Anti-Aging Medicine: Sup Notes 3a | 3b1 | 3b2 | 3b4 | 3b5 | Product B Explorer | 3b6
One, Two, Three,...Infinity: A Lucky Strike.
Telomerase is a 123 Kilodalton enzyme.
Rejuvenation via Cyclic Telomerase Activation (7)

Phase I: For 0 < t < 57.967123 = t0, B = 1,
Model Age = Bt.
Phase II: For 57.967123 < t < 64.3, B = - 5.2 years/yr,
Model_Age = B(delta_t) + t0 = (B/12)N + 57.967123,
N = 1, 2, 3,...,76 months, using astragalus extracts.
Phase III: For 64.3 < t < infinity, B = 0,
Model Age = 25.
Press for Age Transformation's FLIGHT PLAN.

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Highlight Links 3a
[74s] Hair Loss, TERT, Saw Palmetto with Beta-sitosterol, Finasteride, Dutasteride, & PABA.
[75s] Carbonylation of Proteins.
[76s] Nanomedicine.
[77s] Microglia in the Aging Brain are telomere-limited, subject to replicative senescence.
[78s] Jekyll-Hyde Formulas for Life Extension, including Turmeric with Pepper, Cocoa powder drinks, Wasabi, and Astragalus.
[79s] Rejuvenation to produce anti-aging transformations.
[80s] Notes on The Anti-Aging Solution by Giampappa, Pero, and Zimmerman.

Highlight Links 3b1 - Cells Responding to Telomerase Activation & Telomerase Inhibitors
[81s] Life Extension via Telomere Extension in Vivo, with Cells that Respond to Telomerase Gene Transduction.
____Telomerase Inhibitors (1)-(73) with hyperlinked numeric and alphabetic selection guides.

Highlight Links 3b2 - Telomerase Activators
____Telomerase Activators (1)-(185), with hyperlinked numeric and alphabetic selection guides.
[81s/6b] Astragalalus-based small-molecule telomerase activators and others.
[81s/6d] 230 base pairs of telomere growth per 3 months of treatment with TA-65. - TA Sciences, Greta Blackburn letter.
____More Telomerase Activators (7)-(22).

Highlight Links 3b4 - Telomerase Activators
____Still More Telomerase Activators (23)-(64).

Highlight Links 3b5 - Telomerase Activators
____Still More Telomerase Activators (65)-(132).
____Telomere Measurement.
____Telomerase Expression Measurement.
[81bs] Senile purpura.

Highlight Links 3b6 - Telomerase Activators
____Further Telomerase Activators (154) - (185).

[81s] Life Extension via Telomere Extension in Vivo. It seems that a cure is on the horizon for every mechanism of cellular senescence that we know of. However, unless we lengthen our telomeres with telomerase activation (7) by activating hTERT, we will be up against a brick wall, because the telomere-shortening mechanism will eventually destroy the epithelial cells, the lymphocytes, the bone marrow, the lining of the colon, and the microglial cells in the brain that clean out cellular garbage there.
For products to extend telomeres with telomerase activation, see Geron (article), TA Sciences, Terraternal, RevGenetics, Medicinal Nutraceutics, and Sierra Sciences. See also Telomolecular Nanotechnology's Science Library on applications to Aging. Also see Are Telomeres the Key to Aging and Cancer? from the University of Utah, with charts, photos and illustrations of telomere-related diseases, Telomere Shortening and Aging by H. Jiang, Z. Ju, and K. L. Rudolph (2007), and Telomere Remodeling with Cyclic Telomerase Activation.

Cells that Respond to Telomerase Gene Transduction with Improved Replicative Capacity, Function, and/or Resistance to Stress by Organ System [See Geron Report] include:
Bone: Osteoblasts [Images, Papers Books].
____Telomeres are shorter in old osteoblasts, and osteoblast dysfunction is characteristic of osteoporosis. Osteoblasts replace the skeleton in about 10 years, while osteoclasts destroy old material. (M.Fossel, p.183). "When human bone marrow stromal cells are transfected with hTERT, they show increased telomere lengths and continue to proliferate at even 10 times the normal number of population doublings." (M.Fossel, p.188).

Brain and the nervous system: Neurons [Images, Papers, Patents, Books] and neural progenitors [Images, Papers, Patents, Books]. See telomerase activation and neurons and telomerase activation and neural progenitors.

Breast: Mammary epithelial cells. [Images, Papers, Patents, Books]. See telomerase activation and mammary epithelial cells

Connective tissue: Chondrocytes. [Images, Papers, Patents, Books].
___Chondrocytes senesce in arthritis, and should be treatable with telomerase activation. Mesenchymal derived tissues include connective tissue, bone, cartilage, the circulatory system and lymphatic system cells. They do not adequately express the hTR component of telomerase, which can be improved by elevating Sp1 levels with sodium butyrate or HIF-1 levels with ginkgo biloba, fenugreek extract, or exercise. This is believed to have some application to neck rejuvenation.

Endocrine system: Adrenocortical cells [Images, Papers, Patents, Books]. See treating adrenocortical cells with telomerase activation.

Gum tissue: Gingival fibroblasts. [Images, Papers, Patents, Books]. See treating gingival fibroblasts with telomerase activation.

Heart: Cardiomyocytes. [ Images, Papers, Patents, Books; Index/Cardiology].
___Replacement of cardiomyocytes may take place from stem cells (8) or through cell division after myocardial infarction. Most cardiovascular disease is caused by endothelial and vascular cell problems. The most efficient point of intervention in associated human atherosclerosis is may be telomerase therapy (7). (M.Fossel, p.178). See treating cardiomyocytes with telomerase activation.

Immune system (normal): Cytotoxic T cells. [Images, Papers, Patents, Books]
___Immune senescence is thought to cause cancer surveillance to fail in the elderly. Note that stem cells express telomerase upon stimulation, so that the immune system cells are less likely to fail under environmental challenges than other cells. Memory T-cells have shorter telomeres than T-cells without immune memory. (Michael Fossel, , Cells, Aging, and Human Disease, p.194). CD28 expression is required in T-cells for stimulated expression of telomerase. 40% lack CD28 in centenarians, 1% in newborn. "IL-7 appears to stimulate and control telomerase expression in T-cells..." (Michael Fossel, p.198.) In T-cells after telomerase induction, telomerase shows an increase in expression within 24 hours and extending up to 72 hours after stimulation..." (Micheal B. Fossel, Cells, Aging, and Human Disease, pp. 200-201). See treating cytotoxic T-cells with telomerase activation.

Leukocytes (white blood cells) show telomere loss from 20 bp to 40 bp per year, which can be compensated for using astragalus root or astragalus root extract. See Aysel Müezzinlera, Aida Karina Zaineddina, Hermann Brennera (2013), A systematic review of leukocyte telomere length and age in adults, Ageing Research Reviews, 15 January 2013. See VIDA Institute on Astragalus Formulations for their impact on leukocytes.

Lymphocyte Telomere Length in kilobase pairs as a Function of Age.


Immune system (impaired, e.g. HIV/AIDS): Cytotoxic T cells. [Images, Papers, Patents, Books, article1, 2]. See treating HIV-impaired cytotoxic T-cells with telomerase activation.

Liver: Hepatocytes [Images, Papers, Patents, Books], cholangiocytes [Images, Papers, Patents, Books, Saki liver? article]. Normal human hepatocyte telomeres shorten by 55 bp/year, a rate which decelerates in middle age. An absence of telomerase may cause cirrhosis of the liver, and telomerase expression reverses liver cirrhosis. (Michael Fossel, p.269). See treating hepatocytes with telomerase activation and treating cholangiocytes with telomerase activation

Muscle: Skeletal myocytes [Images, Papers, Patents, Books]. Replacement monocytes in muscle derive from a reserve of stem cells or myoblasts. (Michael Fossel, p.256). These cells may senesce and thus benefit from telomerase activation. See treating skeletal myocytes with telomerase activation.

Ovary: Surface epithelial cells. [Images, Papers, Patents, Books]. See treating surface epithelial cells with telomerase activation.

Pancreas: Pancreatic ductal stem cells [Images, Papers, Patents, Books] or precursor cells [Images, Papers, Books]. See treating pancreatic ductal stem cells with telomerase activation.

Eye: Retinal pigmented epithelial (RPE) cells [Images, Papers, Patents, Books]. Senescent retinal epithelial cells show increased lipofuscin both in vivo and in vitro. (M.Fossel,p.280) Age-Related Macular Degeneration - AMD - is the retinal pathology sometimes involving senescent retinal epithelial cells [Images] that is the leading cause of blindness in developed nations. Vascular damage to the elderly retina [Images] is often involved. Thus AMD (macular degeneration) may be treatable with small molecule telomerase activators. The cornea is made of of keratocytes (fibroblasts) and includes sensitive cornea nerve endings. It's cells may senesce, leading to cataracts that can be treated with carnosine and perhaps with small molecule telomerase activators. Glaucoma, on the other hand, is caused by pressure between the cornea and lens that sometimes originates in atherosclerosis, often having its origin in the cellular senescence of vascular endotheial cells treatable with small molecule telomerase activators. Diabetes is a risk factor in most of these eye conditions, probably because the associated hyperglycemia elevates glycation, Maillard reactions, AGEs, and an associated elevation in free radical activity that attacks tissues and leads to inflammation. "There is good circumstantial evidence that senescent cells are present in vitro in the older eye.... In the lens, ocular keratocytes senesce." (M.Fossel, p.279)

Uterus: Endometrial stromal cells [Images, Papers, Patents, Books]. treating endometrial stromal cells with telomerase activation.

Skin:
__Keratinocytes [Images, Papers, Patents, Books],
__Fibroblasts [Images, Papers, Patents, Books],
__Microvascular endothelial cells [Images, Papers, Patents, Books],
__Melanocytes [Images, Papers, Patents, Books].

