Understanding VO₂max: Why Maximum Oxygen Uptake Is an Important Health Marker

Life expectancy continues to rise, yet many people spend an increasingly large proportion of their lives with chronic illnesses. Modern longevity research is therefore focusing more and more on factors that not only extend life but, above all, preserve health into old age.

One biomarker is receiving particular attention: VO₂max, or maximal oxygen uptake. Originally, it was primarily important in performance diagnostics for elite sport. Today, it is considered one of the most informative indicators of cardiorespiratory fitness and ranks among the strongest known predictors of all-cause mortality. Numerous studies show that people with a high VO₂max are less likely to develop cardiovascular disease, type 2 diabetes and other age-related conditions. Their average life expectancy is also higher.

What makes it special is that VO₂max does not describe the performance of a single organ. It reflects how efficiently the lungs, heart, blood vessels, blood and muscles work together to absorb oxygen, transport it and use it in the mitochondria for energy production. It therefore provides a comprehensive insight into the functional capacity of the entire organism.

But what exactly does this value represent? Why does VO₂max decline over the course of life? And why can it still be trained surprisingly well despite the ageing process?

What does VO₂max mean?

The abbreviation VO₂max stands for the body’s maximal oxygen uptake during physical exertion.

More precisely, it describes the greatest amount of oxygen that can be taken in within one minute, transported through the cardiovascular system and used by the working muscles to produce energy.

VO₂max is measured either as absolute oxygen uptake in litres per minute or, more commonly, relative to body weight in millilitres per kilogram of body weight per minute (ml/kg/min). This relative figure enables better comparison between people of different body sizes and body compositions.

In general, the higher the VO₂max, the greater the body’s ability to provide energy through aerobic metabolism. This affects not only athletic performance but also numerous physiological processes closely linked to health and ageing.

Why oxygen is essential for metabolism

Every cell in the body continuously requires energy in the form of adenosine triphosphate, or ATP. This energy carrier is constantly consumed and must be continually regenerated.

During short, very intense exertion, ATP can also be produced without oxygen. However, this anaerobic metabolism provides energy only for a short time and produces significantly less ATP.

During longer periods of exertion, aerobic metabolism takes over the energy supply. Carbohydrates and fatty acids are broken down step by step. The resulting intermediates enter the citric acid cycle and then the mitochondrial respiratory chain.

Oxygen plays a central role there. It acts as the final electron acceptor, thereby enabling the efficient production of large amounts of ATP.

The better the body can absorb and utilise oxygen, the more efficiently this system works. VO₂max reflects precisely this ability.

VO₂max describes a complex interaction between several organs

Maximal oxygen uptake does not depend on the lungs or the heart alone. It results from the smooth interaction of several organ systems.

For oxygen to ultimately reach the mitochondria of the muscle cells, numerous processes must function optimally:

• The lungs absorb oxygen from the air.
• Oxygen passes through the alveoli into the bloodstream.
• Haemoglobin transports oxygen through the body.
• The heart pumps oxygen-rich blood to the working muscles.
• The blood vessels distribute oxygen into the smallest capillaries.
• Muscle cells absorb oxygen.
• Mitochondria use it for ATP production.

An impairment at any one of these points can reduce VO₂max. This is why it is regarded as an integrative marker of overall cardiorespiratory performance.

The Fick principle explains the physiological foundations

The biological basis of VO₂max is described by the so-called Fick principle.

According to this principle, maximal oxygen uptake is determined by two decisive factors:

• cardiac output, meaning the amount of blood pumped by the heart per minute
• the arteriovenous oxygen difference, meaning the amount of oxygen actually extracted from the blood by the muscles

Both components can be improved through regular endurance training.

The heart develops a higher stroke volume and can transport more blood with each heartbeat. At the same time, the number of capillaries in the muscles increases. The number and performance of mitochondria also rise.

This improves not only oxygen supply to the muscles but also their ability to convert oxygen efficiently into energy.

Why VO₂max declines with age

VO₂max usually reaches its peak in young adulthood. It then begins to decline gradually.

On average, it decreases by around five to ten percent per decade of life. This decline often accelerates after the age of 60, particularly in physically inactive people.

