The American Academy of Anti-Aging Medicine (A4M) curated a program that highlights the ways in which practicing clinicians and thought-leaders are changing the field of modern medicine. A large variety of speakers presented including:

William Seeds, MD; Jill Carnahan, MD; Terry Wahls, MD; Julielynn Wong, MD; Pamela Smith, MD; Sara Gottfried, MD; the Knox family; Dian Ginsberg, MD; James Greenblatt, MD; Marvin Singh, MD; Joseph Purita, MD; Neil Riordan, PhD; Joel Osorlo, MD; Derrick DeSilva, MD; Felice Gersh, MD; Deepa Verma, MD; Joel Kahn, MD; Mark Houston, MD; James LaValle, CCN; Clifford Morris, PhD; Stacy Hinz, MS; Van Trokel, MD; Garry Lee, MD; Slavo Komamytsky, PhD; Sahar Swidan, PharmD; William Clearfield, DO; Angela Knapp, ND; Thom Lobe, MD; Andrew Campbell, MD; Carrie Decker, ND; Nathan Bryan, PhD; Joseph Raffaele, MD; Tim Sawyer; Barrie Tan, PhD; Sangeeta Pati, MD; Tara Scott, MD; and Stephen Petternuti, DO.

With a list of presenters this long, FAIM has chosen to pick a few topics of interest to review.

William Seeds, MD

Mitochondrial Function and Anti-Aging: Senescent Cells, Rapalogs, NAD+ and Peptides

Peptides in the cell nucleus communicate with the mitochondria for oxygen efficiency. If this communication is lacking the cell will age. The cells become senescent and stop dividing. The goal is to help the cell regroup, no longer be senescent and continue to divide normally. As the cells age into the senescent phase they can be rescued up to a point. If this point is past then the cell enters into permanent arrest. These cells cause problems by secreting inflammatory cytokines, damaging surrounding cells. Transcription of NF-KB gets into the surrounding cells causing senescence of these cells. If stem cells come to repair the damage they can be affected by the senescent cells and no longer renew. As it stands to reason, if there are senescent cells, stem cell therapy will not be as beneficial.

Characteristics of senescent cells includes hyper secretory activities along with inflammatory cytokine release. The senescent cell can camouflage itself protecting itself from apoptosis, death of the cell. It becomes a critical factor in aging, disease and healing. In the case of neurodegenerative disease, senescent cells cause plaques and tangles. If the senescent cells are eliminated neurodegenerative disease can be reversed.

Mitochondrial function is affected directly by the presence of NAD. If NAD is low, cells progress to be senescent. In a vicious cycle, this degrades more NAD, leading to an increase in CD38 and NADase which degrades NAD precursors. When this cycle gets started the cell cannot recover. Once this cycle is in full motion, supplementing with NAD can feed the cycle and worsen the scenario.

The AMPK/MTor ratio is paramount for homeostasis in the body. In a disease state, MTor is elevated. Low dose Rapamycin slows the geoconversion of Mtor and can slow the development of senescent cells, improving the immune function and lessening infection. Increased ATP conversion can lead to less senescent cell development. Peptides play an important role, specifically GHRH/GHRP by improving oxidative phosphorylation, increasing the AMPK, improving the NAD+/NAD ratio, but most importantly it blocks nuclear transcription of NF-KB. In addition, the FOXO4-p53 peptide induces targeted apoptosis of senescent cells. In mice, targeting apoptosis in this way restored fitness, hair density and renal function.

The International Peptide Society has advanced the science of peptides. Peptides are used to regrow hair by attacking the senescent cells around the hair follicle. They are also finding peptides are beneficial with knee osteoarthritis. There are 9 hallmarks of aging including genomic stability, telomere attribution, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. There are many additional approaches to addressing senescence and anti-aging currently. People can use Senolytics, Rapamycin, Metformin, placenta stem cells, organ regeneration with 3D bio printing, and dietary supplements in the form of NAD+, NMN, and NR.

According to Dr. Seeds additional ways to slow down aging is through the use of supplements including some we have rarely heard of. These include CjC1295, TA1, TB4, MOTS-c, Ketone Ester, Rapamycin and NAD+.

