Microbial and metabolic dysregulation in aging

Aging is characterized by progressive organ decline, with chronic kidney disease and sarcopenia representing major global health challenges. This thesis employs a multi-faceted approach, integrating large-scale population analytics, functional multi-omics, Mendelian randomization (MR), and animal experiments, to elucidate the microbial and metabolic drivers of these conditions. Key findings from the Dutch Microbiome Project reveal 43 bacterial species and 54 metabolic pathways associated with kidney function, highlighting significant sex-dependent (predominantly in females) and age-specific interactions. In the Lifelines-DEEP cohort, 202 plasma metabolites were negatively associated with kidney function, with MR analysis suggesting that impaired renal clearance causally increases levels of certain metabolites. Furthermore, research into the gut-muscle axis demonstrated that individuals with sarcopenia have a lower abundance of Prevotella copri and branched-chain amino acids. Supplementation with live P. copri in aged mice successfully improved muscle mass and function by suppressing proteolytic pathways. Additionally, the thesis explores early-life microbiome stability through CRISPR-phage dynamics and proposes a framework for scientific communication via social media. Ultimately, this work advocates for personalized, microbiome-based diagnostic and therapeutic strategies to mitigate age-related multi-organ decline.