The Four Horsemen of Aging: A Functional Medicine Approach to Longevity

Why waiting for disease is the wrong strategy—and what to do instead

You've done everything right. You eat well (most of the time). You exercise. You see your doctor for annual checkups. Your labs come back "normal."

And yet, something doesn't feel right.

You're more tired than you should be. Your thinking isn't as sharp. The weight around your midsection won't budge no matter what you try. And when you mention these concerns to your doctor, you're told it's just "part of getting older."

But here's what I want you to understand: these symptoms are not an inevitable part of aging. They're signals. Early warnings from a body trying to tell you that something is shifting beneath the surface—long before it becomes a diagnosis.

At Clark Wellness, we practice a different kind of medicine. Instead of waiting for disease to arrive and then managing symptoms, we look upstream. We ask why. And we intervene early, when we can actually change the trajectory.

This approach is built on understanding what Dr. Peter Attia calls the Four Horsemen of Aging—the chronic diseases responsible for stealing the vast majority of years and quality of life in the modern world.

What Are the Four Horsemen?

Over 80% of deaths in people over 50 (who don't smoke) can be traced to four major disease categories:

1. Atherosclerotic Disease — heart attacks, strokes, and vascular disease

2. Cancer — the second leading cause of death

3. Neurodegenerative Disease — Alzheimer's, dementia, Parkinson's

4. Metabolic Dysfunction — the spectrum from insulin resistance to fatty liver to type 2 diabetes

   
   

These conditions don't strike suddenly. They develop over decades, silently, while standard labs remain "normal." By the time conventional medicine catches them, you've often lost years of health you could have preserved.

The Problem with Medicine 2.0

Our current healthcare system operates in what we might call Medicine 2.0—a model designed for acute problems. It's brilliant at treating a broken bone, removing a tumor, or managing a heart attack in progress. But it struggles with chronic disease prevention.

Medicine 2.0 waits. It waits until your hemoglobin A1c crosses 6.5% to diagnose diabetes. It waits until your coronary arteries are 70% blocked to intervene. It waits until you can't remember your grandchildren's names to diagnose Alzheimer's.

The problem? By then, the damage is done.

Functional medicine operates differently. We embrace what some call Medicine 3.0—a proactive, preventive approach that identifies dysfunction years before it becomes disease. We don't just ask "Are you sick?" We ask "Are you thriving?"

A Closer Look at Each Horseman

Cardiovascular Disease: Beyond Cholesterol

Heart disease remains the leading killer in America, yet many people with "normal" cholesterol still have heart attacks. Why? Because total cholesterol and even standard LDL measurements miss the real story.

What functional medicine looks at:

• Apolipoprotein B (ApoB): This measures the actual number of atherogenic particles in your blood—the ones that penetrate artery walls and form plaque. Research consistently shows ApoB is a superior predictor of cardiovascular risk compared to LDL cholesterol alone. Every atherogenic particle carries exactly one ApoB molecule, making it a direct count of the particles driving atherosclerosis.

  
  

• Lipoprotein(a) or Lp(a): This is a genetically inherited particle that significantly increases cardiovascular risk. Roughly 20% of people have elevated Lp(a), and unlike standard cholesterol, diet and statins don't lower it. It's a hidden risk factor most people don't know they have—because most doctors don't test for it.

  
  

• High-sensitivity C-Reactive Protein (hs-CRP): This inflammatory marker helps assess the "fire" inside your arteries. Chronic inflammation accelerates plaque formation.

  
  

• Advanced lipid particle testing: Looking at LDL particle number and size tells us more than LDL concentration alone. Small, dense LDL particles are more atherogenic than large, buoyant ones.

  
  

The key insight: cardiovascular disease is largely preventable when we measure the right markers and intervene early. We don't have to wait for a heart attack to take action.

Cancer: Reducing the Terrain

We can't control every factor in cancer development—genetics, random mutations, and exposures all play roles. But we can influence what functional medicine calls the terrain—the internal environment that either supports or discourages cancer growth.

Factors that create a cancer-permissive terrain:

• Chronic inflammation

• Insulin resistance and metabolic dysfunction

• Oxidative stress

• Immune dysregulation

• Hormonal imbalances

• Toxic burden accumulation

• Poor detoxification capacity

  
  

What functional medicine addresses:

We work to optimize metabolic health, reduce chronic inflammation, support the body's natural detoxification pathways, balance hormones appropriately, and strengthen immune function. This doesn't guarantee cancer prevention, but it creates an internal environment less hospitable to disease.

