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i. Introduction
International Anti-Aging Systems, Theories of Aging, on-line.
Life Extension Magazine, on-line.

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_____Biological Clocks of the Aging Cell [Books, Papers, Links, LifeExtension]

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0. Genetic Theory of Aging [Books, Links, Papers, LifeExtension].

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_____Genomic Instability in Premature Aging

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_____Somatic Mutations and Cellular aging

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_____Gene Silencing and Lifespan [Books, Papers, Links, LifeExtension].

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1. The Free Radical Theory of Aging [Books, Links, Papers, Wikipedia, LifeExtension].

Matthew J. Birket and Mark A. Birch-Machin (2007). Ultraviolet radiation exposure accelerates the accumulation of the aging-dependent T414G mitochondrial DNA mutation in human skin. Aging Cell 6(4): 557-564.

SEBASTIEN MARTIEN AND CORINNE ABBADIE, 2007. Acquisition of Oxidative DNA Damage during Senescence: The First Step toward Carcinogenesis?, Ann. N.Y. Acad. Sci. 1119: 51�63 (2007).

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_____Oxidative Damage to Proteins [Books, Papers, Links, LifeExtension].

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_____Mitochondrial Free Radical Production and Lipid Peroxidation [Books, Links, Papers, LifeExtension].

E. Samper, D. G. Nicholls and S. Melov (October 2003). Mitochondrial oxidative stress causes chromosomal instability of mouse embryonic fibroblasts. Aging Cell, Volume 2 Issue 5 Page 277-285, October 2003.

Lin Liu, James R. Trimarchi, Peter J. S. Smith, David L. Keefe (October 2002). Mitochondrial dysfunction leads to telomere attrition and genomic instability.Aging Cell. Volume 1 Issue 1 Page 40-46, October 2002

J. F. Passos, Gabriele Saretzki and Thomas von Zglinicki, 2007. DNA damage in telomeres and mitochondria during cellular senescence: is there a connection?, Nucleic Acids Research 2007 35(22):7505-7513.

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_____Oxidative Stress probed with Knockout and Transgenic Mice

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2. Hormone Replacement Theory and Endocrine Models for Aging

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3. The Caloric Restriction Theory of Anti-Aging Treatment
UPC proteins
Catherine A. Wolkow, and Wendy B. Iser (2006). Uncoupling protein homologs may provide a link between mitochondria, metabolism and lifespan. Ageing Research Reviews, Volume 5, Issue 2, May 2006, Pages 196-208.

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4. Lipofuscin Wastes and the Aging Cell Membrane

Eveline Hutter, Mette Skovbro, Barbara Lener, Clara Prats Rasmus Rabol, (2007). Oxidative stress and mitochondrial impairment can be separated from lipofuscin accumulation in aged human skeletal muscle. Aging Cell Volume 6 Issue 2 Page 245-256, April 2007.

A Terman, UT Brunk, 1998. Lipofuscin: mechanisms of formation and increase with age., APMIS, 1998.

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_____Lysosomal Degradation and Aging
Bo Yun Jung A. Han, et al., Senescence-associated β-galactosidase is lysosomal β-galactosidase. Aging Cell 5(2), 187�195.

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5. The Glycation Theory of Aging

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6. Insulin Utilization and Aging

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7. Hayflick Limit Theory of Aging Based on Telomeres. See also TA Sciences Science Library.

Carrel, A., 1912. On the permanent life of tissues outside of the organism, J.Exp.Med., 1912, 15: 516-527. Hayflick had to contend with Nobelist Carrel concerning limits to cell division in vitro.

H. Earle Swim and Robert F. Parker, 1957. CULTURE CHARACTERISTICS OF HUMAN FIBROBLASTS PROPAGATED SERIALLY, American Journal of Epidemiology, 1957, Volume 66, Number 2 Pp. 235-243. [Papers]. This paper seems to be the first to have detected a limit to the division of human fibroblasts in culture, a topic covered again by Hayflick and Moorhead in 1961.

Elizabeth H. Blackburn, Carol W. Greider, and Jack W. Szostack, 2006. (Nobel Prize in Medicine, 2009.) Telomeres and Telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging. Nature Medicine, vol. 12, no. 10, October 2006.

RM Cawthon, KR Smith, EO'Brien, A Sivatchenko, RA, et al., 2003. Association Between Telomere Length in blood and mortality in people aged 60 years or older, (direct link to the paper) The Lancet, 2003.

West, MD, 1994. The cellular and molecular biology of skin aging, Archives of Dermatology, 1994 130(1) 87-95.

David Stipp, 1999. The Hunt For The Youth Pill From cell-immortalizing drugs to cloned organs, biotech finds new ways to fight against time's toll. Fortune, October 11, 1999. (TA Sciences: TA-65). Green suggests astragalus extracts, plenty, with perseverance [81s].

Jerry W. Shay and Woodring E. Wright (2000). Hayflick, his limit, and cellular ageing. Nature/Reviews/Molecular Cell Biology, October, 2000. Shows microphotographs of the difference between young and old human fibroblast [Books] diploid cells (strain WI-38).

Hayflick L, Moorehead PS (1961). Serial Cultivation of human diploid cell strains, Exp Cell Res. 25:585-621.

JD Watson, 1972. Origin of concatemeric T7 DNA, Nat New Biol, 239:197-201, 1972. The key initial paper in the end-replication problem [Links, Books, Papers, Images, Amazon/the telomere end-replication problem] involving Okazaki fragments in lagging strand synthesis and RNA primers. Leads to a consideration of incomplete copying of template margin in enzymic synthesis of polynucleotides as developed by Olovnikov for application to cellular age timekeeping.

AM Olovnikov, 1973. A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon as a cellular clock., J Theor Biol, Sep 14,1973;41(1):181-90.

Blackburn EH, Gall JG (1978). A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. J, Mol Biol. 1978 Mar 25;120(1):33-53. (Discovery of the telomere.)

Greider CW and Blackburn EH (1985). Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. (Discovery of telomerase.) Cell 43:405-13.

Moyzis RK, Buckingham JM, Cram LS, Dani M, LL (1988). A Highly Conserved Repetitive DNA Sequence,(TTAGGG)_n, present at the Telomeres of Human Chromosomes. Proc Natl Acad Sci. 85(18): 6622-6626.

