Most physicians order the same twenty-panel metabolic screen at your annual physical. Most of those values tell you almost nothing about how long you will live well. The five biomarkers below are different: each has robust cohort data linking it to all-cause mortality, cardiovascular events, and functional decline, and each responds to targeted intervention. We use these as the foundation of our longevity assessments.
Why ApoB matters more than total cholesterol
Apolipoprotein B (ApoB) counts the number of atherogenic particles in circulation—LDL, VLDL, IDL, and lipoprotein(a)—each carrying exactly one ApoB molecule. Standard lipid panels report LDL cholesterol, which estimates the cholesterol mass inside those particles, but particle number predicts cardiovascular risk more accurately. A 2019 analysis in JAMA Cardiology of over 150,000 participants found that ApoB outperformed LDL-C in predicting myocardial infarction and stroke across all ages.
The threshold that matters: below 60 mg/dL is optimal for longevity-focused individuals; below 80 mg/dL is the general target endorsed by the European Atherosclerosis Society. Standard American adults average 90–110 mg/dL. The intervention that moves it: statins lower ApoB 30–50%, ezetimibe adds another 15–20%, and PCSK9 inhibitors can drive levels below 30 mg/dL when indicated. Dietary saturated fat restriction (under 7% of calories) reduces ApoB by roughly 10% in controlled feeding studies. We measure ApoB at baseline and every 6–12 months in our longevity protocols.
HbA1c and fasting insulin together map metabolic health
Hemoglobin A1c reflects average glucose over 90 days; fasting insulin reveals how hard the pancreas is working to maintain that glucose. The combination distinguishes true metabolic health from compensated insulin resistance. A person with HbA1c of 5.4% and fasting insulin of 15 µIU/mL is not metabolically equivalent to someone with the same HbA1c and insulin of 4 µIU/mL, even though both fall within laboratory reference ranges. The Framingham Offspring Study demonstrated that elevated fasting insulin predicts type 2 diabetes a decade before glucose rises.
The thresholds that matter: HbA1c below 5.4% and fasting insulin below 6 µIU/mL define optimal metabolic function in the Peter Attia framework; above 5.7% and above 10 µIU/mL, respectively, signal early dysfunction. Interventions: time-restricted eating (14–16 hour overnight fast) lowers fasting insulin 20–30% in randomised trials. Resistance training two to three times per week improves insulin sensitivity independent of weight loss. Metformin at 500–1000 mg daily reduces HbA1c by 0.5–1.0 percentage points in prediabetic ranges. We recheck both markers every three to six months when optimising metabolic health.
hsCRP: the inflammation biomarker with 20 years of outcomes data
High-sensitivity C-reactive protein (hsCRP) measures systemic inflammation at levels ten times more precise than standard CRP assays. The JUPITER trial enrolled nearly 18,000 participants with LDL below 130 mg/dL but hsCRP above 2.0 mg/L and found that statin therapy reduced cardiovascular events by 44%, establishing hsCRP as an independent risk factor. The ATTICA study followed over 3,000 adults for a decade and documented a continuous relationship between hsCRP and cardiovascular mortality, with risk doubling above 3.0 mg/L.
The threshold that matters: below 1.0 mg/L is optimal; 1.0–3.0 mg/L is average risk; above 3.0 mg/L warrants intervention. Levels above 10 mg/L suggest acute infection or injury rather than chronic low-grade inflammation. Interventions: the Mediterranean diet lowers hsCRP by 20–40% in meta-analyses of controlled trials. Aerobic exercise at 150 minutes per week reduces hsCRP by approximately 30%. Omega-3 fatty acids (EPA + DHA) at 2–4 grams daily lower hsCRP modestly in individuals with baseline elevation. Addressing sleep apnoea, periodontal disease, and adiposity—particularly visceral fat—also reduces systemic inflammation. We track hsCRP every six months in individuals with baseline elevation.
VO2max: the single strongest predictor of all-cause mortality
Maximal oxygen uptake (VO2max) measures the body's capacity to deliver and utilise oxygen during peak exertion. It integrates cardiac output, haemoglobin concentration, and mitochondrial oxidative capacity into one number. The Mayo Clinic study of over 120,000 cardiopulmonary exercise tests found that VO2max was a stronger predictor of mortality than any traditional cardiovascular risk factor, with each 1-MET increase (3.5 mL/kg/min) associated with 12% lower all-cause mortality. Individuals in the top quintile of aerobic fitness lived years longer than those in the bottom quintile across all age groups.
The threshold that matters: a VO2max above 35 mL/kg/min for women and above 40 mL/kg/min for men at age 50 is considered good; elite fitness reaches 50+ for women and 55+ for men. Attia recommends targeting the 75th percentile for your age and sex as a longevity benchmark. Interventions: high-intensity interval training (HIIT) increases VO2max by 10–15% over 8–12 weeks in systematic reviews. Zone 2 training—sustained effort at 60–70% of max heart rate—builds mitochondrial density and improves oxygen extraction. We assess VO2max via metabolic cart testing or estimate it using validated protocols such as the Bruce treadmill test or the Åstrand-Rhyming cycle ergometer test.
Grip strength and lean muscle mass preserve independence
Grip strength, measured with a hand dynamometer, correlates with total-body muscle strength and predicts disability, hospitalisation, and mortality in adults over 50. The Prospective Urban Rural Epidemiology (PURE) study of nearly 140,000 participants across 17 countries found that each 5-kg decline in grip strength was associated with a 16% increase in all-cause mortality. Lean muscle mass, typically measured via DEXA scan, provides the anatomic substrate: sarcopaenia—age-related muscle loss—begins in the fourth decade and accelerates after 60.
The thresholds that matter: grip strength below 26 kg for women and below 35 kg for men signals weakness; appendicular lean mass below 5.5 kg/m² for women and below 7.0 kg/m² for men meets consensus sarcopaenia criteria. Interventions: progressive resistance training—lifting heavy loads for 6–12 repetitions, two to three times per week—increases muscle mass by 1–2 kg and strength by 25–30% in older adults in Cochrane reviews. Protein intake of 1.6 g/kg body weight daily supports muscle protein synthesis. Creatine monohydrate at 3–5 grams daily enhances strength gains modestly. We measure grip strength at every visit and perform DEXA scans annually in individuals over 50 or with baseline low lean mass.
How we integrate these five into personalised longevity plans
Most patients arrive with one or two of these biomarkers in suboptimal range. The pattern tells us where to focus: an elevated ApoB with normal hsCRP suggests genetic dyslipidaemia; elevated hsCRP with normal ApoB points toward inflammatory drivers such as visceral adiposity or sleep disruption; low VO2max with preserved grip strength indicates undertraining rather than systemic deconditioning. We establish baseline values, set 6- and 12-month targets, and prescribe specific interventions—nutritional adjustments, exercise programming, medications when indicated—then retest to confirm response. The goal is not population-average lab values; it is optimising the five markers most tightly linked to living well for decades.
