Molecular Agents:
What to know
Aloe Vera Kaufmann Number: 1.3.0.0.3.2.1
General Information
The use of Aloe Vera goes back at least 6,000 years. Originally from south eastern Africa, it spread to the Mediterranean and then across the globe. Its uses are varied, and appreciated by innumerable historical figures. In addition to its health benefits, Aloe Vera was also used as papyrus, an embalming fluid and as a hanging plant over doors to ward off evil spirits.
Composition
Aloe contains more than 200 biologically active substances, 20 of the 22 required amino acids, 7 of the 8 essential amino acids.
Other Important Components: anthraquinones: aloe emodin, aloetic acid, antibacterial enzymes, hormones, minerals, saponins, sugars, vitamins (ABCE choline, B12, folic acid), steroids, salicyclic acid and the polysaccharide: acemannan.
Categories:
1 DNA Alterations: 1
•Modifications to DNA occur through a byproduct; acemannan is converted to butyrate, which functions as a histone deacetylase inhibitor (HDACi).
2 Mitochondria: 3
•Aloe contains innumerable antioxidants: a-tocopherol (vitamin E), carotenoids, ascorbic acid (vitamin C), flavonoids, and tannins. It has exhibited significant inhibitory activity against DPPH–, superoxide, NO and hydrogen peroxide.
5 The Immune System: 3
•Inhibits cyclo-oxygenase.
•Reduces prostaglandin E2 production.
•Reduces histamine release.
•Breaks down bradykinin.
•Demonstrates a marked increase in phagocytic and proliferative activity of the reticuloendothelial system.
6 Individual Cell Requirements: 2
•Demonstrated to be beneficial for teeth, bone, and skin
7 Waste Management: 1
•Mild hypoglycemic agent.
Systems Shown to Benefit
•Skin & Wound Healing:
•Aloe stimulates fibroblasts, which produce the collagen and elastin fibers, making the skin more elastic and less wrinkled.
•It positively influences collagen composition as well (more type III), increases collagen cross linking for wound contraction, and increases the synthesis of hyaluronic acid and dermatan sulfate in a healing wound.
Weight Loss:
•Reduces visceral fat accumulation, and influences the metabolism of glucose and lipids.
Side Effects
Can act as a laxative and cause abdominal pain.
Alpha Lipoic aciD Kaufmann Number: 2.3.1.0.2.2.1
General Information
Alpha Lipoic acid exists naturally in human cells, mostly in the mitochondria, where very small quantities are produced endogenously from octanoic acid. Most of our Alpha LA comes from dietary sources. The substance is produced by both plants and animals, with the majority coming from red meat, liver, heart and kidneys. In the plant world, spinach, broccoli and tomatoes yield the most, although there is significantly less than in the animal products.
Because of its molecular arrangement, there are two possible isomers, R-Lipoic Acid and S-Lipoid Acid. In nature, only the R is active. When produced synthetically, however, both isomers are created, but only the R is beneficial.
The agent was first identified in the1930’s in potatoes as a necessary growth factor for specific bacteria; thus it was named the potato growth factor. In 1951, it was isolated from cow liver. It wasn’t until the 1980s that its antioxidant properties were discovered. It can be used for treating toxicities from poison mushrooms and radiation contamination.
Categories
1 DNA Alterations: 2
Inhibits Histone Deacetylase.
Indirectly increases telomere length: Alpha LA induces PCG-1a (Peroxisome proliferator-activated receptor gamma coactivator-1 alpha) which then induces TERT (Telomerase reverse transcriptase), which in turn increases telomere length.
2 Mitochondria: 3
Called the “Universal Antioxidant,” acts as direct and indirect antioxidant.
Free radical scavenger.
Recycles used or “reduced” antioxidants. Thus, molecules such as Vitamin C, Vitamin E and glutathione can be used repeatedly in its presence.
It’s a necessary cofactor in mitochondria for several reactions; without which there would be no energy production.
3 Aging Pathways:1
Modulates AMPKinase.
5 The Immune system: 2
Inhibits Nuclear Factor-kB.
Decreases VCAM (vascular cell adhesion molecule), ICAM ( intercellular adhesion molecule-1) and IL-6
6 Individual cell requirements: 2
Reverses liver and nerve cell damage.
7 Waste management: 1
Hypoglycemic agent.
Possible glycation blocker.
Systems Shown to Benefit:
Known to suppress appetite, improve memory in older rats, reduce osteoporosis in post menopausal rats and decreases neuropathies in people.
Side Effects:
None known.
Andrographolide Kaufmann Number: 1.2.0.1.3.1.1
General Information
Traditionally used in Taiwan, China, India and Southeast Asia for inflammation-related diseases.
AKA: “The King of Bitters,” 14-deoxy-11,12-didehydroandrographolide, the major labdane diterpenoid isolated from A. paniculata.
Categories
1 DNA Alterations: 1
•Epigenetics: Can up-regulate the expression of some miRNAs.
2 Mitochondria: 2
•Increases the activity of antioxidant defense enzymes: catalase, superoxide dismutase, glutathione-S-transferase.
•Inhibits lipid peroxidation.
•Has free radical scavenging activity.
4 Quality control: 1
Modulates Autophagy.
5 The Immune system: 3
Inhibits NF-kappa B.
Prevents anti inflammatory bone loss.
Regulates macrophage activation.
6 Individual cell health: 1
Increases proliferation of human epidermal stem cells (in culture).
7 Waste management: 1
May act as a hypoglycemic agent.
Systems Shown to Benefit
Skin:
•Suppressed damage done by UV radiation.
•Increases collagen content.
•Up-regulates endogenous skin anti-oxidants.
Improves skin hydration, wrinkling and sagging.
Side Effects
Lowers spermatogenesis
Apigenin Kaufmann Number: 2.1.0.1.2.0.0
General Information
Apigenin is found in many herbs, including parsley, celery, onions, oregano and thyme. The most consumed source however, is Chamomile tea.
