are known to be relatively effective for transdermal application of medicines.
Institute for Longevity Research [LifeXLabs/Academic Labs and Programs, Links; Links/Institutes for Longevity Research] [13].
Instrumental Analysis (Encyclopedia)
Insulin [Wikipedia/Insulin, Links, Images, Video, Papers, Patents, Books, Amazon LifeExtension]. Insulin plays a role in metabolic syndrome, caloric restriction, diabetes, hyperinsulinemia, and bodybuilding. Low insulin down-regulates telomerase-activating Sp1 transcription factor. Insulin is used to transport fats and proteins through the cell membrane into the cell. In diabetes, over-production of insulin may lead to insulin supply failure associated with insulin resistance, making it necessary to supplement insulin with injections in order to properly nourish cells. Hyperinsulinemia from obesity or excessive sugar consumption and consequently high blood sugar is a precursor to type 2 (adult-onset) diabetes in which the pancreas cannot sustain insulin production. Hyperinsulinemia increases the risk of cancer, heart attack, hypertension, kidney damage, beta-amyloid accumulation, non-alcoholic fatty liver disease, glycation damage from AGEs, prostate enlargement, vascular diseases [Index], and neurodegenerative disorders.
Insulin-boosters are useful after workouts in bodybuilding:
(1) Alpha Lipoic Acid taken 600-1000 mg after a workout can increase fat-burning and insulin-stimulated glucose uptake.
(2) Banaba Leaf Extract (taken at 32-48 mg with a postworkout shake) improves insulin sensitivity.
(3) Gymnema Sylvestre (400-500 mg with a postworkout shake < 30 min after exercise) stimulates insulin secretion.
(4) Fenugreek seed or Fenugreek Extract [Images] stimulates insulin production via
(5) 4-hydroxyisoleucine [Images] isolated from Fenugreek seeds.

Dextrose may be taken at 25-50 grams to spike insulin, along with whey protein or whey hydrolysates after a bodybuilding workout. Note that glucose depresses the secretion of neuroprotective HGH, however, and leads to glycation that can produce Alzheimer's Disease.
Vanadyl Sulphate [Images, Index] mimics insulin, shunting amino acids and glucose into muscle. In anecdotal reports vanadyl sulphate is thought to improve muscle hardness and fullness.
Insulin phosphorylates Tankyrase 1, a telomeric PARP protein that removes telomere t-loop closure protein TRF1 from the telomere loop for ubiquitination, allowing the telomere loop to open and become accessible to the telomerase molecule. Thus insulin up-regulators may be useful tankyrase-activating adjuvants for use with telomerase activators [Index, List]. Niacinamide (Nicotinamide) is also useful in up-regulating tankyrase 1 expression and in providing NAD+ substrate for poly(ADP-ribosylation) of TRF1 telomere t-loop binding protein. Note that niacinamide is a PARP inhibitor (Chi and Lodish, 2000), so that perhaps NAD+ had better be used as a supplement directly instead of being obtained from a salvage pathway using niacinamide as an input whenever we are attempting to phosphorylate tankyrase 1 for TRF1-stripping with poly(ADP-ribo)sylation using a NAD+ substrate. Small NAD+ doses are used when NAD+ is supplemented, perhaps 2.5 mg every other day. Tankyrase 1 is a PARP enzyme supporting poly(ADP-ribo)sylation from a NAD+ substrate, and if niacinamide inhibits PARP, it seems likely that direct NAD+ supplementation is better. Timing may be crucial for obtaining NAD+ from niacinamide, if best results are to be obtained in TRF1-stripping in the evening before bedtime. Perhaps niacinamide supplementation in the morning would adequately reduce niacinamide to NAD+ by nightfall to avoid niacinamide inhibition of PARP, while improving the expression of tankyrase 1 in the morning. (See the half-life of tankyrase 1.) It is also noteworthy that niacinamide (nicotinamide) is a SIRT1 inhibitor that should probably not be taken with resveratrol, which upregulates SIRT1. Insulin up-regulators should probably be < 30-60 minutes after a workout along with telomerase activators such as the astragalosides and/or Fenugreek extract or seeds. This allows heat shock proteins from exercise to