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Frailty is a condition characterized by increased vulnerability and decline in physical function. It's a growing concern in the aging population, particularly among those with heart disease. A multidisciplinary research team led by the German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), the Faculty of Health Sciences (FGW) at the University of Potsdam and Deutsches Herzzentrum der Charité has now identified the gene S100A1 as a potential biomarker and therapeutic target in muscle tissue of older patients with heart disease, offering the potential to counteract mobility loss and muscle weakness early on. The findings were published in the Journal of Cachexia, Sarcopenia and Muscle.
Frailty, also known as frailty syndrome, is emerging as a significant health challenge for the aging population. It is characterized by increased susceptibility to falls, hospitalizations, complications after surgery, and a general decline in physical function.
Limited physical performance is a crucial factor in frailty among older adults with cardiovascular disease. To optimize health and functional treatment outcomes for this patient group, a better understanding of the underlying biological mechanisms is essential.
Therefore, this study focused on identifying gene expression patterns linked to different levels of frailty in older patients undergoing cardiac surgery, offering new insights that could help guide more personalized treatment strategies.
Collaborative Research Approach
Co-led by PD Dr. Heike Vogel from DIfE as well as PD Dr. Annett Salzwedel and Prof. Dr. Heinz Völler from the FGW at the University of Potsdam, and in close collaboration with the Deutsches Herzzentrum der Charité (PD Dr. Simon Sündermann) and other partner institutions, a total of 63 patients over 70 years of age were examined. These patients were hospitalized for cardiac surgery or transcatheter aortic valve implantation (TAVI).
Before the procedures, the researchers assessed the patients for three frailty phenotypes: gait speed, handgrip strength, and overall mobility.
During cardiac surgery, tissue samples were taken from the thigh muscle to perform a comprehensive gene expression analysis and to capture molecular changes in skeletal muscle using bioinformatics.
The researchers also utilized data from a separate cohort of older, healthy individuals and investigations in cell culture and animal models to validate the identified findings.
Key Gene S100A1 in Focus
The research team identified ten genes whose altered expression was associated with all three frailty phenotypes through gene expression analyses. The gene S100A1 emerged as particularly significant due to its key role in both skeletal and cardiac muscle function.
Individuals with poor muscle strength and impaired mobility showed markedly lower levels of S100A1 in muscle samples. Correspondingly, the validation cohort showed that higher S100A1 blood levels correlated with better grip strength.
A functional link was also demonstrated. Experiments in muscle cells confirmed that reduced S100A1 expression leads to impaired muscle development. Animal models showed that genetically determined higher S100A1 levels correlated with increased muscle mass, and that regular exercise further enhances gene expression.
Maintaining Mobility and Quality of Life in Old Age
“For the first time, we have been able to demonstrate a correlation between reduced gene expression of S100A1 in muscle tissue and frailty phenotypes,” explains doctoral candidate Omar Baritello from the FGW. Study head Heike Vogel emphasized the importance of the findings: “We believe that S100A1 plays a central role in maintaining muscle health, and that it could be key to preventing frailty.” The research offers valuable insight into the biological processes that drive age-related frailty and highlights S100A1 as a potential biomarker for identifying older adults at risk. Moreover, the gene may represent a novel therapeutic target to help preserve muscle strength and mobility in elderly patients with cardiovascular disease.
Future research efforts will focus on validating S100A1 as a clinical marker and investigating its therapeutic utility. This includes developing diagnostics that can measure S100A1 levels and exploring strategies to modulate S100A1 expression, such as targeted muscle training or pharmacological interventions. “This study brings us closer to the goal of not only understanding frailty better but also recognizing it early and actively counteracting it – and thereby improving the quality of life and safety of older people,” says Vogel.
Background Information
Frailty
The term frailty describes a geriatric syndrome characterized by generally increased vulnerability of older individuals to external stressors such as overload, restlessness, and illness. Frailty arises from a combination of physiological aging processes and their pathological consequences. It is characterized by:
• unintentional weight loss of more than 5 kilograms per year
• loss of overall body strength
• subjectively perceived exhaustion
• reduced walking speed and physical activity.
The Three Frailty Phenotypes in the Study
Mobility was assessed using the Timed Up-and-Go test (TUG). The patient sits in a chair with armrests, stands up on command, walks three meters, turns around, and sits back down. Aids such as walking frames are permitted, but assistance from other people is not. The time taken is measured.
Classification:
• ≥ 10 seconds: moderately impaired mobility
• ≥ 20 seconds: significantly impaired mobility
Gait Speed was determined using the 5-meter walk test.
Classification:
• ≥ 6 seconds: low gait speed
Handgrip Strength was measured using a dynamometer. The subject presses against a fixed resistance.
Classification:
• Women: ≤ 16 kg | Men: ≤ 27 kg: low grip strength
S100A1
S100-A1, also known as S100 calcium-binding protein A1, is a protein encoded by the S100A1 gene in humans. S100A1 is strongly expressed in heart and skeletal muscle and plays a crucial role in regulating contractile force and calcium homeostasis. It has a protective effect in heart failure and is also associated with neuronal functions and certain cancers.
PD Dr. Heike Vogel
Department of Experimental Diabetology
Tel.: +49 33 200 88 - 4545
E-Mail: heikevogel@dife.de
Baritello, O., Sündermann, S. H., Espinosa-Garnica, K., Kempfert, J., Jähnert, M., Beetz, N. L., Geisel, D., Gaugel, J., Rominger, J., Müller-Werdan, U., Herpich, C., Norman, K., Chadt, A., Al-Hasani, H., Völler, H., Salzwedel, A., Vogel, H.: Transcriptomic Signature of Frailty in Older Patients With Cardiovascular Disease Undergoing Cardiac Surgery or TAVI. J Cachexia Sarcopenia Muscle 16(3):e13846 (2025). [Open Access]
DOI: https://doi.org/10.1002/jcsm.13846
Gait Speed was determined using the 5-meter walk test.
David Ausserhofer
DIfE
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Biologie, Ernährung / Gesundheit / Pflege, Medizin
überregional
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Gait Speed was determined using the 5-meter walk test.
David Ausserhofer
DIfE
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