VO2max & Zone 2 training: the key longevity biomarker

VO2max describes the maximum amount of oxygen your body can take in, transport and use during maximal exertion. Measured in ml/kg/min, it is considered the gold standard for cardiorespiratory fitness.

The figure reflects the entire oxygen cascade: lung ventilation, cardiac output, oxygen transport in the blood and the mitochondrial capacity of your muscles. A high VO2max signals not only athletic performance, but also fundamentally efficient physiology at a cellular level.

The underlying physiology can be described using the Fick equation: VO2max = maximum heart rate × maximum stroke volume × arteriovenous oxygen difference. Improvements are possible across all three components, which is exactly where targeted training comes in.

The scientific evidence is clear: cardiorespiratory fitness, measured as VO2max, is among the strongest predictors of all-cause mortality. It is comparable to, or even more powerful than, established risk factors such as smoking or high blood pressure. Three major cohort studies, with more than 975,000 participants in total, have shaped the field.

The Cleveland Clinic study (Mandsager 2018) analysed 122,007 patients over 1.1 million person-years. The result: there is no upper limit to the benefit. Even the fittest participants still benefited compared with the second-fittest group. Low fitness was associated with a 3.5 times higher risk of death than smoking.

The largest study to date (Kokkinos 2022, 750,302 veterans) confirmed: unfitness is more dangerous than any cardiac risk factor examined. The relationship was inverse, independent and gradual across all age groups, both sexes and all ethnic groups.

Particularly relevant: it is not only your starting point that counts. Every improvement of 1 ml/kg/min VO2max was associated with 9% lower all-cause mortality, regardless of where you started. Even moderate improvements of just 1 MET between two exercise tests showed significantly lower mortality.

VO2max peaks in your early to mid-20s, then declines steadily: by an average of 10% per decade in adults aged 20 to 65. From age 70, the decline accelerates to 15–20% per decade.

The key distinction is between unavoidable biological ageing and avoidable decline caused by behaviour. Reviews estimate that 50–70% of the decline in VO2max can be prevented through consistent training. Biology determines the gradient, but your behaviour determines how steep the drop becomes.

Physiological causes: maximum heart rate falls by 5–10 beats per decade, mitochondrial efficiency declines, capillary density is reduced and muscle mass decreases (sarcopenia).

Zone 2 training means training at moderate intensity, primarily using the aerobic energy system. It sits below the first lactate threshold (LT1) and feels "comfortably challenging": you can just about speak in sentences, but can no longer sing comfortably.

The crucial point: Zone 2 is not easy cruising. It is the intensity that most strongly stimulates your mitochondria and oxidative capacity without tipping into the anaerobic range. Iñigo San Millán, professor at the University of Colorado and coach to Tour de France riders, describes Zone 2 as targeted metabolic stimulation.

Worth knowing: a 2025 study showed considerable individual variability in Zone 2 markers. Standardised percentages of HRmax do not reflect the actual metabolic demands for everyone. Lactate measurement remains the most accurate proxy.

Zone 2 training works on several levels at once, and that breadth is exactly what makes it so valuable for longevity.

Mitochondrial biogenesis: Your body creates new mitochondria. The transcription factor PGC-1α, the "master regulator" of mitochondrial biogenesis, is activated. Crucially, sessions of 60–90 minutes trigger a stronger response than 30-minute workouts.

Fat oxidation and metabolic flexibility: Zone 2 trains your body to use fat more efficiently as an energy source. Insulin sensitivity improves, blood sugar regulation becomes more stable, and you become less reliant on carbohydrates for fuel.

Cardiovascular adaptations: Stroke volume increases, capillary density in the muscles rises, resting heart rate and blood pressure decrease, and endothelial function improves.

Lactate clearance: Lactate is transported from fast- to slow-twitch muscle fibres and used there as fuel. MCT transporters are upregulated. Lower lactate at the same output = better metabolic health.

Not ideal if your sole focus is improving VO2max: A 2025 narrative review shows that Zone 2 training alone is not the optimal intensity for mitochondrial adaptations, as higher intensities trigger stronger PGC-1α responses. Zone 2 is therefore not recommended in isolation, but as a foundation combined with high-intensity training. Its strength lies in the volume you can tolerate: you can train significantly more hours in Zone 2 than with HIIT, without overloading yourself.

The training concept currently best supported by evidence for longevity is the polarised approach: ~80% Zone 2, ~20% Zone 5. Peter Attia sums it up: "Life is Zone 1, Zone 2, and Zone 5."

A randomised controlled trial involving untrained adults confirms this: polarised training improved VO2max by 12.9%, more than HIIT alone (9.8%) or threshold training (7.3%). Zone 2 builds the "floor" (aerobic base), while Zone 5 raises the "ceiling" (maximum capacity).

Gold standard: cardiopulmonary exercise testing. During cardiopulmonary exercise testing (CPET), oxygen consumption is measured through a mask while effort increases in stages. It offers the highest accuracy and also determines the lactate thresholds VT1 and VT2. Cost: €150–300 at sports medicine centres.

Submaximal tests: The Cooper test, a 12-minute run, the beep test, a shuttle run, or a staged ergometer test provide useful estimates without maximum exertion.

Smartwatch estimates: Apple Watch, Garmin and COROS estimate VO2max using algorithms based on heart rate, pace and movement data. Deviations of ±5–10 ml/kg/min compared with laboratory measurements are possible. However, they are useful as a trend indicator: is it getting better or worse?

Use our heart rate zones calculator to determine your personal training zones.

How to identify Zone 2 without a lab:

• Talk test: You can speak in full sentences, but no longer sing
• Nose test: Breathing solely through your nose is just about possible
• Heart rate: 60–70% of HRmax (rule of thumb: 220 – age)
• Subjective: RPE 3–4 out of 10: challenging but sustainable
• Lactate: 1.5–2.0 mmol/L, if you have a testing device