Vasculature: Endothelial cells [Images, Papers, Patents, Books, senescence of] , smooth muscle cells [images, Books].
____"Cells in areas of high vascular stress showed telomere shortening prior to vascular disease onset." and "death due to atherosclerosis often occurs in progeric children with short telomeres". (M.Fossel, p.168). Endothelial cell senescence is believed to underlie atherosclerosis; some causes of endothelial senescence include toxins, hypertension, lipids, and hyperglycemia. (M.Fossel, p.168). Senescent arterial endothelial cells may be returned to the youthful phenotype by hTERT immortalization. Senescent endothelial cells show increased monocyte adhesion aggravated by heightened TNFα levels, together with lessened eNOS and NO activity. Hyperglycemia alters lipoproteins, forming AGEs and lipoprotein complexes, altering the NO pathway, and leading to elevated homocysteine levels that attack the vascular endothelial cells. Note that homocysteine also promotes telomere erosion and other cellular senescence markers in human in vitro vascular endothelial cells; hypertension does further damage to these cells.

Other:
__Mesenchymal cells [Images, Papers, Patents, Books], and cells that are derived from mesenchymal cells, do not express the hTR component of telomerase adequately without applying transcription factors like Sp1 produced by application sodium butyrate or HIF-1 produced by ginkgo biloba, fenugreek extract, or exercise. This seems to have some application to connective tissues in neck rejuvenation. Mesenchymal derived tissues include connective tissue, bone, cartilage, the circulatory system and lymphatic system cells.

__Hemopoietic stem cells [Images, Papers, Patents, Books].
___Telomerase is expressed in hemopoietic stem cells via cytokine stimulation, showing a low level of telomerase activity incapable of maintaining lifelong stable telomere lengths; hemopoietic stem cell telomeres erode over time. In general, stem cells express telomerase more than other somatic cells and less than germ cells, and should benefit by telomerase activation. (M.Fossel, p.197).
- After Bioexchange Biotechnology News.
Most human cancers are epithelial (90%) and genomic stabilization with telomerase activators may prevent cancer. "...telomerase expression with cell immortalization should lower intracellular risk of malignant transformation by stabilizing the genome." (M.Fossel). On the other hand, "...telomere shortening and senescence may increase risk of carcinogenesis independently of immune system aging." (M.Fossel, p.120). Finally, "telomerase increases genetic stability, arguably lowering risk of clinical malignancy." (p.121).

Lungs: Human fetal lung fibroblasts grown in culture divide about 50 times [article].

Kidney: Telomeres in the human renal cortex shorten by about 29 bp per year, and medullary telomere shortening is less than in the cortex. The glomular filtration rate of the kidey is proportional to (140 - age in years); caloric restriction reduces renal epithelial cell senescence in mice. High-protein diets can induce glomular damage and restrition of protein in the diet is protective. DHEA may benefit renal cells. (M.Fossel, p.247-250).

Gastric Mucosal Cells show a loss of 46 bp/year. (M.Fossel, p.267). Large and small intestine cells demonstrate telomere shortening; it seems related stem cells in gastrointestinal crypts (crypts of Liebes.) may become more numerous with age.

Esophogal mucosa: These cells have telomeres that shorten at about 60 bp/year, and could therefore benefit from telomerase activation. Esophagal stem cells seem to exist. (M.Fossel, p.267).

Colon Mucosa: Telomerase-positive stem cells may present within the colon, the cells of which show telomere shortening with age. Ulcertative colitis (an inflammatory condition) seems to result from telomere shortening leading to end-to-end telomere fusions and chromosomal instability. (M.Fossel, p. 268). Note telomere base pair loss is 44 bp per year in the colon mucosa. (M.Fossel, p.107).
Music[2]: Selections from All That Jazz.


Senescence-Based Diseases and Associated Cell Types - after Sierra Sciences/Disease.
DiseaseSenescent Cell Type
Cardiovascular Disease [Books, Index]Endothelial Cells [Index, Books, Links, Images, Images/senescent endothelial cells]
Alzheimer's Disease [Books, Index]Glial Cells [Books, Images, Index/Microglial Activation]
Progeria [Index]Multiple Cell Types [Wiki, Images]
Osteoporosis [Books, Index]Osteoblasts [Links, Images]
OsteoarthritisChondrocytes [Images]
AIDS & Immunosenescence [Books, (11)]CD8 + T-Cells [Index, Images]
Macular Degeneration [Index]Retinal Pigment Epithelial Cells [Images]
Hepatic CirrhosisHepatocytes [Image]
Skin Aging [Index]Fibroblasts [Images, Index]
Note that runaway cancer cell proliferation may be halted with telomerase inhibitors unless the cancer extends telomeres by the ALT mechanism. There also exist diseases based on unicellular parasites with linear chromosomes and a telomeric mechanism that might be used to halt proliferation if inhibited with telomerase inhibitors. These include malaria (telomere is TTTAGGG repeats, as in Arabidopsis-type flowering plants), African sleeping sickness, amoebic colitis, amoebic dysentry, amoebic abcesses, and fungual diseases. (Fossel, p.123).
See also Michael B. Fossel, Cells, Aging, and Human Disease, Oxford U. Press, 2004, and
Judy M. Y. Wong, Kathleen Collins (2003). Telomere Maintenance and Disease, the Lancet.

Stem cell replacement strategies (8) with infant cord blood or cultured adult stem cells with telomeres externally re-extended can help in this domain, but what we seem to need is a small molecule telomerase activator taken sublingually under the tongue or perhaps one we can swallow like a pill, with subsequent measurement of telomere length to verify that we have got the job done without overdoing it and defeating our innate anticancer trick of chewing out sick runaway cells with telomeres of finite length. Note that telomerase is not a cancer-causing oncogene. Treatment for telomere extension using telomerase activation should probably be periodic, and not continuous, however. When we are treating ourselves to extend our telomeres with telomerase activators we should restrict our ingestion of telomerase inhibitors [Papers]. See Telomere Remodeling with Cyclic Telomerase Activation for how this may be done.

Telomerase Inhibitors [Index, Links, Books, Papers, Patents, LifeExtension, article].
Also see Tsutomu Akama, Ryan Holcomb, Richard L. Tolman, 2000: Geron Patent, Telomerase Inhibitors and Methods of Their Use, Patent number: 6452014, Dec.22, 2000, and Alison C. Chin, et.al, 2000: Geron patent, Telomerase inhibitors and methods of their use, June 2000. Telomerase inhibitors often activate cancer cell apoptosis and may be used in anticancer diets. Treatment of tumors with telomerase inhibitors is more effective when combined with angiogenesis inhibitors [Wiki], which include resveratrol and nutraceuticals such as soy and green tea. See Role of Telomerase in Cancer and Telomerase Inhibitors (2009), which also includes a table of drugs used in cancer chemotherapy, and Laura K. White, Woodring E. Wright, Jerry W. Shay Telomerase Inhibitors, Trends in Biotechnology, V.19,3,March 2001. Some anticancer telomerase inhibitors for cancer cells are also telomerase activators for normal cells. See Anticancer Telomerase Activators.

List Pointers for Telomerase Inhibitors under Investigation [> Telomerase Activators]

(1) Curcumin inhibits telomerase in cancer cells. Probably a telomerase activator (151) for healthy fibroblasts.
(1b) Turmeric inhibits telomerase in cancer cells. Telomerase Activator (151) for healthy fibroblasts.
(2) Resveratrol inhibits telomerase in cancer cells. Telomerase Activator (150) for healthy fibroblasts.
(3) Quercetin inhibits telomerase in cancer cells. Telomerase Activator (149) for healthy fibroblasts.
(4) Melatonin. inhibits telomerase in cancer cells.
(5) Green tea. (via EGCG). inhibits telomerase in cancer cells. Telomerase Activator (141) for healthy fibroblasts.
(6) Vitamin E.
(7) Allicin from Garlic.
(8) EPA.
(9) Silibinin inhibits telomerase in cancer cells, from Silymarin in Milk Thistle.
(9b) Silymarin contains Silybinin in Milk Thistle. Telomerase activator (102) for healthy cells.
(9c) Milk Thistle contains Silibinin from Silymarin; Telomerase activator (146) for healthy human fibroblasts.
(10) G-quadruplex ligands.
(11) Peptide nucleic acids.
(12) 2’-O-MeRNA oligomers.
(13) BPPA.
(14a) BIBR1591. Exotic.
(14b) BIBR1532. Exotic
(15) Geron's GRN163L.
(16) Sulfoquinovosyldiacylglycerol (SQDG).
(17) Rhodacyanine FJ5002.
(18) Cationic 5,10,15,20-tetra(N-methyl-4-pyridyl)porphyrin (TMPyP4).
(19) AZT.
(20) TRT antisense oligonucleotides.
(21) Chimeric oligonucleotides.
(22) RHPS4, a Small-Molecule Pentacyclic Acridine.
(23) BIBR1532.
(24) Ginsenoside Rh2.
(24b) Ginseng.
(24c) Panax Ginseng inhibits telomerase in cancer cells. Telomerase Activator (135) for healthy human fibroblasts.
(24d) Korean Red Ginseng, also see (31).
(25) Green marine algae extract.
(26) Gambogic Acid.
(27) Retinoic Acid. Inhibits P16INK4a expression.
(28) Beta-lapachone.
(29) Interferon-alpha
(30a) E2F-1 transcription factor down-regulating hTERT.
(30b) Mad1 transcription factor down-regulating hTERT.
(30c) TGF-beta transcription factor down-regulating hTERT. See also (60).
(30d)Menin transcription factor down-regulating hTERT.
(31) Korean Red Ginseng Extract.
(32) 15-deoxy-Delta12,14-prostaglandin J2.
(33) Berberine inhibits telomerase in cancer cells. Telomerase Activator (137) in healthy human fibroblasts.
(34) Gemfibrozil.
(35) Cat's Claw extract (Samento).
(36) Cacao bean products (cocoa, chocholate) catechins.
(37) Dictyodendrin B, C, and E are telomerase inhibitors of marine origin.
(38) Dietary polyphenols.
(39) Flaxseed Oil.
(40) Inositol Hexaphosphate (Phytic Acid).
(41) GRN163L Geron Corporation.
(42) Vitamin D3
(43) Tamoxifen.
(44) Wortmannin.
(45) 5,6-trans-16-ene-vitamin D3
(46) Dimethylsulfoxide (DMSO)
(47) Genistein from Soy is a telomerase inhibitor.
(48) Antisense pentadecadeoxynucleotides against C-Myc mRNA.
(49) Human chromosome 3 in the region p14.2-p21.3.
(50) Inducers of cell differentiation may subsequently inhibit telomerase.
(51) Rb protein suppresses expression of hTERT.
(52) p21 protein suppresses expression of hTERT.
(53) HSP90 Blockers such as Geldanamycin.
(54) Tankyrase 1 inhibitors such as MST-312, MST-295, and MST-199.
(55) The Pif1 helicase.
(56) Gamma Rubromycin
(57) Beta Rubromycin
(58) MST-312, MST-295, MST-199. ECGC-related compounds.
(59) Sulforaphane inhibits telomerase in breast cancer cells.
(60) TGF-beta inhibits telomerase. See also (30c).
(61) Transcriptional Repressors of hTERT include Sp3, AP-1, MZF, WT1 and E2F.
(62) Rapamycin inhibits telomerase in cancer cells.
(63) PINX1 (an endogenous molecule) inhibits telomerase in cancer cells.
(64) p53 protein suppresses transcription of hTERT mRNA.
(65) Ginger Extract is a telomerase inhibitor.
(66) IL-4 is a telomerase inhibitor.
(67) DHA is a telomerase inhibitor for cancer cells.
(68) Tea Catechins inhibit telomerase in cancer cells. Telomerase Activator (153) for healthy fibroblasts.
(69) High Polyphenol Diets generate telomerase inhibitors.
(70) TERRA RNAs transcribed from telomeres.
(71) Garlic, from Allicin.
(72) Cholesterol down-regulates hTERT mRNA expression.
(73) FK506 (Tacrolimus) a "most potent" telomerase inhibitor.

