What We Measure in a Longevity Workup — And Why It Matters

A longevity workup is a comprehensive medical evaluation that goes well beyond standard bloodwork — combining advanced biomarker panels, cardiac and total body imaging, cancer screening, genomic analysis, body composition testing, and cardiorespiratory fitness assessment to identify disease risk years before symptoms appear and build a personalized roadmap for healthspan optimization.

Most people have had a physical. You get your cholesterol checked, your blood pressure recorded, maybe a referral or two, and a handshake on the way out. If everything looks "normal," you're told to come back next year.

That kind of evaluation was designed to catch disease. It does a reasonable job of that. What it was never designed to do is help you understand where your health is actually heading, and what you could change right now to alter that trajectory over the next two, three, four decades.

That's the gap a longevity workup is built to close. And the difference between the two — philosophically and clinically — is worth understanding before you decide which kind of care you want.

Why Standard Labs Miss Most of What Matters

The standard lipid panel most internists order has been the cornerstone of cardiovascular risk assessment for decades. It gives you total cholesterol, LDL, HDL, and triglycerides. The problem is that LDL cholesterol — the number almost everyone focuses on — is actually one of the weaker predictors of who will develop cardiovascular disease and who won't.

What matters more is ApoB: apolipoprotein B, a protein that coats every atherogenic lipoprotein particle in your blood. Where LDL measures the cholesterol inside those particles, ApoB counts the particles themselves, and it's the particles — not just their cholesterol content — that drive plaque formation in arterial walls. A 2024 analysis across 15 studies involving 593,354 participants found that ApoB outperformed LDL cholesterol as a predictor of cardiovascular risk in 9 out of 9 head-to-head comparisons. The National Lipid Association now recommends stratified ApoB targets — below 90 mg/dL for average-risk individuals, below 60 mg/dL for very high-risk — rather than relying on LDL alone.

We also measure OxPL-ApoB (oxidized phospholipids on ApoB particles), which captures a more specific inflammatory dimension of cardiovascular risk, along with Lp(a), a genetically determined lipoprotein that standard panels never check and that roughly 20% of the population carries at levels significantly elevating their lifetime cardiac risk with no awareness of it at all.

The hormone picture gets the same level of detail. Thyroid function is evaluated not just with TSH — which alone tells you almost nothing about peripheral thyroid activity — but with Free T3, Free T4, and Reverse T3, so we can understand whether thyroid hormone is actually getting into cells and functioning, not just circulating.

Sex hormone assessment goes well beyond a single testosterone level. For men, we look at total and free testosterone, SHBG, estradiol, DHT, LH, FSH, and DHEA-S — because a "normal" total testosterone with low free testosterone and high SHBG tells a completely different clinical story than the number alone. For women, the picture is equally detailed: estradiol, progesterone, testosterone, SHBG, and DHEA-S across cycle phase where relevant, along with markers of adrenal function. Hormone optimization is a core part of what we do at Makena Health, and we offer both testosterone replacement therapy for men and full hormone replacement therapy for women — not as an afterthought, but as a primary therapeutic lever for energy, body composition, cognitive function, cardiovascular protection, and long-term healthspan.

For patients where we need a deeper look at how hormones are being metabolized — particularly estrogen metabolism pathways and cortisol rhythm — we use the DUTCH Complete test, a dried urine collection that captures hormone metabolites and their downstream patterns in a way that serum labs simply can't. This matters for women on or considering HRT, for patients with symptoms that don't match their serum levels, and for anyone whose history suggests a pattern worth understanding more precisely before initiating or adjusting a protocol.

The metabolic panel includes fasting insulin alongside HbA1c and fasting glucose, because insulin resistance frequently develops 10 to 15 years before a diabetes diagnosis appears, and conventional labs won't catch it until you're already far down that road. We add RBC magnesium rather than serum magnesium, because serum levels are maintained by drawing magnesium out of tissues — they're often normal right up until deficiency becomes clinically significant.

Standard labs tell you if you're sick today. A longevity workup tells you where your health is heading — and gives you time to change course.

Imaging: What Blood Tests Can't See

There are things happening in the body that no blood test will ever reveal. Coronary plaque. Soft tissue changes in the brain. Early organ pathology. For these, imaging is the only way in.

For cardiac risk, we use the Cleerly Heart Exam, an AI-driven analysis of coronary CT angiography that goes well beyond a standard calcium score. Calcium scores only detect calcified plaque — meaning it has to be old and hardened before it shows up. Cleerly quantifies and characterizes all plaque, including low-attenuation non-calcified plaque, which is the type most likely to rupture and cause a heart attack. This matters clinically because patients with normal calcium scores can still have significant soft plaque burden, and without this level of imaging, you'd never know.