Wright WE, Shay JW, Pereira-Smith OM (1989). Reversible Cellular Senescence: implications for immortalization of normal human diploid fibroblasts Mol Cell Biol. 9(7): 3088-3092.

Scott Henderson, Richard Allsopp, David Spector, Sy-Shi Wang, Calvin Harley, 1996. In Situ Analysis of Changes in Telomere Size during Replicative Aging and Cell Transformation, Journal of Cell Biology, Volume 134, 1996, pp 1-12.

Mogfield JE, Liu WR, Reid R, 2006. Adenoviral human telomerase reverse transcriptase dramatically improves ischemic wound healing without detrimental immune response in aged rabbit model., Human Gene Therapy, 2006; 17(6): 651-660. This shows how telomerase may be activated via gene therapy using a viral vector.

Wilson, James M, 2008. Adverse Events in Gene Transfer Trials and an Agenda for the New Year, Human Gene Therapy, Volume 19, #1, January, 2008.

N. R. Forsyth, W. E. Wright, J. W. Shay, 2002. Telomerase and differentiation in multicellular organisms: Turn it off, turn it on, and turn it off again, Differentiation, Volume 69 Issue 4-5 Page 188-197, January 2002.

Carmela P. Morales, Shawn E. Holt, Michel Ouellette, Kiran J. Kaur, Ying Yan, Kathleen S. Wilson, Michael A. White, Woodring E. Wright & Jerry W. Shay, (1999). Absence of cancer−associated changes in human fibroblasts immortalized with telomerase, Nature Genetics 21, 115 - 118 (1999).

Bryce LA, et al., 2000. Mapping the gene for human telomerase reverse transcriptase, hTERT, to chromosome 5p15.33 by fluorescence in situ hybridization, Neoplasia, 2000.

Richard C. Allsopp, H Vaziri, C Patterson, S. Goldstein, E. V. Younglai, A Bruce Futcher, Carol W. Greider and Calvin B. Harley (1992). Telomere Length Predicts Replicative Capacity of Human Fibroblasts, Proc. Natl. Acad. Sci. USA, vol. 89, November 1992.

CB Harley, Futcher, and Greider (1990). Telomeres shorten during aging of human fibroblasts. Nature 345: 458-460.

Calvin B. Harley, 1997. Human Aging and Telomeres, Ciba Found Symp. 1997;211:129-39; discussion 139-44. [Papers].

Richard C. Allsopp, Edwin Chang, Mohammad Kashefi-Aazam, Evgeny I. Rogaev, Mieczyslaw A. Piatyszek, Jerry W. Shay and Calvin B. Harley, 1995. Telomere Shortening Is Associated with Cell Division in Vitro and in Vivo, Experimental Cell Research, Volume 220, Issue 1, September 1995, Pages 194-200.

CP Chiu and CB Harley, 1997. Replicative senescence and cell immortality: the role of telomeres and telomerase, Proceedings of the Society for Experimental Biology and Medicine, Vol 214, 99-106. [Papers, Links, Books].

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.

Griffith, Comeau, and Rosenfield (1999). Mammalian Telomeres end in a Large Duplex Loop, Cell 97: 503-514.

M. A. Blasco, Susan M. Gasser, and Joachim Lingner, (1999). Telomeres and telomerase Genes and Development, Vol. 13, No. 18, pp. 2353-2359, September 15, 1999.

Silvia Di Donna, Kamel Mamchaoui, Racquel N. Cooper, Sophie Seigneurin-Venin, Jacques Tremblay, Gillian S. Butler-Browne and Vincent Mouly (2003). Telomerase Can Extend the Proliferative Capacity of Human Myoblasts, but Does Not Lead to Their Immortalization, Mol Cancer Res 1:643-653.

Chun-Hong Zhu, Vincent Mouly, Racquel N. Cooper, Kamel Mamchaoui, Anne Bigot, Jerry W. Shay, James P. Di Santo, Gillian S. Butler-Browne and Woodring E. Wright (2007). Cellular senescence in human myoblasts is overcome by human telomerase reverse transcriptase and cyclin-dependent kinase 4: consequences in aging muscle and therapeutic strategies for muscular dystrophies., Aging Cell 6(4): 515-523.

Nicholas R. Forsyth, A. Patrice Evans, Jerry W. Shay and Woodring E. Wright (October, 2003). Developmental differences in the immortalization of lung fibroblasts by telomerase.Aging Cell: 2 (5), 235-243.

Jerry W. Shay AND Woodring E. Wright (2005). Use of Telomerase to Create Bioengineered Tissues, New York Academy of Sciences, 2005.

Carmela P. Morales, Shawn E. Holt, Michel Ouellette, Kiran J. Kaur, Ying Yan, Kathleen S. Wilson, Michael A. White, Woodring E. Wright & Jerry W. Shay (1999). Absence of cancer−associated changes in human fibroblasts immortalized with telomerase. Nature Genetics 21, 115 - 118 (1999).

Tony Chih Yuan Chuang, Sharareh Moshir, Yuval Garini, Alice Ya-Chun Chuang, Ian T Young, Bart Vermolen, Richard van den Doe, Virginie Mougey, Mathilde Perrin, Martina Braun, Paul Donald Kerr, Thierry Fest, Petra Boukamp and Sabine Mai1 (2004). The three-dimensional organization of telomeres in the nucleus of mammalian cells. BMC Biology June 2004.

Blackburn, Elizabeth, (2001). Switching and signaling at the telomere., Cell, Vol. 106, 661-673, September 21, 2001.

RC Allsopp, E Chang, M Kashefi-Aazam, EI Rogaev, (1995). Telomere shortening is associated with cell division in vitro and in vivo., Exp. Cell Res., 1995.

RC Allsopp, GB Morin, R DePinho, CB Harley, (2003). Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation, Blood, 15 July 2003, vol. 102, no. 2. pp. 517-520. HSCs are hematopoietic stem cells.

Thomas R. Cech et al, (1997). (Geron Patent) Telomerase, US Patent 6093809.

CP Chiu and CB Harley (1997). Replicative senescence and cell immortality: the role of telomeres and telomerase, Proceedings of the Society for Experimental Biology and Medicine, Vol 214, 99-106.

DG Farwell, KA Shera, JI Koop, GA Bonnet, et al., (2000). Genetic and Epigenetic Changes in Human Epithelial Cells Immortalized by Telomerase, American Journal of Pathology, 2000;156:1537-1547.