Alphabetical List of Telomerase Inhibitors under Investigation [> Telomerase Activators]

2’-O-MeRNA oligomers (12) .
5,6-trans-16-ene-vitamin D3 (45)
15-deoxy-Delta12,14-prostaglandin J2 (32).
Allicin from Garlic (7).
Antisense pentadecadeoxynucleotides against C-Myc mRNA (48).
AZT (19).
Berberine (33) inhibits telomerase in cancer cells. Telomerase Activator (137) in healthy human fibroblasts.
Beta-lapachone (28).
Beta Rubromycin (57)
BIBR1532 (23).
BIBR1532. (14b) Exotic
BIBR1591. (14a) Exotic.
BPPA (13).
Cacao bean products (cocoa, chocholate) catechins (36).
Cat's Claw extract (Samento) (35).
Chimeric oligonucleotides (21).
Cholesterol (72) down-regulates hTERT mRNA expression.
Curcumin (1) inhibits telomerase in cancer cells. Probably a telomerase activator (151) for healthy fibroblasts.
DHA (67) is a telomerase inhibitor for cancer cells.
Dictyodendrin B, C, and E (37) are telomerase inhibitors of marine origin.
Dietary polyphenols (38).
Dimethylsulfoxide (DMSO) (46)
E2F-1 transcription factor down-regulating hTERT (30a).
EGCG (5).
EPA (8).
FK506 (Tacrolimus) (73),a most potent telomerase inhibitor.
Flaxseed Oil (39).
Gamma Rubromycin (56)
Garlic, via Allicin (7).
Geldanamycin (53) and other HSP90 Blockers.
Gambogic Acid (26).
Gemfibrozil (34).
Genistein (47) from Soy is a telomerase inhibitor.
Geron's GRN163L (15 & 41).
Ginger Extract (65) is a telomerase inhibitor.
Ginseng (24b).
Ginsenoside Rh2 (24).
G-quadruplex ligands (10).
Green marine algae extract (25).
Green tea (5) (via EGCG) inhibits telomerase in cancer cells. Telomerase Activator (141) for healthy fibroblasts.
GRN163L from Geron Corporation (15 & 41).
High Polyphenol Diets (69) generate telomerase inhibitors.
HSP90 Blockers (53) such as Geldanamycin.
Human chromosome 3 in the region p14.2-p21.3 (49).
IL-4 (66) is a telomerase inhibitor.
Inducers of cell differentiation may subsequently inhibit telomerase (50).
Inositol Hexaphosphate (Phytic Acid) (40).
Interferon-alpha (29).
Korean Red Ginseng Extract (31). See also (24d).
Mad1 transcription factor down-regulating hTERT (30b).
Melatonin (4).
Menin transcription factor down-regulating hTERT (30d).
Milk Thistle (9c) contains Silibinin from Silymarin; Telomerase activator (146) for healthy human fibroblasts.
Milk Thistle Extract (inhibits telomerase in cancer cells). Telomerase Activator (102) and (143).
MST-312, MST-295, MST-199 (58).
p21 protein (52) suppresses expression of hTERT.
p53 protein (64) suppresses transcription of hTERT mRNA.
Panax Ginseng (24c) inhibits telomerase in cancer cells. Telomerase Activator (135) for healthy human fibroblasts.
Peptide nucleic acids (11).
The Pif1 helicase (55)
PINX1 (63) (an endogenous molecule) inhibits telomerase in cancer cells.
Quercetin (3) inhibits telomerase in cancer cells. Telomerase Activator (149) for healthy fibroblasts.
Rapamycin (62) inhibits telomerase in cancer cells.
Rb protein (51) suppresses expression of hTERT.
Resveratrol (2) inhibits telomerase in cancer cells. Telomerase Activator (150) for healthy fibroblasts.
Retinoic Acid (27).
Rhodacyanine FJ5002 (17).
RHPS4, a Small-Molecule Pentacyclic Acridine (22).
Silibinin (inhibits telomerase in cancer cells), from Silymarin (9) in Milk Thistle.
Silymarin (9b) (Telomerase Activator (102)) contains Silibinin in Milk Thistle. (Telomerase Activator (146)).
Sulfoquinovosyldiacylglycerol (SQDG) (16).
Sulforaphane (59) inhibits telomerase in breast cancer cells.
Tamoxifen (43).
Tankyrase 1 inhibitors (54) such as MST-312, MST-295, and MST-199.
Tea Catechins (68) inhibit telomerase in cancer cells. Telomerase Activator (153) for healthy fibroblasts.
TERRA RNAs (70) transcribed from open telomeres.
TGF-beta transcription factor down-regulating hTERT (30c). See also
TGF-beta inhibits telomerase (60).
TMPyP4 - Cationic 5,10,15,20-tetra(N-methyl-4-pyridyl)porphyrin (18).
Transcriptional Repressors of hTERT include Sp3, AP-1, MZF, WT1 and E2F.
TRT antisense oligonucleotides (20).
Turmeric (1b) inhibits telomerase in cancer cells. Telomerase Activator (151) for healthy fibroblasts.
Vitamin D3 (42).
Vitamin E (6).
Wortmannin (44).

For further possibilities, see:
Jack Li-Yang Chen, Jonathan Sperry, Nancy Y. Ip and Margaret A. Brimble (2011),
Natural products targeting telomere maintenance [Online],
Med Chem Commun, 2011, 2, 229-245.

Telomerase inhibitors under investigation include:
(A) Common telomerase inhibitors:
__(1) Curcumin [Index, Links/Curcumin as a telomerase inhibitor, Papers, Patents, Books; Wikipedia/curcumin, WikiGenes/Curcumin; toxicity; Links/Anticancer applications of curcumin, Papers, Patents, Books]. See Mayank Singh and Neeta Singh, (2009), Molecular mechanism of curcumin induced cytotoxicity in human cervical carcinoma cells, Molecular and Cellular Biochemistry, Volume 325, Numbers 1-2 / May, 2009, Pages 107-119. Recent work suggests that curcumin inhibits telomerase by interfering with the association of hTERT and p23, a component of the molecular chaperone complex HSP90-p23 that normally interacts with the catalytic component of telomerase. (Teiten, Eifes, Dicato and Diederich, 2010).

____(1b) Turmeric (contains Curcumin) is of course also a telomerase inhibitor [Index].
______See Turmeric [Links/Turmeric, Images, Papers, Patents, Books; Wikipedia/Turmeric].

______Turmeric Root Extract (Curcuma longa) is, however, a telomerase activator for healthy fibroblasts,
_______according to The Product B Explorer ((151) Turmeric Root Extract) based on
_______the internationally visible Product B PatentScope.pdf.
_______This may be due to the tendency of antioxidants to confine hTERT to the nucleus.

__(2) Resveratrol [Index, Links/Resveratrol as a telomerase inhibitor, Papers, Patents, Books, WikiGenes/Resveratrol; Links/Anticancer applications of resveratol, Papers, Patents, Books; toxicity]. Resveratrol is also a small molecule sirtuin activator [Papers, Patents, Books], famously life-extending. See LifeExtension/Resveratrol, Terraternal/Resveratrol, RevGenetics/Resveratrol. Resveratrol has been found telomerase-inhibiting in cancer cells and telomerase-activating in endothelial progenitor cells and in healthy fibroblasts according to The Product B Explorer ((150) Resveratrol) based on Product B PatentScope.pdf. Resveratrol condenses chromatin by activating SIRT1, connecting it with gene silencing. However, it also phosphorylates hTERT protein in the cytoplasm for import into the cellular nucleus, so that it is also associated with telomerase activation.

