January 7, 2020
If you listened to my podcast “Why Your DNA Is Worthless (& What You Need To Focus On Instead),” or the podcast “How To Use Precision Medicine To Enhance Athletic Performance, Defy Aging, Balance Hormones, Fix The Heart & Much More.“, then you learned all about personalized genomic analysis, why DNA data alone is insufficient and how my guests on that episode, Drs. Matt Dawson (pictured above) and Mike Mallin of WildHealthMD, have created a new kind of genomics-based personalized medicine software platform.
At Wild Health, they take a number of factors (beyond DNA)—including lifestyle, patient preferences, microbiome data, cholesterol levels, cardiovascular conditions, and more—into account to present a “whole picture” approach allowing for more accurate diagnoses and appropriate recommendations.
I was so intrigued by what Wild Health is doing for the future of personalized medicine that I asked if Matt and Mike if they'd be interested in writing a guest post for today's article, and Dr. Dawson graciously obliged. Enjoy!
The Longevity Secrets of Lucille Ball
“The secret of staying young is to live honestly, eat slowly, and lie about your age.” – Lucille Ball
Ms. Ball was a very wise woman. I can’t disagree with her assessment. However, it turns out there may be a few other secrets to staying young.
While aging itself may not be preventable, the decline in health and rise of disease that we typically associate with aging may be optional. At least that’s what many leading scientists and physicians believe.
This claim may seem out there, but turning back your biological clock has already been proven possible… kind of. A study published this year in the journal Aging Cell showed a 2.5-year reversal in biologic age compared to expected progression of age when using a very specific medication cocktail of DHEA, metformin, vitamin D, zinc, and growth hormone. To be fair, it’s a very small study focused exclusively on the thymus gland, so please take with a massive grain of salt. If you’re interested in hearing more about it we go over this study specifically on The Wild Health Podcast and also discuss it in the last podcast we recorded with Ben.
That particular study aside, this isn’t a new concept. All the hype around compounds like metformin, resveratrol, epitalon, rapamycin, DHEA, NAD, and many more comes from their ability to potentially slow down aging. Many accomplished researchers believe we can go even further—from “slowing down” to “reversing” the aging process. Or at least slow it down so much as to dramatically increase our lifespan. In David Sinclair’s book, Lifespan: Why We Age―and Why We Don't Have To, (Ben interviewed David here) he discusses his experience with longevity research and proposes a compelling theory for several potentially effective strategies. His work is undeniably impressive, but the relatively crude “personalized” approach described only included variations in dose for different patients. With the power of genomics, we can get truly personalized and recommend specific molecules and peptides at the appropriate doses based on an individual’s DNA and current biometrics. A few caveats before we dive in:
- The best longevity strategy is to first get the basics right. You must work hard to optimize your sleep, nutrition, exercise, environment, stress, and relationships first. If you haven’t done that, then stop surfing around for metformin and peptides and instead start working on those. Ben has a number of podcasts and articles that'll show you how to do all or incorporate these natural tactics as a foundation, including:
- 6 Steps To Achieving The Ideal Combination Of Fitness, Longevity, And Looking Good Naked (A Hybrid Training Approach For Anti-Aging & Performance).
- 8 Important Lessons For Longevity – Straight From The Unique Mind Of A Biohacking PhD Nutritionist.
- 12 Basic, Natural & Easy Habits To Enhance Longevity.
- Part 1 Of 2: My Top 10 Steps To Biohack Longevity (& How To Get Many, Many Weird Looks From Your Neighbors)
- Part 2 Of 2: My Top 10 Steps To Biohack Longevity (& How To Get Many, Many Weird Looks From Your Neighbors)
- The 7 Different Reasons You Age (& Potent, Proven Molecules To Enhance Longevity & Slow Aging).
- Ben Greenfield’s Top Anti-Aging Tactics: Basic & Ancestral Strategies To Enhance Longevity.
At Wild Health, we’ve seen incredible improvements in biomarkers and even DNA methylation tests of aging after optimizing these lifestyle factors alone. Using some of the more advanced molecules and peptides discussed below is the metaphorical icing on the cake.