Chamomile was first appreciated by the Egyptians, who dedicated it to the sun god, Rah. Hieroglyphic records show that chamomile was used cosmetically by Egyptian noblewomen, who applied crushed petals to their skin. The oil of Chamomile was additionally utilized in the process of mummification. (This may be the very first time it was used in the quest for immortality…although perhaps it was a little too late)
More recently, Apigenin was isolated from tea in 1914. Luckily it is also found in red wine and beer.
AKA: 4′, 5, 7,-trihydroxyflavone
Categories
1 DNA Alterations: 2
•Inhibits DNMT1 (DNA methyl transferase), DNMT3a, and DNMT3b.
•Inhibits some Histone deacetylases in epidermal skin cells.
2 Mitochondria: 1
•Increases levels of NAD.
4 Quality Control: 1
•There is some evidence that it stimulates nucleotide excision repair genes
5 The Immune System: 2
•Modulates NF-kB.
•Inhibits the production of pro-inflammatory mediators such as IL-6, TNF-a, IL-8, and COX-2.
Systems Shown to Benefit
Skin: In a study of Korean women over the age of 45, apigenin cream daily was applied for one month. The density of their skin much improved, as did the elasticity, moisture, and evenness of the skin texture.
Side Effects
Sleepiness
Astaxanthin Kaufmann Number: 0.3.0.0.2.0.0
General Information
This agent is mainly produced by a unicellular biflagellate green cell, Haematococcus Pluvialis. Under unfavorable or environmentally stressful conditions, the cells produce astaxanthin in small lipid droplets that accumulate in the cytoplasm. This red substance becomes incorporated into the food chain and is the basis for almost all of the red we see in crustaceans, fish and birds. It is the red in salmon, lobsters, crabs and shrimp, the feathers of Roseate Spoonbills and in the eyes of Quail.
Composition
•Xanthophyll Carotenoid
•3,3’-dihydroxy-beta,beta-carotene-4,4’-dione, or C40H52O4,
Categories
2 Mitochondria: 3
•Powerful free radical scavenger and anti-oxidant.
•Stimulates production of the endogenous antioxidant enzymes: catalase, superoxide dismutase, and peroxidase.
5 The Immune system: 2
•Inhibits Reactive Oxygen species (ROS), reduced activation of NF-Kb, which then suppresses the production of IL-1B, IL-6 and TNF-a
•Inhibits cyclooxygenase 2 (COX-2), prostaglandin E2, and C-Reactive Protein (CRP)
Systems Shown to Benefit
•Vision: Improves vision in middle aged subjects.
•Skin: Protects skin and skin DNA from UV radiation. In human skin studies, topical astaxanthin demonstrated improvements in crows feet, age spot size, elasticity, skin texture, and the moisture content of corneocytes.
•Fitness: Prevents exercise related increases in Free Radicals.
•Decreases DNA and protein damage with exertion.
•Increases exercise capacity.
Side Effects
None known
Astragalus Kaufmann Number: 3.0.0.0.2.1.0
General information
Astragalus is infamous for increasing one’s life force or Qi. The plant is endogenous to Northern China, Mongolia and Korea, although presently, it is mostly farmed in China.
Astragalus R. Membranaceus has a very long history and has been used in Chinese medicine for over 2,000 years. It is thought to increase stamina, strength and vitality. Reportedly, it guards also against physical, mental and even emotional stress.
Composition
The astragalus plant is composed of over 100 individual, bioactive agents.
The interesting molecules of note include cycloastrogenol, astragaloside IV, and astragalus polysaccharides.
CYCLOASTROGENOL:
This compound was first studied by the Geron corporation, but then exclusive rights were secured by TA Sciences in 2002. (per their website) The company developed it as a product called TA-65 and introduced it to a select market in 2007. In late 2013 and again in 2014, another company, RevGenetics, determined that TA-65 was cycloastrogenol.
ASTRAGALOSIDE IV:
A related molecule, astragaloside IV, unfortunately cannot compete in terms of telomere enhancement. It does however, have other ways of increasing your Qi.
Categories
1 DNA Alterations: 3
•Increases telomere length (Cycloastrogenol)
5 The Immune System: 2
•Non-specific anti-inflammatory (Astragaloside IV).
•Blocks TNF-a with the downstream effects of reduced cytokines including NF-kB, ICAM (intercellular adhesion molecule-1) and VCAM. (vascular cell adhesion molecule-1) (Astragalus polysaccharides).
6 Individual Cell Requirements: 1
•Improves wound healing (Cycloastrogenol).
•Improves neuron growth and repair (Astragaloside IV).
Systems Shown to Benefit
Vision - Cycloastrogenol study- vision improved after 6 months in patients with macular degeneration.
Improves nerve repair.
Side Effects
None noted.
Carnosine Kaufmann Number: 0.3.0.0.0.0.3
General Information
Carnosine is a dipeptide that is present in all muscle, but it was officially identified by a Russian scientist, V.S. Gulewitch, in 1900. Dipeptide is manufactured within muscle by the enzyme carnosine synthase, using the amino acids alanine and histidine. These usually come from our diet, and usually from animal products. The highest amounts are found in chicken, turkey, and tuna. Vegetarians have 20% or less carnosine in their bodies as compared to omnivores.
The actual amount of carnosine in humans varies with gender and age. Men have significantly more than women, and it appears to be associated with the presence of testosterone. As well, the older we get, the less carnosine we have. There is, on average, a 63% decline between the age of 10 and 70.
Composition
•Dipeptide; L-histidine and B-alanine.
•99% is located in human muscle while 1% is in the brain.
Categories
2 Mitochondria: 3
•Reduces oxidative damage.
•Improves endogenous anti-oxidants; restores depleted levels of glutathione and increases the basal level of superoxide dismutase.
7 Waste management: 3
•Inhibits glycosylation of proteins.
•Blocks AGE formation.
•Prohibits protein-DNA and protein-protein cross linking.
•May actually reverse AGE formation; acts as a transglycating agent.
Systems Shown to Benefit
•Hearing: Protects hearing from loud noises.
•Vision: Prevents presbyopia and cataract formation (via carnosine eye drops).
•Skin: Improves quality of skin
Side Effects
With large dose: A mild paresthesia, or prickly sensation in the skin mostly in the face and head, arms and hands. The tingling can start within 20 minutes or so, but it usually dissipates within the hour. Decreasing the dose remedies this problem.
