3. Evolution Theory and the Biology of Aging And Chronic Degenerative Disease,
www.SelectiveProteinDeficiency.com
George A. Scheele, M.D.
December 15, 2015
The Foundation to Improve World Health
- The Foundation to Improve World Health is dedicated to the use of Molecular Biology and Biochemistry to understand the biological systems that are responsible for chronic degenerative disease and aging.
- The La Jolla Project has already identified specific proteins that appear to be vulnerable to a dietary deficiency of essential and positive-charged amino acids and further determined the presumed molecule pathogenesis for how the loss of these proteins from the expressed proteome will lead to the corresponding metabolic disease, whether that be type-2 diabetes, obesity, Alzheimer’s disease, pancreatitis, cancer or aging.
- The Foundation intends to define the “vulnerability potential” of all 20,000 proteins in the human proteome/Genome to diets deficient in essential and positive-charged amino acids.
- The Foundation will then demonstrate that these diseases may be beneficially treated by correcting the deficiencies in positive charged proteins and pathways associated with the disease.
- This approach is described in detail in (i) The Vision Statement, (ii) The Strategy Statement and (iii) The Operating Plan for the Foundation to Improve World Health.
Summary of the Proposed Causative Factors in Chronic Degenerative Disease and Aging
- The Table below shows the work that we have already done over the past 10 years including the diseases that we have investigated and the proteins that we have already identified as potential causative factors in the molecular pathogenesis of individual diseases. The table is organized according to (i) the disease or condition studied, (ii) the relevant underlying biological system and (iii) the individual proteins whose loss or compromise appears to explain the disease onset and progression.
- Bear in mind that most proteins in the human body, including serum proteins (Albumin, Globulin), Insulin, Insulin Receptor and Sirtuins have low isoelectric points, between pI=3 and pI=6.
- Most proteins that work in the cell nucleus, like DNA repair proteins have high isoelectric points between pI=7 and pI=11.
- Hence, the current protocols for analysis of Albumin and Globulin in human blood samples is inadequate for diagnosing early forms of protein deficiency.
- See the document entitled “Breakthrough Science” and “Primer on Amino Acids in Protein Synthesis” to understand why proteins with high isolectric points due to high content of Lysine (K) and Arginine (R) amino acid residues diminish first under conditions of protein deficiency that lead to chronic degenerative diseases and aging.
- The loss of proteins with relatively high isoelectric points is called “Selective Protein deficiency Syndrome” as first described in Dr. Scheele’s book, entitled “The Obesity Cure,” published in 2011.
- Bear in mind that there are genetic predispositions to chronic degenerative disease, including type-2 diabetes, particularly in Asia, as well as the other chronic degenerative diseases mentioned above.
The Table below, entitled “The Molecular Biology of Selective Protein Deficiency and Chronic Degenerative Disease,” shows the Disease Condition, the Underlying Biological Systems and the predicted Molecular Biology responsible for loss of individual proteins that appear to cause the onset and progression of the metabolic disease. The table also includes the isoelectric point (pI), which serves as an index for the charge of each protein.
In this table we have identified protein candidates that appear to be responsible, in large part, for the diet-related development of (i) obesity, (ii) Type-2 diabetes, (iii) pancreatitis, (iv) toxin-induced liver cancer, (v) colon cancer, (vi) cancers due to loss of DNA repair and P53 tumor suppression, (vii) aging syndromes, (viii) telomere dysfunction leading to premature aging, (ix) age-related sarcopenia (ix) Dementia syndromes and (x) anandamide regulation of well-being and procreation.
Upon signing a Non-Disclosure Agreement, Dr. Scheele will be able to reveal the complete amino acid composition and sequence for each of the proteins that appear to be responsible for the corresponding disease and explain, in detail, how the decrease in these proteins lead to disease.
