Why Some People Never Get Sick (And Others Keep Fighting Disease)

This article explains why some people seem immune to illness while others constantly get sick, and what science reveals about building a stronger, more resilient immune system.

The question isn't whether you'll live to ninety-eight. That's already decided by factors mostly beyond anyone's control. The real question - the one I think about more than I probably should - is what those years will look like when you get there.

Key Factors That Determine Health Span vs. Lifespan

Factor	How It Affects Aging	What You Can Control	Measurable Markers
Chronic Inflammation (Inflammaging)	Drives cardiovascular disease, cognitive decline, muscle loss, and cancer risk through constant immune activation	Diet patterns (Mediterranean diet), regular exercise, stress management	C-reactive protein, interleukin-6, TNF-alpha levels
Genetics	Sets baseline inflammatory response, mitochondrial efficiency, and cellular repair capacity	Minimal direct control; epigenetic factors may be modifiable through lifestyle	Family longevity patterns, genetic testing for longevity markers
Immune System Regulation	Determines whether body responds appropriately to threats or stays chronically activated	Exercise-induced myokines, gut microbiome health through diet, adequate sleep	Inflammatory marker trends, immune cell profiles
Mitochondrial Function	Controls cellular energy production and oxidative stress levels that damage tissues	Exercise, caloric restriction patterns, antioxidant-rich foods	Oxidative stress markers, cellular energy metabolism tests
Gut Microbiome Composition	Regulates systemic inflammation and immune function throughout the body	High-fiber diet, fermented foods, limiting processed foods, antibiotic stewardship	Microbiome diversity testing, gut inflammation markers
Skeletal Muscle Mass	Produces anti-inflammatory myokines; maintains metabolic health and physical function	Resistance training, adequate protein intake, staying physically active	Muscle mass measurements, strength testing, mobility assessments

There's a term for this: health span. The number of years you live well, not just alive. And it's the single most important metric in modern medicine that almost nobody talks about correctly.

I keep coming back to the contrast between my two patients - Mrs. L.R., who won a biological lottery she didn't buy a ticket for, and Mr. R.P., who's been kept functional through decades of aggressive intervention. Both are ninety-eight. Both are still here. But their paths couldn't be more different.

What I'm starting to understand - what the data is starting to show, really - is that we've been asking the wrong questions about aging. We've been focused on why some people live longer, when we should have been asking how we can give more people those extra decades of function.

The Inflammation Problem Nobody's Talking About

Here's something that surprised me when I first encountered it in the literature: chronic low-grade inflammation - the kind that doesn't cause obvious symptoms - is probably the single biggest driver of age-related decline. Not genetics. Not even smoking or obesity, though those certainly matter.

We call it inflammaging. Terrible portmanteau, but accurate concept.

Your immune system, when you're young, is like a well-trained security force. It responds to threats - infections, injuries, damaged cells - and then stands down. Clean, efficient, proportionate. But as you age, that system starts to... drift. It begins reacting to things that aren't actually threats. It stays activated when it should be quiet. Low-level inflammation becomes the background hum of your biology.

This isn't wild speculation. We can measure it. C-reactive protein, interleukin-6, tumor necrosis factor-alpha - all markers of systemic inflammation that creep upward with age in most people. And when they do, everything downstream starts to falter. Cardiovascular disease accelerates. Cognitive decline speeds up. Muscle mass erodes faster. Cancer risk climbs.

The question is: why does this happen to some people and not others?

Mrs. L.R.'s inflammatory markers - when I checked them out of curiosity - were remarkably low. Not "good for her age." Just... good. Period. Mr. R.P.'s, predictably, were elevated. Not dangerously so, but enough to tell you his immune system was chronically on edge.

I don't know why her inflammation stayed quiet. Maybe it's mitochondrial efficiency - her cells producing less oxidative stress. Maybe it's gut microbiome composition, which we're only just beginning to understand as a major regulator of systemic inflammation. Maybe it's epigenetic - certain genes that control inflammatory responses staying properly regulated when others' don't.

Or maybe it's stochastic noise again. Random cellular luck compounding over decades.

What We Can Actually Control

Here's where it gets interesting, though. Because while we can't choose our inflammatory baseline, we can influence it. Not dramatically, but measurably.

The Mediterranean diet - which has become almost cliché at this point - reduces systemic inflammation. Not because of olive oil specifically or fish or any single magic food, but because of the cumulative pattern: high fiber, high polyphenols, low processed food, moderate protein. That combination seems to quiet the immune system's background chatter.

Exercise does the same thing, but through a different mechanism. Skeletal muscle, when you contract it repeatedly, releases myokines - signaling molecules that have anti-inflammatory effects systemically. It's one reason why people who stay physically active into their seventies and eighties have dramatically lower rates of chronic disease. Not because they're "healthier" in some vague sense, but because their muscles are actively suppressing inflammation.