Neurodegenerative Disease: Protecting Your Brain

Without exception, my patients fear dementia more than any other condition. They would rather die from heart disease or cancer than lose their minds—their very selves. I understand this fear deeply.

The devastating truth about Alzheimer's and other dementias is that by the time symptoms appear, significant brain damage has already occurred. Research suggests cognitive changes can begin 20 years before diagnosis.

But here's the hopeful part: what's good for your heart is often good for your brain. The same metabolic dysfunction driving cardiovascular disease also damages cognitive function.

Key factors in brain health:

• Insulin resistance: Sometimes called "Type 3 diabetes," insulin resistance in the brain impairs cognitive function and accelerates neurodegeneration. Cholesterol levels at age 50 have been shown to predict neurological health at age 70.

• Inflammation: Chronic systemic inflammation crosses the blood-brain barrier and damages neurons.

• Hormonal status: Estrogen, testosterone, progesterone, and thyroid hormones all affect cognitive function. Optimal hormone balance supports brain health.

• Sleep quality: During deep sleep, your brain's glymphatic system clears metabolic waste products. Poor sleep means inadequate brain "cleaning."

• Nutrient status: B vitamins, omega-3 fatty acids, vitamin D, and other nutrients directly support neurological function.

• Physical exercise: This is perhaps the single most powerful tool we have for neurodegeneration prevention. Exercise improves blood flow, supports neuroplasticity, and reduces inflammation.

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Metabolic Dysfunction: The Common Thread

Here's the critical insight most people miss: metabolic dysfunction doesn't just cause one horseman—it feeds all four.

Insulin resistance and metabolic syndrome increase your risk of cardiovascular disease, cancer, and dementia. Metabolic health is the foundation everything else rests on.

The spectrum of metabolic dysfunction:

Metabolic disease doesn't start with a diabetes diagnosis. It begins years earlier as:

• Mild insulin resistance (your body needs more insulin to keep blood sugar normal)

• Hyperinsulinemia (elevated fasting insulin)

• Pre-diabetes (blood sugar starting to creep up)

• Type 2 diabetes (blood sugar above diagnostic thresholds)

• Complications (organ damage from prolonged dysfunction)

  
  

By the time hemoglobin A1c crosses 6.5%, the process has been developing for 10-15 years. Waiting for that diagnosis means missing over a decade of intervention opportunity.

Signs of metabolic dysfunction often dismissed as "normal aging":

• Weight gain around the midsection

• Fatigue, especially after meals

• Difficulty losing weight despite effort

• Brain fog and poor concentration

• Afternoon energy crashes

• Increased hunger and sugar cravings

• Skin tags

• Darkened skin patches (acanthosis nigricans)

• Irregular menstrual cycles (in women)

  
  

These aren't inevitable consequences of getting older. They're signals that metabolic dysfunction is developing.

The Functional Medicine Approach: Testing That Reveals the Real Picture

Conventional medicine typically relies on fasting glucose and hemoglobin A1c to assess metabolic health. But these markers can remain "normal" for years while insulin resistance progresses silently.

What comprehensive metabolic testing includes:

• Fasting insulin: Elevated levels indicate insulin resistance often years before blood sugar becomes abnormal. While standard reference ranges accept fasting insulin up to 25 μU/mL, metabolic specialists consider optimal levels to be below 10 μU/mL.

  
  

• HOMA-IR: This calculation uses both fasting insulin and glucose to assess insulin resistance more precisely. A score above 1.9 suggests early insulin resistance; above 2.9 indicates significant insulin resistance.

  
  

• Hemoglobin A1c with context: While 5.7% is the prediabetes threshold, optimal levels are below 5.4%.

  
  

• Triglyceride-to-HDL ratio: This simple calculation from standard lipid panels correlates with insulin resistance. Optimal ratios are below 2:1

  
  

• Continuous glucose monitoring: This technology shows how your blood sugar responds to different foods, exercise, stress, and sleep—revealing patterns that single measurements miss.

  
  

• Leptin: Leptin resistance disrupts appetite regulation and metabolism, creating obstacles to weight management.

  
  

References:

This blog draws on concepts from longevity medicine research, including Dr. Peter Attia's work on the Four Horsemen framework, and evidence-based functional medicine practices from the Institute for Functional Medicine. For individual health concerns, please consult with a qualified healthcare provider.

Understanding Mast Cell Activation Syndrome (MCAS): A Functional Medicine Approach to Healing

What is MCAS?

Mast cells are specialized immune cells that play an important role in protecting your body from threats. However, in Mast Cell Activation Syndrome (MCAS), these cells become overly reactive and release chemicals like histamine, prostaglandins, and other inflammatory substances at inappropriate times—even when there's no real danger.