__(3) Quercetin [Index, Links/Quercetin as a telomerase inhibitor (for cancer cells), Papers, Patents, Books, WikiGenes/Quercetin; Links/Quercetin as a telomerase activator (for normal cells), Papers, Patents, Books; toxicity; sources; Onions, Apples] is a telomerase inhibitor [Links, Books] for cancer cells and a small-molecule SIRT1 activator. However, Quercetin behaves like a telomerase activator for normal healthy fibroblasts according to The Product B Explorer ((149) Quercetin) based on Product B PatentScope.pdf. Thus, quercetin seems to behave like a telomerase inhibitor when applied to cancer cells, and like a telomerase activator when applied to normal cells, although we only have confirmation at this time for normal dermal fibroblasts. Some scientists claim that quercetin is a telomerase-inhibiting dietary polyphenol, period. The telomerase-activating properties of quercetin may be due entirely to its antioxidant properties [Papers, Books], as antioxidants tend to confine hTERT to the cellular nucleus [Papers, Books].
[1] Maria Russo, Carmela Spagnuolo, Idolo Tedesco, Stefania Bilotto, Gian Luigi Russo (2012),
The flavonoid quercetin in disease prevention and therapy: Facts and fancies [PDF],
Biochemical Pharmacology, Volume 83, Issue 1, 1 January 2012, Pages 6–15.
[2] Naasani I, Oh-Hashi F, Oh-Hara T, Feng WY, Johnston J, Chan K, et al. (2003),
Blocking telomerase by dietary polyphenols is a major mechanism for limiting the growth of human cancer cells in vitro and in vivo, Cancer Research 2003;63:824–30.

__(4) Melatonin [Index, List/Telomerase Activators, toxicity]. Melatonin [Links/melatonin as a telomerase inhibitor, Papers, Patents, Books]. Melatonin is famously life-extending. See LifeExtension/Melatonin, Terraternal/Melatonin, WikiGenes/Melatonin. Melatonin upregulates IL-2 and also HGH, both telomerase activators, although melatonin (List) is on the list of telomerase inhibitors. Perhaps melatonin is only a telomerase inhibitor for cancer cells, and a telomerase activator otherwise, as has been seen many times with other drugs.
(Also see Akbulut KG, Gonul B, Akbulut H. (2009), The role of melatonin on gastric mucosal cell proliferation and telomerase activity in ageing, J Pineal Res 2009 Nov;47(4):308-12. "...Melatonin may delay the ageing of gastric mucosa by inhibiting the replicative cellular senescence via its stimulatory effect on telomerase activity and suppressive effect on cellular proliferation and lipid peroxidation.").

Growth Hormone (GH or HGH) may activate telomerase directly through the PI3K signaling pathway [Index] employing phosphatidylinositol 3'-kinase. Note that IGF-1 uses the IGF-1/PI3K/AKT1 pathway, so that we might expect to find a pathway like HGH/PI3K/AKT1 or HGH/IGF1/PI3K/AKT1, since HGH is converted to IGF-1 in the liver. See the article:
L Gomez-Garcia, FM Sanchez, MT Vallejo-Cremades, IA Gomez de Segura and E De Miguel del Campo, Direct activation of Telomerase by GH via phosphatidylinositol 3'-kinase, Journal of Endocrinology, 2005, 185, 421-428. See also Wikipedia/Phosphoinositide 3-kinase, which introduces the family of phosphatidylinositol 3'-kinases. See the hTERT activation pathway for HGH or the HGH hTERT activation pathway.


__(5) Green tea [Index/Green tea; Index/EGCG; toxicity; Links/green tea as a telomerase inhibitor, Papers, Patents, Books; Naasani article]. EGCG (Epigallocatechin Gallate, Index, Links/EGCG as a telomerase inhibitor, Papers, Patents, Books; Links/EGCG toxiticy; WikiGenes/EGCG) in green tea. (Papers/Naasani, et al, 1998). Note that White Tea is also rich in EGCG. However, Green Tea Extract, Black Tea Extract, and White Tea Extract have all three been identified as telomerase activators for healthy fibroblasts according to The Product B Explorer ((141) Green Tea Extract, (138) Black Tea Extract, (153) White Tea Extract) based on Product B PatentScope.pdf.

__(6) Unsaturated vitamin E, tocotrienol. [Index, article, Links/Vitamin E as a telomerase inhibitor, Papers, Patents, Books, Links, Chapter, WikiGenes/Vitamin E; toxicity].

__(7) Garlic's [Index] allicin [Index; toxicity] from crushed garlic is telomerase-inhibiting. [Links/garlic as a telomerase inhibitor, Papers, Patents, Books, WikiGenes/allicin]. Garlic may only inhibit telomerase for cancer cells, not having this effect on normal, heathy cells. (Check.) This is true of quite a few telomerase inhibitors. Note that allicin from garlic is also a powerful antibiotic, in addition to being an anti-cancer telomerase inhibitor. It is usually prescribed at 3-5 cloves/serving, 4x per day, mixed in mustard, barbeque sauce, peppercorn dressing, or honey, take on soda crackers with artificial sweetener. Be sure to wear rubber gloves while slicing cloves.

__(8) EPA [Index, Links/EPA as a telomerase inhibitor, Papers, Patents, Books, WikiGenes/Eicosapentaenoic acid], eicosapentaenoic acid, one of the fatty acid components of SQDG and primary component of fish oil. [article; toxicity]. It is suspected that EPA is a telomerase inhibitor for cancer cells only, and has no telomerase-inhibiting effect on normal cells. However, EPA does not appear on the list of telomerase activators in any case.

__(9) Silibinin [Links, WikiGenes/Silybinin; Links/Silibin; Wikipedia/Silibinin, Wikipedia/Milk_thistle, toxicity] (a major component of silymarin) from Milk Thistle inhibits telomerase in prostate cancer cells. [Links/telomerase inhibition with silymarin Images, Papers, Patents, Books]. Silymarin may seem to behave like a telomerase activator in T-lymphocytes of people suffering from the iron-overload disease beta-Thalassemia, when the superantioxidant property of silymarin counteracts free radical damage to telomeres. However, silibinin, the primary active constituent of silymarin, is a telomerase inhibitor that is effective in anticancer treatment against human prostate adenocarcinoma cells, breast carcinoma cells, ectocervical cancer cells, colon cancer cells, and both small and large lung carcinoma cells (Wikipedia/Silibinin). See Rejesh Agarwall, et. al. (2006), Anticancer potential of silymarin: From bench to bedside, Anticancer Research Nov-Dec 2006, 26(6B);4457-4498. See also P. Thelen, et. al. (2003), Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells, The Journal of Urology, 171(5);1934-1938. In typical anti-aging treatment, Silibinin, Silymarin, or Milk Thistle may be taken as anti-cancer telomerase inhibitors during the 2nd part of a telomerase_activator/telomerase_inhibitor cycle. However, Milk Thistle Extract (Silymarin) behaves like a telomerase activator in a number of documented cases. For instance, Milk Thistle Extract behaves like a telomerase activator when applied to healthy human fibroblasts according to The Product B Explorer ((146) Milk Thistle Extract) based on Product B PatentScope.pdf.

(B) Relatively exotic telomerase inhibitors:

__(10) G-quadruplex ligands [G-quadruplex ligands, Links/G-quadruplex ligands as telomerase inhibitors, Papers, Patents, Books, toxicity].

__(11) Peptide nucleic acids. [Links/Peptide nucleic acids as telomerase inhibitors, Papers, Patents, Books; toxicity]

__(12) 2’-O-MeRNA oligomers. [LifeExtension; Links/2'-O-MeRNA oligomers as telomerase activators, Papers, Patents, Books, toxicity].

__(13) BPPA. BPPA. [Links/BPPA as a telomerase inhibitor, Papers, Patents, Books; toxicity].

__(14) Exotic telomerase inhibitors used in cancer research, such as
_____BIBR1532 (toxicity) {2-[(E)-3-naphtalen-2-yl-but-2- enoylamino]-benzoic acid} and
_____BIBR1591 (toxicity).

__(15) Geron's GRN163L. [Links, Images, Papers, Patents, Books, Geron, Product Description, Cancer News, molecular image; toxicity]. See Tressler R, et al. (2006), GRN163L, a telomerase inhibitor under development for cancer treatment: data guiding clinical trial design, European Journal of Cancer Supplements 4: 188. Also see Dikmen ZG, et al. (2005), In vivo inhibition of lung cancer by GRN163L: a novel human telomerase inhibitor, Cancer Research 65: 7866-73 and Ozawa T et al. (2004), Antitumor effects of specific telomerase inhibitor GRN163 in human glioblastoma xenografts, Neuro-oncology 6: 218-26.

__(16) Sulfoquinovosyldiacylglycerol (SQDG), distributed in plants and seaweeds. [article; Sulfoquinovosyldiacylglycerol as a telomerase inhibitor, Papers, Patents, Books, toxicity]

__(17) Rhodacyanine FJ5002. [article, Links/rhodacyanine FJ5002; Links/rhodacyanine FJ5002 as a telomerase inhibitor; Papers, Patents, Books; toxicity].

__(18) Cationic 5,10,15,20-tetra(N-methyl-4-pyridyl)porphyrin (TMPyP4). [Links/TMPyP4 as a telomerase inhibitor, Papers, Patents, Books; article; toxicity].

__(19) AZT [Links/AZT as a telomerase inhibitor, Papers, Patents, Books, toxicity], used in AIDs therapy and anticancer therapy. AZT inhibits telomerase. In addition, AZT is a reverse transcriptase inhibitor, the major source of its utility in treating HIV infections. See Laura K. White, Woodring E. Wright, Jerry W. Shay Telomerase Inhibitors, Trends in Biotechnology, V.19,3,March 2001. Also see reverse transcriptase inhibitors [Links, Images, Papers, Patents, Books].

__(20) TRT antisense oligonucleotides, both DNA and RNA. [Geron Patent; Links/TRT antisense oligonucleotides as telomerase inhibitors, Papers, Patents, Books, toxicity]. This includes antisense telomeric RNA.

__(21) Chimeric oligonucleotides [Links/Chimeric oligonucleotides as telomerase inhibitors, Papers, Patents, Books; toxicity].

__(22) RHPS4 [Links; Links/RHPs4 as a telomerase inhibitor, Papers, Patents, Books; toxicity], Small-Molecule Pentacyclic Acridines like RHPS4 are very potent telomerase inhibitors. RHPS4 is used in anticancer therapy. See Small-Molecule Pentacyclic Acridines [Papers, Patents, Books].