- As a scientific community, we know infinitely more today about genomics and true personalized medicine than we did a decade ago. That said, a decade from now we will look back and laugh at how little we knew. It’s an exciting time to be alive, as the pace of discovery around genomics is accelerating very quickly. This means that the knowledge in this article could be obsolete very soon. Hence, focus on the basics first.
- This is NOT medical advice. The following information is just that—information. There are countless variables that determine who may benefit and who may be harmed by a given intervention. These decisions should be made in consultation with a trained physician. Remember, focus on the basics and involve a physician or other healthcare provider who understands the whole picture when you’re ready to consider decisions around aggressive longevity and life extension.
With those important caveats out of the way, let’s start by looking at a partial list of molecules (there are too many to discuss them all) that have the potential to slow down and reverse aging:
- Metformin (Learn more about Metformin on Ben's podcast here.)
- DHEA (in the study mentioned)
- Growth Hormone (Very debatable, but used in the study mentioned)
- NAD+ (and its precursors)
- Epitalon (telomere lengthening)
- MOTS-C (mitochondrial biogenesis)
- Semax (Neurogeneration)
- GHK-Cu (skin aging)
- Coenzyme Q10 (CoQ10)
- Vitamin D
- Vitamin E
- Thymosin Alpha
That’s a long list! If you were to take all of them you’d be spending thousands of dollars every month. What’s more, anything that truly works is going to have some associated downside or risk, regardless of how small. Genomics can help identify what may benefit you the most, what dose would be appropriate, and what may even be harmful.
9 Of My Favorite Anti-Aging Compounds
Now, let’s take a look at some individual compounds and discuss how to apply them in a genomics-based precision protocol. Before we do that, though, I want to be very clear about something: Go back and read caveat #1. Have you mastered the basics? If not, then stop reading this and go start working on that. OK, hopefully I’ve stressed that point well enough now.
Are you still reading? Great. Let’s dig in to 10 of my favorite anti-aging compounds.
“Don’t let aging get you down. It’s too hard to get back up.” – John Wagner
MOTS-c is a mitochondrial-encoded peptide that inhibits the methionine-folate cycle and increases PGC-1alpha. It has been shown to enhance metabolic homeostasis and reduce obesity and insulin resistance. It has also been used to enhance sports performance, and certain long-lived Japanese populations have demonstrated a phenotypic expression and biologic link between MOTS-c and an extended lifespan.
The fact that it works by upregulating PGC-1a makes it an interesting option for longevity in people who have lower expression of PGC-1a. PGC-1a is involved in mitochondrial biogenesis (production of new mitochondria), and lower levels could be augmented with this peptide. Cold water, fasting, and exercise also tend to upregulate this enzyme, but everyone’s levels of PGC-1a decline over time. Lower levels of this enzyme are associated with an increased risk of type 2 diabetes. Therefore, if someone has a lower genetic expression of PGC-1a, they may benefit from augmentation sooner than others.
Want to know more about how to get started with peptides and hear about a specific MOTS-c injection and dosage protocol? Check out Ben's podcast with Dr. William Seeds here.
“As you age, the pickings get slimmer, but the people don’t.” – Carrie Fisher
Resveratrol is called a fasting mimetic. This means that it acts similarly to calorie restriction (CR), which has been shown in study after study to increase lifespan in multiple organisms, including primates. Specifically, both resveratrol and CR up-regulate telomerase, increase expression of both SIRT1 and FOXO3, and act via other additional mechanisms. CR slows growth, reduces body fat, delays neuroendocrine and immunologic changes, increases DNA repair capacities, enhances apoptosis, and ameliorates oxidative stress. Resveratrol has been shown to improve the health and lifespan of mice who are fed a high-calorie diet, which is unfortunately what most of us humans eat. But we’re not just big mice, so what does the human data show?
Human studies have shown that resveratrol can reverse some markers of Alzheimer’s disease, improve blood pressure, and improve cognitive performance in patients with diabetes, among other promising effects.
