Inflammation is the terrain on which chronic disease plays out

I still remember a patient—let’s call him John—who came in convinced his “aches and fog” were just part of turning 50. His labs weren’t terrible: borderline cholesterol, fasting glucose a touch high, blood pressure flirting with the line. Nothing that screamed emergency.

But his hs-CRP (a marker of systemic inflammation) was sky-high. We focused on calming his inflammatory load rather than chasing each datapoint in isolation.

Twelve weeks later, through use of a structured program, the joint pain had eased, his sleep sharpened, and his energy returned. His other numbers improved as a side effect. That experience, repeated many times, cemented a core lesson I share with patients and business leaders alike: inflammation isn’t just another variable—it’s the terrain on which chronic disease plays out. If you don’t address the terrain, you’ll always be addressing the end resulting symptoms by not focusing on the true issue causing those symptoms.

What is inflammation?

Inflammation is your body’s damage-control system. You cut your finger, catch a virus, or lift heavy weights; immune cells arrive, chemical signals surge, repair gets done, and the response winds down. That’s acute inflammation—useful, time-limited, and essential for life.

The trouble starts when the “on switch” sticks—when a low-grade, smoldering response never fully resolves. That’s chronic inflammation. It may not be dramatic, but it disrupts cellular function across systems: blood vessels, brain, liver, gut, joints, skin.

Think of it as static in the signal of health. If you're curious how the science works under the hood:

• Pattern recognition and first responders. Cells of the innate immune system (macrophages, neutrophils, dendritic cells) patrol for “danger patterns”—bits of microbes like bacterial lipopolysaccharides (or LPS) or distress signals from damaged cells. Receptors such as toll-like receptors (TLRs) and NOD-like receptors (NLRs) recognize those patterns and flip on inflammatory pathways.

• Molecular amplifiers. Once activated, transcription factors like NF-κB and AP-1 tell the nucleus to produce cytokines—messenger proteins such as TNF-α, IL-1β, IL-6. These recruit more immune cells, increase blood flow, and change how tissues use energy. The NLRP3 inflammasome acts like a molecular match, igniting IL-1β and IL-18 to escalate the response.

• Mitochondria and metabolic crosstalk. Your mitochondria—best known for making ATP, the energy currency we use on a moment by moment basis to live—also serve as danger sensors. When stressed (by nutrient overload, toxins, or poor sleep), they leak reactive oxygen species (ROS) that further activate inflammatory signaling. Inflammation then pushes cells to favor glycolysis (“quick energy”) over efficient respiration, creating a feedback loop leading to more inflammation.

• The brake system. Resolution isn’t passive; it’s an active biological program. Specialized pro-resolving mediators (SPMs)—lipid molecules derived from omega-3s—help immune cells switch from “attack” to “clean-up and repair.” Chronic inflammation often reflects a failure of this resolution phase as much as an overactive start.

• Adipose tissue and the liver. Visceral fat isn’t inert storage; it’s an endocrine organ. Enlarged fat cells, especially those located in vital organs where they should not be stored, release cytokines and free fatty acids that inflame the liver, drive insulin resistance, and create more oxidative stress. The liver, in turn, produces CRP and other acute-phase reactants, keeping the loop alive.

• The gut barrier and microbiome. A healthy gut lining is a selective border: nutrients in, threats out. Dysbiosis (imbalanced microbes), low fiber intake, infections, and chronic stress can loosen tight junctions (“leaky gut”), allowing bacterial fragments like LPS to seep into circulation—a potent trigger for systemic inflammation.

• Senescent cells (the “zombie” crowd). Cells that have stopped dividing but refuse to die secrete a cocktail of inflammatory signals called the SASP (senescence-associated secretory phenotype). As these cells accumulate, they create a pro-inflammatory microenvironment that accelerates tissue aging.

The takeaway: inflammation is not one thing; it’s a network. Metabolism, immunity, microbiome, and mitochondria are all talking—sometimes whispering, sometimes shouting.

“Inflammaging”: when the thermostat drifts as we age

Dr. Mark Hyman popularized the term “inflammaging” (originally described by Claudio Franceschi and colleagues in the early 2000s) to describe a hallmark of getting older: our cellular thermostat for inflammation loses precision. We still need inflammation to heal a cut or fight a cold, but the off switch becomes sluggish. Why?

1. Cumulative micro-insults. Decades of normal metabolism produce oxidative byproducts. Small, daily exposures—to ultra-processed foods, poor sleep, chronic psychological stress, pollutants—layer together like compound interest, nudging immune pathways toward default “on.”

2. Immune system remodeling. With age, innate immune cells skew pro-inflammatory, while adaptive responses (like antibodies to new infections) weaken. The system becomes more trigger-happy and less discerning.

3. Mitochondrial wear. Power plants get less efficient. More ROS, less ATP, more “danger” signals.

4. Senescent cell pile-up. The SASP fog grows, disturbing tissue repair and promoting fibrosis.

5. Hormonal and autonomic shifts. Lower sex hormones, impaired vagal tone, and flattened cortisol rhythms reduce our anti-inflammatory buffering capacity.

This is why a 25-year-old can bounce back from a week of poor sleep with minimal fallout, while a 65-year-old may notice brain fog, higher blood pressure, and a tough-to-shake cold after the same insult.

There is a quote I love from Indiana Jones: ‘It’s not the age, it’s the miles’. The reality is all those ‘miles’ are cumulative and some of us have had decades of hard ‘miles’ through poor eating, less movement, little sleep and high stress on those cellular processes.

