Lung Function as a Biomarker of Ageing

Key Takeaways

Spirometry measures how much air a person can forcibly exhale and how quickly, most commonly using FEV₁, FVC, and their ratio. [1]
Lung function generally declines across later adulthood as respiratory mechanics and reserve change, but individual trajectories vary. [2] [3]
Lower FEV₁ and FVC are associated with mortality and other adverse outcomes in population cohorts. [4] [5]
Lung function is a systems-level marker, not a specific measure of one ageing mechanism or a standalone biological-age clock. [2] [6]

Lung function describes the capacity and mechanical performance of the respiratory system. Spirometry, its most widely used test, provides objective measurements used to assess respiratory health and monitor change over time. [1]

Who This Is Useful For

This page is useful for readers comparing functional biomarkers with molecular measures of ageing. It explains why spirometry can capture respiratory reserve and predict later outcomes while remaining sensitive to early-life development, exposures, disease, body size, test performance, and the reference equation used. [1] [6] [7]

What Spirometry Measures

Forced expiratory volume in one second (FEV₁) is the volume exhaled during the first second of a forced breath. Forced vital capacity (FVC) is the total volume exhaled during the manoeuvre. The FEV₁/FVC ratio describes the fraction expelled in the first second and helps characterize airflow limitation. [1] [6]

These measurements depend on lung and airway mechanics, respiratory-muscle effort, and the ability to perform an acceptable, repeatable manoeuvre. They do not directly measure cellular ageing or identify a single molecular cause of impaired function. [1] [2]

Why Lung Function Changes With Age

Adult ageing is associated with reduced elastic recoil, greater air trapping, a less compliant chest wall, lower respiratory-muscle strength, and changes in gas-exchange surfaces. Together, these changes tend to reduce expiratory flow and respiratory reserve. [2]

Population reference equations model expected spirometric values across age and height rather than treating one fixed value as normal for everyone. Longitudinal data from adults aged 60 to 102 also show average declines in FEV₁ and FVC, with substantial variation related to demographic, smoking, inflammatory, and health characteristics. [3] [6]

Lung Function at a Glance

Measure	What It Reflects	Important Limitation
FEV₁	Expiratory flow and the volume expelled in the first second	Can be reduced by airway disease, restriction, effort, or poor technique
FVC	Total volume expelled during a forced manoeuvre	A low value on spirometry alone does not establish restrictive lung disease
FEV₁/FVC	Proportion of the forced vital capacity expelled in one second	Requires age-appropriate interpretation because the expected ratio changes with age
Z-score	Position relative to an age-, sex-, and height-informed reference distribution	Depends on how well the reference population represents the person tested
Longitudinal change	Trajectory across repeated measurements	Can mix ageing with disease, exposure, technique, and normal measurement variability

Association With Long-Term Outcomes

Large prospective cohorts report that lower FEV₁ is associated with higher all-cause mortality, cardiovascular events, and respiratory hospitalization after adjustment for several measured risk factors. Similar mortality associations have been observed for both FEV₁ and FVC in a general population cohort after accounting for measures of cardiac function. [4] [5]

These are prognostic associations, not proof that a low spirometric value is itself the cause of an outcome. Lung function can reflect smoking, air pollution, occupational exposures, respiratory disease, cardiovascular health, socioeconomic conditions, and development earlier in life. [4] [7] [8]

Trajectories Matter

A low value in later life does not necessarily indicate unusually rapid age-related decline. In three cohorts, some people who developed chronic obstructive pulmonary disease had below-average lung function in early adulthood without a subsequently accelerated FEV₁ decline. This distinguishes the level attained earlier in life from the rate of change thereafter. [8]

Repeated high-quality measurements can therefore add information that a single test cannot. Even then, observed change must be interpreted against biological and technical variability rather than assumed to represent ageing alone. [1] [3]

Reference Values and Measurement Context

The Global Lung Function Initiative derived continuous spirometry equations from healthy nonsmokers aged 3 to 95 years. These equations model the expected distribution across age and body size and illustrate why a fixed percentage or ratio can misclassify older or younger adults. [6]

Interpretation still depends on data coverage and modelling choices. The original equations noted that several geographic and ancestry groups were underrepresented, while technical standards emphasize calibration, operator instruction, maximal effort, acceptability, and repeatability. [1] [6]