So resveratrol seems like a pretty great longevity molecule for anyone, and in fact it probably is. However, some genetic characteristics can make it even more important. For example, if someone has a JAK2 single nucleotide polymorphism (SNP), then they are at increased risk of leukemia and blood cancers. 1000mg of resveratrol may be a better dose for someone with this SNP as opposed to 500mg for someone else. The same may be true for the HSPA1L SNP related to heat shock proteins and autophagy. In addition, since SIRT1 and FOXO3 expression are increased by resveratrol, perhaps a higher dosage would be beneficial if someone has some of the common SNPs that lower baseline expression of SIRT1 and/or FOXO3.
“As we grow older, our bodies get shorter and our anecdotes longer.” – Robert Quillen
Epitalon is a peptide that has been shown to lengthen telomeres in human cells. In one study, patients who received epitalon had decelerated aging of the cardiovascular system, less age-associated impairment of physical endurance, normalized circadian rhythms, and normalized carbohydrate and lipid metabolism. There was also a significant reduction in mortality.
These clinical results and epitalon’s established effect on telomeres make it a very popular peptide. It is normally administered for 15 days twice a year as a general protocol. However, there are several single nucleotide polymorphism (SNP) variants that lead to shorter telomere length in general, such as those found in TERT, TERC, RTEL1, ACYP2, and OBFC1. If someone has multiple of the risk alleles of these SNPs, more frequent dosing of epitalon may be considered.
In addition to Ben's podcast with Dr. Seeds, you can learn more about epitalon dosing protocols in Ben's article “The Little-Known Russian Wonder Compound & The Fringe Future Of Anti-Aging Medicine.”
“As you get older, three things happen. The first is your memory goes, and I can’t remember the other two.” – Sir Norman Wisdom
Dihexa is a peptide that may potently improve cognitive function in animal models of Alzheimer’s. It has been shown to enhance acquisition, consolidation, and recall of learning and memory in animal models. Dihexa is seven orders of magnitude more potent than brain-derived neurotrophic factor (BDNF).
Many people use dihexa as a nootropic for its pro-cognitive effects. It could also be a very good adjunct in aging to decrease cognitive decline. Even without obvious decline, there is a specific SNP related to levels of BDNF. BDNF is involved in both the growth of new neurons, proliferation of existing neurons, and maintenance of synapses. Those with the risk allele of this SNP have decreased short-term plasticity, motor control, speech recognition, and working memory. You can increase BDNF with intense exercise, and dihexa may be a very nice addition to achieve similar results.
Learn more about dihexa in Ben's article “The Dark Side Of Peptides: Why You Need To Proceed With Caution When Using These Powerful But Potentially Carcinogenic Molecules.” Ben prefers to use the transdermal version from Tailor Made Compounding. You can find a physician in your area who can prescribe these types of peptides for you on the International Peptides Society website.
#5. NAD, NR, and NMN
“You are as young as your faith, as old as your doubt; as young as your self-confidence, as old as your fear; as young as your hope, and as old as your despair.” – Samuel Ullman
NAD and its precursors have likely been discussed more than any other longevity molecules, at least in the last year. We know that NAD levels decline as we age, and this may be one of the central mechanisms behind why we age. Nicotinamide riboside (NR), a precursor of NAD, has been shown to promote longevity in many different organisms. (See additional studies here and here.) It works by contributing to longer telomeres, promoting DNA repair, modulating immune-cell signaling, inducing energy-intensive enzymes, activating sirtuins, and supporting energy production.
With all the positive news about NAD, many people have decided that it’s right for them. You can take NR and NMN orally, or you can inject NAD. There is much debate about the best way to supplement, but elevating levels of NAD seems to be of real benefit.
How much should you take, though? The dosages generally taken of NR are in the 250mg-1000mg range. A study published last year showed safety and no increased side effects with the higher dosage,15 but the cost is significant. A one-month supply of Tru Niagen at 300mg/day will set you back $50/mo. If you want to take the full 1000mg dose then you’re talking about spending over $165/mo. In this case, genomics may be helpful in making a dosing decision when money is limited (which it always is). For example, if someone has the G allele of the SIRT1 gene, then they are at risk for a shorter lifespan than those with the A allele. Because NAD+ upregulates SIRT1 then someone with the G:G version may elect to take NR, and possibly in higher doses. Someone with the A:A version may instead stick to the natural activities that upregulate SIRT1 such as exercise and fasting. For more on NAD, check out some of Ben's podcasts and articles:
- The Next Big Anti-Aging Drug: Everything You Need To Know About “NAD.”
