The Advanced Longevity Biomarker Checklist: 12 Markers Your Standard Physical Misses

The standard annual physical includes about 12 routine markers — total cholesterol, HDL, LDL, triglycerides, fasting glucose, HbA1c, complete blood count, basic metabolic panel, TSH. These catch acute disease. They don't stratify longevity risk. The advanced longevity panel — the markers that working clinicians and researchers in the longevity space actually run — includes a different 12. This is that list.

The markers below come from the published cardiovascular and cognitive longevity literature plus the panels used by the working longevity-medicine clinicians. apoB instead of LDL-C. Fasting insulin instead of just fasting glucose. Omega-3 Index. Homocysteine. Lp(a). hs-CRP. ApoE genotype. Each predicts long-term outcome better than the standard-physical version, and each is actionable.

The full PDF reference card — with target ranges per the longevity research, where to test each marker, and retest cadence — is at the bottom of this post.

Tier 1 — Cardiovascular longevity (4 markers)

1. apoB (Apolipoprotein B)

apoB measures the actual particle count of all atherogenic lipoproteins. LDL-C measures cholesterol concentration — which can be the same in two adults with very different particle counts. The discordance literature (Sniderman et al, Circulation 2011) established that apoB outperforms LDL-C as a predictor of cardiovascular events across 12 prospective cohorts, and that ~30% of adults with "normal" LDL-C have elevated apoB.

The longevity-protocol target is apoB <60 mg/dL, with adults who have a family history of early CVD often targeting <50. The lab "normal" range tops out around 90 — too lenient for adults pursuing healthspan extension. Full deep-dive on apoB and Lp(a) here.

2. Lp(a) — Lipoprotein little-a

Roughly 20% of adults have elevated Lp(a). It's a one-time test — levels are genetically determined and essentially fixed for life. Strong independent risk factor for early myocardial infarction and aortic stenosis.

Target: <30 mg/dL (or <75 nmol/L). Adults with elevated Lp(a) need aggressive control of every other modifiable cardiovascular risk factor — statin therapy, apoB targets in the <50 range, blood pressure optimization. The number itself isn't fixable; the surrounding risk profile is.

3. Omega-3 Index

The Omega-3 Index is the percentage of EPA + DHA in red blood cell membranes. Index <4% has roughly 10× higher rates of sudden cardiac death than >8% in the long-cohort data. Average US adult sits at 4-5%; the cardioprotective target is >8%.

The Index is also one of the most actionable markers — supplementation with ~2 g daily EPA + DHA moves most adults into the protective range within 3-6 months. Full Omega-3 Index protocol here.

4. hs-CRP (High-Sensitivity C-Reactive Protein)

hs-CRP captures systemic inflammation that drives atherosclerotic plaque instability. The JUPITER trial (NEJM 2008) established that statin therapy in adults with elevated hs-CRP but normal LDL still reduced cardiovascular events 44%.

Target: <1.0 mg/L (intermediate 1-3, elevated >3). Test twice 2-4 weeks apart to establish stable baseline — single readings are noisy and acute illness can transiently spike values. Full hs-CRP and the JUPITER framework here.

Tier 2 — Metabolic longevity (3 markers)

5. Fasting Insulin

The standard physical runs fasting glucose, which can miss insulin resistance for a decade. Insulin resistance — the "type 3 diabetes" framework — is linked to cardiovascular events, dementia, and metabolic dysfunction long before glucose abnormalities appear.

Target: fasting insulin <7 µIU/mL, with the most aggressive longevity protocols targeting <5. Pair with HOMA-IR for a single interpretable insulin-resistance number.

6. HOMA-IR

HOMA-IR = (fasting insulin × fasting glucose) ÷ 405. A single calculated number that captures insulin resistance at the individual level. Target: <1.0, with >1.5 indicating clinically meaningful insulin resistance.