The goal of smart longevity isn’t to eliminate inflammation—that would be impossible and dangerous—but to retrain the thermostat so we can mount robust, targeted responses and then fully resolve them.

Practical levers to dial down chronic inflammation

You don’t need perfection; you need direction and consistency. Here’s how we help patients—and busy executives—lower inflammatory burden in real life.

1) Eat to resolve (not just to restrict)

• Build your plate around whole foods. Aim for 30–40 g of fiber daily from vegetables, legumes, nuts, seeds, and whole grains (as tolerated). Fiber feeds beneficial gut microbes that produce butyrate, a short-chain fatty acid that strengthens the gut barrier and quiets inflammation.

• Prioritize quality protein. Adequate protein (roughly 1.2–1.6 g/kg/day for most active adults) maintains muscle, which is anti-inflammatory by design. Distribute evenly across meals.

• Favor anti-inflammatory fats. Include omega-3–rich fish (salmon, sardines, mackerel) 2–3 times per week; olive oil, nuts, and seeds as staples. Limit industrial seed oils and deep-fried foods that push omega-6–to–omega-3 ratios into pro-inflammatory territory.

• Color as a metric. Polyphenols in colorful plants (berries, leafy greens, turmeric, cocoa, green tea) act like software updates for your antioxidant and detox pathways.

• Reduce ultra-processed foods and added sugars. They spike insulin and feed dysbiosis, keeping NF-κB humming.

• If you drink, set boundaries. Alcohol raises gut permeability and inflammation; keep it modest and infrequent.

2) Train your inflammation thermostat with movement

• Zone-2 cardio (easy-to-sustain effort, you can converse) 150–180 minutes per week improves mitochondrial efficiency and insulin sensitivity—two direct hits on chronic inflammation.

• Resistance training 2–3 times weekly builds muscle (your metabolic sink), reduces visceral fat, and secretes myokines that are anti-inflammatory.

• Move often, not just hard. Break up long sitting with 2–3 minutes of light activity each hour. Micro-movement smooths glucose and lowers post-meal inflammatory spikes.

3) Treat sleep like therapy

• 7–9 hours, most nights. Sleep is when the brain’s glymphatic system clears waste and the immune system recalibrates.

• Regularity beats heroics. Anchor a consistent wake time, dim lights 2 hours before bed, and keep the bedroom cool and dark.

• Screen apnea. Loud snoring, witnessed apneas, morning headaches, or resistant hypertension? Test and treat. Untreated OSA is an inflammation engine.

  
  

4) Regulate the stress loop (and your vagus nerve)

Chronic psychological stress shifts the immune system toward a pro-inflammatory profile.

• Daily downshifts. 5–10 minutes of breathwork (slow exhale emphasis), prayer, or mindfulness practice stabilizes autonomic tone.

• Sunlight and nature contact. Morning outdoor light anchors circadian rhythms and cortisol curves; green time lowers CRP in clinical studies.

• Social connection. Loneliness is inflammatory. Prioritize relationships like you would a medication with proven benefit.

5) Mind your environment

• Air and water quality. Use HEPA filtration if you live with smoke, smog, or allergens; filter drinking water. Reduce indoor VOCs by choosing low-tox cleaners and ventilating well.

• Oral health. Periodontal inflammation contributes to systemic inflammation. Brush, floss, and keep routine cleanings.

6) Support the gut barrier

• Feed the right microbes. Fiber diversity and fermented foods (if tolerated) help. If you’re sensitive, start low and go slow.

• Elimination trials, not forever diets. Short, structured trials removing common irritants (ultra-processed foods, excess alcohol; and for selected individuals, gluten or dairy) can identify triggers. The goal is re-introduction and flexibility, not permanent restriction.

• Consider targeted supplements when indicated: omega-3s, curcumin, magnesium, vitamin D (if low), and, for those with impaired resolution, clinically guided SPMs. Use these to support lifestyle change, not to replace it.

7) Track a few meaningful markers

What you measure, you can improve:

• hs-CRP (systemic inflammation), fasting insulin and A1c (glycemic load), triglycerides/HDL ratio (metabolic health), ALT (liver), and vitamin D. In selected cases, consider LP-IR, ApoB, or a continuous glucose monitor for a few weeks to map personal triggers.

• Subjective metrics matter. Energy on waking, joint stiffness, post-meal clarity, and resilience to stress are real-world readouts of your inflammatory terrain.

  
  

8) Create frictionless habits

• Plan your protein and produce first when grocery shopping.

• Put walking shoes by the door and your yoga mat where you see it.

• Batch-cook once, benefit all week.

• Schedule sleep like a meeting you can’t miss.

Bringing it together

When leaders ask me how to future-proof their health, I tell them to think like operators. Inflammation is an operating condition, not a symptom. Lowering the inflammatory set-point improves the performance of every system built on top of it—metabolism, cognition, mood, recovery, and longevity.

John didn’t “cure” his joints. He changed his terrain. He learned to eat like someone feeding a trillion gut allies, to move in ways that teach his mitochondria efficiency, to guard sleep like a board meeting, and to treat stress management as daily hygiene. His labs followed his life, not the other way around.

Aging will always bring its share of miles. Inflammaging is real. But it’s not destiny. With steady, practical steps, you can restore the nuance of your immune response—the ability to fight when you must and fully resolve when you should. That’s the difference between accumulating years and compounding health.