- How To Keep Your NAD Levels Elevated (Without IVs) For Staving Off Aging, Cellular Health, Full Body Repair & Much More.
- The New Darling Supplement Of The Anti-Aging Industry (& The Truth About Whether It Actually Works).
- How To Get Your Own Vitamin and NAD IVs, The Truth About Umbilical Stem Cells, Peptide Injections & Much More With Dr. Craig Koniver.
While dosing protocols for NAD widely vary, Ben prefers beginning with a series of 3-5 500-1000 NAD IV's in a medical clinic, then following that up with a monthly IV, and daily use of oral or intranasal NAD or NAD precursors (Ben currently uses the Alive By Nature NMN sublingual tablets for this and their intranasal NAD/CBD spray). In addition, for long haul airplane flights, Ben uses NAD patches that he orders from the NAD Clinic in San Diego.
#6. FGL, RG3, Semax, and Selank
“Age is an issue of mind over matter. If you don’t mind, it doesn’t matter.” – unknown
FGL is a peptide with neurotrophic and memory-enhancing properties. Selank has been used for anxiety, depression, immune modulation, PTSD, ADHD, and metabolic syndromes. Semax has been used for conditions like anxiety, memory improvement, stroke, nerve regeneration, and chronic diseases such as ALS, Parkinson’s, and Alzheimer’s. RG3 is anti-neuroinflammatory.
Together these medications may be helpful for those with age-related cognitive issues, but they can be considered sooner rather than later when someone has genomic findings that predispose and increase their risk for diseases such as Alzheimer’s. If someone has two copies of an APOE4 allele, then they are 11-13x more likely to develop Alzheimer’s disease. Couple this with an MTNR1A polymorphism, which also increases their risk, and the risk starts to get high enough that there may be an earlier role for some of these interventions as “prophylaxis.” Ben also has more information about Semax in the nootropics/smart drugs section of his new book Boundless. Again, you can find a physician in your area who can prescribe these types of peptides for you on the International Peptides Society website.
#7. Vitamin D
“Whatever a man’s age, he can reduce it several years by putting a bright-colored flower in his button-hole.” – Mark Twain
Vitamin D has multiple roles and deficiency has been associated with an increased risk of age-related chronic diseases including Alzheimer’s disease, Parkinson’s disease, cognitive impairment, and others. It isn’t thought of traditionally as a life extension molecule, but preventing those diseases is clearly a good idea if you want to live a long and healthy life.
There are multiple SNPs associated with a higher risk of Vitamin D deficiency, but the main determinant of whether or not to supplement should be your Vitamin D blood level. If your level is normal, then your level is normal, there are no tricks here. However, most people in our practice naturally present with a level of less than 50, which we consider to be the optimal level. We simply live in a time when we don’t get enough sun, and how much to supplement can be informed somewhat by genomics. For example, supplementing 1000 IUs of Vitamin D per day will generally raise Vitamin D levels by 5-10. However, if someone has a CYP2R1 polymorphism then they often need higher levels of supplementation for the same increase in Vitamin D levels. Supplementation needs can also be affected by an individual’s vitamin D binding protein SNP.
Vitamin D supplementation is a perfect example of how genomics, blood testing, and the specific patient all need to be taken into consideration before a decision is made. How low is their serum Vitamin D level? How many polymorphisms do they have and are they homozygous or heterozygous? How close to the equator do they live? Are we entering summer or winter? Are they at risk for bone disease or other conditions that Vitamin D deficiency worsens? All of these things inform a supplementation strategy.
“I’m young at heart, but slightly older in other places.” – unknown
CoQ10 is an essential component of mitochondrial energy transfer, so as levels fall, mitochondrial dysfunction increases and aging is accelerated. CoQ10 levels have been shown to be an independent risk factor for mortality in cardiac patients. CoQ10 fed to a group of rats on a high-fat diet extended their lives by what would have been the equivalent of 9 human years.