JW Shay and WE Wright (2005). Senescence and Immortalization: the role telomeres and telomerase, Carcinogenesis, Volume 26, Number 5 Pp. 867-874.

WD Funk, CK Wang, DN Shelton, CB Harley, GD Pagon, et al., (2000). Telomerase Expression Restores Dermal Integrity to in Vitro-Aged Fibroblasts in a Reconstituted Skin Model., Experimental Cell Research, Volume 258, Number 2, August 2000 , pp. 270-278(9).

Robert F. Newbold, (2002). The significance of telomerase activation and cellular immortalization in human cancer, Mutagenesis, Vol. 17, No. 6, 539-550, November 2002.

Yu-Sheng Cong, Woodring E. Wright, and Jerry W. Shay, Human Telomerase and Its Regulation, Microbiology and Molecular Biology Reviews, Sept. 2002.

Kami Ahmada and Kent G. Golica (1999). Telomere Loss in Somatic Cells of Drosophila Causes Cell Cycle Arrest and Apoptosis, Genetics, Vol. 151, 1041-1051, March 1999.

Ali Ahmed, MD, MPH, and Trygve Tollefsbol, PhD, 2001. Telomeres and Telomerase: Basic Science Implications for Aging, Journal of the American Geriatrics Society, Volume 49 Issue 8 Page 1105-1109, August 2001.

Are Telomeres the Key to Aging and Cancer? from the University of Utah's Genetic Science Learning Center, with charts, photos, and illustrations of telomere-related diseases.

Maria A Blasco, 2005. Mice with bad ends: mouse models for the study of telomeres and telomerase in cancer and aging, The EMBO Journal, (2005) 24, 1095�1103.

Christine Kim Garcia, Woodring E. Wright and Jerry W. Shay, 2007. Human diseases of telomerase dysfunction: insights into tissue aging, Nucleic Acids Research, 2007, Vol. 35, No. 22 7406-7416.

QIN OUYANG, GABRIELA BAERLOCHER, IRMA VULTO and PETER M. LANSDORP, 2007. Telomere Length in Human Natural Killer Cell Subsets, Hematopoietic Stem Cells VI, Volume 1106 published June 2007, Ann. N.Y. Acad. Sci., 1106: 240�252 (2007).

Laure Crabbe, Anna Jauch, Colleen M. Naeger, Heidi Holtgreve-Grez, and Jan Karlseder, 2007. Telomere dysfunction as a cause of genomic instability in Werner syndrome, PNAS, February 13, 2007, vol. 104, no. 7, 2205-2210.

Judy M.Y. Wong, and Kathleen Collins, 2006, Telomerase RNA level limits telomere maintenance in X-linked dyskeratosis congenita, GENES & DEVELOPMENT 20:2848-2858, 2006.

H. Jiang, Z. Ju, and K. L. Rudolph (2007). Telomere Shortening and Aging Z Gerontol Geriat, 40:314-324 (2007).

Izumi Horikawa, P. LouAnn Cable, Cynthia Afshari and J. Carl Barrett, 1999: Cloning and Characterization of the Promoter Region of Human Telomerase Reverse Transcriptase Gene , Cancer Research, 59, 826-830, February 1, 1999 [Papers, Books].

Tobias Else, (2009), Telomeres and telomerase in adrenocortical tissue maintenance, carcinogenesis, and aging, Journal of Molecular Endocrinology, (2009) 43, 131-141.

Geraldine Aubert and Peter M. Lansdorp, (2008), Telomeres and Aging, Physiol. Rev. 88: 557-579, 2008.

Collected Papers of Elizabeth Blackburn: [Papers, Patents, Wikipedia, Links].
Collected Papers of Carol W Greider [Papers, Patents, Wikipedia, Links].
Collected Papers of C.B.Harley: [Papers, Patents, Links, Abstracts].
Collected Papers of Eric Kool: [Papers, Patents, Links].
Collected Papers of Jerry W. Shay: [Papers, Patents, Links, Shay/Wright Laboratory, Resume w/Papers].
Collected Papers of Woodring E. Wright: [Papers, Patents, Links, Resume w/Papers].
T.R. Cech, telomerase-related patents. [Patents, Papers, Links, Books].

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_____Aging Damage to Telomeres

Judy M. Y. Wong, Kathleen Collins (2003). Telomere Maintenance and Disease, the Lancet, May 13, 2003.

Bennet DC, Medrano EE, 2002. Molecular Regulation of Melanocyte Senescence, Pigment Cell Research, 2002.

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_____Small Molecule Telomerase Activators

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____________Geron Telomerase Activators mostly based on Astragalus and Ginsenosides

Steven Russell Fauce, Beth D. Jamieson, Allison C. Chin, Ronald T. Mitsuyasu, Stan T. Parish, Hwee L. Ng, Christina M. Ramirez Kitchen, Otto O. Yang, Calvin B. Harley and Rita B. Effros, Telomerase-Based Pharmacologic Enhancement of Antiviral Function of Human CD8+ T Lymphocytes, The Journal of Immunology, 2008, 181: 7400-7406. Test of telomerase activator TAT2. "Enhanced antiviral effects were abrogated in the presence of a potent and specific telomerase inhibitor, suggesting that TAT2 acts primarily through telomerase activation." See also the associated Geron News Release.

Calvin B. Harley, et al. (2005). Compositions and Methods for Increasing Telomerase Activity (Geron patent ap.) [Papers, Links].
___See also A' alternate version: Compositions and Methods for Increasing Telomerase Activity, or A''.

Calvin B. Harley, Hong Kong U. Patent, (2005). Formulations Containing Astragalus Extracts and the Uses Thereof, European Patent Office.

Calvin, B. Harley, et. al, for Geron Corportation, (2005). Compositions and Methods for Skin Conditioning including small molecule telomerase activators such as astragaloside IV, cycloastragenol, astragenol, and astragaloside IV 16-one in glycerin, ect.

Calvin B Harley (2005). Telomerase Therapeutics for Degenerative Diseases. Current Molecular Medicine, Volume 5, Number 2, March 2005 , pp. 205-211(7)

Lei H, Wang B, Li WP, Yang Y, Zhou AW, Chen MZ (2003). Anti-aging effect of astragalosides and its mechanism of action., Acta Pharmacol Sin. 2003 Mar;24(3):230-4.