transport telomerase activators into the cell nucleus. Fenugreek may also be useful, to elevate testosterone for superior muscle contrations. However, I prefer to take it after a workout, as the insulin Fenugreek produces via 4-hydroxyisoleucine removes sugar from the blood, producing hypoglycemic (low blood sugar) fatigue. Instead, testosterone can be boosted prior to a workout by some other agent such as forskolin, DHEA, or tribulus. I note that insulin interacts with cells at cell-surface insulin receptors, so that it can never interact directly with tankyrase 1. According to my notes, phosphorylation of tankyrase 1 is accomplished by insulin stimulation. "The phosphorylation of tankyrase upon insulin stimulation is stoichiometric, suggesting that tankyrase is an important insulin signaling target." (Chi and Lodish, 2000). Tankyrase 1 has more than 1 function in the cell. "Tankyrase 1 is a novel signaling target of mitogen-activated protein kinase (MAPK); it is stoichiometrically phosphorylated upon insulin stimulation. Phosphorylation enhances the poly(ADP-ribose) polymerase activity of tankyrase 1..." (Nai-Wen Chi and Harvey F. Lodish, 2000). See
insulin mimetics [Links, Images, Video, Papers, Patents, Books, LEF],
insulin mimetics interacting with the insulin receptor [Links, Images, Papers, Patents, Books], and
supplements up-regulating insulin [Links, Images, Video, Papers, Patents, Books, LEF].
Insulin Overload [LEF/Insulin Overload & appetite suppressant pinolenic acid, Links/Insulin Overload, Images, Video, Papers, Patents, Books, Amazon LifeExtension]. See Pinolenic acid, Index/Diabetes, Index/Obesity, Index/Caloric Restriction, and Index/Glucoregulatory Agents.
Insulin Resistance & Metabolic Syndrome - LEF/Insulin Resistance & Metabolic Syndrome [Links, Images, Video, Papers, Patents, Books, Amazon LibCong, LifeExtension]. High insulin resistance and metabolic syndrome are often associated with obesity. See Index/Diabetes, Index/Obesity, Index/Caloric Restriction, Index/Glucoregulatory Agents, Index/N-acetyl-cysteine. With aging or excess calorie consumption, cell membranes become less sensitive to insulin, manifesting insulin resistance. The pancreas, responding to high blood sugar, tries to compensate by producing more insulin. Thus hyperglycemia can drive hyperinsulinemia. Excess insulin results in:
(1) Fat stores go up as excess glucose is stored.
(2) Triglyceride and C-reactive protein levels rise.
(3) HDL/LDL and HDL/VLDL cholesterol ratios decline as HDL levels go down.
(4) Sodium balance is upset, driving blood pressure up.
(5) Resulting high blood pressure (hypertension) may contribute to kidney damage.
(6) Hyperglycemia, High triglycerides, Low HDL/LDL, and high blood pressure lead to elevated glycation and vascular disease.
(7) Cancer risks increase with high triglycerides, glycation, and systemic inflammation characterized by high C-reactive protein levels associated with obesity. (See Julius Goepp MD, Block Absorption of Killer Carbohydrates, Life Extension Magazine, Feb 2010).
Supplements useful in overcoming insulin resistance include vitamins B1, B3, B6, B12, and folate, vitamin D, alpha lipoic acid, beta carotene, chromium picolinate, garlic, ginger root extract, ginseng, green tea extract, magnesium, manganese, potassium, and selenium. See Susan Machado (2012), Nutrient Cocktail Delays Aging and Extends Life Span, Life Extension Magazine, May 2012. "Nutrients that overcome insulin resistance... aid in normalizing energy utilization, enhancing cognitive function, preventing metabolic syndrome from emerging, improve glucose and insulin responses during exercise, while of course lowering acute and chronic blood glucose, reducing hemoglobin A1C levels, and delaying complications of diabetes". See Evans JL, Maddux BA, Goldfine ID (2005), The molecular basis for oxidative stress-induced insulin resistance, Antioxidants and Redox Signaling 2005, July-August;7(7-8):1040-52. See also Song D, Hutchings S, Pang CC (2005), Chronic N-acetyl cysteine prevents fructose-induced insulin resistance and hypertension in rats, European Journal of Pharmacology 2005 Jan 31;508(1-3):205-10.