Nathan Bryan, PhD

Strategies to Optimize Regenerative Medicine Outcomes: The Role of Nitric Oxide

What is nitric oxide (NO) and why is it so important? It is a key donor of electrons acting as a vasodilator. It is essential to get the oxygen released from the red blood cells. It is instrumental in controls and regulations in the body, important for telomere health, enhances mitochondrial function and stem cell mobilization. Low NO precedes issues such as atherosclerosis, insulin sensitivity, skin aging, etc.

How is it made in the body? Nitrate converts to nitrite. Nitrite converts to NO. This is done along the L arginine pathway. NO utilizes intracellular L arginine from L citrulline. Supplements work with the nitrate in the saliva and bacteria in the stomach. Thus they are typically in the form of lozenges.

What are the benefits of NO? It lowers blood pressure, creates healthy skin, reverses cardiovascular disease, and lowers plaque, to mention just a few.

The Knox Family: Dr. Jessica Knox, Dr. Janice Knox, Dr. David Knox, and Dr. Rachel Knox

The Future of Cannabis in Medicine

The Knox family is a family of doctors who want to change the way you think about weed. Their goal is to educate clinicians on the therapeutic applications of clinical cannabis. They have created the ADVENT Academy for this purpose.

In 1982 scientists discovered the body has an endocannabinoid system which plays a key role in health. By 2000 key players in the endocannabinoid system were identified. Two of them include 2-Arachidonoylglycerol (2-AG) and anandamide. There are cannabinoid cell receptors throughout the body including CB1 found mainly in the brain and the central nervous system, CB2 in the brain, immune system, digestive tract and nerves, GPR18 in the bone marrow and immune system, TRPV1 in the brain, bone marrow, muscles organs and skin, GRP55 in the brain, bone marrow, immune system, reproductive organs and gut, and GRP119 in the pancreas and digestive tract. It is clear the endocannabinoid system is an intricate system integral to homeostasis and health.

We also know there are phyto (plant) forms that are similar to the 2-AG and anandamide. These phytocannabinoids are many with the most well-known being CBD and THC from hemp and marijuana. These plants have been considered medicinal as far back as 2727 BC and have been used by many cultures ever since.

So why is there such an uproar over their use today? A little history will help clarify the scenario.

Spanish settlers brought it to the Americas in the 1500s and colonists grew marijuana and hemp. In 1850 Cannabis was added to the American Pharmacopeia and was broadly used, available through many pharmacies.

In the 1930s and 40s there was an extreme anti-Mexican sentiment and the U.S. government started a campaign connecting marijuana with Mexican drug use suggesting dangerous homicidal tendencies brought on if you used cannabis. Harry Anslinger ruled over the Federal Narcotics Bureau. He oversaw Prohibition, not giving that much concern to cannabis and marijuana. However, when Prohibition ended, Anslinger, concerned about losing his job, came up with a new threat to the American Way, creating the drug war. He successfully vilified marijuana giving rise to the 1937 Marijuana Tax Act.

In 1968 the Nixon White House also mounted a campaign against it resulting in the 1970 Nixon Controlled Substance Act classifying it as a Schedule 1 drug along with heroin, LSD, cocaine and ecstasy. As a result, very little research confirming the medicinal benefits has been possible.

Since then many states have made marijuana legal for medicinal use and/or recreational use.

As with all systems in the body the key is to be balanced free of excess or deficiency. When there is deficiency, the phytocannabinoids in hemp and marijuana can help bring the system back into balance. This imbalance can result from too many or too few receptors, for example.

Each individual has a unique endocannabinoid tone that can be affected by stress, emotions, chemicals, diet, drugs, genetics and aging. As an example, when a person is stressed, anandamide is lowered so that cortisol can be increased. It is all a balance.

The phytocannabinoids have a multitude of therapeutic effects. THC is analgesic, anti-inflammatory, anti-nausea, anti-tumorigenesis, muscle relaxant, anti-oxidant, anticonvulsant, anti-depressant and neuroprotective. CBD is analgesic, anti-inflammatory, anti-nausea, anti-tumorigenesis, muscle relaxant, anti-oxidant, anticonvulsant, anti-anxiety and depression, and antipsychotic. As in many whole plants the CBD balances the THC.