Lei Hong, Wang Ben, et al., 2003: Anti-Aging Effects of Astragalosides and its Mechanism of Action, Acta Pharmacol Sin March 2003 24 (3), 230-234.
____Mice: "The results of many studies showed that AST was ineffective at 10, 20, 30 mg/kg, while it was effective at 40, 80, and 90 mg/kg."
____Long-telomere mice can tolerate large astragalus extract doses until antioxidant effects of astragalus inhibit aging.

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________Bioavailablility of Astragalosides and Small-Molecule Telomerase Activators

Maria Jose Cano-Cebrian, et al., 2005: Intestinal Absorption Enhancement via the Paracellular Route by Fatty Acids, Chitosans, and Others: A Target for Drug Delivery, Current Drug Delivery, 2005, 2, 9-22. Chitosan increases the bioavailability of astragaloside IV.

Huang CR, Wang GJ, Wu XL, Li H, Xie HT, Lv H, Sun JG, 2006. Absorption enhancement study of astragaloside IV based on its transport mechanism in caco-2 cells, Eur J Drug Metab Pharmacokinet. 2006 Jan-Mar;31(1):5-10.

Huang CR, Wang GJ, Wu XL, Li H, Xie HT, Lv H, Sun JG, 2006. Absorption enhancement study of astragaloside IV based on its transport mechanism in caco-2 cells, Eur J Drug Metab Pharmacokinet, 2006, Jan-Mar;31(1):5-10. The bioavailability of astragaloside IV [Article, Papers], can be increased by chitosan [Wiki/chitosan, Links/chitosan] or sodium deoxycholate [Links/sodium deoxycholate, Books].

Calvin B Harley, Xu-Rong Jiang, Choy-Pik Chiu (2006). Enhancing cell migration by increasing telomerase activity,
United States Patent 20060239974.

Jean-Louis Mergny, et al., 2002. Natural and Pharmacological Regulation of Telomerase, Nucleic Acids Research, 2002, volume 30, number 4, 839-864.

Arlona Tarkanyi, PhD thesis, Pharmacological Regulation of Telomerase:..., phd.okm.gov.hu.

Takakura, et al., 2001. Telomerase activation by histone deacetylase inhibitor in normal cells, Nucleic Acids Research, 2001, Vol. 29, No. 14 3006-3011

Michael D. West, Jerry Shay, Woodring E. Wright (1998). Method for screening for agents which increase telomerase activity in a cell, United States Patent 5830644, assigned to Geron Corporation, November 3, 1998. Contains many valuable references.

Michael D. West, Jerry Shay, Woodring E. Wright (1997). Methods and Reagents for Lengthening Telomeres, United States Patent 5686306, November 11, 1997, assigned to the Board of Regents, The University of Texas System. Prescribes making available to the cell oligonucleotides as nucleic acids typically including at least 2 to 3 telomeric repeat sequences, which in humans is 5'-TTAGGG-3' (SEQ. ID. NO:2).

Christopher M. Counter and Blaine N. Armbruster (2007). Telomere Elongation, United States Patent 20070020722, filed in 2004, published 2007. Identifies a hPot1-hTERT fusion protein deliverable in liposomes and otherwise to rapidly enlongate telomeres.

Won, J., Kim, M., Kim, N., Ahn, J.H., Lee, W.G., Kim, S.S., Chang,K.-Y., Yi, Y.-W., and Kim, T.K. (2006). Small molecule-based reversible reprogramming of cellular lifespan. Nat. Chem. Bio. 2:369-74, 2006.

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______DNA Nanocircles and Telomere Elongation: Eric T. Kool's Work.

Ulf M. Lindstrom, Ravi A. Chandrasekaran, Lucian Orbai, Sandra A. Helquist, Gregory P. Miller, Emin Oroudjev, Helen G. Hansma, and Eric T. Kool (2002). Artificial human telomeres from DNA nanocircle templates, PNAS, December 10, 2002, vol. 99, no. 25, 15953-15958.

Jorg S. Hartig and Eric T. Kool (2004). Small circular DNAs for synthesis of the human telomere repeat: varied sizes, structures and telomere-encoding activities, Nucleic Acids Research 2004 vol.32(no.19): pg.152.

Dr. Eric T. Kool, (2003). (WO/2003/057849) TELOMERE-ENCODING SYNTHETIC DNA NANOCIRCLES, AND THEIR USE FOR THE ELONGATION OF TELOMERE REPEATS, World Intellectual Property Organization.

Alan K. Meeker, Jessica L. Hicks, Christine A. Iacobuzio-Donahue, Elizabeth A. Montgomery, William H. Westra, Theresa Y. Chan, Brigitte M. Ronnett and Angelo M. De Marzo, (2004). Telomere Length Abnormalities Occur Early in the Initiation of Epithelial Carcinogenesis, Clinical Cancer Research Vol. 10, 3317-3326, May 15, 2004.

Michael A. White, 2000: METHODS AND COMPOSITIONS FOR INHIBITING OR STIMULATING TELOMERASE ASSEMBLY
____Phosphoprotein 23 or p23, heat shock proteins 40,70, and 90, and HOP (also called p60) improve telomerase assembly.

Bekaert s, Koll S, et al., 2002. Comparing telomere lengths of sister chromatids in human lymphocytes using 3-dimensional confocal microscopy, Cytometry, 2002.

Cerni, C, 2000. Telomeres, telomerase, and Myc, Mutat. Res., Volume 462, Issue 1, January 2000, Pages 31-47.

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.

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.

Kayo Furumotoa, Eiji Inouea, Norio Nagaoa, Eiso Hiyamab and Nobuhiko Miwa, 1998. Age-dependent telomere shortening is slowed down by enrichment of intracellular vitamin C via suppression of oxidative stress, Life Sciences, Volume 63, Issue 11, 7 August 1998, Pages 935-948.

HANNON, Gregory, J. WANG, Jing, BEACH, David, H., 1999. (WO/1999/035243) EXTENSION OF CELLULAR LIFESPAN, METHODS AND REAGENTS, [Links].

Hideki Mizuno1, Shilagardi Khurts, Takahiko Seki, Yasuhide Hirota, Shuichi Kaneko and Seishi Murakami, 2007. Human Telomerase Exists in Two Distinct Active Complexes In Vivo (one is complexed with HSP 90), Journal of Biochemistry, 2007 141(5):641-652.

Hashimoto K., et.al, (2001 & 2003). Skin tissue regeneration promoters comprising ginsenoside Rb1, United States Patent 20030104079.