Sleep matters too, though the mechanism is less clear. Chronic sleep deprivation - anything less than six hours regularly - correlates strongly with elevated inflammatory markers. It might be cortisol dysregulation. It might be impaired glymphatic clearance - the brain's waste removal system that operates primarily during deep sleep. Either way, the effect is real.

And then there's stress. Psychological stress. The kind that most people dismiss as "just in your head."

Chronic stress - especially the unpredictable, uncontrollable kind - activates the hypothalamic-pituitary-adrenal axis. That's the system that governs your cortisol response. When it's constantly firing, cortisol stays elevated. And chronically elevated cortisol is profoundly pro-inflammatory.

This isn't soft science. We can measure it. People under chronic stress show elevated inflammatory markers. They develop cardiovascular disease faster. Their immune systems age prematurely, something called immunosenescence - where your T cells and B cells lose their ability to respond effectively to new threats.

Mrs. L.R., incidentally, is one of the calmest people I know. She paints. She plays games with friends. She reads. She doesn't watch the news obsessively or scroll Twitter for hours. I don't know if that's cause or effect - maybe low inflammation made her naturally calmer - but I suspect it's a bit of both. A feedback loop.

Mr. R.P., by contrast, is anxious. Has been his whole life, according to his wife. Always worrying about something. Always catastrophizing minor symptoms. I've spent a lot of time trying to manage that anxiety alongside his cardiac disease, and I'm not sure I've succeeded.

The Real Breakthrough: Senescent Cells

There's a concept I think about more than almost any other these days: cellular senescence.

As you age, some of your cells stop dividing but don't die. They just... sit there. Metabolically active but functionally useless. Worse than useless, actually - they secrete inflammatory molecules that damage surrounding tissue. We call this the senescence-associated secretory phenotype, or SASP.

It's like having saboteurs embedded in your own tissues. They're not doing their job, and they're actively making it harder for neighboring cells to do theirs.

For years, this was just an interesting biological observation. But recently - within the last decade - we've started testing drugs that can selectively clear these senescent cells. Senolytics, they're called. Compounds like dasatinib and quercetin that trigger apoptosis - programmed cell death - specifically in senescent cells while leaving healthy ones alone.

The early results in animal models are striking. Mice treated with senolytics show improved cardiovascular function, better cognitive performance, reduced frailty, and increased lifespan. Not just lifespan - health span. They stay functional longer.

Human trials are underway now. Small studies, mostly in people with idiopathic pulmonary fibrosis or osteoarthritis, but the preliminary data suggests the same pattern: reduce the burden of senescent cells, and you slow the functional decline.

I think about this often with Mr. R.P. His repeated cardiac interventions bought him time, but they didn't address the underlying biology. He still accumulates senescent cells. His inflammation still creeps upward. His health span, despite our best efforts, is shorter than his lifespan.

What if we could change that?

The Problem With Prediction

Here's something that frustrates me: we're getting much better at predicting who will develop chronic disease, but we're not much better at preventing it in most cases.

Polygenic risk scores - algorithms that analyze hundreds or thousands of genetic variants to estimate disease risk - are now commercially available. You can get one for cardiovascular disease, Alzheimer's, type 2 diabetes, even certain cancers. And they're reasonably accurate. If your score says you're in the top 10% for heart disease risk, you probably are.

But knowing doesn't automatically translate to prevention. We don't have a pill that lowers your genetic risk. What we have are the same interventions we've always had: diet, exercise, blood pressure control, cholesterol management, smoking cessation.

Those work. They absolutely work. But they require sustained behavior change, which is notoriously difficult for most people. Especially when the threat is abstract and decades away.

This is where I think medicine is headed, though. Not just prediction, but early intervention at the biological level. Targeting inflammation before it causes disease. Clearing senescent cells before they accumulate enough to matter. Modulating the gut microbiome to optimize immune function. Addressing mitochondrial dysfunction before it cascades into metabolic disease.

We're not there yet. But the pieces are starting to fall into place.

What This Means for You

I don't have a neat conclusion here. I'm not going to tell you that if you eat right and exercise, you'll live to ninety-eight in perfect health. Mrs. L.R.'s existence proves that's not how it works.

What I will say is this: health span is more malleable than most people think. Not infinite, not perfectly controllable, but responsive to effort in ways we're only just beginning to quantify.

The basics still matter. They've always mattered. But the newer interventions - the ones targeting inflammation, cellular senescence, metabolic dysfunction - are starting to show real promise. Not as magic bullets, but as tools that might extend the window of functional life by five, ten, maybe fifteen years.

That's significant. Not because it gets you to 105 instead of 90, but because it means those extra years might look more like Mrs. L.R.'s life and less like Mr. R.P.'s.

I think about that whenever I see them. Both still here at ninety-eight. Both remarkable in different ways. But only one of them painting award-winning oils and driving herself to appointments.

The gap between those two realities - that's what we're trying to close.