Insulin Resistance from Cellular Senescence [Refs 9]
Cellular senescence causes cells to become more resistant to insulin signaling. This is due to the vanishing of caveolae on the cell surface containing signaling receptors caused by the elevation of caveolin-1 (gene CAV1) in the senescent state, which modifies cellular morphology and inhibits cell signaling with growth factors. See Phillips, P.D., Kaji, K., and Cristofalo, V.J. (1984), Progressive loss of the proliferative response of senescing WI-38 cells to platelet-derived growth factor, epidermal growth factor, insulin, transferrin, and dexamethasone, Journals of Gerontology 39, 11-17. Furthermore, high LDL cholesterol levels can upregulate caveolin-1 to produce cellular senescence driving insulin resistance, as can high FOXO transcription factor levels controllable with AKT kinase via IGF-1 from, say, exercise and creatine monohydrate. Caveolin-1 expression can also be reduced with cyclic AMP from forskolin or exercise.
Insulin Utilization Theory [Links/insulin metabolism, Images, Video, Papers, Patents, Books, Amazon LibCong/insulin utilization, LifeExtension], (6). See Index/Diabetes, Index/Obesity, Index/Caloric Restriction, Index/Glucoregulatory Agents.
Integrins (Encyclopedia) includes Hemidesmosomes.
See also Neck Rejuvenation.
Interferons [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension, LibCong/interferon, Amazon]. A subset of glycoproteins, cytokines, involved in the immune response to foreign RNA.
Interleukins [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension, LibCong/interleukins, Amazon; Links/Anti-inflammatory interleukins, Papers, Books; Links/Inflammatory interleukins, Papers, Books].
Interleukin 2 [Telomerase Activators/IL2, Intimm/Interleukin 2, Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension]. Interleukin 2 for lymphocytes is a small-molecule telomerase activator [Index] (7). This is a larger molecule of about 15,500 Daltons (still capable of passing through the nuclear pore), the cytokine also termed IL-2 (interleukin 2), a "lymphokine" which augments the expression of mRNA for human telomerase in T-cell lymphocytes. IL-2 "has been approved by the Food and Drug Administration (FDA) for the treatment of cancers (malignant melanoma, renal cell cancer), and is in clinical trials for the treatment of chronic viral infections (for example cytomegalovirus, or CMV), and as a booster (adjuvant) for vaccines." - [Wikipedia]. Interleukin 2's telomerase-enhancing role in T-lyphocytes has been noted by other investigators. [Links/interleukin-2 and telomerase activation, Images, Papers, Patents, Books, article]. Exercise elevated expression of telomerase-activating IL-2 (1.43 fold) in Frank Zaldivar, Jessica Wang-Rodriguez, Dan Nemet, Christina Schwindt, Pietro Galassetti, Paul J. Mills, Lori D. Wilson and Dan M. Cooper (2006), Constitutive pro- and anti-inflammatory cytokine and growth factor response to exercise in leukocytes, Journal of Applied Physiology 100:1124-1133, 2006. Interleukin 2 can also be upregulated by melatonin.
Interleukin 6 [Telomerase Activators/IL-6, Links, Images, Video, Papers, Patents, Books, LifeExtension, Amazon]. Interleukin 6 is an inflammatory cytokine produced by exercise [List] that generates heat shock protein [Index] HSP90, which is complexed with nuclear superfamily transcription factors prior to their transport into the cellular nucleus. HSP70 also claims this role. It may be important in the process of activating telomerase via cycloastragenol from the astragalosides. HSP90 accelerates telomerase assembly by guiding hTERT protein folding. Thus HSP90 increases telomerase levels in the cell by mediating the assembly of telomerase. HSP90 and p23 are functionally required in telomerase complexes. (GB Morin, DO Toft, JW Shay, WE Wright, MA White, et al., 1999). Interleukin 6 upregulates STAT3, which rapidly upregulates hTERT mRNA in primary fibroblasts.
