Kevin A. Negrete - President DNA Workshop (Bologna, Italy) To live better… longer To increase the quality of life after 40 90 80 70 60 50 40 30 20 10 0 Neanderthal Paleolithic (12000 BC) Neolithic Stone Classic Roman Midevil England Age (9500 BC) (500's - 1400's) (1500's) 1800's West 1900's West 2000 West Two main factors contributing longer (historical) lifespan Public Health Nutrition Two main factors contributing to limited lifespan Environmental (controllable) Genetic (non-controllable) Cellular Oxidation Preprogrammed Methyl Group Loss Oxidative Stress (Free Radicals) Preprogrammed shortening of Telomere length reduce cellular oxidation the formation of nascent oxygen (O2) and the elimination of free radicals (O+) Two main factors contributing to limited lifespan Environmental (controllable) X X Genetic (non-controllable) ? ? Cellular Oxidation Preprogrammed Methyl Group Loss Oxidative Stress (Free Radicals) Preprogrammed shortening of Telomere length or is it? Research has allowed scientists to identify central aging system in cells – and specifically the aging clock in DNA The two basic DNA markers that regulate aging are Telomere length and Methyl Group Loss Inside the center or nucleus of a cell, our genes are located on twisted, double-stranded molecules of DNA called chromosomes. Telomere At the ends of the chromosomes are stretches of DNA called telomeres, which protect our genetic data, make it possible for cells to divide. Telomeres have been compared with the plastic tips on shoelaces because they prevent chromosome ends from fraying and sticking to each other, which would scramble an organism's genetic information to cause cancer, other degenerative diseases, or death. Each time a cell divides the telomeres get shorter (by 30-200 BP). Healthy cells only divide between 50-70 times. When telomeres get too short, the cells no longer can divide and becomes inactive, sustain genetic damage and ultimately die. Conception Birth Death 15,000 Base Pairs 10,000 Base pairs 1,500 Base Pairs Similar to telomere shortening – the loss of Methyl Groups (CH3) shows a specific preprogrammed degradation throughout mammalian lifespan. The degradation is accelerated by oxidative stress, poor nutrition, lack of exercise, and environmental toxins. H H H H H H H H H Final Common Pathway of Aging – DNA Demethylation Birth 10% loss 25 yrs 20% loss 50 yrs 30% loss 75 yrs 40% loss Death Understand true anti-aging (DNA) mammalian chemistry consists of 2 goals: elongate telomers and increase DNA methylation. ENHANCED NUCLEOTIDE SUPPLEMENATION Longevity of Control vs. Treated Animals 2500 2000 1500 1500 1000 75 0 150 750 Control 750 Treated Record mammalian longevity achieved through weekly injection of DNA and RNA • Study began with 750 day old rats with usual longevity of 800 to 900 days • Identical conditions except treated animals received nucleic acid injections • Post 8 weeks control rats lost fur and vitality, whereas treated animals increased muscle mass, libido, and activity levels • Control animals all died in less than 150 days from start of study • Treated animals lived a minimum of 850 up to 1500 additional days from start of study, doubling and even tripling the usual life span Understand true anti-aging (DNA) mammalian chemistry consists of 2 goals: elongate telomers and increase DNA methylation. HOMOCYSTEINE What is Homocysteine? Homocysteine is a toxic amino acid by-product produced by our own organism and accumulates in the bloodstream. Elevated homocysteine is not only the indicator of, but is the CAUSE of many major diseases includin Alzheimer’, Arthritis, Cancer, Chronic Fatigue, Depression, Diabetes, Heart Attacks, Infertility, Obesity, Strokes, Thyroid Problems, and Ulcers Homocysteine also accelerates the oxidation of LDL Homocysteine Level VS Cardiac Risk Ratio Research has shown that higher HOMOCYSTEINE levels are directly related to demethylation and telomere shortening 3 ways to detoxify HOMOCYSTEINE Methionine ATP S-adenosyl-methionine (SAMe) DMG Betaine (TMG) B12 Folic Acid Choline Homocysteine (Hcy) Zn Methyl Group Transfer Metabolic Pathways Vitamin B6 Cysteine Glutathione Donates CH3 to: S-adenosylhomocystei DNA Proteins ne (SAH) Lipids Carbohydrates Myelin Detox Pathways Neurotransmitter Production And others We have developed THE ENGINE OF REMETHYLATION making cells younger through Enhanced Nucleotide Supplementation DNA RNA Purines Pyrimidines Adenine Cytosine Guanine Thymine Adenine Cytosine Guanine Uracil Methionine ATP S-adenosyl-methionine (SAMe) DMG Betaine (TMG) B12 Folic Acid Choline Homocysteine (Hcy) Zn Methyl Group Transfer Metabolic Pathways Vitamin B6 Cysteine Glutathione Donates CH3 to: S-adenosylhomocystei DNA Proteins ne (SAH) Lipids Carbohydrates Myelin Detox Pathways Neurotransmitter Production And others Could life-extension and anti-aging be as simple as supplying the body with DNA and RNA? DNA RNA Purines Pyrimidines Adenine Cytosine Guanine Thymine