Limitations as an Ageing Biomarker

Spirometry is organ-system specific. It does not directly capture cognition, renal function, immune ageing, or molecular damage. Within the respiratory system, spirometry also does not fully characterize gas transfer, static lung volumes, respiratory symptoms, or structural abnormalities. [1] [2]

A result can also be influenced by current illness, airway disease, smoking history, environmental exposure, body proportions, and test execution. These influences make lung function informative about functional state and risk, but mechanistically nonspecific as a marker of ageing. [1] [7]

Evidence Quality and Interpretation

Confidence is strong that spirometric indices vary systematically with adult age and that lower FEV₁ and FVC are associated with adverse outcomes. This is supported by large reference datasets, longitudinal cohorts, and international population studies. [3] [4] [5] [6]

Confidence is lower when a single result is translated into a person's overall “biological age.” There is no universal spirometric conversion that separates ageing from development, exposure, disease, and measurement context across all populations. [6] [7] [8]

What This Does Not Mean

It does not mean that lower lung function is an inevitable consequence of age alone. [7] [8]
It does not mean one low FEV₁ value identifies the mechanism responsible. [1]
It does not mean that a value within a reference range excludes respiratory disease or future decline. [6]
It does not mean results from poor-quality or non-comparable tests describe a true trajectory. [1]

Practical Interpretation Examples

If FEV₁ is low for the reference distribution: the result indicates reduced expiratory performance, but its cause requires clinical context and may not be ageing. [1] [6]
If repeated values decline: the trajectory may be informative when tests are standardized, but exposure, illness, and measurement variability still need consideration. [1] [3]
If FEV₁/FVC is interpreted with a fixed cutoff: age-dependent reference limits may produce a different classification, especially at the ends of the adult age range. [6]

Summary

Lung function is a well-established measure of respiratory performance and a useful functional biomarker of ageing-related reserve. Spirometric values change with age and predict important outcomes, but they remain shaped by development, exposure, disease, and measurement quality. Lung function is therefore best interpreted as one organ-system marker rather than a complete measure of biological ageing. [2] [4] [8]

References

Graham, B. L., Steenbruggen, I., Miller, M. R., et al. (2019). Standardization of spirometry 2019 update: an official American Thoracic Society and European Respiratory Society technical statement. American Journal of Respiratory and Critical Care Medicine, 200(8), e70-e88. https://pubmed.ncbi.nlm.nih.gov/31613151/
Janssens, J. P., Pache, J. C., & Nicod, L. P. (1999). Physiological changes in respiratory function associated with ageing. European Respiratory Journal, 13(1), 197-205. https://pubmed.ncbi.nlm.nih.gov/10836348/
Vaz Fragoso, C. A., Beavers, D. P., Hankinson, J. L., et al. (2019). Relative and absolute lung function change in a general population aged 60-102 years. European Respiratory Journal, 53(3), 1701812. https://pubmed.ncbi.nlm.nih.gov/30578401/
Duong, M., Islam, S., Rangarajan, S., et al. (2019). Mortality and cardiovascular and respiratory morbidity in individuals with impaired FEV₁ (PURE): an international, community-based cohort study. The Lancet Global Health, 7(5), e613-e623. https://pubmed.ncbi.nlm.nih.gov/31000131/
Magnussen, C., Ojeda, F. M., Rzayeva, N., et al. (2017). FEV₁ and FVC predict all-cause mortality independent of cardiac function: results from the population-based Gutenberg Health Study. International Journal of Cardiology, 234, 64-68. https://pubmed.ncbi.nlm.nih.gov/28214081/
Quanjer, P. H., Stanojevic, S., Cole, T. J., et al. (2012). Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. European Respiratory Journal, 40(6), 1324-1343. https://pubmed.ncbi.nlm.nih.gov/22743675/
Vaz Fragoso, C. A., & Gill, T. M. (2012). Respiratory impairment and the aging lung: a novel paradigm for assessing pulmonary function. The Journals of Gerontology: Series A, 67(3), 264-275. https://pubmed.ncbi.nlm.nih.gov/22138206/
Lange, P., Celli, B., Agustí, A., et al. (2015). Lung-function trajectories leading to chronic obstructive pulmonary disease. New England Journal of Medicine, 373(2), 111-122. https://pubmed.ncbi.nlm.nih.gov/26154786/

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