For brain health, we incorporate MRI with NeuroQuant — a volumetric analysis tool that measures the size of key brain structures and compares them against a normative database adjusted for age and sex. The hippocampus, for instance, begins to show measurable volume loss years before any cognitive symptoms emerge. Catching that early gives us something to act on: sleep optimization, metabolic intervention, targeted exercise, and if appropriate, hormonal support — all of which have demonstrated effects on brain structure and cognitive trajectory.

We also check plasma amyloid and phosphorylated tau (pTau) biomarkers from a blood draw — tests that can detect the biological hallmarks of Alzheimer's disease one to two decades before symptoms appear. This is one of the most significant developments in preventative neurology in the last several years. Amyloid accumulation and tau pathology begin silently, long before any measurable cognitive decline, and having that signal early means there's actually time to intervene — with metabolic optimization, sleep treatment, targeted supplementation, hormonal support, and emerging therapies — rather than waiting for a diagnosis that arrives too late to meaningfully change the outcome.

Total body MRI protocols provide high-resolution views of abdominal and pelvic organs. We prefer dedicated organ-specific protocols over general screening services, because they produce higher diagnostic accuracy and fewer incidental findings that generate unnecessary follow-up anxiety without clinical clarity.

Low-dose CT lung screening remains the standard of care for lung cancer detection in appropriate-risk individuals — one of the few screening tools with a proven survival benefit in randomized controlled data.

Cancer Screening Beyond the Standard Tests

Roughly 70% of cancer deaths in the United States come from cancers that have no recommended screening test — pancreatic, ovarian, esophageal, and others that are typically found late, when outcomes are dramatically worse.

The Galleri multi-cancer early detection test changes that calculus. It analyzes cell-free DNA in a blood sample, looking for methylation patterns that indicate a cancer signal, and then predicts the cancer signal origin with 87% accuracy based on real-world data across more than 100,000 participants published in Nature Communications. The test screens for more than 50 cancer types, and its specificity is 99.5% — meaning the false positive rate is under 1%.

It's worth being precise about where Galleri performs well and where it doesn't, because that honesty is actually what makes it useful. The test's sensitivity is strongest for stage III and IV cancers, where circulating tumor DNA is more abundant in the bloodstream. For early-stage disease, sensitivity drops considerably — and for some of the most common cancers, including breast and prostate, Galleri is not a reliable primary screening tool. We don't use it as one. Mammography, PSA, and other organ-specific screens remain essential and are incorporated separately based on each patient's age, sex, and risk profile.

Where Galleri earns its place is in the cancers that have no other screening option at all — pancreatic, ovarian, esophageal, liver, and others that are typically silent until they're advanced and far harder to treat. For those, a positive signal from Galleri can be the difference between catching something operable and finding out too late. That's why it's part of a comprehensive program rather than a standalone solution, and why we're explicit with every patient about what it can and can't do.

Genomics: What You Were Born With

Genomic analysis is where longevity medicine starts to become truly personalized rather than population-based. Standard medicine treats everyone with similar lab values largely the same way. Genomics changes that, because two people with the same ApoB and the same blood pressure can have fundamentally different cardiovascular risk trajectories depending on what their genes say about inflammation, lipid metabolism, coagulation, and oxidative stress response.

We offer two genomic options depending on the patient's goals. IntellXX DNA provides highly detailed pharmacogenomic and nutrigenomic analysis, connecting genetic variants to clinical recommendations in a format built for physician interpretation. The 3x4 Genetics panel takes a systems biology approach, looking at metabolic pathways across inflammation, methylation, detoxification, and hormonal signaling — particularly useful for patients interested in understanding the root mechanisms behind conditions they've been managing for years.

Neither replaces clinical judgment, and raw genetic data without physician context is often more anxiety-producing than useful. The goal is integration — using genetic findings to refine the direction and specificity of the overall protocol, not to hand someone a printout and call it a plan.

Lifestyle First: Building the Foundation Before the Penthouse

No amount of testing, supplementation, or advanced therapy will overcome a broken foundation. This is something we're direct about with every patient from the first conversation.

Before we layer in hormone optimization, peptide therapy, or regenerative treatments, we spend real time on the fundamentals — nutrition, sleep, movement, stress, and relationships. Not because these are obvious, but because they're almost always where the highest leverage actually is, and because every advanced intervention we offer works better, lasts longer, and costs less when the foundation underneath it is solid.

Nutrition gets individualized attention, not a handout. We look at what someone is eating, how their labs and body composition reflect it, and what's actually sustainable for their life here in Maui or wherever they spend most of their time. Sleep is treated as a primary clinical variable, not an afterthought — because no hormone protocol in the world will work properly in someone sleeping six fragmented hours a night. Movement is prescribed with the same specificity as a medication: type, intensity, frequency, and progression, built around the patient's fitness data and goals.

