US 20140079836A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0079836A1 McDaniel (43) Pub. Date: Mar. 20, 2014 (54) METHODS AND COMPOSITIONS FOR (52) U.S. Cl. ALTERING HEALTH, WELLBEING AND CPC ............... A61K 36/74 (2013.01); A61 K3I/122 LIFESPAN (2013.01) USPC ............. 424/777; 514/690: 435/375; 506/16; (71) Applicant: LifeSpan Extension, LLC, Virginia 435/6.12 Beach, VA (US) (72) Inventor: David H. McDaniel, Virginia Beach, VA (57) ABSTRACT (US) Described herein are the results of comprehensive genetic (73) Assignee: LifeSpan Extension, LLC expression and other molecular analysis p the effect s anti oxidants on biological systems, including specifically differ (21) Appl. No.: 14/084,553 ent human cells. Based on these analyses, methods and com (22) Filed: Nov. 19, 2013 positions are described for modifying or influencing the lifespan of cells, tissues, organs, and organisms. In various Related U.S. Application Data embodiments, there are provided methods for modulating the activity of the gene maintenance process in order to influence (60) Continuation of application No. 13/898.307, filed on the length and/or structural integrity of the telomere in living May 20, 2013, which is a division of application No. cells, as well as methods for modulating the rate/efficiency of 12/629,040, filed on Dec. 1, 2009, now abandoned. the cellular respiration provided by the mitochondria, mito (60) Provisional application No. 61/118,945, filed on Dec. chondrial biogenesis, and maintenance of the mitochondrial 1, 2008. membrane potential. Exemplary lifespan altering compounds include natural and synthetic antioxidants, such as plant anti Publication Classification oxidant and polyphenol compounds derived from coffee cherry, tea, berry, and so forth, including but not limited to (51) Int. Cl. caffeic acid, chlorogenic acid, ferulic acid, quinic acid, proan A6 IK36/74 (2006.01) thocyanidins, ubiquinone, idebenone, or a synthetic form or A6 IK3I/122 (2006.01) derivatives thereof. Patent Application Publication Mar. 20, 2014 Sheet 1 of 23 US 2014/0079836A1 Figure 1 Patent Application Publication Mar. 20, 2014 Sheet 2 of 23 US 2014/0079836A1 ***3. *• Patent Application Publication Mar. 20, 2014 Sheet 3 of 23 US 2014/0079836A1 Q §338&#3 {{{2}#33-*?.~~~+~$3 8·~ Patent Application Publication Mar. 20, 2014 Sheet 4 of 23 US 2014/0079836A1 o'º.ul^[][].— }}{} Patent Application Publication Mar. 20, 2014 Sheet 5 of 23 US 2014/0079836A1 ,!^^^^^^<>+~~~~); ~º„aeropae Patent Application Publication Mar. 20, 2014 Sheet 6 of 23 US 2014/0079836A1 Figure 3 The Coffee Cherry Fruit • Pulp (exocarp & outer finesocarp) • Nucilage finner triesocarp} go thu of hisk :'''''''''''' (endocarpi.. 8 Seeds (green beans. Figure 4 Ros?Free Radicais XN. Eacity Estokisses s ifie3ssificiis Cacer Ericicki: &etatiocyte&:ys Eyssuiciis. toes: 8&laysics; 3EEaciosis infantatio. 383 ge. Breakiswa Premature Aging Patent Application Publication Mar. 20, 2014 Sheet 7 of 23 US 2014/0079836A1 Figure 5 Causes of Premature Agrig Cancer NA & Beiere fantration Strictite E3riage i.e.:3. Membrane Camage oysfunction Dysfiriction Ribosernal Eysfunction histochondrial Ramagef E?ectron Transport Systern Cysfutction Patent Application Publication Mar. 20, 2014 Sheet 8 of 23 US 2014/0079836A1 Figure 7 8Green Tea E3cedefore Figure 8 Human Cardiac Myocytes in Response to Coffeeberry 9 s d d S b d b o s Sgs 0.01% 0.00% 0.000%, 0.0000% 0.00000% Coffeeberry Patent Application Publication Mar. 20, 2014 Sheet 9 of 23 US 2014/0079836A1 Figure 9 Expression of VEGFA in human fibroblast 24 hours after exposure to coffee cherry 1.5 Concentration of CoffeeCherry 0.01% O.OOO1% OOOOOO1% Figure 10 Expression of HMOX1 in human fibroblast 24 hours after exposure to coffee cherry Concentration of CoffeeCherry O.01% OOOO% OOOOOO1% Patent Application Publication Mar. 20, 2014 Sheet 10 of 23 US 2014/0079836A1 Figure 11 Expression of CCL41 in human skin fibroblasts 24 hours after exposure to chlorogenic acid or coffee cherry O - - O.OOOOO1%, O.OOO1%, 0.01% CoffeeCherry -1 -O.OOOOOO5%,O.OOOO5%, O .005%, Chlorogenic Acid -2 Figure 12 Expression of DDC in human skin fibroblasts 24 hours 5 after exposure to chlorogenic acid or coffee cherry 4. 3 s s 2 g - - 0.000001%, 0.0003%, 0.01% CoffeeCherry 5 1 -0.0000005%,0.00005%, O .005%, Chlorogenic Acid O -1. -2 : - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Patent Application Publication Mar. 20, 2014 Sheet 11 of 23 US 2014/0079836A1 Figure 13 Expression of NOS2A in human skin fibroblasts 24 hours after exposure to chlorogenic acid or coffee cherry 4. -1.