Richard C. Allsopp, Samuel Cheshier and Irving L. Weissman (2002), Telomerase Activation and Rejuvenation of Telomere Length in Stimulated T Cells Derived from Serially Transplanted Hematopoietic Stem Cells, JEM, 2 December 2002. Antigenic stimulation activates telomerase in T-cells.

Kavita Y. Sarin, Peggie Cheung, Daniel Gilison, Eunice Lee, Ruth I. Tennen, Estee Wang, Maja K. Artandi, Anthony E. Oro, and Steven E. Artandi, 2005. Conditional telomerase induction causes proliferation of hair follicle stem cells, Nature, 2005 August 18; 436(7053): 1048-1052. See also iGrowHair Telomerase, which purports to communicate telomerase to the scalp using an acidophilus bacterium.

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_____Sierra Sciences: the hTERT Promoter and Methods and Compositions for modulating hTERT expression

William H. Andrews, C.A.Foster, S. Fraser, Hamid Mohammedpour, of Sierra Sciences, 2004: Methods and Compositions for Modulating Telomerase Reverse Transcriptase (TERT) Expression, United States Patent No. 6,686,159 B2, Andrews, et al., Feb 3, 2004. Explains the hTERT repressor in the hTERT promotor and means of interfering with hTERT repression.

William H. Andrews, Laura Briggs, Lancer K. Brown, Christopher A. Foster, Mieczyslaw A. Piatyszek, Assignee: Sierra Sciences, Inc., 2005. Assays for TERT promoter modulatory agents..., US Patent # 7226744.

Andrews; William H., Foster; Christopher A., Fraser; Stephanie, Mohammadpour; Hamid, Briggs; Laura, Assignee: Sierra Sciences, Inc., April 16, 2004. Methods and compositions for modulating telomerase reverse transcriptase (TERT) expression., Appl. No.: 10/826,466.

Yi-hsin HSU, Jing-jer LIN, 2005, Telomere and telomerase as targets for anti-cancer and regeneration therapies, Acta Pharmacologica Sinica, 2005 May; 26 (5): 513-518.

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___________Nitric Oxide as a Telomerase Activator

M. Vasa, K Breitschopf, AM Zeiher, S Dimmeler, 2000. Nitric Oxide Activates Telomerase and Delays Endothelial Cell Senescence, Circulation Research, 2000, 87: pp. 450-452. - Am Heart Assoc.
____PDF sup_notes: Nitric Oxide Activates Telomerase and Delays Endothelial Cell Senescence, Univ. of Frankfort.

Toshio Hayashi, Hisako Matsui-Hirai, Asaka Miyazaki-Akita, Akiko Fukatsu, Jun Funami, Qun-Fang Ding, Sumitra Kamalanathan, Yuichi Hattori, Louis J. Ignarro, and Akihisa Iguchi, Endothelial cellular senescence is inhibited by nitric oxide: Implications in atherosclerosis associated with menopause and diabetes, PNAS, November 7, 2006, vol. 103, no. 45, pp. 17018-17023.

Erusalimsky JD, 2009, Vascular endothelial senescence: from mechanisms to pathophysiology, J. Ap. Physiology, 106/1/326, 2009.

Hong Y, Quintero M, Frakich NM, Trivier E, Erusalimsky JD, 2007, Evidence against the involvement of nitric oxide in the modulation of telomerase activity or replicative capacity of human endothelial cells, Exp Gerontol 42: 904-910, 2007.

Judith Haendeler, 2006. Nitric oxide and endothelial cell aging, European Journal of Clinical Pharmacology, Volume 62, Supplement 1 / February, 2006.

Farsetti A, Grasselli A, Bacchetti S, Gaetano C, Capogrossi MC (2009), The telomerase tale in vascular aging: regulation by estrogens and nitric oxide signaling, J Appl Physiol 106: 333-337, 2009.

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___________Novel Wistar Institute Small-Molecule Telomerase Activators.

Novel Telomerase Activators, Ben Gurion University on the Negev. BGN Technologies.

Andrew J. Gillis, Anthony, P. Schuller & Emmanuel Skordalakes, Structure of the Tribolium castaneum telomerase catalytic subunit TERT, Nature, 455:633-637, 2008. Referenced in The Wistar Institute/Design of Novel Molecules That Regulate Telomerase.

Rouda S, Skordales E. Structure, 2007, Nov. 15(11):1403-12. Structure of the RNA binding domain of telomerase: Implications for RNA recognition and binding. Referenced in The Wistar Institute/Design of Novel Molecules That Regulate Telomerase.
____See Decipering Of Telomerase Structure Opens Door To New Cancer, Aging Treatments at Medical News Today describes work by Emmanuel Skordalakes on telomerase structure.

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___________Androgens as Small-Molecule Telomerase Activators.

Rodrigo T. Calado, William T. Yewdell, Keisha L. Wilkerson, Joshua A. Regal, Sachiko Kajigaya, Constantine A. Stratakis, and Neal S. Young, 2009, Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells, Blood,, 10 September 2009, Vol. 114, No. 11, pp. 2236-2243.

Chuanhai Guo, Blaine N. Armbruster, David T. Price, Christpher M. Counter, (2003), In Vivo Regulation of hTERT Expression and Telomerase Activity by Androgen, Journal of the American Academy of Dermatology, Volume 170, Issue 2, Part 1, Pages 615-618 (August 2003).
____Other investigators speculate that androgens are converted to estrogens before interacting with the hTERT promoter to activate telomerase.

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_____7.3 Telomerase Inhibitors [SupNotes3b/telomerase inhibitors].

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. The effectiveness of curcumin for this application derives from its properties as a telomerase inhibitor.

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., J Ethnopharmacol. 2009 Jan 21;121(2):304-12.

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: Int J Oncol. 2009 May; 34(5): 1363-1372.

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____The hTERT Promoter

Horikawa I., Cable P. L., Afshari C., Barrett J. C., 1999. Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene, Cancer Research, 59: 826-830, 1999.

William H. Andrews, C.A.Foster, S. Fraser, Hamid Mohammedpour, of Sierra Sciences, 2004: Methods and Compositions for Modulating Telomerase Reverse Transcriptase (TERT) Expression, United States Patent No. 6,686,159 B2, Andrews, et al., Feb 3, 2004. Explains the hTERT repressor in the hTERT promotor and means of interfering with hTERT repression.