Adenine Cytosine Guanine Uracil Primary source of nucleotides is endogenous synthesis from amino acids and simple precursors • Therefore nucleic acids have generally been considered nonessential nutrients • Under stress, however, some tissues unable to produce enough nucleotides to support tissue needs • In these conditions, nucleic acids bases may become essential nutrients for optimum tissue repair and function • Glycine, Serine, Aspartic Acid, Glutamine Nucleic Acids : Food & Supplementation So why doesn’t everyone just take a giant nucleic acid pill? Orally ingested nucleic acids undergo intensive metabolic degradation in upper GI tract • Over 99% of purine bases oxidized to uric acid before entering portal circulation • About 95% of pyrimidines are metabolized before leaving intestinal lining • Only 3% of ingested pyrimidines reach liver Photo Acoustic Resonance Laser Laser Enhancement Technology Nutrient molecules get distorted during food or supplementation processing. Result: reduced nutrient assimilation by the cells. Laser Enhancement Technology reshapes nutrient molecules. Result: increased nutrient assimilation by the cells. Control Betaine HCl Laser Homogenized Betaine HCl Crystal Extensive experimental and clinical evidence for benefit from nucleotide supplementation • Increased survival in mice with Staph aureus bacteremia from 21% to 71% • Significantly increased survival in mice with Candida sepsis – greater effect with parenteral nucleotides than oral administration • Survival in animals with high dose radiation exposure increased from 5% to 50% • Single injection of RNA in mice post tumor immunization improved outcome from 0% to 40% long term survival • Rate of liver regeneration in rats post 70% hepatectomy significantly greater if IV nucleic acid bases given • In young rats with chronic diarrhea, appearance and enzyme function of intestine greatly improved • Improved growth and maturation in young animals • Infants given formula supplemented with nucleotides to mimic content of breast milk showed more benevolent intestinal flora an less diarrhea (50 times more nucleic acids in breast milk vs. formula which is significant in developing countries) • Supplemented infants had better lipid profiles with higher HDL cholesterol • Significant improvement in human cellular immune function • Significant improvement in memory in animals and humans • Accelerated wound healing ATP delivery specifically associated with numerous benefits • • • • Improved pulmonary function, even in cystic fibrosis Enhanced cardiac function – strengthening the heart Relief of nerve pain and improved nerve conduction Direct antitumor effects (RNA nucleotide) specifically incubation with ATP breast and prostate cancer • Synergistic antitumor effects in conjunction with chemotherapy – in vitro studies suggest up to 90% dose reduction possible for certain cell types • IV ATP has halted progression of tumor cachexia (advanced cancer with rapid weight loss) 50 mcg/kg/minute x 24 hours x 3 weeks • Protection of tissues from radiation injury • Increased natural killer cell function • Survival of patients in ICU for shock (multi-organ failure) increased from 70% to 100% Current research Enhanced Nucleotide Supplementation Reducing Homocysteine reduces the risk of death from the top 5 killer diseases: Heart Attack Strokes Cancer Diabetes Alzheimer's by 80% by 82% by 33% by ??% by 50% Homocysteine Levels (units = micromoles/litre) Below 6.3 = Very Low Risk 6.4 - 9.0 = Low Risk 9.1 - 15.0 = High Risk + 15.0 = Very High Risk Every 5 point decrease in homocysteine level = 50% reduced risk of cardiovascular death 26% reduced risk of cancer death Methylation Formula Study Dose Response Curve Homocysteine Level- Treatment Group (n=22) 11 10 9.2 9 8 7.1 7 6.8 P=.00001 6.1 P=.0000 1 6 0 1 2 P=.00001 3 Active Supplementation Group Months 0-3 Methylation Formula Study Dose Response Curve Homocysteine Level- Placebo Group (n=11) 9 7.9 8 7.8 P= NS 7.3 7 7.9 P= NS P= NS 6 0 1 2 3 Methylation Formula Study Dose Response Curve 14 Homocysteine Level- Treatment Group for subjects with Baseline Homocysteine Level > 10 (n=7) 13.2 12 10 9.3 8.3 P=.009 8 P=.001 7.3 P=.00001 0 1 2 3 Active Supplementation Group Months 0-3 Population study completed in Western Norway with over 18,000 subjects – Hordaland Study Directly established a relation between homocysteine levels and chronological aging Homocysteine level of >13 was associated with someone 65 years old Homocysteine level of <7 was associated with someone 25 years old Bryan Maphalala - AIDS Victim CD4 Count Viral Load CD4 vs. T-Cells Normal 600/ul 0/ml 30%-60% AIDS 200/ul 50,000/ml 10% Brian 10/ul 201,000/ml 1.17% Bryan Maphalala - AIDS Victim Before taking CELLFOOD and CELLFOOD DNA-RNA CD4 Count: 10 units; Viral Load: 201,000 After taking CELLFOOD & CELLFOOD DNA-RNA for 6 months Mrs. Winnie Mandela congratulated him for his work with HIV and AIDS people Does it really work?