This overreaction can cause symptoms throughout your entire body:

• Skin reactions: flushing, hives, itching

• Digestive issues: bloating, diarrhea, nausea, abdominal pain

• Neurological symptoms: brain fog, headaches, anxiety

• Cardiovascular: rapid heartbeat, blood pressure changes, dizziness

• Respiratory: shortness of breath, wheezing, throat tightness

• Constitutional: fatigue, temperature dysregulation, night sweats

Many patients struggle for years with these seemingly unrelated symptoms before receiving a correct diagnosis.

The Functional Medicine Difference

While traditional medicine typically addresses MCAS with antihistamines and symptom management, functional medicine asks a deeper question: Why are your mast cells overreacting in the first place?

Our approach focuses on:

• Identifying and addressing root causes (gut dysfunction, infections, toxic exposures, chronic stress)

• Stabilizing mast cell activity

• Reducing total inflammatory burden

• Supporting your body's natural healing mechanisms

• Personalizing treatment to your unique triggers and biochemistry

Below are three foundational tools we may use at Clark Wellness to help our MCAS patients reclaim their health.

1. Low Dose Naltrexone (LDN): Rebalancing Your Immune System

Low Dose Naltrexone is a compounded medication that works quite differently from standard naltrexone (used for addiction). At very low doses (0.5mg to 4.5mg), LDN temporarily blocks certain receptors in your body, which triggers a rebound effect—your body responds by producing more of its own natural "feel-good" chemicals called endorphins.

Here's what makes this interesting: these endorphins don't just affect mood and pain—they also help regulate your immune system.

How LDN helps MCAS:

• Calms down excessive immune activation

• Reduces inflammatory signaling throughout your body

• Helps stabilize mast cells indirectly

• Improves your body's resilience to triggers like stress, infections, or environmental exposures

• Many patients notice improvements in energy, mental clarity, and overall inflammatory symptoms

What to expect: LDN isn't a quick fix—it typically takes 2-3 months to see full benefits. We start at very low doses and adjust based on your individual response. Some patients experience vivid dreams initially, which usually resolves within a few weeks.

2. Ketotifen: Direct Mast Cell Support

Ketotifen offers powerful dual benefits for MCAS by working through two different mechanisms simultaneously.

How it works:

• Mast cell stabilization: Prevents your mast cells from releasing histamine and other inflammatory chemicals in the first place

• Antihistamine action: Blocks histamine receptors so any histamine that does get released causes fewer symptoms

This makes ketotifen particularly effective for patients experiencing frequent reactions or multi-system symptoms.

What to expect: We typically start with a low dose (0.5mg) at bedtime since drowsiness is common initially. Most patients find this sedation improves significantly after 2-3 weeks. We gradually increase your dose as your body adjusts.

Ketotifen serves as an important bridge—helping control your symptoms while we work together to address the deeper issues driving your mast cell dysfunction.

3. Anti-Inflammatory Nutrition: Lowering Your Baseline Inflammation

What you eat directly impacts mast cell activity. Food can either fuel healing or trigger more inflammation—which is why nutrition is foundational in MCAS management.

Key dietary strategies:

Remove high-histamine foods:

• Fermented foods (sauerkraut, kombucha, yogurt)

• Aged cheeses and cured meats

• Alcohol and vinegar

• Leftovers (histamine increases as food ages)

• Certain fish like tuna, mackerel, and sardines

Eliminate common triggers:

• Gluten and conventional dairy

• Artificial colors, preservatives, and additives

• Foods you know cause reactions

Focus on fresh, healing foods:

• Freshly prepared vegetables (especially leafy greens, zucchini, carrots, sweet potatoes)

• Low-histamine fruits (blueberries, apples, pears)

• Fresh proteins prepared and eaten immediately (grass-fed meats, pasture-raised poultry)

• Anti-inflammatory fats (olive oil, coconut oil, avocado)

• Bone broth and collagen peptides for gut healing

  
  

Supportive nutrients:

• Quercetin: A natural mast cell stabilizer found in foods and supplements

• Vitamin C: Helps break down histamine

• DAO enzymes: Support your body's ability to process dietary histamine

• Omega-3 fatty acids: Reduce overall inflammation

  
  

Gut healing is critical: Since approximately 70% of your immune system lives in your gut, healing intestinal permeability ("leaky gut") is often essential for calming mast cell over reactivity. We address this through targeted protocols including L-glutamine, specific probiotics (introduced carefully), and gut-soothing nutrients.