__(23) BIBR1532 [Links, Papers, Patents, Books, toxicity], the most promising anticancer small molecule telomerase inhibitor described up until 2002, from Boehringer Ingelheim Pharma (Damm et al., 2001; Pascolo et al., 2002). BIBR1532 is a synthetic non-nucleosidic telomerase inhibitor disrupting telomere maintenance in tumor cells "by inhibition of the processivity of telomerase through a non-competitive mechanism", similar to that mediated by inhibitors of HIV1 reverse transcriptase.

__(24) Ginsenoside Rh2 [Links, Images, Papers, Patents, Books; toxicity] is a telomerase inhibitor. [article].

____(24b) Ginseng seems to be a telomerase inhibitor in cancer cells. (check).
______See Ginseng [Links/as a telomerase inhibitor, Images, Papers, Patents, Books].

____(24c) Panax Ginseng seems to be a telomerase inhibitor in cancer cells. (check).
______See Panax Ginseng [Links/as a telomerase inhibitor, Images, Papers, Patents, Books].

______Asian Ginseng Root Extract (Panax Ginseng) is a telomerase activator
______for healthy human fibroblasts, however, according to
______The Product B Explorer ((135) Asian Genseng Root Extract), based on Product B PatentScope.pdf.

____(24d) Korean Red Ginseng (List (31)) is a telomerase inhibitor in leukemia cells.
See Korean Red Ginseng [Links/as a telomerase inhibitor, Images, Papers, Patents, Books]. See Park SE, Park C, Kim SH, Hossain MA, Kim MY, Chung HY, Son WS, Kim GY, Choi YH, Kim ND (2009), Korean red ginseng extract induces apoptosis and decreases telomerase activity in human leukemia cells., Journal of Ethnopharmacology, 2009 Jan 21;121(2):304-12.

__(25) Green marine algae extract [Links/Green marine algae extract, Images, Papers, Patents, Books; Links/green marine algae extract as a telomerase inhibitor; Papers, Patents, Books; toxicity]. Green marine algae extract shows strong telomerase inhibition properties. [article].

__(26) Gambogic Acid [Links/Gambogic Acid, Images, Papers, Patents, Books; Links/Gambogic Acid as a telomerase inhibitor, Papers, Patents, Books; Images Gambogic Acid supplements; toxicity]. Gambogic acid inhibits Human Telomerase Reverse Transcriptase Gene Expression. "Gambogic acid (GA), a major active ingredient of gamboge resin, obtained from Garcinia hanburyi tree (Fam. Guttiferae), is an effective telomerase inhibitor and exhibits potent anticancer activity both in vitro and in vivo." Reference: Guo. Q.L., Lin. S.S., You. Q.D., Gu. H.Y., Jun Yu., Zhao. L., Qi. Q., Liang. F., Tan. and Z., Wang. X. (2006). Inhibition of human telomerase reverse transcriptase gene expression by gambogic acid in human hepatoma SMMC-7721 cells. Life Sciences 78: 1238-1245.

__(27) Retinoic Acid (a dietary metabolite of retinal or retinol) inhibits telomerase in certain cancer cell lines and inhibits P16INK4A expression in a wider variety of cell lines. [TA/Retinoic Acid, Links/Retinoic acid, Images, Papers, Patents, Books; Links/retinoic acid as a telomerase inhibitor, Papers, Patents, Books; toxicity]. Retinoic acid [Telomerase Activators/(28) Retinoic Acid] seems to maintain telomerase activity in normal cells and inhibit telomerase activity in acute promyelocytic leukemia cancer cells and cervical cancer cells. There are other instances of substances such as silymarin (Milk Thistle Extract) that behave like telomerase inhibitors in cancer cells, but then seem to work as telomerase activators in normal cells. "Retinoic acid at the micromolar concentration down-regulates telomerase activity in human (acute promyelocytic) leukemia cells. Long-term treatment of acute promyelocytic leukemia cells with retinoic acid leads to telomere shortening and eventually cell death." - After Yi-hsin HSU, Jing-jer LIN2 (2005), Telomere and telomerase as targets for anti-cancer and regeneration therapies, Acta Pharmacologica Sinica 2005 May; 26 (5): 513–518.

Retinoic acid (say, from carrots) has been reported to down-regulate telomerase in HPV-transformed model cervical cancer cells by Z Ding, AG Green, X Yang, G Chernenko, SC Tang, et al. (2002), Retinoic Acid Inhibits Telomerase Activity and Downregulates Expression but Does Not Affect Splicing, Experimental Cell Research, 2002. [Papers/Retinoic acid and telomerase activation]. "All-trans-retinoic acid (ATRA) treatment of HPV-immortalized HEN-16-2 cells and transformed/MDR HEN-16-2/CDDP cells inhibited telomerase activity and downregulated expression of hTERT mRNAs..." (Z Ding, AG Green, et al, 2002).

However, retinoic acid was reported to maintain telomerase activity in human oral keratinocytes [You, et al., 2000, according to Michael Fossel, Cells, Aging, and Human Disease, p.158.]. See also Yong-Ouk You, Gene Lee and Byung-Moo Min, 2000. Retinoic Acid Extends the in Vitro Life Span of Normal Human Oral Keratinocytes by Decreasing p16INK4A Expression and Maintaining Telomerase Activity, Biochemical and Biophysical Research Communications, Volume 268, Issue 2, 16 February 2000, Pages 268-274. See also Maurelli, Zambruno, et al. (2006), Inactivation of p16INK4a (inhibitor of cyclin-dependent kinase 4A) Immortalizes Primary Human Keratinocytes By Maintaining Cells in the Stem Cell Compartment, The FASEB Journal, 2006;20:1516-1518.

Retinoic acid is also a telomerase inhibitor for acute promyelocytic leukemia cells according to (Cong, Wright, and Shay, 2002). "Inhibition of telomerase and repression of hTERT expression have been observed in a variety of cell lines upon induction of cellular differentiation by several reagents, such as retinoic acid and dimethyl sulfoxide (31, 109, 130, 208, 258, 270). "An inspection of the references yields remarks on the effect of retinoic acid on several cancer cell lines, including primarily leukemic cell lines such as transformed leukemic HL-60 cells. It seems only leukemia was effectively treated by retinoic acid among the tested cancer cell lines, although we now know it to also be effective against certain cervical cancer cell lines.

"Patients with acute promyelocytic leukemia can be treated effectively by administration of retinoic acid, which induces differentiation and blocks continued cell division." - Geoffrey M. Cooper and Robert E. Hausman, The Cell: A Molecular Approach, 4th edition, 2007, Chapter 18. Cancer, p.745. Other inducers of cell differentiation [(50)] have been noted to subsequently inhibit telomerase in cells that they could differentiate, including 12-O-tetradecanoylphorbol-13 acetate and nerve growth factor. Retinoic acid should probably be used during the telomerase inhibitor phase of cyclic treatment to oppose the build-up and expression of P16INK4A, which makes replicative senescence irreversible.

Retinoic acid [Images], a telomerase inhibitor on our list, extends cellular lifetimes by reducing p16INK4a expression.

Vitamin A is usually converted into retinal and retinoic acid, and is converted to retinol in the small intestine. Retinoic acid is a dietary metabolite of retinal [Wikipedia/Retinal (sources)], one of the compounds of vitamin A. ("Retinol (sources) is produced in the body from the hydrolysis of retinyl esters, and from the reduction of retinal." - Wikipedia/Retinol.) Once retinol has been taken up by a cell, it can be oxidized to retinal and then retinal can be oxidized to retinoic acid. The conversion of retinal to retinoic acid is irreversible, such that the production of retinoic acid is tightly regulated, due to its activity as a ligand for nuclear receptors. 23,000 IU of vitamin A are contained in 1/2 cup serving of canned carrots. Retinol can be synthesized in the body from beta-carotene. Vegetables rich in retinoic acid and vitamin A include dark leafy greens such as spinach, kale, collard greens and broccoli. See retinol [Links, Images, Video, Papers, Patents, Books]. Retinoic acid is obtained from retinol [Links, Images, Papers, Patents, Books] after retinol has penetrated the cell membrane. See the preparation of retinol from carrots [Papers, Patents, Books] and retinol sources.

__(28) Beta-lapachone [Links; Links/Beta-lapachone as a telomerase inhibitor; Papers; Patents; Books; toxicity] inhibits telomerase expression in prostate carcinoma cells.

__(29) Interferon-alpha [Index; Links/Interferon-alpha, Images, Papers, Patents, Books; Links/Interferon-alpha as a telomerase inhibitor, Papers, Patents, Books; toxicity]. Interferon-alpha down-regulates telomerase activity [Xu, et.al, 2000, Blood]. "Interferon-alpha represses hTERT activity within 4 hours in malignant and non-malignant human hemopoietic cell lines, primary leukemic cells, and normal T-lymphocytes." (Cong, Wright, and Shay, 2002). See leukemia.

__(30) hTERT transcription factors [Links, Images, Papers, Patents, Books]. Transcription factors down-regulating hTERT transcription include:
E2F-1, (Images, Papers, Patents, Books, toxicity),
Mad1 (Images, Papers, Patents, Books, toxicity),
TGF-β (Images, Papers, Patents, Books, toxicity, (60)), and
Menin (Images, Papers, Patents, Books, toxicity).
See Shuwen Wang and Jiyue Zhu, 2004: The hTERT Gene is Embedded in a Nuclease-resistant Chromatin Domain, Journal of Biological Chemistry, vol 279, No.53, Dec.31, 2004, pp 55401-55410. See also (61) Transcriptional Repressors of hTERT. Note that c-Myc [List, Index] dimerizes with MAD to repress hTERT transcription, and with MAX to promote hTERT transcription. For more transcriptional repressors of hTERT, see (60) TGF-beta and (61) Transcriptional Repressors.