Should you take CoQ10? The list of potential supplements is starting to get long at this point, but this is yet another example where genomics can help. The CoQ2 gene encodes for CoQ10, thus someone with the risk allele may benefit from supplementation. This is especially true in someone taking statins, as this SNP has been associated with an increased risk of statin-related myopathy. Additional information such as a CoQ10 blood level and use of statin therapy will help inform the supplementation decision.
For CoQ10, Ben recommends use of the Almsbio sublingual glutathione/CoQ10/PQQ blend and holding in the mouth for 1-2 minutes after dosing.
#9. Vitamin E
“I stay away from natural foods. At my age, I need all the preservatives I can get.” – George Burns
Vitamin E is an antioxidant. A large percentage of people around the world take it for its antioxidant effects, assuming this will increase longevity as inflammation is a major driver of aging. However, there are conflicting studies demonstrating both beneficial and harmful effects of vitamin E supplementation.
Learn more about some of the potentially harmful effects of some forms of vitamin E on Ben's podcast “Why Your Vitamin E Supplement Could Be Harming You (& The “One Plant Wonder” Alternative That Could Be The Single Most Powerful Molecule If You’re Stranded On A Desert Island).”
This is a classic example where statistics and epidemiology can lead us astray, but genomics-based precision medicine can clarify the issue. There is a SNP called GSTP1 that codes for the glutathione S-transferase enzyme. Individuals with the A:A genotype have normal GSTP1 activity and in these cases, vitamin E has been shown to increase pro-inflammatory cytokines such as IL-6. However, individuals with the G:G version have decreased pro-inflammatory cytokins with supplemental vitamin E. Interestingly, approximately half of the population has the A:A genotype. It’s no surprise that the studies were conflicting.
If you are going to take Vitamin E, be sure to use a blend of tocotrienols and tocopherols, such as the Designs For Health Annatto-E blend.
Now, we just covered the basics of some of the more common aging molecules. There were certainly more on our initial list and many more beyond that, but I think you get the point.
Just in case you don’t, though, to break it down simply and make sure you do:
- Aging is complex.
- You must master the basics first if you want to truly live a long and healthy life.
- There are too many life extension molecules to simply take every single one that shows some promise. Personalized genomics can help you decide which may be best for you and not just best for “most people.”
- Each decision is fairly complex and requires the consideration of genomics, lab testing, biometrics, your specific history, lifestyle, preferences, goals, and other factors. These decisions are best made in a partnership between you and a physician who can help guide you through this process. If you don’t have someone who can help, then go to Wild Health and we can help.
Though it may seem outrageous to make the statement “aging is optional,” we truly believe science will support this idea in the very near future. For this reason, while there will surely be more aging studies in the near future, rather than wait, we at Wild Health are already applying the current aging science in clinical practice. Standing on the shoulders of giants and using the science created by researchers, such as Dr. David Sinclair and Dr. Steve Horvath, we’ve developed some very specific longevity protocols. These protocols use many of the molecules above, but we personalize the protocols to your specific genomics, labs, and goals.
It is critical to measure success (or failure) and to be as data-driven and objective as possible. For this reason, we use DNA methylation tests based on the Horvath Clock to actually measure your biological age and follow along to make sure we’re helping you accomplish your goals. We routinely track more traditional biomarkers that increase or decrease your risk of disease, but the DNA methylation test gives us a very nice overall picture of what we’re ultimately trying to affect – aging.
To be clear (and to state it one more time), the best, most powerful strategy to slow or reverse aging is to first optimize your sleep, diet, nutrition, stress levels, etc. Once you’ve got the basics down, though, a genomics-based longevity optimization plan is certainly an option worth considering. It’s an exciting time to be alive!
Whether or not we can truly reverse aging, always remember the following and start here:
“There is a fountain of youth: it is in your mind, your talents, the creativity you bring to your life and the lives of people you love. When you learn to tap this source, you will truly have defeated age.” – Sophia Loren
Do you have any questions for Matt or me on aging or anything discussed in this article? Leave them in the comments section below.