It is interesting to keep in mind that the endocannabinoid system is balanced not only through supplementing CBC and THC but also through the use of foods, herbs, spices, essential oils, acupuncture, exercise, massage and meditation. Even a smile and a hug to a friend can help balance the system.

As our understanding of the endocannabinoid system has progressed so has our understanding of marijuana and hemp. There are over 500 chemicals found in weed that are all active in the body, including phytocannabinoids, terpenes, flavonoids and waxes.

So how is a person supposed to determine what is right for them? There are so many options available on the market today. In states where marijuana is legal people can get full spectrum marijuana. This is the most medicinal form with nothing removed. It is whole plant nutrition with a full suite of phytocannabinoids and other phytochemicals like the terpenes and flavonoids mentioned.

The next step down is Broad Spectrum with only partial plant nutrition and mechanical extraction of phytocannabinoids and phytochemicals.

Then there are the THC-free products that have no THC and lack the synergism of CBD and THC.

Lastly are the Isolates which are CBD only with carrier oil. This form lacks synergistic effect, is the least desirable and can have side effects.

Research has shown a correlation between aging and depletion of CB1 receptors in the brain. Low dose THC reverses age-related decline in cognitive performance of aging mice which holds hope for humans.

So what should the consumer think about when looking for a phytocannabinoid supplement? Retail stores should have proof of testing for toxins, labeling for terpene content, proof of organic origin, etc. so request to see the tests. Also importantly, start low and go slow.

For ingestion it can be smoked, vaped or inhaled which will last for a shorter duration. Smoking can be an irritant, but research has shown smoking cannabis can be protective against lung cancer (especially if you smoke tobacco).

Ingestibles come in the form of oils and tinctures and last about 4-6 hours. Oral ingestion and bioavailability will vary but increases with fat ingestion.

For more information on training go to the ADVENT Academy website.

Neil Riordan, PhD

Stem Cell Therapy: A Rising Tide: Experiences in Panama and the United States

Dr. Riordan has a clinic in Panama, The Stem Cell Institute, where they are able to harvest umbilical cord mesenchymal stem cells (MSC) to help patients with MS, autism, rheumatoid arthritis, cerebral palsy, heart failure, spinal cord injury and diabetes to mention a few. They treat a variety of autoimmune illnesses. The clinic has a relationship with a birthing center where the mothers are screened, the mesenchymal stem cells are gathered and prepared. The MSCs have an influence on central inflammatory conditions, modify the immune system, and stimulate regeneration.

How is this done? Once the MSC’s are infused into the patient they go to the site that needs attention and set up shop. For a period of time they become factories that deliver cytokines, exosomes and other trophic factors for healing. For example, in joints the MSCs remain there for months secreting trophic factors. Ultimately they participate in the regeneration of the tissue.

They are very safe, but Dr. Riordan emphasized that not all products that are on the market are the same. A therapeutic dose is necessary to see benefit. This is typically 120 million cells. Dr. Riordan’s clinic gives approximately 40 million cells via IV three days in a row totaling 120 million. In the case of rheumatoid arthritis they saw the inflammatory markers of TNF-a and IL-6 decline 50% after the first infusion and an additional 50% decline with the second infusion. He clarified that umbilical cord blood basically has no MSCs and is only approved for hematopoietic restoration.

The use of stem cells in the United States is more limited than what can be delivered in Panama. Practitioners in the United States offering stem cell therapy must be vigilant to observe the regulations put forth by the FDA, FTC, State Medical Boards, State Pharmacy Boards, and State Attorney Generals. For more information visit the Stem Cell Institute website.

The other presentations during the conference concentrated on Longevity, Fasting, Regenerative Medicine, Medical Cannabis, Anti-Aging, The Brain, Individualized Patient Care, and Cancer Prevention and Treatment. For more information on future A4M events visit the American Academy of Anti-Aging Medicine (A4M) website.