The Molecular Biology of Selective Protein Deficiency, Chronic Degenerative Disease and Aging
|
Disease/Condition |
Biological Systems
|
Molecular Biology Hypothesis: Disease onset & progression due, in large part, to diet-induced loss of the following proteins related to Selective Protein Deficiency Syndrome |
|
Sarcopenia 1% loss in muscle tissue per year after age 50 Sure sign of protein deficiency |
Associated with low bone density, insulin resistance & loss of hormones (HGH and Testosterone) |
Rx: Double daily protein intake. Compared to generic protein powders, Factor4 Health Products increase protein absorption by more than 10-fold through Accelerated Amino Acid Delivery Technologies (AAADT) |
| DNA stability during cell cycle replication |
Stem Cell Turnover and tissue regeneration |
More than 30 Histone genes that control synthesis of Histone isoforms Isoforms with pI>9.8 Isoforms with pI>11 |
|
Aging Cancer |
DNA Repair:
Double-strand breaks shift with age from NHEJ to MMEJ, a less precise form of DNA repair that leads to frequent mutations |
More than 169 Enzymes:
|
| Cancer Prevention |
P53 Tumor Suppressor “Guardian of the Genome” Shuttles between the nucleus & cytoplasm. In response to DNA damage (UV, IR, oxidative stress, osmotic shock, heat shock, ribo-N depletion, oncogene expression) it binds to DNA & regulates gene expression to support DNA repair during cell cycle delay versus Apoptotic cell death. In normal cells P53 is targeted to Proteasomes to lower P53 |
The C-terminal domain, from 102 to 393, is positive-charged & contains the DNA binding domain, the tetramer affinity domain & nuclear Localization signal (NLS: PQPKKKPLDG). It is: KR-rich: 40 KR; 30 DE The N-terminal domain (AD1 & AD2), which activates Tx factors and activates apoptosis, is negatively-charged (1 KR; 16 DE) |
|
Colon Cancer Pancreatic Cancer |
2/3 of Cancers cannot be explained (Burt Vogelstein) Tumor Suppressor Genes suppress colorectal and pancreatic cancer (WNT Pathway)
|
Tumor Suppressor Genes APC (Adenomatous Polyposis Coli, pI=7.84)
|
|
Aging Cancer |
|
Telomere repair: TERT: Rev Tx, pI 10.54 DKC1 Dyskerin (Aging Syndrome), pI 9.46 TEP: Telomerase-associated protein, pI 8.26 ATM Kinase required for lengthening telomeres
|
|
Alzheimer’s Disease (AD)
|
Beta-Amyloid plaque formation in the brain APP cleaved into:
|
Gamma Secretase: acts as an aspartyl protease, like pepsin, to process Amyloid Precursor Protein (APP) with the following subunits:
All 4 subunits are required for activity. Amyloid plaque leads to neurofibrillary tangles (microtubules with phosphorylated Tau protein) |
|
Alzheimer’s Disease (AD) Frontotemporal Dementia Lewy Body Dementia Mild cognitive impairment |
Healthy AD pts produce REST Unhealthy AD pts do not REST stimulates neuronal growth, protection, survival, differentiation & synapto-genesis
|
REST Protein is a nuclear protein: Huge protein with 1097 amino acids (pI 6.30) But Domain 121-600 is positive charged (99+ vs 59-) |
| Satiety/Voracious Hunger |
Satiety/Hyperphagia signal in Hypothalamus BDNF stimulates neuronal growth, protection, survival, differentialtion & synaptogenesis
|
Brain-Derived Neurotrophic Factor (BDNF) is a small hormone secreted in the Hypothalamus with pI 9.01 247 AAs, 35+/29- |
Diabetes (Type 2)
|
Fox 01 Transcription agents (13 different isotypes) |
Fox Homolog 2 isoforms 4 (pI=8.48), 5 (pI=8.99), 6 (pI=8.48) Fox Homolog 2, isoforms 1 (pI=7.7), 2 (pI=7.79) Other Homologs 3 show pI>6.0 |
| Obesity |
Cellular Lipases controlling Lipid metabolism and transport |
Cell Lipases:
|
| Liver cancer |
P450 Enzymes that activate toxins like Aflatoxin found in a fungus grown on peanuts Activated Aflatoxin causes liver cancer |
P450 classes encoding more than 50 P450 enzymes:
|
| Pancreatitis |
PSTI inhibits premature activation of pancreatic enzymes in the pancreatic tissue |
Pancreatic Secretory Trypsin Inhibitor (PSTI)
|
|
Regulation of Procreation including copulation, conception, pregnancy, childbirth, breast feeding & neonatal growth
|
Anandamide regulates:
|
Fatty Acid Amide Hydrolase (FAAH) regulates Anandamide levels (pI=7.82; 579 AAs)
|
Biology of CDD & Aging
Nutrient Sensor Hypothesis
George A. Scheele, M.D.
