DNA, Peptides & Personalized Health

DNA, Peptides & Personalized Health with Jennifer Little-Fleck A workshop on longevity, personalized health, and optimizing wellness through genomics ________________ Introduction Jennifer Little-Fleck: Hello, and welcome. I'm Jennifer Little-Fleck from The Genomics Company. We provide a full breadth and depth of genetic testing — specifically a test called the Precision Panel, along with several lifestyle panels. Peptides are one of the areas we test for. You're probably thinking, "Can you actually test whether peptides will work with my body?" The answer is absolutely yes. Tony Medrano: I'm Tony Medrano, CEO of LongevityPlan. We help people optimize peptide therapy and other health and fitness strategies based on their goals. We've partnered with Jennifer and The Genomics Company. I had my peptide genomics test completed, and it honestly shocked me how closely the report mirrored my personal experience with the peptides I'd already been taking. Looking back, I should have taken the test before starting peptide therapy — not after. Jennifer Little-Fleck: Tony knows better now: test first, then take the next step. At some point, everyone asks the same questions. Why can my friend drink an espresso at 10:00 p.m. and sleep like a baby, while I have one iced coffee at noon and lie awake replaying every conversation since 2009? Why do some people feel great eating kale, while for others it's the worst thing that ever happened to their digestive system? We tend to file these things away as personality quirks, but they're really biology. Most of the answers are sitting right there in your DNA, and today we can read that information to better understand why our bodies respond the way they do. My philosophy is simple: you shouldn't have to wait until something goes wrong before you get the instruction manual for your own body. In the United States, we often don't learn about our biology until we're already sick — that's a bit like reading your car insurance policy from inside the car after you've already had an accident. What I do is read your genetic code and translate it into something meaningful, so you can understand your own biology out of curiosity, not just out of necessity. ________________ Your Genome Is the One Input That Doesn't Change Jennifer Little-Fleck: The really exciting part is that your genome is the one piece of information that doesn't change. Everything else in a longevity protocol expires at some point. Your lab results are out of date in about 90 days. Your wearable data is already outdated by tomorrow, because you have new data every day. And your peptide stack will probably rotate several times throughout the year. But your genome was completed before you were born, and it's the one longevity input you have for life. Once your DNA has been sequenced, it can be interpreted and reinterpreted for a lifetime — I reread my own genome regularly, because new research and insights are constantly emerging. Let's define the terms, because they determine what you can actually act on. Your genome is all of your DNA — roughly three billion base pairs, about 99% of which is identical between any two people. Genomics is the science of how variations within that remaining 1% influence biology from one person to another. Rather than looking at just one or two genes, genomics examines many genes together as a system. Think of your genome like a department within a company: individual genes are like individual employees, each bringing a specific skill, but it's the way all of those contributions work together that determines how well the department functions. Then we have SNPs — single nucleotide polymorphisms — single-letter differences at specific locations in your DNA. They make up much of that 1% variation and are the primary units we evaluate. To give you a sense of how significant that 1% is: the odds of two unrelated people having the exact same genetic information are approximately 1 in 14.5 quintillion. Two important things to remember. First, genes set probabilities, not destinies. Second, your outcomes are influenced by both your genetics and your environment — typically your environment accounts for about 40% of how your body functions, while your genomics account for the other 60% or so. There are four major areas that drive the longevity conversation: lifespan and resilience (genes such as FOXO3 and APOE); methylation and detoxification (MTHFR and COMT); oxidative stress (SOD2, GPX1, NQO1); and growth hormone and tissue repair signaling (the growth hormone receptor GHR, IGF-1, and COL1A1). To explain how it all works, we'll look at three different people with three very different genetic profiles. ________________ Marcus: The GLP-1 Question Jennifer Little-Fleck: Marcus wants the shot everyone has been talking about. He's 46, carrying about 30 pounds he can't seem to lose, and watching his friends lose weight on semaglutide. But Marcus has done his research and already had his genomics tested. He's not just chasing a number on the scale — he wants meaningful metabolic health improvements for decades to come. The real question isn't whether he should use a GLP-1 medication, but whether his biology will support it as a long-term solution. What we discovered is that his appetite isn't a character flaw — his hunger and fullness signals are largely hardwired into his brain. Three specific genes influence how well a GLP-1 therapy may work. The first is FTO, often called the fat and obesity gene; certain risk variants are associated with increased hunger and a higher BMI, often beginning in early adulthood. Next is MC4R, the master switch for satiety in the hypothalamus — variants like the ones Marcus has weaken the brain's "I'm full" signal. These are exactly the individuals for whom GLP-1 and GIP therapies, not crash dieting, are often the most appropriate tools. We also evaluate the GLP-1 receptor, TCF7L2 (insulin sensitivity), and GCGR (the glucagon pathway). Before using a GLP-1, there's one important step: we determine whether Marcus carries a RET gene variant associated with a hereditary form of thyroid cancer that may be a contraindication. It's a simple test. Most people