There are several reasons for this.

As age increases, maximal heart rate declines. Stroke volume also often decreases. Additional factors include changes in vascular function, age-related loss of muscle mass and reduced mitochondrial performance.

However, lifestyle is a major factor.

A substantial proportion of the age-related decline in VO₂max can be explained by physical inactivity. Studies show that older people who perform regular endurance training often achieve substantially higher values than much younger but physically inactive individuals.

Ageing alone therefore does not determine VO₂max. What matters more is how actively the cardiovascular system is challenged over the years.

VO₂max and the hallmarks of ageing

Maximal oxygen uptake is not one of the official hallmarks of ageing. Nevertheless, high cardiorespiratory fitness influences numerous biological processes closely connected with the molecular mechanisms of ageing.

Improved mitochondrial function

Mitochondria provide most of the cell’s energy. Their performance often declines with age.

Regular endurance training activates, among other factors, the transcriptional coactivator PGC-1α, which stimulates the formation of new mitochondria. At the same time, the function of existing mitochondria improves.

This increases not only ATP production but also the cells’ ability to utilise oxygen efficiently.

Less oxidative stress

Reactive oxygen species are continuously produced during energy generation. In moderate amounts, they perform important signalling functions. When produced in excess, however, they can damage proteins, lipids and DNA.

Regular endurance training increases the activity of the body’s own antioxidant enzymes. At the same time, mitochondria work more efficiently and produce fewer excess oxygen radicals at the same level of exertion.

Over the long term, this improves the balance between oxidative stress and antioxidant protection mechanisms.

Lower chronic inflammatory activity

With age, many people develop low-grade chronic inflammation, often referred to as inflammaging.

Good cardiorespiratory fitness is associated with lower concentrations of various inflammatory markers. Regular exercise also improves the function of adipose tissue and reduces visceral abdominal fat in particular, which releases numerous pro-inflammatory signalling molecules.

Autophagy and cellular cleansing

Physical exertion activates various cellular signalling pathways, including AMPK. This enzyme responds to increased cellular energy demand and promotes autophagy, among other processes.

Autophagy is the body’s own recycling process in which damaged proteins and defective cellular components are broken down and reused.

In this way, regular exercise helps preserve cellular quality over the long term.

AMPK and metabolic adaptation

AMPK, or AMP-activated protein kinase, is considered one of the cell’s most important energy sensors. Whenever energy consumption rises and ATP reserves fall, this signalling pathway is activated.

During intensive endurance exercise, AMPK activity increases considerably. This triggers a range of adaptation processes:

• glucose uptake into the muscles increases
• fatty acid oxidation increases
• new mitochondria are formed
• insulin sensitivity improves

These changes increase not only performance but also metabolic health and are associated with a lower risk of numerous chronic diseases.

Why VO₂max is considered one of the strongest health markers

In preventive medicine, there are few measurements whose predictive value is as consistently supported as that of VO₂max or cardiorespiratory fitness.

While traditional risk factors such as blood pressure, cholesterol and blood sugar each capture only individual aspects of health, VO₂max integrates numerous physiological systems into a single measurement.

Among other things, it reflects:

• the performance of the cardiovascular system
• lung function
• the oxygen-carrying capacity of the blood
• vascular health
• mitochondrial performance
• the metabolic health of the muscles

This is precisely why it has such exceptionally high prognostic value.

What large long-term studies show

One of the best-known investigations is the Aerobics Center Longitudinal Study (ACLS), which followed tens of thousands of adults over several decades.

The researchers examined how cardiorespiratory fitness affected mortality. The result was remarkable: people with high fitness had a substantially lower risk of dying from any cause than those with low fitness.

This association remained even after age, smoking, blood pressure, diabetes and other risk factors were taken into account statistically.

Later cohort studies and meta-analyses involving several hundred thousand participants found similar results.

It is particularly striking that the greatest health benefit is often achieved by moving from very low to moderate fitness. Further improvements remain beneficial, but the strongest effect is seen in physically inactive people who begin endurance training.

VO₂max and the risk of chronic disease

Low cardiorespiratory fitness is associated with an increased risk of numerous diseases.