William H. Andrews, Laura Briggs, Lancer K. Brown, Christopher A. Foster, Mieczyslaw A. Piatyszek, Assignee: Sierra Sciences, Inc., 2005. Assays for TERT promoter modulatory agents..., US Patent # 7226744.

Morin, et.al, the Aug. 17, 2004 Geron patent Telomerase promoter driving expression of therapeutic gene sequences.

M Wick, D Zubov, G Hagen, 1999, Genomic organization and promoter characterization of the gene encoding the human telomerase reverse transcriptase (hTERT), Gene, Volume 232, Issue 1, 17 May 1999, Pages 97-106.

Cong, YS, The Human Telomerase Catalytic Subunit hTERT: organization of the gene and characterization of the promoter, Human Molecular Genetics, 1999, vol.8, no.1, 137-142.

Yu-Sheng Cong, Woodring E. Wright, and Jerry W. Shay, Human Telomerase and Its Regulation. Izumi Horikawa, P. LouAnn Cable, Cynthia Afshari and J. Carl Barrett, (1999), Cloning and Characterization of the Promoter Region of Human Telomerase Reverse Transcriptase Gene , Cancer Research, 59, 826-830, February 1, 1999. [Papers, Books].

Takakura, M., Kanaya,T., et al, 1999, Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells, Cancer Research, 59, 551-557.

M.P. Mattson, MP, Telomerase, Aging and Disease (Advances in Cell Aging and Gerontology), Elsevier, 2001.

Wu, (1999), c-Myc activates hTERT promoter, Nature Genetics, 1999. [Links, Books, Papers].
Theodora R. Devereux, Izumi Horikawa, Colleen H. Anna, Lois A. Annab, Cynthia A. Afshari and J. Carl Barrett, (1999), DNA Methylation Analysis of the Promoter Region of the Human Telomerase Reverse Transcriptase (hTERT) Gene, Cancer Research 59, 6087-6090, December 1, 1999.

Joseph C. Poole, Lucy G. Andrews and Trygve O. Tollefsbol, Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT), Gene, Volume 269, Issues 1-2, 16 May 2001, Pages 1-12.

Sang Sun Kang, Taegun Kwon, Do Yoon Kwon, and Su Il Do, (1999), Akt Protein Kinase Enhances Human Telomerase Activity through Phosphorylation of Telomerase Reverse Transcriptase Subunit, J Biol Chem, Vol. 274, Issue 19, 13085-13090, May 7, 1999.

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_____Telomere Epigenetics

Maria A. Blasco, 2004. Telomere epigenetics: a higher-order control of telomere length in mammalian cells, Carcinogenesis, Vol. 25, No. 7, 1083-1087, July 2004.
___ hRAP1 is recruited by TRF2 to human telomeres. hRAP1 is the homologue of yeast RAP1 protein and its over-expression causes telomere elongation.

Isabelle Guilleret, Pu Yan, 2002. Hypermethylation of the human telomerase catalytic subunit (hTERT) gene correlates with telomerase activity, International Journal of Cancer, Volume 101, Issue 4 , Pages 335 - 341, 7 Aug 2002.

Theodora R. Devereux, Izumi Horikawa, Colleen H. Anna, Lois A. Annab, Cynthia A. Afshari and J. Carl Barrett, 1999. DNA Methylation Analysis of the Promoter Region of the Human Telomerase Reverse Transcriptase (hTERT) Gene, Cancer Research 59, 6087-6090, December 1, 1999. This paper includes an analysis of the hTERT promoter.

Farwell, Shera, et al., 2000. Genetic and Epigenetic Changes in Human Epithelial Cells Immortalized by Telomerase, Am J Pathol. 2000 May; 156(5): 1537�1547.
___It may be necessary to down-regulate p16INK4a and p14ARF in breast cell or foreskin tissue for these to become immortal.

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_____The Telomere Position Effect and Youthful Patterns of Gene Expression
[Books/Telomere Position Effect, Papers, Links; Books/Epigenetic Control]

Joseph A. Baur, Ying Zou, Jerry W. Shay, Woodring E. Wright (2001). Telomere Position Effect in Human Cells. Science 15 June 2001: Vol. 292. no. 5524, pp. 2075 - 2077.

Carmia Borek (2002). Telomere Control and Cellular Aging, Life Extension, September 2002.

DE Gottschling, OM Aparicio, BL Billington, VA, et al. (1990). Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell, Vol 63, 751-762, 16 November 1990.

Joseph A. Baur, Woodring E. Wright, Jerry W. Shay (2004). Analysis of Mammalian Telomere Position Effect, in Epigenetics Protocols, 2004.

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______7.6 Telomere T-Loop and D-Loop.

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_____7.7 Telomere Capping Proteins

Hiroshi Aoki, Eiji Iwado, Mark S. Eller, Yasuko Kondo, Keishi Fujiwara, Guang-Zhi Li, Kenneth R. Hess, Doris R. Siwak, Raymond Sawaya, Gordon B. Mills, Barbara A. Gilchrest and Seiji Kondo (2007). Telomere 3' overhang-specific DNA oligonucleotides induce autophagy in malignant glioma cells. The FASEB Journal 2007;21:2918-2930.

K.G. Murti and D.M.Prescott (1999). Telomeres of polytene chromosomes in a ciliated protozoan terminate in duplex DNA loops. PNAS, December 7, 1999, Vol 96, No. 25, pp.14436-14439.

Ling Wu, Asha S. Multani, Hua He, Wilfredo Cosme-Blanco, Yu Deng, Jian Min Deng, Olga Bachilo, Sen Pathak, Hidetoshi Tahara, Susan M. Bailey, Yibin Deng, Richard R. Behringer and Sandy Chang (2006). Pot1 Deficiency Initiates DNA Damage Checkpoint Activation and Aberrant Homologous Recombination at Telomeres. Cell, Volume 126, Issue 1, 14 July 2006, Pages 49-62.

Kristine Kelly, (2006). Evidence of rapid evolution is found at the tips of chromosomes. Rockefeller Newswire.

Fd'Adda di Fagagna, SH Teo, SP Jackson (2004). Functional links between telomeres and proteins of the DNA-damage response, [direct link] Genes & Development, 18:1781-1799, 2004.

