title: A natural product telomerase activator as part of a health maintenance program.
abstract: Most human cells lack sufficient telomerase to maintain telomeres, hence these genetic elements shorten with time and stress, contributing to aging and disease. In January, 2007, a commercial health maintenance program, PattonProtocol-1, was launched that included a natural product-derived telomerase activator (TA-65®, 10-50 mg daily), a comprehensive dietary supplement pack, and physician counseling/laboratory tests at baseline and every 3-6 months thereafter. We report here analysis of the first year of data focusing on the immune system. Low nanomolar levels of TA-65® moderately activated telomerase in human keratinocytes, fibroblasts, and immune cells in culture; similar plasma levels of TA-65® were achieved in pilot human pharmacokinetic studies with single 10- to 50-mg doses. The most striking in vivo effects were declines in the percent senescent cytotoxic (CD8(+)/CD28(-)) T cells (1.5, 4.4, 8.6, and 7.5% at 3, 6, 9, and 12 months, respectively; p = not significant [N.S.], 0.018, 0.0024, 0.0062) and natural killer cells at 6 and 12 months (p = 0.028 and 0.00013, respectively). Most of these decreases were seen in cytomegalovirus (CMV) seropositive subjects. In a subset of subjects, the distribution of telomere lengths in leukocytes at baseline and 12 months was measured. Although mean telomere length did not increase, there was a significant reduction in the percent short (<4 kbp) telomeres (p = 0.037). No adverse events were attributed to PattonProtocol-1. We conclude that the protocol lengthens critically short telomeres and remodels the relative proportions of circulating leukocytes of CMV(+) subjects toward the more "youthful" profile of CMV(-) subjects. Controlled randomized trials are planned to assess TA-65®-specific effects in humans.
authors.affiliation: Geron Corporation, Menlo Park, California, USA. charley@telomehealth.com
authors.forename: Calvin B
authors.initials: CB
authors.lastname: Harley
authors.forename: Weimin
authors.initials: W
authors.lastname: Liu
authors.forename: Maria
authors.initials: M
authors.lastname: Blasco
authors.forename: Elsa
authors.initials: E
authors.lastname: Vera
authors.forename: William H
authors.initials: WH
authors.lastname: Andrews
authors.forename: Laura A
authors.initials: LA
authors.lastname: Briggs
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Raffaele
mesh_terms: D001688:Biological Products / Q000494:pharmacology*; D002452:Cell Count; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000166:cytology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006262:Health; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007231:Infant, Newborn; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism; D013997:Time Factors
chemical_list: D001688:Biological Products; D020536:Enzyme Activators; D019098:Telomerase
references.citation: Hormones (Athens). 2009 Jan-Mar;8(1):7-22
references.pmid: 19269917
references.citation: Biochimie. 2008 Jan;90(1):60-72
references.pmid: 18006207
references.citation: J Gerontol. 1993 Sep;48(5):M207-12
references.pmid: 7690056
references.citation: J Clin Endocrinol Metab. 2006 Feb;91(2):635-40
references.pmid: 16303830
references.citation: Trends Immunol. 2009 Jul;30(7):325-33
references.pmid: 19541535
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17747-52
references.pmid: 17965232
references.citation: Immunol Today. 1997 Sep;18(9):450-4
references.pmid: 9293162
references.citation: Mol Hum Reprod. 2001 Oct;7(10):947-55
references.pmid: 11574663
references.citation: Proc Natl Acad Sci U S A. 1998 May 12;95(10):5607-10
references.pmid: 9576930
references.citation: Nucleic Acids Res. 2007;35(22):7406-16
references.pmid: 17913752
references.citation: Cell. 2004 Apr 30;117(3):323-35
references.pmid: 15109493
references.citation: Exp Gerontol. 2003 Jun;38(6):653-9
references.pmid: 12814800
references.citation: J Immunol. 2009 Aug 15;183(4):2356-64
references.pmid: 19605693
references.citation: J Exp Med. 1999 Jul 19;190(2):157-67
references.pmid: 10432279
references.citation: Nucleic Acids Res. 2002 May 15;30(10):e47
references.pmid: 12000852
