
Age may seem like a straightforward measure of health, but biology tells a more complex story.
Can you judge an adult’s physical condition based only on their age? The answer is: “It depends.”
While the body’s performance generally declines over time and the risk of age-related diseases increases, people of the same age can differ greatly in health and physical aging. Chronological age only partly reflects biological age, which represents the body’s true physiological state and is shaped by lifestyle, genetics, and environmental factors.
So how can biological age be measured more accurately?
This question drives the international MARK-AGE consortium. In a large cross-sectional study across Europe, researchers identified age-related patterns in ten key blood biomarkers for men and women. These markers can be combined to estimate biological age.
In a recent publication led by Maria Moreno-Villanueva and Alexander Bürkle of the University of Konstanz, the team tested this “bioage score” and used it to uncover additional biomarkers linked to aging.
One biomarker is not enough
Earlier studies have proposed individual biomarkers as indicators of biological age, but none has proven reliable on its own.
“The biological aging process is very complex. It affects all of the body’s tissues and organs, and it is not the result of a single cause. As a result, single biomarkers are not enough to reliably determine a person’s biological age,” Morena-Villanueva explains. “On top of this, there are also differences in how men and women age.”
To address this, the MARK-AGE team developed sex-specific combinations of biomarkers to calculate biological age more accurately. They analyzed data from about 3,300 participants across eight European countries and measured 362 biomarkers per person. From this large dataset, they identified ten key biomarkers for each sex and used them to calculate an individual bioage score that reflects biological aging.
Aging as an individual process
“If we look at the bioage scores of a lot of people born in the same year, we see a wide range of values. This shows very clearly that each person has their own individual biological aging process and, for example, that some people are significantly younger biologically than their chronological age would seem to indicate,” Morena-Villanueva says.
The researchers validated their method by comparing results across specific groups. The findings matched established scientific expectations. People with trisomy 21, a genetic condition linked to faster aging, showed a much larger gap between biological and chronological age (“age difference”).
In contrast, women over 50 who received hormone replacement therapy appeared biologically younger than those who did not. Among women who smoke, the “age difference” increased with lifetime cigarette use, indicating that smoking accelerates aging in this group.
“Against the backdrop of current research on the aging effects of smoking, hormone replacement therapy, or trisomy 21, all of these results are plausible and confirm the validity of our bioage score,” Bürkle explains.
A step toward a new kind of preventive medicine
The team also used the bioage score to identify biomarkers tied specifically to biological age rather than chronological age. These included common clinical measures related to bone health, fat metabolism, and immune function: 25-hydroxy-Vitamin D, HDL (High-Density Lipoprotein), and the proportion of T helper cells among leukocytes (CD3+CD4+/CD45+ ratio). People with a younger biological age were more likely to have these values within ranges considered healthy, suggesting these markers may directly influence the aging process.
Overall, the study advances how biological age can be measured and applied. “Reliable biomarkers for biological aging provide key tools for tracking the aging process – even in healthy individuals – as well as for identifying people who have a higher risk of developing an age-related illness or physical impairment. This could open doors for new approaches to individualized preventive medicine,” Bürkle concludes.
Reference: “Biologically Younger Individuals, as Identified by MARK-AGE Biological Age Scores, Display a Distinct Favourable Blood Chemistry Profile Regardless of Age” by María Moreno-Villanueva, Michael Junk, Grażyna Mosieniak, Ewa Sikora, Miriam Capri, Paolo Garagnani, Chiara Pirazzini, Nicolle Breusing, Jürgen Bernhardt, Christiane Schön, María Blasco, Gerben Zondag, Florence Debacq-Chainiaux, Beatrix Grubeck-Loebenstein, Birgit Weinberger, Simone Fiegl, Eugenio Mocchegiani, Marco Malavolta, Robertina Giacconi, Francesco Piacenza, Sebastiano Collino, Efstathios S. Gonos, Daniela Gradinaru, Martijn E. T. Dollé, Eugène Jansen, Michel Salmon, Peter Kristensen, Helen Griffiths, Claude Libert, Valerie Vanhooren, Andreas Simm, Duncan Talbot, Paola Caiafa, Maria Giulia Bacalini, Michele Zampieri, Bertrand Friguet, Isabelle Petropoulos, P. Eline Slagboom, Rudi Westendorp, Antti Hervonnen, Mikko Hurme, Richard Aspinall, Sheila Govind, Daniela Weber, Wolfgang Stuetz, Jan H. J. Hoeijmakers, Iuliia Gavriushina, Oliver R. Sampson, Gastone Castellani, Michael R. Berthold, Tilman Grune, Claudio Franceschi and Alexander Bürkle, 13 March 2026, Aging Cell.
DOI: 10.1111/acel.70437
Project funding to the tune of 12 million euros was provided through the seventh framework program of the European Community (FP7).
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