December 20, 2016
As described in the Amino Acid Primer associated with www.SelectiveProteinDeficiency.com, humans cannot make all of the 20 amino acids required to synthesize the human proteome, consisting of approximately 23,000 proteins. Under conditions of good health humans can only make 11 amino acid residues. Under conditions of poor health humans can only make 5 amino acid residues. Consult the Amino Acid Primer to understand the definition of essential, semi-essential and non-essential amino acids.
Currently it is an enigma why humans, as well as other mammals and vertebrates, are deficient in the ability to synthesize all the necessary amino acids. After all plants, bacteria and yeast can synthesize all 20 of the amino acids required for protein synthesis This website has been constructed in an attempt to explain this conundrum.
The discovery of Selective Protein Deficiency by GA Scheele (see www.SelectiveProteinDeficiency.com) demonstrates that positive-charged proteins, with isoelectric points (pI) ranging between 7.0 and 11.5, disappear first from the expressed proteome under conditions of a deficiency of amino acids in the diet. Furthermore the potential for disappearing from the proteome appears to correlate with pI values, starting with the highest pI values.
It follows from these seminal observations that the most positive-charged proteins may serve as “Nutrient Sensors” throughout the body. Under conditions of limited protein intake through dietary mechanisms, we may hypothesize that the concentrations of putative nutrient sensors may diminish and that lower concentrations of these sensors may account for metabolic dysfunctions in the Metabolome.
We may also hypothesize that other Nutrient Sensors may serve as signals for hunger and satiety throughout the body. When levels of nutrient sensors are high they might signal satiety. Conversely, when levels of nutrient sensors are low they might signal hunger. Brain-Derived Neurotrophic Factor (BDNF) is clearly one of these positive-charged proteins that serve as a Nutrient Sensor that provides powerful signals for hunger and satiety in the hypothalamus.
The following notes provide nine examples of recent achievements in Biology and Medicine that underscore the importance of essential and semi-essential amino acids in combatting chronic degenerative disease to preserve optimal health and productivity in today’s society. Each of these examples suggest that positive-charged proteins may serve as nutrient sensors in the human Metabolome.
- Brain-Derived Neurotrophic Factor (BDNF) Signals Hunger & Satiety
Brain-Derived Neurotrophic Peptide (BDNP), which is a paracrine hormone secreted into the blood circulation of the Hypothalamus in the vicinity of the Appetite Center (Arcuate Nucleus). This small peptide has 247 amino acids with a pI of 9.01. High levels of BDNF in the hypothalamus signal satiety and low levels signal hyperphagia, enormous hunger and appetite leading to voracious eating in experimental mice. Within this short peptide there are 35 Lysine and Arginine residues (positive-charged amino acids) and 29 Aspartate and Glutamate residues (negative-charged amino acids).
BDNF has also been shown to stimulate neuronal growth, protection, differentiation and synaptogenesis, which suggests that BDNF supports brain health and combats dementia syndromes like Alzheimer’s Disease. BDNF appears to be Exhibit A for a positive-charged Nutrient Sensor that functions to signal hunger and satiety in an organism while simultaneously providing trophic factors which optimize normal brain health.
- Telomere Health, Aging and Chronic Degenerative Disease
The Subject of the 2009 Nobel Prize awarded to Elizabeth Blackburn, Carol Greider and Jack Szostak was the discovery of Telomeres, stretches of DNA that cap the ends of chromosomes. Aging appears to shorten telomeres as a function of cumulative rounds of cell division. Science has linked short telomeres with chronic degenerative disease, including (i) heart disease, (ii) diabetes and (iii) cancer.
