Juulia Jylhävä is a Senior research fellow at the Tampere University, Finland, and Principal researcher at Karolinska Institutet, Sweden. She is leading the Systems Biology of Aging group that focuses on unraveling the causes and consequences of biological aging through genomic methods. Her recent  work includes identification of various omics determinants of age-related frailty and other aging traits, integrating genetics, epigenomics, metabolomics and proteomics methods. She applies large-scale genetic data in genome-wide association studies and Mendelian randomization, to explore genetic and molecular factors causally contributing to frailty and age-related diseases. Her research aims to bridge the gap between molecular biology and clinical applications, providing insights into potential biomarkers and therapeutic targets for healthier aging. She collaborates extensively across disciplines, contributing to international consortia and advancing precision medicine in geroscience.

Decoding biological aging and frailty through genomic methods

Frailty is a complex, clinically significant phenotype and a measure of biological aging at the
whole-organism level, characterized by multisystem physiological decline. However, its
biological underpinnings remain poorly understood. To advance our understanding of its
underlying mechanisms, we studied the genetic, metabolic, and epigenetic determinants of
frailty. We performed a genome-wide association study of ~1 million individuals in FinnGen
and UK Biobank identified 53 loci associated with frailty, including 45 novel variants. Key
genes such as CHST9, ILRUN, KHK, MET, APOE, CGREF1 and PPP6C were implicated through
colocalization with expression and splicing quantitative loci and proteomics analyses. Our
complementary metabolomics work in ~90,000 individuals in the UK Biobank identified 59
biomarkers, notably glycoprotein acetyls, indicating a causal role of chronic inflammation in
frailty. Further, Mendelian randomization highlighted creatinine and lipid-related markers as
secondary to kidney and cardiometabolic conditions. Epigenetic analyses across twin
cohorts revealed 589 frailty-associated CpG sites, many previously linked to aging and agerelated diseases, including regions in genes related to neuronal and immune pathways.
Together, these findings illuminate the multifactorial biology of frailty and support a
geroscientific framework, wherein frailty is shaped by immunological, neurological and lipid
metabolism-related processes. This integrative evidence paves the way for early risk
stratification and hopefully targeted interventions to extend healthspan.