Chebulic acid Kaufmann Number: 0.2.0.0.2.1.3
General Information
Chebulic acid has been used for centuries in Ancient Chinese, Tibetan and Ayurvedic medicine and originally was from south Asia, India, Nepal, Southern China, Malaysia, and Vietnam.
The molecule is derived from the dried fruit of a plant Terminalia Chebula, which also contains gallic acid, elegiac acid and innumerable other substances.
Composition
It is frequently used in a triad with Emblica officinalis and Terminal belerica, and referred to as Triphala. This formulation is the most utilized herbal mixture in Ayurvedic tradition.
Categories
2 Mitochondria: 2
•A potent anti-oxidant.
•Increases endogenous superoxide dismutase.
•Inhibits lipid peroxidation.
5 The Immune system: 2
•Decreases inflammatory markers, esp TNF-a, IL-6, MMP-3, COX-2.
•Decreases severity in arthritis models; decreases cartilage destruction and bone erosion.
6 Individual Cell requirements: 1
•Demonstrated to protect liver cells.
7 Waste management: 3
•Blocks formation of AGEs. Some evidence that it can even break AGEs. (This is crucial)
•Hypoglycemic agent.
Systems Shown to Benefit
•Improves liver enzymes.
•Improves arthritis.
Side Effects
None known.
Cistanche deserticola Kaufmann Number 1.2.0.1.3.2.0
General Information
Cistanche deserticola is a holoparasitic plant, meaning it has no chlorophyll and thus gets its nutrients and water from other plants. Specifically, it is parasitic on the roots of a desert shrub.
It is native to China and Inner Mongolia, where it is collected in the spring.
The plant has been used about 2,000 years; its use first recorded during the Eastern Han Dynasty. It was reported to strengthen Yin, and boost Qi. Thus, it is a treatment for Yang deficiency.
In China, the plant is considered a tonic for the kidneys, or for “kidney-deficiency syndrome” and associated medical issues such as infertility, forgetfulness, hearing lost, and chronic constipation.
In an ancient, famous combination of many herbs known as the “Youth returning Pill” or Huan Shao Dan, Cistanche was component #14. Sometimes known as the Lyceum Formula, it was thought to restore youth in Japan and Taiwan.
Composition:
Phenylethanoid glycosides (PhGs) , iridoids, iridoid glycosides, lignans, polysaccharides, free amino acids, ash elements and minerals.
20 types of PhGs…some of which are known for “fast repair of DNA damage”
Iridoids: 6-deoxycatapol, geniposide, cistanin, catapol, bartsioside, gluroside, 8-epiloganic acid
1 DNA Alterations: 1
•Increases telomerase activity (as measured in heart and brain tissue) in aging mice.
2 Mitochondria: 2
•Cistanoside A, tubuloside : antioxidant/ free radical scavenging.
•Nine compounds identified with significant free radical scavenging activities.
•Increased activity of SOD in serum and brain of aged mice.
4 Quality Control: 1
•Cisanoside B: Increases speed of DNA damage repair.
5 The Immune system: 3
•Immuno-stimulant.
•Increases in naive T and natural killer cells.
•Inhibits NF-KB.
•Increases phagocytic activity of peritoneal macrophages in mice.
6 Individual cell requirements: 2
•Improves bone
Systems Shown to Benefit:
•Anti-fatigue.
•Improves endurance.
•Extends lifespans in senescence accelerated mouse model and in flies.
•Increased learning and memorizing in aged mice.
•Improves depression and cognition.
•Helps with weight loss.
Curcumin Kaufmann Number: 2.3.1.0.3.0.3.
General Information
Curcumin was first used in Vedic India four thousand years ago. It arrived in China somewhere near 700 AD, and then East Africa by 800 AD. Curcumin was praised by Avicenna, a Persian Physician, in a famous medieval medical text called “The Canon” (his name was actually Abu Ali al Husain Ebn Abdullah Ebn Sina 980-1037) who was considered to be the most learned and influential physician at the time. Curcumin was then smuggled to Europe by Marco Polo in 1280.
AKA: Diferuloylmethane
Composition
Curcumin is one of the active molecules from the spice turmeric. Turmeric, meanwhile, comes from the roots or the rhizomes of Curcuma longa. This herbaceous, perennial plant belongs in the ginger family, Zingiberaceae.
Unfortunately, curcumin constitutes only 3 to 5% of the turmeric.
Categories
1 DNA Alterations: 2
•Affects histone acetylation; Represses the addition of an acetyl group onto histone proteins.
•Inhibits p300/CREB-specific acetyl transferase.
2 Mitochondria: 3
•Strong free radical scavenger.
•Antioxidant.
•Inhibits lipid peroxidation.
•Enhances production of endogenous antioxidants; catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (-GR), heme oxygenase-1 (OH-1), and glutathione-S-transferase (GST).
3 Aging Pathways: 1
•Activates AMP Kinase
5 The Immune system: 3
•Blocks NF-kb, TNF-a.
•Modulates multiple cell signaling molecules; pro-inflammatory cytokines, cyclooxygenase-2 (COX-2), STAT3, CRP, GSH
•Inhibits gene expression for RAGE production…less inflammatory factors released.
7 Waste management: 3
•Decreases lipofuscin accumulation in brain cells.
Side Effects
Considered to be “generally recognized as safe” by the FDA. Of the few side effects noted, huge quantities may result in diarrhea, a headache, a rash, or yellow stool.
Issues
Poor bioavailability. Poor absorption. Poor half life. Standard curcumin blood levels peak at 2 hours, but are gone by 4.5 hours, giving it a half life of 2.6 hours.
Options:
Biocurcumax or BCM 95. Studies have shown it to be 6.93 or 7 fold more bioavailable than standard curcumin. As compared to regular curcumin, this formulation peaks at 2 hours, but is gone by 8 hours with a half life of 4.9 hours. (Antony 2008)
Metacurcumin is a super curcumin made by a company called RevGenetics that packages the curcumin in a micelle, and has the highest absorption rate (277 X that of regular curcumin), fastest absorption rate and highest plasma concentration after 24 hours.