Qin Yang, Ran Zhang, Izumi Horikawa, Kaori Fujita, Yalda Afshar, Antti Kokko, P�ivi Laiho, Lauri A. Aaltonen and Curtis C. Harris, 2007. Functional Diversity of Human Protection of Telomeres 1 Isoforms in Telomere Protection and Cellular Senescence, Cancer Research 67, 11677-11686, December 15, 2007.

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________Telomerase Functional Environment

Venteicher AS, Abreu EB, Meng Z, McCann KE, Terns RM, Veenstra TD, Terns MP, Artandi SE, (2009), A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis, Science (2009). Identifies the roles of dyskerin [Links] and TCAB1 [Links] in detailed telomerase activity, and includes an analysis of other important factors.

Eva Sykorova and Jiri Fajkus (2009), Structure-Function relationships in Telomerase Genes, Biol. Cell (2009), 101, 375-392.

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________Telomerase and Protection of Mitochondrial DNA [Papers]

Haendeler J, Jakob S, Altschmied J, Goy C, Spyridopoulos I, Zeiher AM, Brandt U, Dimmeler S, et al., (2009), Mitochondrial telomerase reverse transcriptase [?] binds to and protects mitochondrial DNA and function from damage, Arterioscler. Thromb. Vasc. Biol. (2009). "Mitochondrial TERT exerts a novel protective function by binding to mitochondrial DNA, increasing respiratory chain activity and protecting against oxidative stress-induced damage."

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______Measuring Telomere Length
_________7.11.1 Measuring Telomere Length with PCR Methods (Cawthon).
Richard M. Cawthon, Telomere length measurement by a novel monochrome multiplex quantitative PCR method, Nucleic Acids Res. 2009 February; 37(3)

Biotechniques.com/A quantitative real-time PCR method for absolute telomere length

Marcel E. Gil and Thérèsa L. Coetzer, (2004), Real-time quantitative PCR of telomere length, Molecular Biotechnology, Volume 27, Number 2, June, 2004.

_________7.11.2 Measuring with Southern blot analysis of telomere restriction fragments.
_________7.11.3 Measuring with Quantitative fluorescence in situ hybridization with digital fluorescence microscopy (Q-FISH).
_________7.11.4 Measuring with Quantitative fluorescence in situ hybridization with flow cytometry (flow-FISH).
_________7.11.5 Measuring with Quantitative fluorescent in situ hybridization laser scanning cytometry (Q-FISHLSC).

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8. Stem Cell Technology and Anti-Aging Therapy
(hard to access) Telomeres in Hematopoietic Cells , Medscape Internal Medicine. [Links, Books, Papers].

Young Blood Revives Aging Muscles, Researchers Say, Science News, March 1, 2005.

Gallegos R Pi , Bolman R Mi I I I . Stem Cell�Induced Regeneration of Myocardium. Cohn Lh, ed. Cardiac Surgery in the Adult. New York: McGraw-Hill, 2008:1657-1668.

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9. Aging and Exercise

Adam Steensberg, Charlotte Keller, Thore Hillig, Christian Fr�sig, Jurgen F. P. Wojtaszewski, Bente Klarlund Pedersen, Henriette Pilegaard and Mikael Sander (2007). Nitric oxide production is a proximal signaling event controlling exercise-induced mRNA expression in human skeletal muscle. The FASEB Journal 2007;21:2683-2694.)

Martin L. Adamoa and Roger P. Farrar (2006). Resistance training, and IGF involvement in the maintenance of muscle mass during the aging process. Ageing Research Reviews Volume 5, Issue 3, August 2006, Pages 310-331.

Irina M. Conboy, Michael J. Conboy, Amy J. Wagers, Eric R. Girma, Irving L. Weissman and Thomas A. Rando (2005). Rejuvenation of aged progenitor cells by exposure to a young systemic environment, Nature 433, 760-764 (17 February 2005). [Notch signaling, muscle rejuvenation].

Young Blood Revives Aging Muscles, Researchers Say, Science Daily, March 1, 2005.

Protein Transforms Sedentary Muscles Into Exercised Muscles, Researchers Report, Science Daily, August 15, 2002.

Lynn F. Cherkas, PhD; Janice L. Hunkin, BSc; Bernet S. Kato, PhD; J. Brent Richards, MD; Jeffrey P. Gardner, PhD; Gabriela L. Surdulescu, MSc; Masayuki Kimura, MD, PhD; Xiaobin Lu, MD; Tim D. Spector, MD, FRCP; Abraham Aviv, MD, 2008. The Association Between Physical Activity in Leisure Time and Leukocyte Telomere Length, Arch Intern Med. 2008;168(2):154-158.

Amy J. Wagers and Irina M. Conboy, 2005. Cellular and Molecular Signatures of Muscle Regeneration: Current Concepts and Controversies in Adult Myogenesis , Cell, Volume 122, Issue 5, 9 September 2005, Pages 659-667.

Eric B. Larson, MD, Li Wang, MS; James D. Bowen, 2006. Exercise Is Associated with Reduced Risk for Incident Dementia among Persons 65 Years of Age and Older , Annals of Internal Medicine, 17 January 2006, Volume 144, Issue 2, Pages 73-81.

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10. Aging and DNA Repair

R. W. Hart and R. B. Setlow, 1974. Correlation between Deoxyribonucleic Acid Excision-Repair and Life-Span in a Number of Mammalian Species, PNAS, June 1, 1974, vol. 71, no. 6, 2169-2173.

Ben Best, XI. DNA Damage and DNA Repair, from Mechanisms of Aging, online, under development.

Hyung-Lyun Kang, Seymour Benzer, and Kyung-Tai Min, 2002. Life Extension in Drosophila by Feeding a Drug, PNAS, January 22, 2002, vol. 99, no. 2, 838-843. On sodium 4-Phenylbutyrate and chromatin remodeling for life extension in Drosophila.

Sheng Y, Li L, Holmgren K, Pero RW, 2001: DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study, Phytomedicine, 2001 Jul;8(4):275-82. See also AC-11.

K Grube and A Burkle, 1992. Poly(ADP-Ribose) Polymerase Activity in Mononuclear Leukocytes of 13 Mammalian Species Correlates with Species-Specific Life Span, Proceedings of the National Academy of Sciences, Vol 89, 11759-11763. See also Wikipedia/PARP and Inotek on PARP.

Scientists from Newcastle University, 2005. Anti-Ageing Breakthrough, Posted in Genetic Research on Mon October 24, 2005. Increasing PARP-1 levels improves DNA repair.