__(31) Korean Red Ginseng Extract [Links/Korean Red Ginseng Extract, Images, Papers, Patents, Books; Links/Korean Red Ginseng Extract as a telomerase activator, Papers, Patents, Books; toxicity]. See Park SE, Park C, Kim SH, Hossain MA, Kim MY, Chung HY, Son WS, Kim GY, Choi YH, Kim ND (2009), Korean red ginseng extract induces apoptosis and decreases telomerase activity in human leukemia cells., Journal of Ethnopharmacology, 2009 Jan 21;121(2):304-12. See also (24d).

__(32) 15-deoxy-Delta12,14-prostaglandin J2 [Links/15-deoxy-Delta12,14-prostaglandin J2, Papers; Patents; Books; toxicity]. See Moriai M, Tsuji N, Kobayashi D, Kuribayashi K, Watanabe N, (2009), Down-regulation of hTERT expression plays an important role in 15-deoxy-Delta12,14-prostaglandin J2-induced apoptosis in cancer cells, 1: International Journal of Oncology, 2009 May; 34(5): 1363-1372.

__(33) Berberine [Wikipedia, Links/Berberine, Images, Papers, Patents, Books; Links/Berberine as a telomerase inhibitor, Images, Papers, Patents, Books; toxicity]. Berberine inhibits telomerase [Links/Berberine inhibits telomerase]. However, Berberine Rhizome Extract (Coptis Chinensis) is a telomerase activator according to The Product B Explorer ((137) Berberine Rhizome Extract), based on Product B PatentScope.pdf. See Lingyi Fu, Wangbing Chen, Wei Guo, Jingshu Wang, Yun Tian, Dingbo Shi, Xiaohong Zhang, Huijuan Qiu, Xiangsheng Xiao, Tiebang Kang, Wenlin Huang, Shusen Wang mail, Wuguo Deng (2013), Berberine Targets AP-2/hTERT, NF-kB/COX-2, HIF-1alpha/VEGF and Cytochrome-c/Caspase Signaling to Suppress Human Cancer Cell Growth, PLOS|one 8(7): e69240. Berberine may be used to treat lung cancer and other cancers.

__(34) Gemfibrozil [Images, Papers, Patents, Books; Links/Gemfirbozil as a telomerase inhibitor, Papers, Patents, Books; toxicity]. Gemfibrozil inhibits telomerase.

__(35) Cat's Claw extract (Samento, Links/Cat's Claw extract as a telomerase inhibitor, Papers, Patents, Books; toxicity) is a telomerase inhibitor according to RevGenetics/Astral Fruit C literature. This was not easy to confirm immediately. There are clues that this may be true: "The antiproliferative and apoptotic effects of highly purified oxindole alkaloids have been investigated, namely isopteropodine (A1, toxicity), pteropodine (A2, toxicity), isomitraphylline (A3, toxicity), uncarine F (A4, toxicity) and mitraphylline (A5, toxicity) obtained from Uncaria tomentosa (toxicity), a South American Rubiaceae, on human lymphoblastic leukaemia T cells (CCRF-CEM-C7H2). Four of the five tested alkaloids inhibited proliferation of acute lymphoblastic leukaemia cells. Furthermore, the antiproliferative effect of the most potent alkaloids pteropodine (A2) and uncarine F (A4) correlated with induction of apoptosis." - after N Bacher, M Tiefenthaler, S Sturm, H Stuppner, MJ Ausserlechner, R Kofler, G Konwalinka, "Oxindole alkaloids from Uncaria tomentosa induce apoptosis..", Br J Haematol (2006) 132: 615-22.

___(36) Cacao bean products (cocoa, chocholate, toxicity). Cacao bean products may contain catechins that effectively inhibit telomerase. Check Cocoa catechins inhibit telomerase. Cacao bean products such as cocoa and chocolate inhibit telomerase according to Terraternal. See (38) Dietary Polyphenols.

___(37) Dictyodendrin [Images, Papers, Patents, Books] (toxicity), Dictyodendrin B (toxicity), Dictyodendrin C (toxicity), and Dictyodendrin E (toxicity). Dictyodendrins are telomerase inhibitors of marine origin. See Alois Fürstner, Mathias M. Domostoj, and Bodo Scheiper (2006), Total Syntheses of the Telomerase Inhibitors Dictyodendrin B, C, and E, J. Am. Chem. Soc., 2006, 128 (24), pp 8087–8094.

___(38) Dietary polyphenols. "Degraded dietary polyphenols are potent telomerase inhibitors". Telomerase inhibitors include not only ECGC (found in green tea, toxicity), but also epicatechin (toxicity) and quercetin (toxicity), myricetin (toxicity), naringin (toxicity), and biochanin A (toxicity) at neutral or alkaline pH. Cacao is a telomerase inhibitor according to Terraternal, no doubt because of its abundance of polyphenols, the flavonoids and flavinols including catechins, epicatechins, and procyanidins. See Imad Naasani, Fujiko Oh-hashi, et al., (2003), Blocking Telomerase by Dietary Polyphenols is a Major Mechanism for limiting the growth of Human Cancer Cells in Vivo, Cancer Research, Feb 15, 2003, 63: 824. This is impacting to our telomere lengthening program of 30-day cycles of 15 days telomerase activation ON, 15 days telomerase inhibition ON. Polyphenols including cocoa beverages or chocolate presently taken for antioxidant effect should be dropped during the first 15 days to avoid interference with telomerase activation during the first part of the cycle. Polyphenols should be taken only during the 2nd 15-day period, when telomerase inhibitors are applied. This should result in a faster rate of telomere growth to support rejuvenation.

___(39) Flaxseed Oil [Links, Papers, Patents, Books; toxicity] is possibly a telomerase inhibitor, as a correspondent has suggested. Flaxseed oil seems to have some anti-cancer effect. See Dietary flaxseed lignan or oil combined with tamoxifen treatment affects MCF-7 tumor growth through estrogen receptor- and growth factor-signaling pathways. Flaxseed oil also protects against prostate cancer. Fish oil supposed to be a telomerase inhibitor, and since flax seed oil is a rich source of omega-3 fatty acids, it is a good bet that it is a telomerase inhibitor on that basis. See Ray Sahelian's entry on flax seed oil for more details on flax seed oil. I could not immediately find flaxseed oil on a list of telomerase inhibitors, however. A comparison of the omega-3 fatty acid content of fish oil with the omega-3 fatty acid content of flax seed oil may be useful.

___(40) Inositol Hexaphosphate (Phytic Acid) was reported as a telomerase inhibitor by Wikipedia. See Links/Inositol Hexaphosphate (Images, Papers, Patents, Books; toxicity), Links/Phytic Acid (Images, Papers, Patents, Books, toxicity), and Links/Experimental Cancer Treatment.

___(41) GRN163L [Links, Papers, Patents, Books; toxicity] is a telomerase inhibitor marketed by Geron Corporation.

___(42) Vitamin D3 [Links, Papers, Patents, Books; toxicity] turned up as a telomerase inhibitor in an initial Google search. Vitamin D preserves telomere length, apparently by inhibiting inflammation (J. Brent Richards, et. al., 2007). Vitamin D has been shown to inhibit telomerase in cancer cells. This may be associated with its role as an inhibitor of inflammation, as TNF-alpha and NF-kappaB are telomerase activators. "...There is evidence of direct action on telomerase by vitamin D and retinoic acids.... studies suggest that Vitamin D and retinoic acids are potential anti-telomerase agents that directly down-regulate hTERT transcription." - after Satoru Kyo and Masaki Inoue (2002), Complex regulatory mechanisms of telomerase activity in normal and cancer cells: How can we apply them for cancer therapy?, Section (2) Differentiation inducing agents, Oncogene, 21 January 2002, Volume 21, Number 4, Pages 688-697. The authors also describe details of the Vitamin D3 telomerase inhibition pathway and the use of vitamin D3 and retinoic acids as anti-cancer drugs for various cancers, including hematological malignancies.
Should vitamin D be taken together with astragaloside IV? Maximum Telomere Support from Medicinal Nutraceutics offers Astragaloside IV with Vitamin D. Vitamin D conserves telomere length by inhibiting inflammation (J. Brent Richards, et. al., 2007). However, vitamin D3 inhibits telomerase in cancer cells, for instance in hematoloical malignancies, and probably also in normal cells (Satoru Kyo and Masaki Inoue, 2002). Vitamin D3 and retinoic acids are naturally applied together in anti-cancer treatment. Vitamin D3 and retinoic acid receptors form a heterodimer which interacts with DR3 and DR3' regions in the hTERT promoter to inhibit telomerase. "DR3 consists of two directly repeated pairs of AGGTGA motifs spaced by three nucleotides (DR3), and modulates the expression of Vitamin_D3-responsive genes as a cis-element. Notably, the sequence 5'-AGTTCATGGAGTTCA-3' (named DR3') located at -2530 on the hTERT promoter is similar to DR3." Thus it may be better not to use high-level Vitamin D3 treatment during a telomerase activation phase of telomere enlongation, but to save it for the telomerase inhibition phase of a (monthly) cyclic treatment period.

Note that c-Myc [List] promotes hTERT transcription, and that Vitamin D Inhibits the Production and Function of cMYC [Links, Papers, Patents, Books]. "We discovered that vitamin D controls both the rate of production and the degradation of cMYC. More importantly, we found that vitamin D strongly stimulates the production of a natural antagonist of cMYC called MXD1 [Links, Papers, Patents, Books], essentially shutting down cMYC function." - Dr. John White (McGill University), according to Natural News.

___(43) Tamoxifen [Links, Images, Papers, Patents, Books; toxicity]. Tamoxifen reduces telomerase activity. (Cong, Wright, and Shay, 2002). "Anti-estrogens like tamoxifen are often applied in the treatment of breast cancer." - Ralf Janknecht, ed. Varda Rotter (2004), On the road to immortality: hTERT upregulation in cancer cells, FEBS Letters, Volume 564, Issues 1-2, 23 April 2004, Pages 9-13. "Tamoxifen is a non-steroidal anti-estrogen with wide use as an adjuvant therapy for breast cancer. In breast cancer cells, tamoxifen antagonizes estrogen action and inhibits telomerase activity (Aldous et al., 1999)." - from Satoru Kyo and Masaki Inoue (2002), Complex regulatory mechanisms of telomerase activity in normal and cancer cells: How can we apply them for cancer therapy? Oncogene, 21 January 2002, Volume 21, Number 4, Pages 688-697. Tamoxifen abolishes the effects of both estradiol and androgens on telomerase function. - after Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells [PDF], Blood 2009 114:2236-2243.