Delphinidin Kaufmann Number: 1.3.0.1.2.0.0
General Information
Delphinidin as found in Maqui berries is native to central and southern Chili and is popular in Chilean folk medicine.
The Maqui berry, from the plant Aristotelia chilensis has the highest concentration of delphinidin than any other plant, (it is three times higher in Maqui berry than any other), but it is also found in blackcurrant, blueberries, and bilberries.
Composition
•Anthocyanin.
•Standard extract sold called Delphinol,.
Categories
1 DNA Alterations: 1
•Histone acetyltransferase inhibitor…suppresses inflammatory signaling.
2 Mitochondria: 3
•Extremely high free radical scavenging activity.
4 Quality control: 1
•Increases autophagy.
5 The Immune system: 2
•Inhibits NF-Kb, COX-2.
Systems Shown to Benefit
•Prevents osteoporosis by suppressing osteoclasts.
•Prevents muscle atrophy with disuse.
•Prevents obesity.
•Effectively reduces intracellular lipid accumulation and promotes lipolysis.
Side effects
None known.
Ecklonia Cava Kaufmann Number 0.2.2.2.2.2.1
General Information
Ecklonia Cava is a folk medicine from the coastal waters off of Korea and Japan.
It comes from an edible, brown seaweed. The Seaweed is rich in vitamins, minerals, dietary fibers, proteins, polysaccharides and various functional polyphenols.
For our purposes, E. cava has been identified as a producer of carotenoids, fucoidans and phlorotannins.
Categories
2 Mitochondria: 2
•Strong radical scavenging activity.
3 Aging Pathways: 2
•Activates AMP Kinase, SIRT 1.
•Dieckol inhibits adipogenesis by activating the AMPK pathway.
4 Quality Control: 2
•Up regulates DNA repair mechanisms.
5 The Immune system: 2
•Inhibits NF-kB, MMP-1 expression.
•Inhibits histamine release.
•Down regulates the expression of iNOS, COX-2, and pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β.
6 Individual cell requirements: 2
•Increased osteoblastogenesis, bone formation.
•Suppresses fat formation.
7 Waste Management: 1
•Hypoglycemic agent.
Systems Known to Benefit
Skin:
Inhibition of MMP-2 and MMP-9.
Inhibits melanogenesis.
Weight loss:
Decreases BMI, body fat ratio, waist circumference, waist/hip ratio, total cholesterol, low-density (LDL) cholesterol, and total cholesterol/ high-density lipoprotein (HDL).
Blocks fat production.
Promotes hair growth.
Side Effects
None known.
EGCG Kaufmann Number: 2.2.1.2.1.1.2
(Epigallocatechin-3-gallate)
General Information
ECGC is one of the most active molecules found in green tea.
About 5,000 years old, green tea was originally brewed by the Chinese, and was brought to Japan by Buddhist monks a thousand or so years later.
The health benefits of tea were described in 1211 by a Japanese Zen priest by the name of Yeisai. Years later, somewhere between 1630 and 1714, a doctor during the Edo period in Japan named Ekiken Kaibara, also mentioned the tea in a book entitled “Yojokun” or Lessons for Health Promotion. He however, proclaimed that the drinking of green tea was not beneficial as it led to weight loss.
Green tea is brewed from the leaves and buds of the plant Camellia sinensis. Importantly, it is not fermented. Black tea, meanwhile, comes from the same plant and is fermented, while oolong tea is semi-fermented.
There are 70 to 90 mg of EGCG per cup of green tea. By comparison, the average capsule has between 400 to 500 mg.
Categories
1 DNA Alterations: 2
•Epigenetic modifier.
•DNMT (DNA methyltransferase) inhibitor.
•Histone Deacetylation inhibitor.
2 Mitochondria: 2
•Free radial scavenger.
•Stimulates endogenous antioxidants.
3 Aging Pathways: 1
•Activates AMP Kinase.
4 Quality control: 2
•Modulates autophagy.
5 The Immune system: 1
•Inhibits TNF-a•
•Reduces C-reactive protein.
•COX-2 inhibitor.
6 Individual cell requirements: 1
•Modulates output of stem cells.
7 Waste management: 2
•Decreases AGE production.
•Hypoglycemic agent.
Systems Shown to Benefit
Helps with weight control.
Acts as a pro-osteogenic agent in stem cells.
Has Neuroprotective properties.
Side Effects
Nausea and heartburn.
Ellagic Acid Kaufmann Number 1.2.2.0.2.0.1
General Information
This agent is found in green tea, pomegranates, strawberries, blackberries, raspberries, cloudberries, walnuts, pistachios, cashews, pecans, and eucalyptus bark.
Berries provide ellagic acid in the form of ellagitannnins (compounded molecules…broken down in the gut).
The Absorption into the body is complex: In the stomach, some of the substance is absorbed as Ellagic acid. Ellagitannins, other complexed form of ellagic acid, is hydrolyzed or broken down, and releases Ellagic acid in the small intestine.
Some of both Ellagic acid and Ellagitannins make it to the colon where they are converted into Urolithins by microbiota (bacteria that live in the gut).
Urolithins have a higher absorption rate and they last longer in the circulation (the conversion rate into Urolithins is dependent on type of microbiota in the individuals gut).
Composition
Polyphenol
Categories
•1 DNA Alteration: 1
•Up-regulates HDAC9 expression.
2 Mitochondria: 2
•Increases the activity of endogenous antioxidants, SOD, CAT and GXP.
3 Aging Pathways: 2
•AMP Kinase activator
5 The Immune system: 2
•Reduces gene expression levels of tumor necrosis factor-a and IL-6.
•Reduces histamine release.
7 Waste management: 1
•Blocks AGE formation.
Systems Shown to Benefit
•Significantly reduces lipid accumulation, reduces early adipogenic markers.
•EA inhibits histone arginine methyltransferase 4 (CARM1), an enzyme necessary for adipogenesis.
•Whitens skin.
Side effects
None known.