-------------------------- a Y 3 :--------------------------------------------------- 1 Y d 2 :----------------------------- 1------------------------------------------------------------------------------------ Y Y Y - - O.OOOOO1%, 0.0001%, 0.01% CoffeeCherry -0.0000005%,0.00005%, O .005%, Chlorogenic Acid O -1. -2. ---------------------------------------------------------------------------------------------------------------------- 3. 2 3 Figure 14 Expression of SIRT1 in human skin fibroblasts 24 hours - - - - - - - - - - - - - -after exposure to chlorogenicacid or coffeecherry 2 1. cap O S. - - 0.00000%, 0.0001%, 0.01% CoffeeCherry 5-1 -0.0000005%,0.00005%, O .005%, Chlorogenic Acid -2 -3 -4 . Patent Application Publication Mar. 20, 2014 Sheet 12 of 23 US 2014/0079836A1 Figure 15 Expression of TERT in human skin fibroblasts 24 hours 5 after exposure to chlorogenic acid or coffee cherry 4. --------------------------------------------------------------------------------------------------------------------------------------------------------2-1.------------ M Y Y w Y 3 :---------------------------------------------->- a-------------------------------------------------------, Y Y s a 2 1---------------------------------------------------------------------------- 9. Y 1 a -0.000001%, 0.0001%, 0.01% CoffeeCherry S -O.OOOOOO5%,O,OOOO5%, O .005%, Chlorogenic Acid Figure 16 Expression of PTGS2 in human skin fibroblasts 24 hours after exposure to chlorogenic acid or coffee cherry w - - 0.000001%, 0.0001%, 0.01% w CoffeeCherry Y -0.0000005%,0.00005%, O 0.05%, Chlorogenic Acid Patent Application Publication Mar. 20, 2014 Sheet 13 of 23 US 2014/0079836A1 Figure 17 Expression of F144 in human skin fibroblasts 24 hours after exposure to chlorogenicacid or coffee cherry N - - 0.000.001%, 0.0001%, 0.01% 4. V CoffeeCherry : Y -0.0000005%,0.00005%, O -6 to V------------------------------------ .005%, Chlorogenic Acid Relative expression of SIRT1-4 in human skin fibroblasts 24 hours after exposure to coffee cherry 2.0 10 OO SRT1 N SIRT4 - 1.0 - - - - re- ---. -- a -2.0 screer-T. - - - - - - - - 0.000.001% CoffeeCherry --- 0.0001%. CoffeeCherry -0.01%. CoffeeCherry Patent Application Publication Mar. 20, 2014 Sheet 14 of 23 US 2014/0079836A1 Figure 19(a) Relative expression of select genes in human skin fibroblasts 24 hours after exposure to chlorogenic acid & 0.000005%, Chlorogenic Acid -4 i.--------------------------------------------------------------------------&t.005% Chlorogenic Acid : 0.0005% Chlorogenic Acid Gene & 0.005%, Chlorogenic Acid Figure 19(b) Relative expression of select genes in human skin fibroblasts 24 hours after exposureto chlorogenic acid & CEO00005% Chlorogenic Acid & 0000005% Chlorogenic Acid & 0.00005% Chlorogenic Acid Gene : 0.05% Chlorogenic Acid & 0.005% Chlorogenic Acid Patent Application Publication Mar. 20, 2014 Sheet 15 of 23 US 2014/0079836A1 Figure 19(c) Relative expression of select genes in human skin fibroblasts 24 hours after exposure to chlorogenic acid 2 th & 0.0000005% chlorogenic Acid ...9 ...A. ... f.soooooos. chlorogenic Acid W W A f '. 0.00005% Chlorogenic Acid 1. M. '. a.0005% Chlorogenic Acid A A. 80.005% Chlorogenic Acid Figure 20(a) Relative expression of select genes in human fibroblasts 24 hours after exposure to coffee cherry & 0.000001%CoffeeCherry : 0.0001%. CoffeeCherry & 0.02% CoffeeCherry Patent Application Publication Mar. 20, 2014 Sheet 16 of 23 US 2014/0079836A1 Figure 20(b) Relative expression of Select genes in human fibroblast 24 hours after exposure to coffee cherry 80.000003%CoffeeCherry 12 . .8.0.0001% coffeecherry & 0.01% CoffeeCherry Figure 20(c) Relative expression of select genes in human ... fibroblasts 24 hours after exposure to coffee cherry A. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 3. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 2 -:- 1 . 0 t 38.Y.S&S&S&S88:S:38&S&3&X. - - - - - - - - - - - - - - - - - - - - - - - - -8-8-83& . & . .8. - - - - - - - - - - - - - - - - - - - - - - - - - - - 3 :- - - - - - - - - - - - - - - - - - - - - - - & 0.000003%CoffeeCherry : 0.0002% CoffeeCherry X 0.01%. CoffeeCherry Patent Application Publication Mar. 20, 2014 Sheet 17 of 23 US 2014/0079836A1 Figure 20(d) Relative expression of select genes in human fibroblasts 24 hoursafter exposure to coffee cherry s . s e & 0.000001%. CoffeeCherry 4 ir: (.0001% Coffeecherry & 0.01%. Coffeecherry Figure 20(e) Relative expression of select