We think of it this way: the advanced therapies are the penthouse. Lifestyle is the foundation. You can build a penthouse on a cracked foundation, but it won't stand for long — and it won't perform the way it should. Our job is to make sure the structure underneath is sound before we build upward, and then to keep refining both as we go.

Cardiorespiratory Fitness: The Number That Predicts More Than Any Lab

If I had to pick one number from a longevity workup that carries more predictive weight than any other, it's VO₂ max.

A 2018 study published in JAMA Network Open followed 122,007 adults through treadmill exercise testing and found that cardiorespiratory fitness — measured by VO₂ max — was the single strongest predictor of survival they identified, stronger than smoking status, blood pressure, diabetes, and coronary artery disease. Moving from low fitness to below-average fitness is associated with roughly a 50% reduction in all-cause mortality over a decade. Going from low to above-average reduces risk by closer to 70%. The research consistently shows that low VO₂ max carries a mortality hazard comparable to being a smoker with heart disease.

We use the Q-NRG Max metabolic testing system, which uses hospital-grade breath-by-breath gas analysis and is available with both treadmill and cycle ergometer protocols. This matters because fitness levels vary enormously, and a testing modality that works for a recreational runner may be inappropriate or inaccurate for someone who hasn't exercised seriously in years. The data we get from this assessment drives our aerobic training recommendations at the zone level — not "exercise more" as a generic instruction, but a specific, individualized prescription.

Body Composition: Beyond Weight and BMI

Weight tells you almost nothing useful about health trajectory. Body composition tells you quite a bit.

We use the SECA BIA medical-grade bioelectrical impedance device to measure segmental lean mass, fat mass, visceral fat, and intracellular versus extracellular fluid distribution. For longevity, the metric that matters most is skeletal muscle mass — specifically, whether someone is maintaining adequate muscle relative to their frame as they age, and whether their current trajectory is heading toward sarcopenia or away from it.

Visceral fat — the metabolically active fat stored around organs in the abdominal cavity — is independently associated with insulin resistance, cardiovascular risk, and systemic inflammation at levels that subcutaneous fat doesn't produce. You can't assess visceral fat from a scale. A patient at a "normal" BMI can carry high visceral adiposity and be at substantially elevated metabolic risk.

The body composition data integrates directly with the rest of the workup. If fasting insulin is elevated and visceral fat is high, we have both a metabolic and a body composition signal pointing in the same direction. That's actionable. Treating either in isolation misses the picture.

What Happens With the Data

Ordering tests is the easy part. The value of a longevity workup is entirely in what happens afterward — how the findings are synthesized into a coherent picture, and how that picture translates into a specific, prioritized plan.

At Makena Health, after all results are compiled, I review everything and produce a detailed final report that connects the findings across systems. Not just "your ApoB is elevated — here's a statin." More like: your ApoB is elevated, your OxPL-ApoB suggests active oxidative burden, your fasting insulin is trending up, your body composition shows early visceral fat accumulation, and your VO₂ max puts you in the bottom quartile for your age — and here is the sequence of interventions, ranked by leverage and urgency, that addresses the root mechanisms driving all of those findings simultaneously.

One patient I think about often came to us at 55, newly relocated from the mainland. Active enough, eating reasonably well by most standards, no major complaints. His prior physician had cleared him without any flags. What the workup found was a different picture: fasting insulin above 30, free testosterone at 30 ng/dL, a BMI of 33 carrying significant visceral adiposity, and enough clinical signs to refer him to Empower Sleep — where he was formally diagnosed with obstructive sleep apnea that had been running undetected for years.

None of that would have appeared on a standard annual lab panel. None of it.

We restructured his nutrition around whole, unprocessed foods — high protein, fresh local produce, the kind of eating that's actually sustainable here in Maui — added structured weight training twice a week with a personal trainer, started tirzepatide for metabolic support, initiated testosterone replacement therapy, and got the sleep apnea treated. Eighteen months later he's down 40 pounds and, more importantly, he feels like himself again for the first time in years. His insulin is normalized, his testosterone is optimized, and his sleep is no longer silently destroying his recovery every night.

That's not a remarkable case. It's actually a common one. The remarkable part is that most people in that situation never find out what's wrong because no one looked carefully enough.

Ready to Understand Your Numbers?

The executive physical at Makena Health is how most members begin. It's a structured, comprehensive evaluation that puts all of this testing in one place, followed by a personalized action plan built around your specific findings — not population averages.

If you're already a Makena Health member and want to discuss which components of this workup apply to your current care plan, reach out directly and we'll build from where you are.