Intermittent Claudication [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Intermittant claudication, which is associated with peripheral artery disease [PubMed] and arteriosclerosis, is typically a symptom of atherosclerosis arising from atherosclerotic plaque that makes walking intermittently painful. Peripheral artery disease is a common disorder that usually affects men over age 50. People are at higher risk if they have a history of:
Abnormal cholesterol.
Heart disease (coronary artery disease).
High blood pressure (hypertension).
Kidney disease involving hemodialysis.
Stroke (cerebrovascular disease).
Ginkgo biloba is used to improve circulation in treating intermittent claudication [Images, Video, Papers, Patents, Books, LifeExtension]. Treatments for atherosclerosis should be useful with this disorder, including higher testosterone for reverse transport of cholesterol and a combination of vitamin K2 and vitamin D3 to prevent or reverse calcification of arterial plaque. Arginine at 5-10 grams/day induces nitric oxide to refresh the vascular endothelium by lengthening the telomeres of vascular endothelial progenitor cells. A homocysteine blocker to prevent damage to arterial wall encouraging the adhesion of monocytes should be useful.
International Anti-Aging Systems [IAAS, Links, Video], [57].
International Units (IU) [Links, Video, Wikipedia, Links/International Unit conversion Table].
Intravenous Anti-Aging Therapies [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension]. This might include a program of injections using by-injection-only telomerase activators such as Epithalon Peptide or Tricostatin A. Metal Ion chelation is sometimes done by injection or intravenously using EDTA, perhaps as an emergency procedure for metal ion poisoning, but also as anti-aging therapy. The ROS scavenger MnTBAP is also given by injection. It is desirable to replace needle-oriented therapies with pill-oriented therapies when the pill approach is adequate. Thus orally bioavailable telomerase activators and orally bioavailable metal ion chelation drugs and nutraceuticals such as nanoencapsulated curcumin are likely to supercede the class of injection-based treatments. Liposome liposprays may also be a better-selling method of application. Insulin for treating diabetes or supporting bodybuilding is often be given by injection at this time, and this applies to many peptide-chain preparations, not all of which can pass through the blood-brain barrier. Insulin-boosters such as 4-hydroxyisoleucine, Fenugreek extract, and Gymnema Sylvestre are not always suitable for our medical application. See medicines given by injection only.
Intravenous techniques [Links, Images, Video, Papers, Patents, Books, Amazon LibCong, Books/Intravenous Therapies; Links/venipuncture, Images, Video, Papers, Patents, Books, Index/Venipuncture]. See Phlebotomy [Links, Wikipedia/Venipuncture, LibCong/Venipuncture, Amazon/Phlebotomy] and Biopsy.
IPS Cells See Induced Pluripotent Stem Cells.
Irish Moss (Chondrus crispus, a carrageenan source) [Links, Images, Video, Papers, Patents, Books, LEF]. Carrageenan [Links, Images, Video, Papers, Patents, Books, LEF] is an HPV-inhibitor that may be extracted from Irish Moss, and used for a skin lotion or a personal lubricant to inhibit genital warts. It may be used with other ingredients such as Acetyl Tetrapeptide-2 [Links, Images, Video, Papers, Patents, Books, LEF] in advanced skin cream applications. See Gary Goldfaden Md and Robert Goldfaden (2013), Unique Peptide Repairs Aging Skin, Life Extension Magazine, June 2013. Also see Young EG, Smith DG (1958), Amino acids, peptides, and proteins of Irish Moss, Chondrus crispus, Journal of Biological Chemistry, 1958 Aug; 233(2):406-10.