test negative, but occasionally someone discovers they're a carrier, in which case GLP-1 medications may not be appropriate. With that in mind, let's talk about the peptides that are a good fit. We'll start at the bottom of the list because most people are familiar with semaglutide — the first GLP-1 to become widely available, a proven therapy and solid first step with a single mechanism of action. Because Marcus also has longevity goals, we'd typically pair it with something like MOTS-c to support mitochondrial function. Tirzepatide is also a GLP-1 but with a dual mechanism, targeting both GIP and GLP-1 receptors; it's FDA-approved and particularly suited to people with MC4R-driven appetite regulation. Then there's retatrutide, a triple-mechanism therapy — in Phase 3 trials, participants experienced an average weight loss of about 28%, one of the most effective results studied to date. Retatrutide is still investigational and not yet FDA-approved, though that may happen in 2027. One note: its glucagon component can cause mild skin tingling (dysesthesia), and with tirzepatide the GIP component may increase nausea, so it's important to increase the dose gradually. For someone like Marcus, what's most important is comparing his progress to his own baseline, not to how his friends respond. The best approach is to start low, go slow, and pay close attention to changes in satiety — that's one of the best indicators the therapy is working. ________________ Diane: Aging in Fast-Forward Jennifer Little-Fleck: Diane is 54 but says she feels closer to 70. She bruises easily, takes a long time to recover from a pulled muscle, and lost skin elasticity earlier than her friends. When we reviewed her genomic results, we identified two major concerns: reduced mitochondrial defense and slower collagen remodeling. For the first time, she had an explanation for what had been happening to her body. People often underestimate how valuable it is simply to understand why their body behaves the way it does. Her genome showed that her mitochondria produce higher levels of oxidative stress and clear cellular damage more slowly, and that her collagen is genetically programmed to remodel at a slower rate. This isn't simply a case of needing more rest — she can get all the sleep in the world, but because her repair systems are genetically less efficient, sleep alone won't produce the same results it might for someone else. Specifically, her SOD2 and GPX1 variants play an important role; these two genes work hand in hand to clear oxidative byproducts. Think about a fireplace: you burn wood and it produces energy in the form of heat — but it also produces smoke. Your mitochondria work the same way, generating reactive oxygen species (ROS) as a byproduct of producing energy. SOD2 converts ROS into hydrogen peroxide, and then GPX1 breaks the hydrogen peroxide down into water and oxygen. Unfortunately, Diane carries less efficient versions of both genes, so her body is slower at each step. On top of that, she has a collagen gene variant that alters collagen structure, meaning her skin, bones, and tendons remodel more slowly. Overall, she's simply a slower healer. For someone like Diane, we'd consider peptides such as GHK-Cu, BPC-157, and TB-500 to support collagen, connective tissue, and overall tissue repair, along with MOTS-c, Humanin, and SS-31 for mitochondrial support. Given her elevated ROS profile, MOTS-c would likely be a first-line option, and SS-31 helps stabilize the inner mitochondrial membrane where energy production takes place. For these peptides to work optimally, Diane also needs the proper nutrients — the building blocks for collagen, including adequate dietary protein. Vitamin C is absolutely critical; you cannot build new collagen without it. Glycine is also important. One important point: some of these peptides can increase IGF-1 levels, so if you have a history of hormone-sensitive cancers, elevated IGF-1 may be contraindicated, and it's important to discuss these therapies with your physician. ________________ Sam: Treatment-Resistant Mood Jennifer Little-Fleck: Sam has tried three antidepressants, and none have worked — he's been labeled treatment-resistant. Traditionally, when someone seeks help for anxiety or depression, physicians are often doing their best with limited information, essentially throwing darts in the dark. With genomic testing, we can help narrow down what to try first, second, or third — and what to avoid because it's likely a waste of time. The first areas we evaluate are folate metabolism and methylation — you can't maintain healthy neurotransmitter production without properly functioning folate and methylation pathways. Next we evaluate how his body processes dopamine and serotonin. In Sam's case, his genetics suggest SSRIs are unlikely to be an effective first-line treatment, and he has lower baseline neuroplasticity signaling. The body's "methyl group factory" wasn't adequately supplied, which helps explain why standard antidepressants weren't producing results. One of the primary genes we examine is MTHFR; in Sam's case it was functioning at roughly 30% efficiency. When we evaluate methylation we actually look at about nine different genes, and MTHFR is one of the most important and well-studied. Looking at COMT, Sam is a fast metabolizer — he clears neurotransmitters very quickly, so if he produces dopamine, it's broken down relatively quickly. We also looked at 5-HTTLPR and BDNF, and unfortunately he carries less favorable variants of both; the short allele of 5-HTTLPR is associated with a slower, weaker response to SSRIs, and his BDNF results suggest lower baseline neuroplasticity. The goal is to support the pathways, not force them. For Sam, helpful therapies may include L-methylfolate, which bypasses the MTHFR bottleneck and provides the active form his body needs. Semax and Selank are peptides that act within the brain, helping increase BDNF while modulating dopamine and serotonin activity — nootropic peptides that can provide additional mood support. It's important to emphasize that depression should always be managed by a qualified healthcare professional; these peptides are not a replacement for appropriate