Telomerase is an enzyme that has the capacity to lengthen telomeres and reverse the metabolic dysfunctions observed with telomere shortening. All three protein subunits of Telomerase are positive-charged proteins. The Reverse Transcriptase called TERT has a pI of 10.54. The DKC1 subunit, which is responsible for an Aging Syndrome, has a pI of 9.46 and TEP, the Telomerase Associated Protein, has a pI of 8.26. It appears likely that all three of the protein subunits, described above, act as Nutrient Sensors, monitoring the nutrient content of dietary amino acids that enter the body.
Dyskeratosis Congenita 1 is a congenital syndrome related to the DKC1 subunit that shows premature aging with hair loss and/or greying, dental loss, osteoporosis, aplastic anemia, nail dystrophy, oral leukoplakia, abnormal skin pigmentation and liver and pulmonary fibrosis.
- Cancer and DNA Repair Proteins
The 2015 Nobel Prize in Chemistry was awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar for the elucidation of three DNA repair mechanisms, including Base Excision Repair, Nucleotide Excision Repair and Mismatch Repair. All of the proteins involved in DNA repair, including DNA Polymerase forms, DNA ligase forms, Topoisomerase forms, and Flap Endonuclease forms are positive-charged proteins with pI values between 8.8 and 9.33. As such, DNA Repair proteins may function as Nutrient Sensors, functioning at peak levels only when dietary substrates provide sufficient essential and semi-essential amino acids to the organism.
- Gastrointestinal Cancer, Tumor Suppressor Proteins and APC
Burt Vogelstein has called attention to the fact that two-thirds of cancers cannot be explained by environmental factor like ultraviolet irradiation (skin cancer) or smoking (lung cancer). However, tumor suppressor genes appear to be involved in many cancers throughout the body. According to Vogelstein’s work, tumor suppressor genes, and their counterpart proteins, suppress colorectal and pancreatic cancer through what is known as the WNT Pathway.
Colon and pancreatic cancer appear under conditions of diminished levels of Adenomatous Polyposis Coli (APC), which serves as a tumor suppressor protein. APC is, in fact, a positive-charged protein, with a pI of 7.84. While numerous factors may compromise the levels of APC inside the cell, one factor that stands out is a diet poorly enriched in positive-charged amino acid residues. Hence APC may function as a Nutrient Sensor.
- Cancer Prevention and the P53 Tumor Suppressor Gene
P53 is a Tumor Suppressor Gene known as the “Guardian of the Genome.” P53 protein binds to DNA in the cell nucleus and regulates gene expression to support DNA repair during cell cycle delay versus apoptotic cell death.
P53 protein has two subdomains. The N-terminal domain from residue 1 through 102 is negative-charged and functions to activate transcription factors and cellular apoptosis. The C-terminal domain from residue 102 through 393, is positive-charged with 40 Lysine and Arginine residues versus 30 Aspartate and Glutamate residues. The C-terminal domain contains the DNA binding domain and a nuclear localization signal (NLS: PQPKKKPL). Note that this signal contains 4 essential amino acids (3K & L) and 4 semi-essential amino acid residues (3P and Q).
P53 protein shuttles between the nucleus and the cytoplasm. In the cell nucleus it binds to DNA and regulates gene expression to support DNA repair in response to DNA damage events, including UV radiation, infrared radiation, oxidative stress, osmotic shock, heat shock, ribonucleotide depletion and oncogene expression. Given its enrichment in positive-charged amino acid residues, P53 appears to function as a Nutrient Sensor signaling the quantity of essential amino acid residues like Lysine and Arginine in the diet.
- Alzheimer’s Disease & Gamma Secretase Functions
Alzheimer’s disease occurs in the brain as Beta-Amyloid Plaque builds up in the extracellular space of neurons when Amyloid Precursor Protein (APP) is cleaved releasing either Amyloid Beta-40 (normal peptide) or Amyloid Beta-42 (abnormal peptide), which contains two additional hydrophobic amino acid residues. Normal neuronal cells release Amyloid Beta (Ab) peptides in a ratio of 90% Ab40 and 10% Ab42. In contrast, Alzheimer’s patients release Ab peptides in a ratio of 50% Ab40 and 50% Ab42.
Amyloid Plaque leads to neuronal death evidenced by neurofibrillary tangles associated with microtubules and phosphorylated Tau protein.