Your Path Forward

MCAS doesn't have to control your life. While this condition can feel overwhelming, especially when symptoms affect so many body systems, effective treatment is possible.

At Clark Wellness, we combine:

• Appropriate medications like LDN and Ketotifen for symptom control

• Personalized anti-inflammatory nutrition plans

• Comprehensive testing to identify your specific triggers

• Targeted protocols to address root causes like gut dysfunction, chronic infections, mold exposure, or toxic burden

• Ongoing support and adjustments as you heal

  
  

Every patient's MCAS journey is unique. What triggers one person may not affect another. What helps one patient might need adjustment for you. This is why personalized, functional medicine care is so important.

You deserve to feel heard, understood, and supported as we work together to identify your triggers, calm your overactive mast cells, and address the root causes keeping you stuck in this cycle.

Ready to take the next step?

If you're struggling with unexplained symptoms that seem to involve multiple body systems, or if you've been diagnosed with MCAS and aren't getting better with conventional treatment alone, we're here to help.

Clark Wellness specializes in root-cause approaches to complex conditions like MCAS. Our comprehensive functional medicine evaluations help identify what's driving your symptoms so we can create a personalized healing plan.

Contact us to schedule your initial consultation:

Clark Wellness Functional Medicine in Waco | Personalized Care

Disclaimer: This information is for educational purposes only and should not replace personalized medical advice. MCAS treatment should always be supervised by a qualified healthcare provider familiar with mast cell disorders.

What Does a Functional Medicine practitioner Do for Hormones?

You've tried everything. You've told your doctor about the exhaustion that doesn't improve with sleep, the stubborn weight that won't budge no matter what you eat, the mood swings that make you feel like a stranger in your own body. And every time, you hear the same thing: "Your labs look normal."

But you know something isn't right.

If this sounds familiar, you're not alone—and you're not imagining things. The truth is, conventional medicine often looks at hormones through a very narrow lens. A functional medicine approach sees the bigger picture.

How Is This Different From My PCP or GYN?

Your primary care physician and gynecologist are valuable members of your healthcare team—but they're trained in a system designed for acute care and disease management, not optimization.

Here's what that looks like in practice:

Time constraints. Your PCP typically has 10-15 minutes to address whatever brought you in that day, plus review all of your medications, check your vitals, and document everything. There simply isn't time to dig into the complex web of symptoms that hormone imbalances can create. You might mention fatigue, and they'll order a basic thyroid panel. You mention weight gain, and they'll suggest eating less and moving more. Each symptom gets addressed in isolation, if it gets addressed at all.

Limited testing. Conventional providers typically order the bare minimum possibly because of insurance coverage limitations: TSH for thyroid, maybe an estrogen or testosterone level. But hormones are far more complex than a single marker can reveal. Without looking at free hormone levels, how your body metabolizes hormones, your cortisol patterns, or the inflammatory and gut factors that influence hormone function, you're only seeing a fraction of the picture.

"Normal" isn't optimal. When your labs come back, they're compared against reference ranges that represent the middle 95% of the population—including people who are sick, stressed, and struggling. Falling within that range doesn't mean you're thriving. It means you're not flagged as diseased. There's a vast difference between "not sick" and "actually well."

Symptom management vs. root cause. If your PCP or GYN does identify a hormone issue, the solution is typically a prescription: birth control pills to regulate your cycle, synthetic thyroid medication, maybe an antidepressant for your mood symptoms. These interventions can be helpful, but they don't ask why your hormones became imbalanced in the first place. They manage symptoms without addressing the underlying dysfunction.

Fragmented care. In the conventional system, your thyroid is managed by an endocrinologist, your reproductive hormones by your GYN, your mood by a psychiatrist, and your gut issues by a gastroenterologist. But your body doesn't operate in separate departments. Hormones interact constantly, and what looks like a thyroid problem might actually be driven by chronic stress, blood sugar imbalance, or gut dysfunction. Functional medicine connects the dots that specialty care often misses.

This isn't a criticism of your PCP or GYN—they're doing important work within a system that wasn't designed for the kind of comprehensive, personalized care that some hormone issues may require. Functional medicine fills that gap.

The Functional Medicine Approach

Functional medicine takes a different path. Instead of asking, "Is this lab value within range?" we ask, "Why is your body producing this hormone at this level, and what does it tell us about your overall health?"

Hormones don't operate in isolation. Your thyroid, adrenals, sex hormones, insulin, and cortisol are all in constant communication—a symphony that needs every instrument playing in harmony. When one system struggles, the others compensate, and eventually, the whole orchestra falls out of tune. A functional medicine practitioner listens for the discordant notes and traces them back to their source.