medical treatment. ________________ Tony's Peptide Genomics Report Jennifer Little-Fleck: I'd like to share Tony's peptide genomics report and have him talk about his experience. Tony Medrano: I started peptide therapy on April 1st. I used LongevityPlan's Digital Twin to track which peptides I was taking, along with my dosages. About a month ago, I completed my peptide genomics test — so by the time I received my genomic results, I already had about three months of real-world data to compare them against. From April 1st until now, I've lost 40 pounds. During that time I used about ten different peptides — not all at once, but cycling through different therapies. I wanted to experience them myself before recommending them to others. Some peptides worked very well; others didn't, at least from my perspective. Some are easier to evaluate than others. With retatrutide, weight loss is measurable and obvious. With BPC-157, you can often tell whether an injury is healing more effectively. And with GHK-Cu, you can visibly notice improvements in your skin and hair. Jennifer Little-Fleck: What you're looking at is a summary of Tony's peptide genomics results, showing where he may experience greater or lesser benefit from specific peptides — we evaluate whether the expected response is optimal, moderate, or neutral. One strength of this report is that peptides often have multiple effects throughout the body. For example, with AOD-9604, Tony's results suggest a more neutral benefit for macronutrient response but a stronger benefit for weight maintenance. Tony Medrano: I started AOD-9604 about two weeks after beginning retatrutide, so roughly mid-April. That period was when I experienced my greatest weight loss. I attribute most of that to retatrutide, since it's the more aggressive therapy, but AOD-9604 was part of my protocol and I think it contributed. I started at about 22% body fat, and now I'm below 11%. With retatrutide, I increased my dosage according to the schedules used in the clinical studies, and at the higher doses I experienced the same side effects reported in the trials — skin tingling, some gastrointestinal discomfort, and a general feeling of malaise. Once I did, I quickly reduced the dosage. On Semax, I can definitely tell when I'm taking it — I use it before podcast interviews because it makes me feel mentally sharper; my thoughts come together more easily. I cycle it strategically. Selank is often paired with Semax but is more focused on anxiety; personally I didn't notice much benefit, though I don't feel anxiety is something I struggle with. I'm also taking Dihexa right now — it's hard to tell the benefits because it's more of a preventive therapy intended to help repair neurons. I tried FOXO4 during a more intensive weekend cycle; the idea is that it helps clear senescent, or "zombie," cells, so it's used only once or twice a year. I'm using Epitalon right now, a 30-day protocol at a moderate dose that I'll repeat once or twice a year. Jennifer Little-Fleck: Let's talk about one of your favorites. Tony Medrano: GHK-Cu. I'm not someone who uses a lot of beauty products, but this one really worked. My hair became thicker, my skin felt softer and more supple, and I felt like I looked younger — and my skin healed more quickly. It's also one of the peptides that can be used for longer periods without cycling off. It's found in a lot of women's skincare products, but I found the injectable route produced much stronger, systemic results. I also recently started a GHK-Cu spray; the research on men's hair regrowth was very compelling — it appeared to be two to three times more effective than Rogaine, which I've used for about 10 years — and it worked pretty well for me. Jennifer Little-Fleck: Did you try Melanotan II? Tony Medrano: Yes. At first I made fun of it because I didn't think I needed to be more tan, but since I don't spend much time in the sun, it actually worked — it made me look healthier, and it also seemed to have some appetite-suppressing effects along with some positive effects on sexual function. I still use it occasionally. Jennifer Little-Fleck: I tried it too, but it didn't agree with my system — it made me extremely nauseous, so I didn't stay on it long. On growth hormone peptides, the name often scares people; they think it's something meant for bodybuilders, but it's mostly about supporting tissue repair, recovery, and healthy aging. For the right person these therapies can make a tremendous difference, though people with a history of cancer should be very cautious and work closely with their provider. I also want to mention BPC-157. Many people assume it benefits everyone, but that's not the case — there are people who don't experience any noticeable benefit, and a few who can't take it because they've had reactions, including allergic reactions. Tony Medrano: I started BPC-157 and TB-500 right at the beginning, on April 1st, because I had a torn meniscus in my left knee dating back about 30 years to my time in the military. It seemed to heal within about two weeks. I used a combination of local injections around the knee along with standard systemic abdominal injections. I had no side effects and an unbelievable recovery — that knee had been bothering me for 30 years, and now it's better. I also started CJC-1295 at the beginning of my protocol, and the timing matched well with the initial phase of my weight loss and improvements in my skin. I'm not weaker — in fact I'm considerably stronger, even after losing 40 pounds. ________________ Closing Jennifer Little-Fleck: We're coming up on the hour, and this webinar was only supposed to last 30 minutes, so thank you all for staying with us. If you have additional questions, please feel free to reach out to either Tony or me. Tony Medrano: You can find me on LinkedIn by searching for Tony Medrano, or visit LongevityPlan.ai. We also offer most of the peptides we've discussed today. Jennifer Little-Fleck: And you can find me at TheGenomicsCompany.com, where you'll find information about our genomic testing packages. You can also schedule a consultation to talk through your health goals and determine which testing options may be the best fit for you.