Amyloid beta peptides are released by Gamma Secretase, which acts as an aspartyl protease (pepsin-like) to process APP with the following four subunits, which must be available in stochiometric amounts to function correctly. Two of the subunits (Presenilin and Nicastrin) are negative-charged with pI values between 4.36 and 5.7. Subunit #3 called APH-1A or APH-1B have pI values of 8.23 and 8.42, respectively. Subunit #4 (Pen-2) has a pI value of 9.49. All four subunits are required for activity of gamma secretase.
In the presence of protein deficiency in the diet, it is reasonable to conclude that subunits #3 and #4 will be made in diminished amounts leading to a deficiency of these critical components in the gamma secretase tetramer. Delays in production and assembly of tetrameric subunits in gamma secretase may allow processing of amyloid beta in cellular compartments with altered pH values changing the point of scission for release of Ab peptides favoring Ab-42 peptides over Ab-40 peptides. Should misprocessing of Ab occur in this manner the pathological events may be responsive to improved diets supplying critical concentrations of essential and semi-essential amino acids to maintain the assembly of gamma secretase in cellular compartments that promote normal processing of Amyloid Beta favoring Ab-40 peptides.
- Alzheimers Disease and REST Protein
Another aspect of Alzheimers Disease (AD) relates to the presence or absence of REST protein in the brain. It has been observed in clinical-pathological studies that healthy AD patients produce REST protein and unhealthy AD patients do not. Like Brain-Derived Neurotrophic Factor (BDNF), REST protein also promotes neuronal growth, protection, survival, differentiation and synaptogenesis.
REST is a large protein with 1097 amino acid residues and an overall pI of 6.30. However, the amino-terminal domain of REST protein (residue 137 to 603) is positive-charged with 99 residues of Lysine and Arginine and 59 residues of Aspartate and Glutamate. The sheer size of REST protein and its positive-charged domain suggests that dietary deficiencies in amino acids may lead to diminished levels of REST protein in the brain and diminished levels of REST protein may tip the patient toward Alzheimer’s symptoms.
Hence REST protein also appears to function as a Nutrient Sensor.
- Type-2 Diabetes and FOXO1 Regulation of Metabolic Pathways
Type-2 Diabetes is associated with elevated blood sugar levels, Insulin resistance and Leptin resistance.
FOXO1 is a regulator of gene expression in the nucleus where it serves to decrease adipogenesis leading to a “lean” phenotype. Sirtuin-2, a Class 3 NAD-dependent deacetylase, deacetylates FOXO1, which allows it to remain in the nucleus where Lysine residues interact with chromosomal DNA.
When FOXO1 is acetylated on its Lysine residues it shuttles from the cell nucleus to the cell cytoplasm. In the cytoplasm it is phosphorylated on serine-253 in the presence of insulin. These modification steps trap FOXO1 in the cytoplasm where it stimulates adipogenesis and fat deposition leads to an “obese” phenotype.
There are a number of FOXO1 homologs distributed throughout the body. FOXO1 homolog 2 isoforms are all positive charged proteins, including class 1 isoforms which show pI values of 7.7, class 2 isoforms which show pI values of 7.79, class 4 isoforms which show pI values of 8.48, Class 5 isoforms which show pI values of 8.99 and Class 6 isoforms which show pI values of 8.48.
The high isoelectric values for FOXO1 homologs suggest that these regulators of gene expression function as Nutrient Sensors capable of inhibiting fat deposition according to the dietary composition of amino acids in the diet, specifically in relationship to the nutrient content of the diet in supplying positive-charged amino acid residues that act as limiting factors in the synthesis of positive-charged proteins.
In this way poorly nourished diets deficient in essential amino acids would diminish the role of FOXO1 to achieve “lean” phenotypes. Conversely, highly nourished diets rich in essential and semi-essential amino acids, including Lysine and Arginine residues, respectively, would enhance the role of FOXO1 to achieve “lean” phenotypes.
- Autophagy Functions to Recycle Essential and Semi-essential Amino Acids
The 2016 Nobel Prize in Medicine was awarded to Yoshinori Ohsumi for discovering the molecular events required for autophagy (mitophagy, ribophagy, lipophagy and xenophagy) in health and disease. During periods of starvation autophagy works to recycle long-lived proteins, and their amino acids, associated with cell organelles and compartments. One of the central figures in autophagy is mTOR Kinase, a Ser/Thr kinase that regulates the autophagic process in higher cells.