You can compute it yourself once you have fasting insulin + glucose, or services like Function Health report it directly on their panel.

7. HbA1c

Average blood glucose over ~3 months. Standard physical includes this, but the longevity target is tighter than the diabetes prevention threshold (5.7%).

Longevity target: <5.4%. Adults above 5.6% are at elevated risk despite being "normal" by clinical definition. CGM data adds resolution to HbA1c — see the CGM protocol here.

Tier 3 — Cognitive longevity (2 markers)

8. Homocysteine

Homocysteine elevation predicts brain atrophy + cognitive decline + cardiovascular events. The VITACOG trial (Smith et al 2010) showed B-vitamin supplementation slowed brain atrophy 30% in older adults with elevated homocysteine. Approximately 30% of the population has the MTHFR C677T variant that elevates homocysteine — often unrecognized.

Longevity target: <7 µmol/L. Standard "abnormal" threshold is >15 — far too lenient. The intervention: methylated B12 + 5-MTHF (methylfolate) + B6 (P5P). Most homocysteine reduction occurs within 4-6 weeks. Full homocysteine + methylation protocol here.

9. ApoE Genotype

ApoE4 carriers — roughly 25% of the population — face 3-12× higher Alzheimer's risk depending on heterozygous vs homozygous status. One-time genetic test, fixed for life.

What to do with the result: ApoE4 carriers benefit disproportionately from sleep architecture optimization, intermittent fasting, and aggressive cardiovascular risk control. The result doesn't change destiny — it changes which longevity interventions deserve more weight.

Tier 4 — Hormonal & thyroid (3 markers)

10. Free T3 + Free T4 + TSH

TSH alone (the standard physical) can miss subclinical hypothyroidism that affects energy, weight, and cognition. Adding Free T3 + Free T4 catches conversion issues — adults whose thyroid produces T4 fine but converts poorly to active T3.

Longevity target: TSH 1.0-2.5 mIU/L (standard "normal" goes up to 4.5), Free T3 toward upper third of reference range, Free T4 mid-range.

11. 25-Hydroxyvitamin D

Bone, immune, cardiovascular, and cognitive outcomes all track with vitamin D status. 70%+ of US adults fall below the 40-60 ng/mL range that longevity-focused clinicians target.

Longevity target: 50-80 ng/mL. The RDA targets only 600-800 IU daily — far too low for most adults. Personalized dosing protocol here.

12. Free Testosterone (men) or Estradiol + Progesterone (women)

Often dismissed as "age-related decline" when in fact substantially reversible. For men: Free T >15 ng/dL is the longevity-tier target. For women: estradiol and progesterone targets are context-dependent (pre- vs post-menopause), with luteal phase progesterone the key marker for cycling women.

How to actually get tested

The pragmatic path: a Function Health panel (~$250) plus a one-time ApoE genotype (~$99 via 23andMe + free interpretation, or $50-150 standalone) covers 11 of the 12 markers. Free testosterone in men is usually on Function's panel; estradiol/progesterone for women requires cycle-day timing.

The retest cadence

Some markers are one-time (genetic). Some respond to intervention in weeks. Some take months. The retest cadence matters as much as the initial test.

Putting it together

The advanced biomarker panel doesn't replace the standard physical — it sits alongside it. Use the standard physical for acute disease screening. Use the advanced panel for longevity risk stratification and protocol calibration.

The downloadable PDF below organizes all 12 markers into a one-page reference card with target ranges, where to test, and retest cadence. Print it. Bring it to your next blood draw. The conversation goes much better when you walk in with the markers already specified.

Reference framework drawn from the published longevity panel literature (Sniderman et al for apoB discordance; Harris & von Schacky for Omega-3 Index; JUPITER trial for hs-CRP; VITACOG for homocysteine; CARDIA, MESA, Framingham cohort data for population thresholds). This guide does not constitute medical advice. Test results should be interpreted by a qualified clinician familiar with your full health context.