Honokiol Kaufmann Number 0.2.2.0.2.0.1
General Information
Honokiol, a natural biphenolic pleiotropic lignan isolated from the bark of Magnolia officinalis, Magnolia dealbata, Magnolia grandiflora, Magnolia biondii, and Magnolia obovata.
The agent is widely known to have anti-inflammatory, anti-oxidative, anti-tumor, anti-thrombotic, anti-arrhythmic and neuroprotective properties. It ameliorates microbial infection, inflammation, and gastrointestinal disorder in traditional Asian medicinal systems such as traditional Chinese medicine and Kampo medicine in Japan.
Honokiol is also known for its anxiolytic, analgesic and antidepressant properties.
Categories
2 Mitochondria: 2
•Free radical scavenger (similar to reactivity of ascorbic acid).
•Boosted the endogenous antioxidant defense system: elevated the levels of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH).
•Increased the levels of Nrf2, glutathione and the activity of glyoxalase I.
3 Pathways: 2
•Enhances SIRT3 expression nearly two-fold.
•AMP Kinase activator.
5 The Immune systems: 2
•Inhibits NF- κβ, NO, tumor necrosis factor-α (TNF-α) , IL-1B, IL-6, PGE 2, COX-2.
•STAT3, epidermal growth factor receptor, m-TOR, beta catenin and HIF1α.
7 Waste management: 1
Systems Shown to Benefit
•Prevented hyperglycemia and weight gain in vivo.
•Reduced development of rAGEs.
•Improved Arthritis
•Treatment for : Dengue, the most widespread arbovirus infection
•Helps ameliorate obesity
•Promotes improved sleep
•Improves bone quality
Side Effects
None known.
Melatonin Kaufmann Number: 2.2.1.2.2.2.0
General Information
Melatonin exists in almost every cell type, from single celled organisms to plants, to us. As everyone knows, it helps control the circadian cycle so we can sleep, but it does much more. In fact, scientists believe it developed 3.2ish billion years ago as an antioxidant.
In the mid-1970s, scientists discovered the circadian nature of melatonin in mammals, and it wasn’t until 1993 that its antioxidant qualities were realized. In the quest to make a dollar, melatonin was patented as an over the counter sleep aid in 1995 to a Dr. Wurtman at MIT.
As with everything useful, over a lifetime, the concentrations of melatonin change. The highest nocturnal rise occurs between the ages of 4 to 7, and then declines again until puberty. Unfortunately, as we all know, life goes down hill sometime after puberty, as does the concentrations of melatonin.
AKA: N-acetyl-5-methoxytryptamin
Categories
1 DNA Alteration: 2
•Modulates DNA methylation and histone acetylation pathways
2 Mitochondria: 2
•Antioxidant and Free radical scavenger.
•Up-regulates endogenous antioxidants: Cu/Zn-superoxide dismutase, Mn-superoxide dismutase, catalase and glutathione peroxidase
3 Aging Pathways: 1
•The control of circadian rhythms affects the Sirtuin pathway.
4 Quality control:2
•DNA repair mechanisms linked to circadian rhythms.
•Modulates autophagy.
5 The Immune system: 2
•Reduces inflammatory cytokines: IL-1B, TNF-a, IL-6, CRP.
6 Individual cell requirements:2
•Affects bone formation through enhancing osteogenic differentiation.
•Mesenchymal stem cells are more likely to become osteoblasts or bone-producing cells than fat cells.
Systems Shown to Benefit
•Modulates body weight.
•Improves memory, cognitive function, and motor skills.
•Promotes the expression of type I collagen, up-regulates bone marker proteins, and stimulates the formation of mineralized matrix in Bone.
Side Effects
Makes you sleepy, vivid dreams.
Metformin Kaufmann Number: 3.1.3.2.2.2.3
General Information
Earlier use of the base plant, Galega officinalis or the French Lilac, was documented in Medieval Europe as an herbal remedy for diabetic symptoms.
Metformin was officially discovered in 1922. Human studies didn't begin until the 1950s, however. It was then that the French physician Jean Sterne introduced the substance to her countrymen as a prescription medication in 1957. The compound debuted in the United States in 1995. Presently, up to 150 million people are on the agent.
Interest in the medication as an anti-aging agent was peaked by a study released in 2014. Type 2 diabetics on either metformin or sulfuronureas (a different type of glucose controlling agent) were retrospectively compared with non-diabetics on neither of these drugs. Comparing 150,000 people, the type 2 diabetics on metformin had higher survivability. Let me rephrase…The diabetics did better than non-diabetics. In fact, among patients in their 70’s, mortality was reduced by 15% in the metformin group.
Composition: Metformin is a biguanide (N,N-Dimethylimidodicarbonimidic diamide), also known by the trade name Glucophage.
Stats
Prescription medication: Oral bioavailability: 50-60%.
Peak plasma concentrations: 1 to 3 hours immediate release / 4-8 hours with extended-release formulations.
Uptake can be delayed 30 minutes if taken with food.
Protein binding in plasma: Minimal.
Half life: 1.7 to 4.5 hours
Categories
1 DNA Alteration: 3
•Epigenetic modular; it induces genome-wide DNA methylation
•Modulates the activity of S-adenosylhomocystein hydrolase, an enzyme in the methylation cycle.
•Decreases genomic instability.
•Stimulates telomeric length
2 Mitochondria: 1
•Activates endogenous antioxidants: heme-oxygenate-1, glutamate cysteine ligase, glutathione S-transferase, glutathione peroxidase, SOD, catalase, sulfiredoxin and thioredoxin.
•Works through the Nrf2-ARE pathway (nuclear factor-like 2 - Antioxidant Response Elements).
3 Aging Pathways: 3
•AMP KInase activator.
•Depresses MTOR pathway.
4 Quality control: 2
•Increases DNA repair efficacy.
5 The Immune system: 2
•Blocks the activity of the transcription factor nuclear factor-kB (NF-kB).
•Inhibits the differentiation of monocytes to macrophages.
6 Individual cell requirements: 2
•Boosts the formation of new nerve cells.
7 Waste management: 3
•Reduces blood glucose.
•Reduces AGE formation.
•Slows lipofuscin accumulation.
•Benefits the Cardiovascular system.