Iron, Oxygen, and Free Radicals in Brain Aging [Video/Brain Aging; Links, Images, Video, Papers, Patents, Books, LifeExtension, LibCong/Brain Aging, Amazon], [11s]. Iron accelerates Fenton reactions involving ROS (Reactive Oxygen Species), and can cause lipid peroxidation reactions leading to inflammation and dementia as a consequence. Iron deposits in the brain [Images] can be seen in images prepared with PET scan technique. They may result from too much beef consumption, since beef is high in iron and copper. Furthermore, beef fats support colon cancer, so that soy protein alternatives are attractive. Many experiments have been done on aging rodents in which extra excess iron was included in the pellets, resulting in decreased life span and/or dementia. Japanese have a lower incidence of dementia in the elderly, because their diet includes less iron. Too little iron, however, can result in anemia. See optimal iron dosage in functional nutrition.
Irvingia [Links, Images/Irvingia Supplements, Video, Papers, Patents, Books, LifeExtension]. Irvingia gabonensis is a wild African mango which has an extract [Images] useful in producing weight loss, partly by inhibiting the enzyme amylase, helping to control exposure to carbohydrates in the discipline of caloric restriction. Irvingia also reduces the activity of Glycerol-3-phosphate dehydrogenase, an enzyme involved in converting ingested starch and sugar into body fat.
Ischemia [Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension, LibCong/Adult Stem Cells]. - A restriction in blood supply, generally due to as atherosclerotic plaque in the blood vessels, with resultant damage or dysfunction of tissue, as in an ischemic stroke [Images, Video, Papers, Patents, Books, LifeExtension]. Platelet aggregation preventable with aspirin, ginkgo biloba, and fish oil is often a factor. See nutraceuticals for preventing ischemia [Links, Images, Video, Papers, Patents, Books, LifeExtension] and nutraceuticals for treating ischemia [Links, Images, Video, Papers, Patents, Books, LifeExtension].
Ischemic Reperfusion Injuries [Links, Images, Papers, Patents, Books, Amazon, LifeExtension]. Ischemic reperfusion injuries occur when blood flow is returned to obstructed areas after a blockage or restriction in blood flow. There are nutraceuticals and drugs for treating ischemic reperfusion injuries. There are also nutraceuticals (such as resveratrol) and and drugs for preventing ischemic reperfusion injuries. Resveratrol is renoprotective, preserving kidney structure and function by preventing ishcemia/reperfusion injury, observed perhaps as a consequence of sepsis (massive bacterial infection) following surgical operations.
Isoflavones [Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension]. Isoflavones and Lignans [Index] are two classes of phytoestrogens [Index] related to human estradiol and estrogen useful in treating estrogenic cancers, osteoporosis, and cardiovascular diseases. Soy isoflavones are anticancer and reduce the incidence of heart disease and osteoporosis, and soy phytoestrogens have been shown to reduce cholesterol, LDL cholesterol, and triglyceride levels. Soy isoflavones have been shown to reduce lung cancer rates. (LEF, Marc Ellman, Soy Protective Against Lung Cancer, June 2010; Am J. Clin Nutr. 2010 Mar;91(3):722-8.)
Isoprostanes [Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension], (1). Three major areas of oxidative stress exist: LDL peroxidation, protein carbonyls, and isoprostanes [107].
Isothiocyanates [Wikipedia/Isothiocyanates, Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension; Images/isothiocyanate supplements]. Isothiocyanates are anticancer, from wasabi, broccoli, and watercress.
Itching Skin [Links/Itching Skin, Images, Video, Papers, Patents, Books; Links/Itching Winter Skin, Images, Video, Papers, Patents, Books]. Low humidity can produce dry, itching skin in the winter. Oils and moisturizers such as glycerin can help relieve the itching syndrome. Hydrocortizone cream (1%) may be used to relieve itching [Images, Videos, Papers, Patents, Books]. Benadryl Itch Stopping Cream [Images] may also be useful. Fewer hot showers are recommended in the winter to preserve skin oils. I note that boiling water on 4 burners of a stove can quickly humidify and heat dry winter air, although it may resemble a scene from MacBeth. Phytoceramides can be used to improve the barrier function of the stratum corneum, preventing skin dehydration and dryness, also improving skin elasticity with ceramide elastase inhibitors. See also Skin Itching.

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