Transcriptomic Insights into Frailty and Aging: From Predictors to Interventions

• Applicant: Dr. David Meyer
• Subject Area: Biogerontology and Geriatric Medicine ; Bioinformatics and Theoretical Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 570621149

As the global population ages, the number of people affected by age-related conditions such as frailty and chronic kidney disease (CKD) is rapidly increasing. Frailty is a syndrome marked by a decline in physical, mental, and immune system reserves, making older adults more vulnerable to disease, hospitalization, and poor outcomes. While frailty is often assessed using clinical tools, these methods offer little insight into the underlying biological changes that drive aging and frailty. In this project, we aim to close this gap by developing and validating molecular tools, so-called “aging clocks” and “frailty predictors”, that can estimate a person’s biological age and frailty level directly from a simple blood sample. These tools are based on gene expression patterns, and allow to gain insights into how the body is aging and which pathways may be driving frailty. We tailor our predictions to the Multidimensional Prognostic Index (MPI), a clinically established tool that captures not just physical health, but also psychological, cognitive, and social dimensions. This means our approach doesn’t just identify who is frail, but also provides a molecular window into the bio-psycho-social subdomains of frailty. To validate and improve these predictors, we will analyze blood samples from a newly recruited clinical cohort of elderly patients (aged 60+) who are being evaluated for kidney transplantation. CKD is an ideal model for this research: CKD accelerates aging and increases frailty risk, but kidney transplantation can, in some patients, restore health and potentially reverse aspects of biological aging. This makes it possible for us to study not just the development of frailty, but also whether the aging process can be slowed, or even partially reversed, following successful treatment. Participants in this cohort undergo thorough clinical assessments, including frailty scoring, and are randomly assigned either to standard care or a tailored geriatric intervention. Blood samples taken at baseline and after one year will allow us to study how gene expression changes over time, how it relates to frailty progression or improvement, and how it is influenced by psychological and social factors. In the long term, our goal is to use these insights to identify potential drug targets. By comparing gene expression in frail versus non-frail individuals, and tracking how these signatures change over time, we can screen for compounds that may “reset” harmful aging patterns. Validated candidates will be tested in a specialized mouse model with known signs of frailty and accelerated aging in the kidney. Together, this project will help build the foundation for personalized aging assessments and future interventions that target the biology of aging, not just its symptoms.

• DFG Programme: Research Grants