•Cancer reduction.
•Delays menopause in female mice.
Side Effects
•The side effects are generally not too bad; GI upset, transient diarrhea, abdominal pain, cramps and excess gas.
•Worst case scenario: Lactic acidosis. 3 cases/100,000 patients.
•Factors that increase this risk include age greater than 60, decreased liver, kidney or cardiac function, diabetic ketoacidosis, surgery, respiratory failure, ethanol intoxication and fasting.
•The drug blocks the metabolism of a few vitamins, so long term therapy should be accompanied by the addition of supplemental B12 and folate. (Take your vitamins).
Nicotinamide Kaufmann Number: 0.3.3.3.0.0.0
General Information
Nicotinamide is made naturally in the body, beginning with the amino acid tryptophan. Eight steps later, it is converted into our usable substance, NAD or nicotinamide adenine dinucleotide. There is also a salvage pathway which is more efficient.
What does NAD do? It is crucial for cellular activity. Specifically it does the following:
1) In mitochondria, it is an essential part of electron transport chain which is necessary to produce cellular energy.
2) It is necessary for DNA repair. The molecule itself gets disassembled, and its pieces are used as replacement parts in the actual DNA.
3) It provides communication between nucleus and mitochondria
4) It acts as a necessary Co-factor for the sirtuin family
Composition
Nicotinamide adenine dinucleotide consists of two nucleotides joined together by their phosphate groups. One nucleotide contains an adenine base, the other a nicotinamide. Thus the name.
The problem and the solution:
1) We require more NAD with aging.
2) We have less at our disposal with increasing age.
Thus, the demand for NAD rises with age, while the supply diminishes. Therefore, we see a failure in energy production, a failure in SIRTUIN activation, a failure of DNA repair, and increased aging.
Repletion of the nicotinamide has demonstrated to reverse the declines that we see over time.
The actual type of repletion becomes the question however as there are various forms of Nicotinamide replacements available.
Which nicotinamide to use?
Nicotinamide riboside (NR) seems to be the winner thus far, and in fact many very brilliant scientists are staking their reputations and pocket books on it. NR can be converted to usable NAD in 2 metabolic steps. ( Sauve 2007) It turns out this formulation is stable, easy to produce and reasonably inexpensive.
Categories
2 Mitochondria: 3
•Necessary for function of Mitochondria
3 Aging Pathways: 3
•Necessary co-factor for SIRTUIN activation
4 Quality control: 3
•Necessary for DNA repair.
•Prevents hearing loss after loud noises.
•Increase in Overall Energy.
Side Effects
None known
Naringenin Kaufmann Number: 1.2.1.2.2.3.0
General Information
Whereas the molecule was officially identified in Java in 1857 in the flowers of grapefruit trees, Naringenin has been with us for much longer.
The Chinese have utilized this agent for thousands of years, but they have an alternative plant source; a fern called Drynaria. In Mandarin, naringenin is called Gu Sui Bu, which translates into (gu= bones, sui=broken, bu=bones); mend broken bones. It has other beneficial properties as well, but its apparent strength lies in bone and tooth health.
We know today that the molecule is found predominantly in citrus fruits, especially the grapefruit ( 800mg/ L), but it is also in oranges, and the skin of tomatoes.
Regardless of where the molecule comes from, we generally consume it as molecular naringin. Thereafter, it gets metabolized to various forms of naringenin, including a free form, naringenin glucuronide and naringenin sulfate. In all, about 23 metabolites have been identified.
Categories
1 DNA Alteration: 1
•Reduces DNA damage.
2 Mitochondria: 2
•Strong free radical scavenging activity.
•Prevents lipid perioxidation.
•Activates endogenous antioxidant enzymes: Superoxide dismutase, catalase, and GPx.
3 Aging Pathways: 1
•Activates AMP Kinase.
4 Quality Control:2
•Stimulates the repair of DNA through the Base excision repair (BER) pathway, most notably repairing cyclobutane pyrimidine dimers, which are pieces of DNA that get melted together by UV radiation.
•Specifically, this occurs by induction of the mRNA expression of three major enzymes of the BER pathway.
5 The Immune System: 2
•Suppresses TNF-a function and antagonizes NF-kB signaling pathway.
6 Individual Cell Requirements: 3
•Enhances osteogenic differentiation and thus enhances bone formation.
•Improves bone density and healing.
•Suppresses fat accumulation.
Side Effects:
Naringin causes a decreased absorption and thus reduces the bioavailability of some medications, such as pitavastatin, imatinib, and some B2 agonists. At the same time it can block the breakdown and thus extend the life of minoxidil. It increases the bioavailability of some calcium channel blockers, such as verapamil.
Polypodium Leucotomos Kaufmann Number: 0.2.0.3.2.0.0
General Information
A fern from the Polypodiaceae family, native to central and south America. It is a traditional remedy for skin diseases, especially psoriasis and atopic dermatitis. Presently, it is marketed/sold as Fernblock, which is an extract of Polypodium leucotomos and has been available in Europe since 2000, and in the US since 2006. It can be either topical or oral, and offers skin protection from UV radiation.
AKA: Fernblock
Composition
It is composed of many bioactive compounds, including phenolic components: chlorogenic acid, coumaric acid, vanillic acid, caffeic acid ferulic acid.
Categories
2 Mitochondria: 2
•Strong anti-oxidant
•Increases endogenous antioxidants
4 Quality Control: 3
•Enhanced repair of DNA, especially cyclobutane pyrimidine dimmers secondary to UV radiation
5 The Immune System: 2
•Blocks prostaglandins, histamines, leukotrienes, and other cytokines: COX-2, NF-KB, TNF-α, iNOS.
•Enhances endogenous antioxidant enzymes.
•Prevents photo-aging by inhibiting MMPs, inducing TIMP.
Side Effects
None known
Pyridoxamine Kaufmann Number: 0.0.0.0.0.0.3
General Information
A subtype of vitamin B6, Pyridoxamine has been found to be potent AGE blocker, and thus part of diabetes treatment as well as aging.