These include in particular:

• cardiovascular disease
• type 2 diabetes
• high blood pressure
• non-alcoholic fatty liver disease
• chronic kidney disease
• certain types of cancer
• dementia

VO₂max is probably not an independent cause. Rather, it reflects the functional condition of numerous organ systems.

People with a higher VO₂max often also have better insulin sensitivity, a more favourable body composition, less visceral fat and lower systemic inflammatory activity. These factors influence one another and together contribute to a lower risk of disease.

What role does VO₂max play in brain health?

The brain consumes around twenty percent of the body’s total oxygen despite accounting for only about two percent of body weight.

A good oxygen supply is therefore essential for the function of nerve cells.

Regular endurance training improves blood flow to the brain and increases the production of various growth factors. Particularly well studied is brain-derived neurotrophic factor (BDNF), which supports the formation of new neuronal connections and contributes to brain plasticity.

Observational studies show that people with higher cardiorespiratory fitness are, on average, less likely to develop cognitive impairment. Their risk of neurodegenerative diseases such as Alzheimer’s disease is also lower.

It is not yet possible to determine conclusively whether improving VO₂max alone is responsible or whether it simply reflects an overall healthy lifestyle. Several mechanisms probably contribute to this relationship simultaneously.

How is VO₂max measured?

The most precise determination is performed using cardiopulmonary exercise testing.

During the test, participants complete progressively increasing exercise on a treadmill or cycle ergometer. At the same time, respiratory gas analysis continuously measures oxygen uptake and carbon dioxide output.

VO₂max is reached when oxygen uptake no longer increases despite a further increase in workload.

Cardiopulmonary exercise testing is considered the gold standard because it measures actual maximal oxygen uptake directly.

There are also numerous estimation methods.

Sports watches and fitness trackers calculate VO₂max using heart rate, speed and other movement data. These values can be useful for monitoring trends but do not replace medical performance diagnostics.

Field tests such as the Cooper test or Rockport walking test also provide a rough estimate of cardiorespiratory fitness. Their accuracy depends on test execution and individual factors.

Which VO₂max values are considered good?

VO₂max differs considerably between age groups and between men and women.

There is therefore no universally applicable ideal value.

Age- and sex-specific reference values are generally used for interpretation. What matters less is an absolute peak value than one’s position within the relevant age group.

Even an improvement of only a few millilitres of oxygen per kilogram of body weight per minute can be associated with a substantial improvement in prognosis.

For long-term health, preserving one’s VO₂max as effectively as possible over the years is often more important than aiming for exceptionally high performance values.

Can everyone improve their VO₂max?

Genetic predisposition influences baseline values and the individual response to training.

Nevertheless, numerous intervention studies show that almost everyone can increase VO₂max through regular training.

The extent of improvement depends on factors including:

• age
• training status
• training intensity
• training volume
• genetic factors
• existing diseases

In untrained people, increases of ten to twenty percent within a few months are not uncommon. Older adults also benefit considerably from structured endurance training.

Even in people in their seventies or eighties, heart function, muscle metabolism and oxygen uptake can often still be improved measurably.

Which type of training increases VO₂max most effectively?

Not every form of physical activity affects VO₂max equally.

The strongest evidence supports regular endurance training.

Particularly effective forms include:

• brisk walking
• jogging
• cycling
• swimming
• rowing
• cross-country skiing

In recent years, high-intensity interval training, or HIIT, has also received considerable attention.

It alternates short periods of very high exertion with active recovery phases. Several meta-analyses show that HIIT can improve VO₂max at least as effectively as, and sometimes more strongly than, continuous moderate endurance training.

However, this does not mean that high-intensity exercise is always superior. What matters is that training is performed regularly over the long term. For many people, moderate endurance training is therefore more sustainable and easier to integrate into everyday life.

Strength training also plays an important role. Although it generally improves VO₂max less strongly than traditional endurance training, it helps preserve muscle mass, metabolic health and functional capacity in old age.

For most people, a combination of endurance and strength training offers the greatest health benefits.

Which factors influence VO₂max?

Maximal oxygen uptake is determined by an interaction of genetic, physiological and lifestyle-related factors. Some can hardly be changed, while others respond very well to targeted measures.