Digging Into Root Causes

When you come in with symptoms of hormone imbalance—whether that's fatigue, weight gain, brain fog, hair loss, irregular cycles, low libido, or sleep disturbances—the first step isn't to immediately prescribe a hormone replacement. The first step is to understand why your hormones are out of balance in the first place.

This requires comprehensive testing that goes far beyond what you'd receive in a standard physical. We look at the full picture: not just your TSH, but your free T3, free T4, reverse T3, and thyroid antibodies. Not just your total testosterone or estrogen, but how your body metabolizes those hormones and whether those pathways are functioning properly. We examine your cortisol rhythm throughout the day, your fasting insulin, your inflammatory markers, and the health of your gut—because yes, your gut has everything to do with your hormones.

The goal is to identify the upstream factors that are driving the imbalance. Is chronic stress depleting your adrenals and stealing resources from your sex hormones? Is blood sugar instability creating a cascade of hormonal chaos? Is inflammation from food sensitivities or a compromised gut barrier interfering with hormone signaling? Is your liver struggling to properly detoxify excess hormones?

These are the questions that get us to real answers.

A Personalized Path to Balance

Once we've identified the root causes, we build a treatment plan tailored specifically to your body and your life. This might include targeted nutritional interventions, specific supplements to support hormone production or metabolism, lifestyle modifications that address sleep and stress, and when appropriate, bioidentical hormone therapy.

But here's what makes functional medicine different: we don't just hand you a prescription and send you on your way. We partner with you. We educate you about what's happening in your body so you understand not just what to do, but why it matters. We retest and adjust. We celebrate your wins and troubleshoot the setbacks.

Because balancing hormones isn't about chasing a number on a lab report. It's about helping you feel like yourself again—energized, clear-headed, and fully present in your life.

Why Should You Try This Approach?

Maybe you've been managing your symptoms for years. Maybe you've accepted that feeling tired, foggy, and not quite like yourself is just part of getting older. Maybe you've wondered if it's worth trying something different when nothing else has worked.

Here's why functional medicine is worth considering:

You get answers, not just prescriptions. Understanding why your body is struggling is empowering. When you know the root cause, you can make informed decisions about your health instead of just taking medications indefinitely without knowing what they're actually addressing.

Your whole story matters. In functional medicine, we spend time—real time—listening to your history, your symptoms, your lifestyle, and your goals. We connect patterns that have been overlooked. That headache, your afternoon energy crash, your difficulty losing weight, and your irregular cycles might all be connected. We find that thread.

You're treated as an individual. Your hormone imbalance isn't identical to anyone else's, and your treatment shouldn't be either. Cookie-cutter protocols don't work because your body, your stress load, your gut health, your genetics, and your life circumstances are unique to you.

You address problems before they become diseases. Conventional medicine excels at crisis intervention, but it often waits until dysfunction has progressed to diagnosable disease before taking action. Functional medicine identifies and corrects imbalances early—before that pre-diabetes becomes diabetes, before that sluggish thyroid becomes full-blown hypothyroidism, before those hormone imbalances contribute to more serious conditions down the road.

You become an active participant in your health. This isn't passive medicine where things are done to you. You'll understand your body better than you ever have. You'll learn which foods, habits, and lifestyle factors support your hormones and which ones sabotage them. That knowledge stays with you for life.

You deserve to feel good. Not just "fine." Not just "functional." Actually good—with steady energy, a clear mind, a healthy weight, and a body that feels like home. That's not an unrealistic expectation. It's what's possible when your hormones are truly balanced.

When to Seek Help

If you've been struggling with symptoms that seem hormonal but you've been told everything is "fine," trust your instincts. If you're exhausted despite sleeping eight hours, gaining weight despite eating well and exercising, feeling anxious or depressed without an obvious cause, or experiencing changes in your menstrual cycle, libido, or body composition—these are all signals worth investigating.

You deserve more than a dismissive pat on the shoulder and a suggestion to reduce stress. You deserve a thorough evaluation, real answers, and a plan that addresses the why behind your symptoms.

At Clark Wellness, we specialize in helping patients uncover the root causes of hormone imbalance and restore optimal function. As the only IFM-certified practitioner in the Waco area, Angelica Clark, PA-C, IFMCP, brings over 17 years of clinical experience and a deeply personal commitment to ensuring every patient feels heard and understood. If you're ready to stop settling for "normal" and start pursuing optimal, we'd love to help.

www.clarkwellnestx.com

Contact Clark Wellness today to schedule your consultation.