___(44) Wortmannin [Links, Images, Papers, Patents, Books, toxicity]. "Wortmannin inhibits telomerase activity in human melanoma cells in a dose-dependent manner." (Cong, Wright, and Shay, 2002).

___(45) 5,6-trans-16-ene-vitamin D3 [Links, Images, Papers, Patents, Books; toxicity].

___(46) Dimethylsulfoxide (DMSO) [Wikipedia/Dimethyl sulfoxide, Links, Images, Papers, Patents, Books; sources, toxicity]. DMSO represses hTERT transcription. hTERT mRNA levels in the presence of DMSO are used as the null levels in comparative telomerase activator studies by Geron. DMSO causes a garlic-like taste in the mouth when exposed to the skin, although it is of low toxicity and has anti-inflammatory and antioxidant properties. See DMSO as a drug carrier [Links, Images, Papers, Patents, Books].

___(47) Genistein from Soy [Index/Genistein, Links/Genistein, Images, Papers, Patents, Books; toxicity]. Genistein, a telomerase inhibitor, may be used to treat prostate cancer. See Jagadeesh S, Kyo S, Banerjee PP (2006), Genistein represses telomerase activity via both transcriptional and posttranslational mechanisms in human prostate cancer cells, Cancer Res, 2006 Feb 15;66(4):2107-15. "Li et al. demonstrated a genistein-induced repression of hTERT (human telomerase reverse transcriptase), the catalytic component of the human telomerase enzyme in human breast benign and cancer cells" (Li et al., 2009) from Nutrition in Epigenetics by Mihai D. Niculescu and Paul Haggarty from John Wiley and Sons.

___(48) Antisense pentadecadeoxynucleotides against C-Myc mRNA (toxicity) can be used to inhibit telomerase expression in human leukemic cells (Jun-Ping Liu, 2001).

___(49) Human chromosome 3 in the region p14.2-p21.3 inhibits telomerase expression. A transplant of an entire extra copy of Chromosome 3 inhibits telomerase in experimental cell cultures, but an extra copy of the region p14.2-p21.3 in Chromosome 3 will also inhibit telomerase expression and thus down-regulate telomere size.

___(50) Inducers of cell differentiation have been noted to subsequently inhibit telomerase in cells that they could differentiate, including retinoic acid (toxicity), 12-O-tetradecanoylphorbol-13 acetate (toxicity) and nerve growth factor (toxicity).

(51) Rb protein [Images, Papers, Patents, Books, toxicity]. Rb protein suppresses expression of hTERT.
See Geraldine Aubert and Peter M. Lansdorp (2008), Telomeres and Aging, Physiological Review, 88: 557-570, 2008, page 562 with fig. 3. Includes 248 reference footnotes.

(52) p21 protein [Images, Papers, Patents, Books, toxicity]. P21 protein suppresses expression of hTERT.
See Geraldine Aubert and Peter M. Lansdorp (2008), Telomeres and Aging, Physiological Review, 88: 557-570, 2008, page 562 with fig. 3. Includes 248 reference footnotes.

(53) HSP90 Blockers [Images, Papers, Patents, Books; Index/HSP90]. HSP 90 blockers include Geldanamycin [Images, Papers, Patents, Books]. "Telomerase is a target for hsp90-mediated assembly of the functional enzyme. Therefore, inhibition of hsp90 function by blocking agents would likely inhibit telomerase, but not in a specific manner. Hsp90 blocking agents, such as geldanamycin and its derivatives are touted as anticancer compounds and are currently undergoing clinical trials." after Satoru Kyo and Masaki Inoue (2002), Complex regulatory mechanisms of telomerase activity in normal and cancer cells: How can we apply them for cancer therapy?, Oncogene, 21 January 2002, Volume 21, Number 4, Pages 688-697.

(54) Tankyrase Inhibitors [Links, Images, Papers, Patents, Books]. Tankyrase 1 is overexpressed in human breast cancer, so that novel tankyrase inhibitors (MST-312, MST-295, and MST-199) have been developed to function as telomerase inhibitors for application to anticancer therapy. See Seimiya H, Oh-hara T, Suzuki T, Naasani I, Shimazaki T, Tsuchiya K, Tsuruo T (2002) Telomere shortening and growth inhibition of human cancer cells by novel synthetic telomerase inhibitors, MST-312, MST-295, and MST-199, Molecular Cancer Therapy 1: 657–665.

(55) The Pif1 helicase [Links, Images, Papers, Patents, Books; Links/inhibits telomerase, Images, Papers, Patents, Books, Gene Cards/Pif1]. The Pif1 helicase inhibits telomerase. See Zhang, D.-H., Zhou, B., Huang, Y., Xu, L.-X., Zhou, J.-Q. (2006). The human Pif1 helicase, a potential Escherichia coli RecD homologue, inhibits telomerase activity. Nucleic Acids Research 34: 1393-1404.

(56) Gamma Rubromycin [Links, Images, Papers, Patents, Books; Links/inhibits telomerase, Images, Papers, Patents, Books].

(57) Beta Rubromycin [Links, Images, Papers, Patents, Books; Links/inhibits telomerase, Images, Papers, Books].
"Beta-rubromycin appears to be a lead structure for the development of more potent and selective inhibitors of human telomerase." - Ueno T, Takahashi H, Oda M, Mizunuma M, Yokoyama A, Goto Y, Mizushina Y, Sakaguchi K, Hayashi H. (2000), Inhibition of human telomerase by rubromycins: implication of spiroketal system of the compounds as an active moiety, Biochemistry, May 23;39(20):5995-6002.

(58) MST-312, MST-295, MST-199.
Seimiya H, Oh-hara T, Suzuki T, Naasani I, Shimazaki T, Tsuchiya K, Tsuruo T (2002), Telomere shortening and growth inhibition of human cancer cells by novel synthetic telomerase inhibitors, MST-312, MST-295, and MST-199, Molecular Cancer Therapy 1: 657–665. "In this study, to circumvent disadvantages of EGCG, we have synthesized a series of stable compounds that have EGCG-related moieties and have tested their ability to inhibit telomerase activity."

(59) Sulforaphane [Index, Links/Sulforaphane as a telomerase inhibitor, Images, Papers, Patents, Books]. Sulforaphane inhibits telomerase in breast cancer cells. See Syed M. Meeran, Shweta N. Patel, and Trygve O. Tollefsbol (2010), Sulphoraphane Causes Epigenetic Repression of hTERT Expression in Human Breast Cancer Lines, PLos One, July 2010, vol.5, issue 7, e11457 and Dong-Oh Moona, Sang-Hyuck Kanga, Ki-Cheon Kima, Mun-Ock Kimb, Yung Hyun Choic and Gi-Young Kim (2010), Sulforaphane decreases viability and telomerase activity in hepatocellular carcinoma Hep3B cells through the reactive oxygen species-dependent pathway, Cancer Letters, Volume 295, Issue 2, 28 September 2010, Pages 260-266.

(60) TGF-beta (Transforming Growth Factor beta) [Wikipedia/TGF-beta, Links, Images, Papers, Patents, Patents, Books; (30c)]. TGF-beta behaves like a telomerase inhibitor in cancer cells. See Yang H, Kyo S, Takatura M, and Sun L. (2001), Autocrine transforming growth factor beta suppresses telomerase activity and transcription of human telomerase reverse transcriptase in human cancer cells, Cell Growth Differ. 2001 Feb;12(2):119-27. hTERT transcription factors [Links, Books, Papers, Patents] down-regulating hTERT include E2F-1 (toxicity), Mad1 (toxicity), TGF-β (toxicity, (60)), and Menin (toxicity). See Shuwen Wang and Jiyue Zhu, 2004: The hTERT Gene is Embedded in a Nuclease-resistant Chromatin Domain, Journal of Biological Chemistry, vol 279, No.53, Dec.31, 2004, pp 55401-55410. C.J. Cairney and W.N. Keith, 2007 picture Sp1 as a transcriptional activator of hTERT. According to their paper, the 5 Sp1 binding sites in the hTERT promoter are used for transcriptional repression of hTERT by transcription factors CtBP, p53, p73, and TGF-beta. Thus TGF-beta inhibits hTERT transcription by interacting with Sp1 binding sites. It is noteworthy that TGF beta 1 improves the expression of components of the extracellular matrix, and is included in some skin creams. See R A Ignotz and J Massagué (1986), Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix, The Journal of Biological Chemistry, March 25, 1986, 261, 4337-4345.
Palmitoyl tripeptide 3 [Images, Papers, Books] (Syn-coll), a small peptide which removes wrinkles and increases collagen production by 119%, is related to TGF-beta, featuring a unique sequence to mimic the human body’s own mechanism to produce collagen via TGF-beta. TGF-beta (1-3) controls additional cell functions such as cellular growth and cellular proliferation and also regulates cell death. Studies at Cornell, Vanderbilt and Jefferson show that TGF-beta stimulates the expression of both collagen and elastin. TGF-beta is taken from human cells and used in products by Jan Marini, A&G and ReLuma. Note that TGF-beta is a component of colostrum [Images] and colostrum skin creams [Images]. For instance, consider Sequel Rejuvenating Colostrum Skin Cream, which contains TGF-beta to inhibit telomerase and reconstruct the extracellular matrix including both collagen and elastin. It also contains many other telomerase-activating growth factors found in growth factor skin creams including TGF-alpha, EGF, IGF-1, IGF-2, VEGF, FGF, and PDGF.