references.citation: Nucleic Acids Res. 2009 Feb;37(3):e21
references.pmid: 19129229
references.citation: Immunol Rev. 2005 Jun;205:147-57
references.pmid: 15882351
references.citation: Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9857-60
references.pmid: 7937905
references.citation: Heart. 2008 Apr;94(4):422-5
references.pmid: 18347373
references.citation: Soc Sci Med. 2009 Feb;68(4):699-707
references.pmid: 19152993
references.citation: Mech Ageing Dev. 2003 Jan;124(1):71-7
references.pmid: 12618008
references.citation: Rev Med Virol. 2009 Jan;19(1):47-56
references.pmid: 19035529
references.citation: Exp Gerontol. 2007 Aug;42(8):753-61
references.pmid: 17606347
references.citation: PLoS One. 2010 Jan 08;5(1):e8612
references.pmid: 20072607
references.citation: Eur Rev Med Pharmacol Sci. 2009 Jul-Aug;13(4):245-78
references.pmid: 19694341
references.citation: Blood. 2008 Nov 1;112(9):3679-87
references.pmid: 18728248
references.citation: Curr Mol Med. 2005 Mar;5(2):205-11
references.pmid: 15974874
references.citation: J Immunol. 2004 Nov 15;173(10):6303-11
references.pmid: 15528369
references.citation: Nucleic Acids Res. 1997 Jul 1;25(13):2595-7
references.pmid: 9185569
references.citation: Nature. 1990 Aug 30;346(6287):866-8
references.pmid: 2392154
references.citation: Trends Biochem Sci. 2002 Jul;27(7):339-44
references.pmid: 12114022
references.citation: Exp Gerontol. 1999 Jun;34(3):435-43
references.pmid: 10433398
references.citation: Exp Gerontol. 2008 Aug;43(8):718-28
references.pmid: 18586079
references.citation: Immunol Cell Biol. 2004 Aug;82(4):415-20
references.pmid: 15283852
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5300-5
references.pmid: 17369361
references.citation: Hematology Am Soc Hematol Educ Program. 2009;:338-43
references.pmid: 20008219
references.citation: Clin Exp Immunol. 2009 Mar;155(3):423-32
references.pmid: 19220832
references.citation: Lancet. 2003 Feb 1;361(9355):393-5
references.pmid: 12573379
references.citation: J Leukoc Biol. 2000 Jan;67(1):40-5
references.pmid: 10647996
references.citation: Blood. 2007 Sep 1;110(5):1439-47
references.pmid: 17468339
references.citation: Am J Med Sci. 2009 Jul;338(1):40-4
references.pmid: 19593102
references.citation: EMBO Rep. 2001 Sep;2(9):800-7
references.pmid: 11520856
references.citation: Alzheimers Dement. 2009 Nov;5(6):463-9
references.pmid: 19896585
references.citation: J Immunol. 2006 Feb 15;176(4):2645-53
references.pmid: 16456027
references.citation: Cell. 2001 Oct 5;107(1):67-77
references.pmid: 11595186
references.citation: Clin Cardiol. 2009 Jul;32(7):365-72
references.pmid: 19609891
references.citation: J Immunol. 2008 Nov 15;181(10):7400-6
references.pmid: 18981163
references.citation: Nat Med. 2006 Oct;12(10):1133-8
references.pmid: 17024208
references.citation: Mol Hum Reprod. 1997 Sep;3(9):769-73
references.pmid: 9358002
references.citation: Exp Gerontol. 2007 May;42(5):416-20
references.pmid: 17182206
references.citation: Nat Protoc. 2006;1(5):2365-76
references.pmid: 17406480
references.citation: J Am Coll Cardiol. 2007 Apr 3;49(13):1459-64
references.pmid: 17397675
references.citation: N Engl J Med. 2007 Mar 29;356(13):1317-26
references.pmid: 17392301
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17312-5
references.pmid: 15574496
references.citation: Br J Surg. 2009 Sep;96(9):990-8
references.pmid: 19672935
references.citation: Nat Rev Rheumatol. 2009 Oct;5(10):583-8
references.pmid: 19798035
references.citation: Expert Opin Investig Drugs. 2006 Oct;15(10):1191-200
references.pmid: 16989596
references.citation: Curr Opin Cell Biol. 2006 Jun;18(3):254-60
references.pmid: 16617011
references.citation: Mech Ageing Dev. 2008 Jan-Feb;129(1-2):35-47
references.pmid: 18160098
references.citation: N Engl J Med. 2009 Dec 10;361(24):2353-65
references.pmid: 20007561
references.citation: Ann Thorac Surg. 2009 Jan;87(1):139-47
references.pmid: 19101287
references.citation: Oncogene. 2002 Jan 21;21(4):494-502
references.pmid: 11850774
references.citation: Circulation. 2009 Oct 6;120(14):1364-72
references.pmid: 19770396
references.citation: Nature. 1990 May 31;345(6274):458-60
references.pmid: 2342578