When the cell is well fed with essential amino acid nutrients, mTOR Kinase is activated which inhibits the autophagic process through hyperphosphorylation of critical Atg13 subunits. Conversely, during periods of starvation (absence of essential amino acids) mTOR is inactivated leading to an increase in autophagy events. Through Autophagy, which requires PI3 Kinase and two ubiquitin-like conjugation cascades, the cell recycles obsolete cellular structures to reclaim essential amino acid residues.
The Autophagy process demonstrates the critical need for cells to conserve essential and semi-essential amino acids under conditions where dietary mechanisms are insufficient in supplying these critical components to the organism.
Furthermore there is a selective uptake process by which lysosomes select proteins which contain signal sequences consisting of KFPRQ for degradation. It is noteworthy that this signal pentapeptide contains two essential amino acid residues (KF) followed by three semi-essential amino acid residues (PRQ).
Through the 2016 Nobel Prize Autophagy is now recognized as a fundamental process in cell physiology with major implications for human health and disease. Autophagic processes are conserved throughout the complete phylogenetic tree. If the process of evolution has evolved complex mechanisms for recycling cell components that are rich in essential and semi-essential amino acids, it is clear that these groups of amino acids are critical to the survival of all living organisms on earth.
It now becomes abundantly clear that dietary access to essential amino acids, which humans can never produce, and semi-essential amino acids, which may only be produced in healthy humans, devoid of chronic disease, is also critical not only for survival but for maximal health and productivity.
Conclusions:
Given the 9 examples shown above we may tentatively conclude as follows:
Positive-charged proteins appear to function as Nutrient Sensors that regulate the health of metabolic pathways throughout the body and therefore determine the overall function or dysfunction of the organism related to the appearance of a diverse array of chronic degenerative diseases due to a deficiency in positive-charged amino acids, as well as other essential and semi-essential amino acids in the diet.
Specific positive-charged proteins provide hunger and satiety signals at strategic locations within the body, most notably in the Hypothalamus that contains the appetite center (Arcuate Nucleus) for the whole organism.
Addendum: Subcellular Localization of Positive-Charged Proteins
The Theory of Selective Protein Deficiency proposes that positive-charged proteins disappear first from the human proteome under conditions where dietary nutrients are deficient in essential and semi-essential amino acids. If these proteins act as Nutrient Sensors, as suggested in this presentation, it becomes important to determine where in the cell reside most of the positive-charged proteins.
The clinical markers for protein sufficiency/deficiency in the body comprise albumin and globulins in the blood stream. However, both albumin (pI 5.92) and globulin are negative-charged proteins. Hence the clinical markers for protein deficiency in clinical medicine are incapable of diagnosing Selective Protein Deficiency.
Hormones which appear in the blood circulation, like Insulin, Glucagon or Leptin are negatively charged as well. Most of the proteins observed in the cytoplasmic space, such as metabolic enzymes, are also negatively charged.
However, most of the proteins that interact with DNA in the nucleus are positive charged proteins. In fact, histone isoforms show the highest charge (isoelectric points) among proteins that reside in the human proteome. A number of Histone isoforms have isoelectric points approaching 11.5. In addition, most of the proteins that regulate gene expression in the nucleus are positive-charged proteins with isoelectric points ranging between pI 7.0 and 11.5.
The Future of Selective Protein Deficiency and Nutrient Sensors
The basic tenants of “Selective Protein Deficiency” and “Nutrient Sensors” appear to be established by preliminary work conducted by Dr. Scheele and his collaborators in the Institute to Improve World Health, a 501c3 non-Profit Organization in La Jolla, CA. We now intend to build a database containing all 23,000 proteins in the Human Proteome organizing this DB according to protein charge (isoelectric points) as well as subcellular localizations of target proteins.
We also intend to identify metabolic enzymes that may be critical to the health of the organism focusing on those proteins that may suffer from diet-induced Selective Protein Deficiency as causative agents in chronic degenerative disease. Some of these positive-charged proteins are described in this article. However, more await to be discovered. The DB will not only serve as a storage site for amino acid sequences and annotations on metabolic functions but will also provide color-coded functions for highlighting individual amino acid residues.
