Biomarkers of frailty and sarcopenia (Nutrition-, age- and muscle-related biomarkers in relation to frailty and sarcopenia)

Contact Persons: Dr. Bastian Kochlik, Prof. Dr. Kristina Norman

The prevalence of both sarcopenia and frailty increases during aging, and sarcopenia and frailty are both accompanied with a higher risk for falls, hospitalization, disability and loss of quality of life. Therefore, reliable approaches for diagnosis and risk assessment of sarcopenia and frailty is of high importance in the context of their prevention and intervention. Diagnostic approaches are imaging parameters and functional examinations which mainly assess frailty and sarcopenia criteria; however, these measures can have limitations in clinical settings. Thus, finding and evaluating suitable biomarkers (metabolites or substances measured in biological fluids like blood) are becoming more relevant regarding diagnosis and risk assessment of frailty and sarcopenia. However, there is no single diagnostic biomarker described up to date, and it is suggested, that it will need a combination of different biomarkers for the reliable diagnosis of sarcopenia and frailty.

Frailty and sarcopenia share some underlying characteristics like loss of muscle mass, low muscle strength, and low physical performance. These can be caused by a catabolic muscle state e.g. an elevated muscle protein degradation. In general, the causes for the development of frailty and sarcopenia are multifactorial; however not fully understood. Beside age-associated musculoskeletal changes there are additional suggested potential risk factors like low plasma micronutrient concentrations, patterns low in circulating fat-soluble vitamins and carotenoids, and high concentrations of biomarkers of oxidative stress (OS) which are associated with frailty. Furthermore, the balance between anti- and pro-inflammatory substances, in which fatty acids (FAs) like anti-inflammatory omega-3-FAs (n-3 PUFAs), and FA ratios seem to play a crucial role for sarcopenia and frailty development.

Previous cross-sectional data showed that plasma concentrations of 3-MH (3-methylhistidine), 3-MH/Crea (3-MH normalized to creatinine) and 3-MH/eGFR (3-MH normalized to estimated glomerular filtration rate) were positively associated with frailty (Kochlik et al., J. Clin. Med. 2019). Thus, we concluded that these plasma biomarkers might be suitable to identify frail individuals or individuals at higher risk to be frail. Furthermore, we suggest that the diagnostic use of these biomarkers might be extended to sarcopenia. In a further study, cross-sectional data showed that low plasma concentrations of specific fat-soluble micronutrients (vitamin D3, tocopherols, retinol, carotenes, lycopene, lutein/zeaxanthin, und β‑cryptoxanthin) together with high protein carbonyl concentrations in plasma were associated with frailty and pre-frailty (Kochlik et al., J Cachexia Sarcopenia Muscle 2019). Thus, we concluded that a diet rich in micronutrients might improve the redox status and could subsequently be supportive in the prevention of frailty as well as sarcopenia.

Future studies with simultaneous measures of a variety of circulating biomarkers like nutrition-related fat-soluble micronutrients and fatty acids, oxidative stress biomarkers and muscle-related biomarkers in sarcopenic and frail individuals need to be performed to deepen our understanding of underlying mechanisms and the potential influence of the nutritional status on frailty and on sarcopenia. These studies could possibly provide specific biomarker combinations or circulating biomarker patterns for the diagnosis of sarcopenia and frailty, or to get a better insight into the mechanisms leading to sarcopenia and frailty.

These objectives will be addressed in a planned study (“Patterns of circulating nutritional, oxidative stress and muscle protein biomarkers, and cross-sectional associations with frailty and sarcopenia in geriatric patients of the WONDER Study.”) within already recruited geriatric patients of the “WONDER-Study”. The planned study follows an interdisciplinary approach and is carried out in cooperation with the Departments of Molecular Toxicology and Molecular Epidemiology at the DIfE, and with the Charité ─ Universitätsmedizin Berlin. The study is financed in parts by the “NutriAct Research Stimulus Grant”.