Christine Brabeck, Ragen Pfeiffer, Alan Leake, Sascha Beneke, Ralph Meyer, and Alexander B�rkle, 2003. L-Selegiline Potentiates the Cellular Poly(ADP-Ribosyl)ation Response to Ionizing Radiation, JPET (Journal of Pharmacology And Experimental Therapeutics), 306:973-979, 2003. See also L-Selegiline, Deprenyl.

Sheng Y, Pero RW, Olsson AR, Bryngelsson C, Hua J., 1998: DNA repair enhancement by a combined supplement of carotenoids, nicotinamide, and zinc, Cancer Detect Prev, 1998;22(4):284-92. See Nicoplex [Links].

Mitochondrial DNA Repair

Christopher K. Mathews1 and Shiwei Song (2007). Maintaining precursor pools for mitochondrial DNA replication. The FASEB Journal 2007;21:2294-2303.

Kirk B. Goodall, 2003. In Search of the Fountain of Youth: Preliminary Analysis of Deuterium's Role in DNA Degradation, The Nutrition Notebook, July 22, 2003.

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11. The Immune System and Aging

H Vaziri, F Sch�chter, I Uchida, L Wei, X Zhu, R Effros, D Cohen, and C B Harley (1993). Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am J Hum Genet. 52(4): 661-667.

Milena Nasi and L. Troiano, Thymic output and functionality of the IL-7/IL-7 receptor system in centenarians: implications for the neolymphogenesis at the limit of human life. Aging Cell: 5 (2), 167-175.

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12. Aging and Chelation of Metallic Wastes

Bartzokis G, Sultzer P, et al., 2000. In Vivo Evaluation of Brain Iron in Alzheimer Disease Using Magnetic Resonance Imaging, ARch Gen Psychiatry, 2000.

Shannon S. A. Coates, Bruce E. Lehnert, Sunil Sharma, Susan M. Kindell, and Ronald K. Gary , 2007. Beryllium Induces Premature Senescence in Human Fibroblasts, Journal of Pharmacology And Experimental Therapeutics Fast Forward, March 29, 2007.

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13. The Membrane Theory of Aging

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14. The Proteasome and Aging

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_____Aging and the Proteasome [Books, Links, Papers, LifeExtension, LifeExtension/Proteasome]

Vita A. Vernace, Lisette Arnaud, Thomas Schmidt-Glenewinkel1 and Maria E. Figueiredo-Pereira1 (2007). Aging perturbs 26S proteasome assembly in Drosophila melanogaster. The FASEB Journal 2007;21:2672-2682.

Magda Katsiki, Niki Chondrogianni, Ioanna Chinou, A. Jennifer Rivett, Efstathios S. Gonos, 2007. The Olive Constituent Oleuropein Exhibits Proteasome Stimulatory Properties In Vitro and Confers Life Span Extension of Human Embryonic Fibroblasts, Rejuvenation Research, 2007, 10(2): 157-172.

Regina Gonzalez-Dosal, Morten Draeby S�RENSEN, Brian F.C. Clark, Suresh I. S. Rattan and Peter Kristenson, (2006). Phage-Displayed Antibodies for the Detection of Glycated Proteasome in Aging Cells, Understanding and Modulating Aging Volume 1067 published May 2006, Ann. N.Y. Acad. Sci. 1067: 474-478 (2006).

Gaczynska M, Osmulski PA, Ward WF, (2001). Caretaker or undertaker? The role of the proteasome in aging, 1: Mech Ageing Dev. 2001 Mar;122(3):235-54.

Geraldine Carrard and Bertrand Friguet, The Proteasome in Aging, from Aging at the Molecular Level By Thomas von. Zglinicki, Springer, 2003.

B. Friguet, Proteasome and Oxidative Stress, from Protein Degradation in Health and Disease By Mich�le Reboud-Ravaux, p.25, Springer, 2002.

Shringarpure R.; Davies K.J.A., (2002). Protein turnover by the proteasome in aging and disease, Free Radical Biology and Medicine, Volume 32, Number 11, 1 June 2002 , pp. 1084-1089(6).

Niki Chondrogianni, Fiona L.L. Stratford, Ioannis P. Trougakos, Bertrand Friguet, A. Jennifer Rivett, and Efstathios S. Gonos (2003). Central role of the proteasome in senescence and survival of human fibroblasts: Induction of a senescence-like phenotype upon its inhibition and resistance to stress upon its activation, J. Biol. Chem, 10.1074/jbc.M301048200, Submitted on January 30, 2003, Revised on April 30, 2003, Accepted on May 7, 2003.

Anne-Laure Bulteau, Bertrand Friguet, (2004). Are Expanded Polyglutamine Proteins a Proteasome Substrate?, Rejuvenation Research, 2004, 7(4): 239-242.

Sangsoo Ohb, Hyun Seok Honga, Enmi Hwanga, Hae Jin Simb, Woojin Leec, Su Jeon Shina and Inhee Mook-Jung, (2005). Amyloid peptide attenuates the proteasome activity in neuronal cells, Mechanisms of Ageing and Development Volume 126, Issue 12, December 2005, Pages 1292-1299.

Bence, NF, et al. 2001. Impairment of the ubiquitin-proteasome system by protein aggregation., Science, 2001.

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15. Other Mechanisms of Aging

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_____Non-Oxidative Transformations of DNA and Proteins in Aging

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_____Dysregulation of Transcription and Translation in Aging

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_____RNA Damgage and Aging, Oxidative RNA damage and Aging

Xiu Shan, Yueming Chang and Chien-liang Glenn Lin (2007). Messenger RNA oxidation is an early event preceding cell death and causes reduced protein expression. The FASEB Journal 2007;21:2753-2764.
_____Cigarette Smoke causes premature aging of lung fibroblasts.

Toru Nyunoya, Martha M. Monick, Aloysius Klingelhutz, Timur O. Yarovinsky, Jeffrey R. Cagley and Gary W. Hunninghake, 2006. Cigarette Smoke Induces Cellular Senescence, American Journal of Respiratory Cell and Molecular Biology, Vol. 35, pp. 681-688, 2006.

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16. Telomerase Inhibitors [SupNotes3b/telomerase inhibitors].

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. The effectiveness of curcumin for this application derives from its properties as a telomerase inhibitor.

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., J Ethnopharmacol. 2009 Jan 21;121(2):304-12.

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: Int J Oncol. 2009 May; 34(5): 1363-1372.