This will facilitate the testing of future hypotheses regarding the functions of individual amino acid residues in proteins distributed throughout the organism. As such this DB will provide functions that will allow hypothesis testing as well as storage of structural information.
Synopsis of Dr. Scheele’s Medical, Scientific and Business Career
- Dr. Scheele worked under Joshua Lederberg, Head of the Rockefeller University in the 80s. Dr. Lederberg consulted Dr. Scheele on his novel research on numerous occasions. Dr. Lederberg counseled Larry Ellison to setup a Foundation devoted to medical research focused on chronic degenerative disease and aging.
- Dr. Scheele worked closely with two Nobel Prize teams and played a central role in the research that led to Nobel Prize awards to Dr. George Palade in 1974 and Dr. Gunter Blobel in 1999.
- Dr. Scheele’s invention of 2-dimensional gel electrophoresis allowed, for the first time, the complete analysis of the secretory pathway in mammalian cells according to cell fractionation studies (1974 Nobel Prize)
- Dr. Scheele discovered that all pancreatic secretory proteins (n=23) were synthesized with an N-terminal extension, which allowed for their transport from the cytoplasmic space into the Rough Endoplasmic Reticulum. This was the first research that identified secretory peptides in Biology (1999 Nobel Prize).
- Dr. Scheele achieved Professor status at the Rockefeller University, Yale University School of Medicine and Harvard Medical School
- Dr. Scheele’s thorough training in clinical medicine at Johns Hopkins Medical School, the Osler House-staff and the House-staff at the University of California in San Francisco combined with his thorough training in basic science research at the Rockefeller University between 1970 and 1988 gives Dr. Scheele a unique position in solving Medical Problems through an understanding of the biochemistry and molecular biology of mechanisms responsible for evolutionary biology.
- Dr. Scheele is also responsible for founding the following Biotechnology companies
- AlphaGene, a Human Genome Company, in 1994
- Viral Shield Pharmaceuticals with a treatment for Herpes Simplex Virus in 2000
- NovaLife, Inc., in 2000, to develop Accelerated Amino Acid Delivery Technologies (AAADT) for the prevention and treatment of chronic degenerative diseases and aging.
Reasons to Fund The Foundation & Institute to Improve World Health to Conduct Projects Related to the Biology of Aging and Chronic Degenerative Diseases:
- To fund the La Jolla Project to determine the vulnerability of proteins to dietary deficiencies in essential and positive-charged amino acids among all 20,000 proteins expressed in the human genome.
- To determine the molecular pathogenesis of chronic degenerative diseases as they relate to the loss of key positive-charged proteins in metabolic pathways that define individual disease states.
- To determine methods to correct the deficiencies in positive-charged proteins that lead to individual chronic degenerative diseases.
- To formulate patent-protected products (Medical Foods) capable of preventing and treating individual chronic degenerative diseases, including overweight disorders, obesity, type-2 diabetes, cholesterol disorders, cardiovascular disease, autoimmune disorders, Alzheimers Disease and Aging.
- To support Dr. Scheele and his Foundation and Institute to Improve World Health in his efforts to publish articles, books and compendia on Metabolic Health related to Evolutionary Theory, Metabolic Health and Nutrition.
- To support the Foundation in its attempts to provide a working model of all metabolic pathways in the human body, including the enzymes that regulate these pathways and the specific loss of proteins that explain chronic degenerative disease on the internet.
- To setup an internet website (www.MyMetabolicHealth.com) that is capable of monitoring all citizens across the United States in relation to their personal health, their risk factors for chronic degenerative diseases and the medications that are deemed appropriate for either prevention or treatment of these metabolic diseases. As patients use this website, they will receive interactive educational training on how to understand, prevent and treat the diseases or conditions they suffer from.
- To train a new generation of research scientists who understand Evolution Theory and the Biology of Aging and Chronic Degenerative Disease.
- To hold an annual Conference on Evolution Theory and the Biology of Chronic Degenerative Disease & Aging in La Jolla, CA for medical researchers interested in these fields.
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