(61) Transcriptional Repressors of hTERT [Links, Images, Papers, Patents, Books].
hTERT Promoter: hTERT Transcriptional Repressors].
These include transcription factors from the following 3 lists:
(1a) Sp3 [Links, Images, Papers, Patents, Books, Gene Cards/Sp3, toxicity],
(2a) AP-1 [Links, Images, Papers, Patents, Books, toxicity],
(3a) MZF [Links, Images, Papers, Patents, Books, toxicity],
(4a) WT1 [Links, Images, Papers, Patents, Books, Gene Cards/WT1, toxicity] and
(5a) E2F [Links, Images, Papers, Patents, Books, toxicity].
____(C.J. Cairney and W.N. Keith, 2007).
(1b) E2F-1 [Links, Images, Papers, Patents, Books, toxicity],
(2b) Mad1 [Links, Images, Papers, Patents, Books, toxicity],
(3b) TGF-β [Links, Images, Papers, Patents, Books, toxicity, (60)], and
(4b) Menin [Links, Images, Papers, Patents, Books, toxicity].
____(Shuwen Wang and Jiyue Zhu, 2004).
(1c)The MAD1/MAX heterodimer
___[Links/MAD1/MAX heterodimer, Images, Papers, Patents, Books, Gene Cards/Mad, Gene Cards/Max].
(2c) Mad [Links, Images, Papers, Patents, Books, Gene Cards/Mad],
(2bc) Mad dimerizes with c-Myc to repress activation of hTERT by c-Myc.
___[Links/the c-Myc/Mad dimer, Images, Papers, Patents, Books, Gene Cards/Mad].
___C-Myc inhibits the effect of Mad in a concentration-dependent manner and conversely,
___Mad inhibits the effect of c-Myc in a concentration-dependent manner, and
___Mad competes with c-Myc for binding to Max. C-myc/Max activates, Mad/Max inhibits.
___Mad may also recruit histone deacetylases to repress hTERT transcription.
(3c) The tumor suppressor p53 [Index/p53, Links, Images, Papers, Patents, Books].
___P53 interacts with Sp1 to inhibit hTERT transcription.
(4c) MZF-2 [Links, Images, Papers, Patents, Books]. (K.Fujimoto & M.Takahashi, 1997).
___Multiple sites exist on the hTERT promoter for MZF-2 binding.
___Mutations of the MZF-2 (Myeloid-specific Zinc Finger Protein 2) gene
___promote hTERT transcription.
(5c) Wilms tumor 1 suppressor gene [Index/p53, Links, Images, Papers, Patents, Books].
___WT1 binds on the hTERT promoter at -307 to -423.
(6c) p21WAF1/Cip1 overexpression downregulates hTERT transcription
___in glioma cell lines and in immortalized keratinocytes. (Jun-Ping Liu, 2001).
(W. Klapper, R. Parwaresch, and G. Krupp, 2001).
(7a) CtBP [Links, Images, Papers, Patents, Books]. See (60) TGF-beta.
___CtBP inhibits hTERT transcription by binding at Sp1 sites on the hTERT promoter.
(7b) p73 [Links, Images, Papers, Patents, Books]. See (60) TGF-beta.
___p73 inhibits hTERT transcription by binding at Sp1 sites on the hTERT promoter.
See also (30) hTERT transcription factors downregulating hTERT.

(62) Rapamycin [Links/Rapamycin, Images, Papers, Patents, Books; Links/Rapamycin and cellular aging, Images, Papers, Patents, Books; Links/Rapamycin and telomerase activation, Images, Papers, Patents, Books]. Actually, it seems that rapamycin is a telomerase inhibitor. "Milk thistle(silymarin) protects telomerase activation from rapamycin in vitro." Rapamycin reverses aging in cells taken from Hutchinson-Gilford progeria patients and extends the lifespan of mice. Rapamycin is an immunosuppressant drug used to prevent rejection of transplanted organs. - Biosingularity, July 2011. Immunosuppressant drugs may not be suitable for our application. Many telomerase activators improve immune system performance, so that immune system enhancing drugs such as astragalus are often targets for telomerase activation testing. See Kan Cao, John J. Graziotto, Cecilia D. Blair, Joseph R. Mazzulli, Michael R. Erdos, Dimitri Krainc, and Francis S. Collins (2011), Rapamycin Reverses Cellular Phenotypes and Enhances Mutant Protein Clearance in Hutchinson-Gilford Progeria Syndrome Cells, Sci Transl Med, 29 June 2011: Vol. 3, Issue 89, p. 89ra58. See also Chunxiao Zhou, Paola A. Gehrig, Young E. Whang and John F. Boggess Rapamycin Inhibits Telomerase Activity by Decreasing the hTERT mRNA Level in Endometrial Cancer Cells, Molecular Cancer Therapeutics, August 2003 2; 789. Rapamycin is sometimes harmful. See Parzonko A, Naruszewicz M., Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Warsaw, Poland (2010), Silymarin inhibits endothelial progenitor cells senescence and protects against the antiproliferative activity of rapamycin: preliminary study, Journal of Cardiovascular Pharmacology, December 2010 56(6), 610-618. "Rapamycin, an antiproliferative agent used on drug-eluting stents, induces endothelial progenitor cells (EPCs) senescence through telomerase inactivation and may impair the reendothelization of an injured arterial wall, leading to thrombosis. We examined whether silymarin, a complex of flavonolignans with hepatoprotective and antioxidative properties, can protect EPCs against rapamycin-induced senescence."

(63) PinX1 [Links, Images, Papers, Patents, Books; Gene Cards/PINX1]. PINX1 is an endogenous telomerase inhibitor that suppresses carcinogenesis. Low levels of PinX1 contribute to cancer development. Xiao Zhen Zhou, Kun Ping Lu (2001), The Pin2/TRF1-Interacting Protein PinX1 is a Potent Telomerase Inhibitor, Cell 2 November 2001, 107(3):347-359.

(64) P53 [Index/p53; Links, Images, Papers, Patents, Books].
"P53 transcriptionally represses hTERT." (Cong, Wright, and Shay, 2002).

(65) Ginger Extract [Links, Images, Papers, Patents, Books, Telomerase Activators/C-myc].
Ginger extract is a telomerase inhibitor [Papers, Patents, Books]. The ethanolic extract and ethyl acetate fractions of ginger extract inhibit hTERT expression. Ginger extract inhibits both hTERT and c-Myc expression.

(66) IL-4 is a telomerase inhibitor. [Links/IL-4, Images, Video, Papers, Patents, Books; Links/IL-4 inhibits telomerase, Images, Video, Papers, Patents, Books]. IL-4 inhibits telomerase in rat lung fibroblasts and hepatoblastoma cells.

(67) DHA is a telomerase inhibitor for cancer cells. [Index/DHA, Links/DHA, Images, Video, Papers, Patents, Books; Links/DHA inhibits telomerase, Images, Video, Papers, Patents, Books]. DHA inhibits telomerase in cancer cells. See Eitsuka T, Nakagawa K, Suzuki T, Miyazawa T. (2005), Polyunsaturated fatty acids inhibit telomerase activity in DLD-1 human colorectal adenocarcinoma cells: a dual mechanism approach [PubMED], Biochim Biophys Act, 2005 Oct 15;1737(1):1-10. Epub 2005 Sep 13. Note that DHA improves the expression of dopamine, which boosts the telomerase activator HGH, so that DHA is a telomerase activator for normal, healthy cells that are targets of HGH.

(68) Tea Catechins inhibit telomerase [Links/tea catechins inhibit telomerase, Images, Video, Papers, Patents, Books]. Naasani I, et al (1998), Telomerase inhibition, telomere shortening, and senescence of cancer cells by tea catechins, Biochem Biophys Res Commun 249: 391-96. However, Green Tea Extract, Black Tea Extract, and White Tea Extract have all three been identified as telomerase activators for healthy fibroblasts according to The Product B Explorer ((141) Green Tea Extract, (138) Black Tea Extract, (153) White Tea Extract) based on Product B PatentScope.pdf. Note that tea is often included in skin creams.

(69) High Polyphenol Diets generate telomerase inhibitors [Links/High Polyphenol Diets generate telomerase inhibitors, Images, Video, Papers, Patents, Books]. Naasani I, Oh-Hashi F, et al. (2003), Blocking telomerase by dietary polyphenols is a major mechanism for limiting the growth of human cancer cells in vitro and in vivo, Cancer Research, 63:824-30. See High Polyphenol Diets, which includes Low Polyphenol Diets.

(70) TERRA RNAs transcribed from telomeres inhibit telomerase. TERRAs, or telomere-repeat-containing RNAs transcribed from telomeres [Images, Video, Papers, Patents, Books], inhibit telomerase and are negative regulators of telomere length. See Telomere Transcription.

(71) Garlic's [Index] allicin [Index; toxicity] from crushed garlic is telomerase-inhibiting. [Links/garlic as a telomerase inhibitor, Papers, Patents, Books, WikiGenes/allicin]. Note that allicin from garlic is also a powerful antibiotic, in addition to being an anti-cancer telomerase inhibitor. It is usually prescribed at 3-5 cloves/serving, 4x per day, mixed in barbeque sauce with extra sweetener and taken on soda crackers, or with salad dressing. Be sure to wear rubber gloves while slicing cloves.

(72) Cholesterol down-regulates hTERT mRNA expression. Activated receptor Ck, a cell surface receptor specific for cholesterol, was found to down-regulate hTERT mRNA expression by repressing the transcription of c-myc gene. When trying to upregulate hTERT, keep cholesterol low. See Kavleen Sikand, Deepak Kaul and Neelam Varma (2006), Receptor Ck-dependent signaling regulates hTERT gene transcription, BMC Cell Biology 2006 7:2.

(73) FK506 (Tacrolimus) [Links, Images, Papers, Patents, Books].
FK506 was identified as a "most potent" telomerase inhibitor in Chebel A, Rouault JP, Urbanowicz I, Baseggio L, Chien WW, Salles G, Ffrench M (2009), Transcriptional activation of hTERT, the human telomerase reverse transcriptase, by nuclear factor of activated T cells (PubMed), J Biol Chem, 2009 Dec 18;284(51):35725-34.

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