After a few zillion studies in the literature were published touting the positive effects of pyridoxamine on diabetic complications, it became obvious a few years back that the agent was useful. Thus, it wasn’t long until a drug company tried to turn it into a real medication. The company, Biostratum, started testing and producing a drug called Pyridorin, in which the active ingredient was pyridoxamine. The complicating factor here was that our B6 vitamin was already over the counter. Another complicating factor was money; the company cancelled the phase 3 trials in 2005 because they were out of cash. A battle then ensued between the FDA, the drug company and the supplement representatives.
Who won? We did (so far). At the moment, you can get pyridoxamine over the counter.
Categories
7 Waste Management: 3
•AGE formation inhibitor, blocks several steps in the formation process.
Systems Shown to Benefit
•Skin: Reduces arterial wall stiffness of blood vessels
Side Effects
None known
Quercetin Kaufmann Number: 0.3.1.2.2.2.0
General Information
The greatest amount of quercetin is found in cappers (233 mg/100gm), raw yellow chili peppers (50 mg/100gm) and the outer layers of onions (22mg/100gm). Quercetin is present in some fruits as well, mostly in apple peels. It is also in black tea, Chamomile tea and white wine. Recall that resveratrol is also in red wine, so if you prefer the whites just tell your friends you are maximizing the quercetin effect.
Quercetin has been marketed for years for treatment of allergies, asthma, arthritis, gout, hypertension and neurodegenerative disorders.
Composition
3,3,4,5,7- pentahydroxyfavone.
A plant based substance, considered a polyphenol.
Categories
2 Mitochondria: 3
•Powerful antioxidant.
•Activates endogenous antioxidants via the Nrf2 (nuclear factor-like 2) pathway: heme-oxygenate-1, glutamate cysteine ligase, glutathione S-transferase, glutathione peroxidase, SOD, catalase, sulfiredoxin and thioredoxin.
3 Aging Pathways: 1
•Activates AMP Kinase.
4 Quality Control: 2
•Proteosome activator.
5 The Immune System: 2
•Decreases histamine releases.
•Reduces inflammatory cytokines; specifically IL-4, IL-6, IL-8, and IL-13.
6 Individual Cell Requirements: 2
•Senolytic (The only known over the counter substance to have this property).
Side Effects
None known
Resveratrol & Pterostilbene Kaufmann Number: 2.3.3.3.2.2.1
RESEVERATROL
General Information
Resveratrol, a component of Japanese Knotweed, has been used medicinally for just over 2,000 years. It has been sited in Ayurvedic, Japanese and traditional Chinese medicine as a treatment for fungal infections, cardiovascular disease, gastrointestinal disorders, diabetes and general inflammation. Today, Itadori tea, a rich source of resveratrol, is made out of Knotweed, and used as an herbal remedy for heart disease and stroke.
The plant is endemic to East Asia, Japan, China and Korea,and was little known to the western world until the 1990s, when scientists starting referring to something called the “French Paradox.” The French, as is well known, consume a plethora of fatty foods, especially cheese, and smoke cigarettes. They also drink a lot of red wine. They should, by all estimates, be overweight drunks with cardiovascular disease. But, alas, they are not.
Resveratrol is also present in blueberries, blackberries, mulberries, peanuts and over seventy different types of plants, but being present in the skin of grapes which become wine, makes the substance a bit sexy, and thus more popular.
Composition
3,5,4’-trihydroxy-trans-stilbene.
Polyphenol and phytoalexin.
Categories
1 DNA Alteration: 2
•Telomere enhancer; activates human telomerase activity.
•Epigenetic modifier: DNMT inhibitor (DNA methyltransferase), HDAC (Histone deacetylase) inhibitor (Activates SIRT1: a known HDAC inhibitor).
2 Mitochondria: 3
•Free radical scavenger.
•Increases the activity of endogenous antioxidants: catalase, superoxide dismutase, gluathione peroxidase, and glutathione-s-transferase.
3 Aging Pathways: 3
•AMP Kinase activator.
•SIRTUIN activator.
4 Quality Control: 3
•Sirtuin activation enhances DNA repair mechanisms.
5 The Immune System: 2
•Reduces C-reactive protein, Tumor Necrosis Factor, and cyclooxygenase-1.
6 Individual Cell Requirements: 2
•Stimulates stem cells.
7 Waste management: 1
•In human clinical trials, resveratrol significantly improved glycemic control, reduced HGA1C levels and insulin levels.
Systems Shown to Benefit
•Fat reduction
•Cardiovascular
•Bone: Resveratrol promotes spontaneous osteogenesis, or bone formation.
•Neuroprotective (especially in the hippocampus).
•Ovarian: Increased number of ovarian follicles, better and more numerous oocytes in resveratrol treated lady mice
Side Effects
No side effects, however low bioavailability
PTEROSTILBENE
General Information
Cousin of Resveratrol, “a kind of extra-potent version of resveratrol.”
Pterostilbene has a much better bioavailability than resveratrol; this means you can consume less and it works better. Resveratrol had a 20% bioavailability (meaning that only 1/5 of what you ingested was actually helpful), pterostilbene demonstrated a high 80%.
In general, the studies on pterostilbene are not as numerous, but the effects seem comparable.
Pterostilbene is found in many plants including Pterocarpus marsupium heartwood, (thus the name) and red sandal wood trees from India. However, its most prevalent source is blueberries.
Because these compounds are turning out to be extremely close in mode of action, we have considered them together. However, experts are banking on the superiority of pterostilbene.
Composition
A stilbene and phytoalexin.
Categories
1 DNA Alteration: 2
•Epigenetic modifier.
2 Mitochondria: 3
•Free radical scavenger.
•Increases the activity of endogenous antioxidants: catalase, superoxide dismutase, gluathione peroxidase, and glutathione-s-transferase.
3 Aging Pathways: 3
•Activates sirtuins.
•Activates AMP Kinase.
4 Quality control: 3
•Activated SIRTUINs aid in DNA repair mechanisms.
•Increases autophagy.
5 The Immune Cystem: 2
•In some studies, the activities against the COX 1 and 2 cytokines was weaker than resveratrol. It is, however, clearly active against most of the common cytokines including TNF-a, IL-4, IL-1B.