Age

VO₂max naturally declines with age. Factors responsible include changes in heart function, vascular elasticity, muscle mass and mitochondrial performance.

However, the decline does not occur at the same rate in everyone. Regular physical activity can slow it substantially and help preserve functional capacity into old age.

Sex

Men achieve higher average VO₂max values than women. This is due, among other factors, to greater muscle mass, higher haemoglobin levels and a larger heart volume.

However, these differences do not allow conclusions about individual fitness. Comparison with age- and sex-specific reference values remains essential.

Body composition

Because VO₂max is often expressed relative to body weight, body composition influences the measured value.

A high body-fat percentage can lower relative VO₂max even when absolute oxygen uptake remains unchanged. At the same time, greater muscle mass improves the ability to absorb oxygen and use it for energy production.

Genetics

Family and twin studies show that genetic predisposition has a substantial influence on VO₂max. Both baseline values and the individual capacity to adapt to endurance training differ between people.

Nevertheless, genetics explains only part of the differences. Training remains the most important modifiable factor.

Diseases

Various diseases can also reduce maximal oxygen uptake.

Examples include:

• heart failure
• coronary heart disease
• chronic obstructive pulmonary disease (COPD)
• anaemia
• certain metabolic diseases

In these cases, VO₂max is often also used as an important parameter for assessing disease progression and treatment success.

Can VO₂max serve as a biomarker of biological age?

Longevity research has a strong interest in biomarkers that reflect the body’s functional condition more accurately than chronological age.

VO₂max meets many of the requirements of such a marker.

It integrates the function of several organ systems, responds sensitively to lifestyle changes and has high prognostic value for morbidity and mortality.

Nevertheless, it is not a direct marker of biological age.

Epigenetic clocks, proteomic analyses and certain metabolites directly capture molecular changes associated with ageing. VO₂max, by contrast, describes the functional capacity of the organism.

Both perspectives complement one another.

While molecular biomarkers provide indications of biological ageing processes, VO₂max shows how effectively the organism can functionally compensate for these changes.

This is precisely why it is gaining increasing importance in geroscience.

What does a low VO₂max mean in everyday life?

Low maximal oxygen uptake is not noticeable only during sport.

Everyday activities can also become more demanding.

Climbing stairs, taking longer walks or carrying heavy shopping bags requires a greater proportion of the maximum available capacity. As a result, perceived exertion rises more quickly.

This becomes even more important in old age.

People with a higher VO₂max have greater physical reserves. This often allows them to maintain independence for longer, even when facing illness or recovering from surgery.

In geriatrics, cardiorespiratory fitness is therefore considered an important component of functional health.

How often should VO₂max be checked?

For healthy people, there is generally no need to have VO₂max measured regularly in a laboratory.

However, people who train with specific goals or want to monitor changes in their fitness may benefit from repeated measurements.

For recreational athletes, a check every six to twelve months is often sufficient.

In elite sport or medical rehabilitation, cardiopulmonary exercise testing is often performed much more frequently because it provides important information for training control and exercise tolerance.

Regardless of the measurement method, individual values are less informative than their development over a longer period.

Conclusion

VO₂max is far more than a metric from sports medicine. It describes the body’s ability to absorb oxygen efficiently, transport it and use it in the mitochondria for energy production. It therefore reflects the interaction between the heart, lungs, blood vessels and muscles and provides a comprehensive impression of functional health.

Scientific evidence consistently shows that high cardiorespiratory fitness is associated with a lower risk of cardiovascular disease, type 2 diabetes, neurodegenerative disease and all-cause mortality. At the same time, regular endurance training influences numerous biological processes that also play a central role in ageing research. These include mitochondrial function, insulin sensitivity, chronic inflammation, oxidative stress and autophagy.

VO₂max is therefore not merely a performance metric for athletes. It is a functional biomarker that provides information about the capacity of the entire organism and, unlike many other risk factors, can be deliberately improved through regular exercise.

The aim is not to achieve peak values. Even a moderate improvement in cardiorespiratory fitness can substantially reduce long-term disease risk. For healthy ageing, what matters most is maintaining VO₂max at a good level for as long as possible.

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