6 Individual Cell Requirements: 2
•(Not known as of yet).
7 Waste Management: 1
•Hypoglycemic agent.
Systems Shown to Benefit
•Fat reduction.
•Improves cardiovascular health.
Side Effects
None known
Rosmarinic acid Kaufmann number: 0.3.0.1.2.0.3
General Information
Medicinal use of Rosmarinic acid dates from Middle ages and originates from the Mediterranean, Central and Southern Europe, Asia, and Northern Iran.
The highest levels of the substance are found in a a plant called lemon balm.
AKA: Lemon Balm officially Melissa Officinalis, family Kamiaceae
Composition
Lemon balm has up to 40 bioactive compounds including hydroxycinnamic acid derivatives, flavonoids with caffeic acid, m-coumaric acid, eriodictyol-7-O-glucoside, naringin, hesperidin, rosmarinic acid, naringenin, and hesperetin.
Rosmarinic acid considered to be the most important. Lemon balm leaf contains roughly 36.5±0.8 mg rosmarinic acid per gram.
Categories
2 Mitochondria: 3
•Has exceptionally high antioxidant activity.
•Improves intrinsic levels of catalase, superoxide dismutase, and glutathione peroxidase.
•The reduction in free radicals is associated with a marked reduction in DNA damage in human studies.
4 Quality Control: 1
•Demonstrated high capacity to repair DNA strand breaks in cell models.
5 The Immune System: 2
•Inhibits TNF-a induced NF-kB activation.
•Inhibits lipoxygenase and cyclooxygenases.
•Interferes with the complement cascade.
7 Waste Management: 3
•Strong anti-glycation activity, possible ability to break crosslinks
•Hypoglycemic agent.
Systems Shown to Benefit
Skin: Suppresses matrix metalloproteinase - 9.
Improves arterial stiffness of blood vessels.
Side Effects
High doses in rats: EKG changes including prolonged QRS interval, and Prolonged QTc intervals. Same study: no effect on heart rate, blood pressure or other HR marker.
Sulforaphane Kaufmann Number: 3.2.0.1.0.2.0
General Information
This story begins with a Dr. Tony Talalay, at the Laboratory for Molecular Pharmacology at the John Hopkins University School of Medicine, who discovered the health-promoting properties of sulforaphane glucosinolate in the Brassica family of vegetables, most notably, in broccoli. What did this amazing substance do? Prevent cancer!
In 1992, these results were announced to the world and everyone was shocked in amazement. Today we know that many substances can reduce the risk of cancer, and this is just one of them.
There are several interesting things about sulfuraphane however. For one, it is a very unstable molecule and isn’t actually in the vegetable. However its precursor, glucoraphanin, is. Sulforaphane only becomes active when it is mixed with this enzyme, myrosinase. When the plant cell ruptures, by some sort of trauma to the plant, (i.e., human chewing), the two mix and produce sulforaphane.
Several commercial products tried unsuccessfully to develop a stable form of sulforaphane, and a lot of money was spent in the process. Finally, however, it was realized that we humans have the enzyme myrosinase in our own guts, so we actually don’t need the unstable compound, just its precursor.
Regardless, the product is usually sold as sulforaphane.
AKA: Isothiocyanate, a molecule found in cruciferous vegetables, especially in broccoli, but also in kale, cabbage, and Brussel sprouts.
Categories
1 DNA Alteration: 3
•Epigenetic modifier.
•Inhibits Histone deacetylase, thus enhancing global histone acetylation
•Inhibits DNA methytransferases
•Regulates micro RNA’s
2 Mitochondria: 2
•Up regulates the endogenous antioxidants through Nrf2.
4 Quality Control: 1
•Modulates mitochondrial dynamics
6 Individual Cell Requirements: 2
•Promotes stem cell proliferation, and protects cells from apoptosis and senescence
Systems Shown to Benefit
•Cancer risk reduction.
Side Effects
None known
Yerbe MatE Kaufmann Number: 0.2.2.2.2.0.2
General Information
Yerba Mate is a popular tea in Brazil, Argentina, Uruguay, and Paraguay and is made from the plant llex paraguariensis, a native south american tree.
The tea is mixed and consumed from a gourd and a metal straw called a “Bombilla”. The dry leaves are packed into the gourd, and steaming hot water is poured over them. The drink is considered very social or communal; the tea filled gourd is passed from person to person.
Composition
It’s a natural compound, thus Yerba Mate has innumerable active substances.
Phenols: ferulic acid, caffeic acid, syringes acid, coumarin acid, chlorogenic acid, gallic acid, caffeine, theobromine, quercetin, kaempferol, rutin, amino acids, minerals and vitamins
Of note: Green tea contains Catechins and EGCG, while Yerbe Mate has chlorogenic acid.
Categories
2 Mitochondria: 2
•Significant free radical scavenging activity
•Increases endogenous antioxidants
•Inhibits lipid peroxidation
•Enhances total antioxidant status
•Demonstrates DNA protective properties
3 Aging Pathways: 2
•Activates AMPKinase (secondary to chlorogenic acid).
4 Quality Control: 2
•Enhances DNA repair mechanisms.
5 The Immune Systems: 2
•Inhibits NF-kB pathway.
•Attenuates cytokines: COX-2, IL-1B, TNF-.
7 Waste Management: 2
•Significantly reduces AGE formation, as well as RAGE formation.
•Hypoglycemic agent (secondary to chlorogenic acid).
Systems Shown to Benefit
•Fat reduction: Yerba mate suppresses body weight gain and visceral fat accumulation.
•It decreases serum levels of cholesterol, triglycerides, LDL cholesterol, glucose, insulin, pancreatic lipase and leptin.
•It down-regulates the expression of genes that responsible for regulating adipogenesis
•It Increases the expression of uncoupling proteins
Side Effects
There is a reported association between the consumption of Yerba Mate and the risk of cancer, especially esophageal and mouth cancers. Researchers have tried to get to the bottom of this and while many studies have been done, there remains no clear answer. There is some evidence that the association is based on the drinking of extremely hot beverages, as well as the combination of poor diets, smoking and alcohol consumption.