This study investigates the genetic architecture of biological age gaps (BAGs) across nine human organ systems using data from 377,028 participants of European ancestry in the UK Biobank. BAGs were calculated using cross-validated support vector machines, incorporating imaging, physical traits, and physiological measures. The study identified 393 genomic loci-BAG pairs (P < 5 × 10⁻⁸) associated with the brain, eye, cardiovascular, hepatic, immune, metabolic, musculoskeletal, pulmonary, and renal systems. These genetic variants are predominantly specific to their respective organ systems but also show pleiotropic links with other systems. Genetic correlations between the nine BAGs mirror their phenotypic correlations, indicating shared genetic underpinnings. A multiorgan causal network, established through two-sample Mendelian randomization and latent causal variance models, revealed potential causality between chronic diseases (e.g., Alzheimer’s disease and diabetes), modifiable lifestyle factors (e.g., sleep duration and body weight), and multiple BAGs. The study highlights the potential for improving human organ health through multiorgan networks, including lifestyle interventions and drug repurposing strategies. Biological aging is complex and influenced by genetics, environmental exposures, and modifiable lifestyle factors across multiple organ systems. Understanding the phenotypic landscape and genetic architecture of biological aging in multiple human organ systems is crucial for precision medicine, including identifying vulnerability and resilience factors. Previous research has made progress in studying the interconnectedness of multiorgan systems in human health. The study expands on prior research by depicting the genetic architecture underlying biological aging across nine human organ systems, including the brain, cardiovascular, eye, hepatic, immune, metabolic, musculoskeletal, pulmonary, and renal BAGs. The study's results illustrate the potential for improving human organ health through a multiorgan network, including lifestyle interventions and drug repurposing strategies. The findings also highlight the importance of considering the genetic covariance of age-related diseases in clinical practice. The study found a bidirectional causal relationship between the hepatic and musculoskeletal BAGs, suggesting that liver function and metabolic health significantly impact musculoskeletal health. The study also identified potential causal effects of chronic diseases, body weight, and sleep duration on the nine BAGs. The results provide insights into the shared mechanisms underlying the nine BAGs, their relationships with chronic diseases, and cognition. The study underscores the importance of understanding the complex, multifaceted nature of biological aging and its impact on organ health.This study investigates the genetic architecture of biological age gaps (BAGs) across nine human organ systems using data from 377,028 participants of European ancestry in the UK Biobank. BAGs were calculated using cross-validated support vector machines, incorporating imaging, physical traits, and physiological measures. The study identified 393 genomic loci-BAG pairs (P < 5 × 10⁻⁸) associated with the brain, eye, cardiovascular, hepatic, immune, metabolic, musculoskeletal, pulmonary, and renal systems. These genetic variants are predominantly specific to their respective organ systems but also show pleiotropic links with other systems. Genetic correlations between the nine BAGs mirror their phenotypic correlations, indicating shared genetic underpinnings. A multiorgan causal network, established through two-sample Mendelian randomization and latent causal variance models, revealed potential causality between chronic diseases (e.g., Alzheimer’s disease and diabetes), modifiable lifestyle factors (e.g., sleep duration and body weight), and multiple BAGs. The study highlights the potential for improving human organ health through multiorgan networks, including lifestyle interventions and drug repurposing strategies. Biological aging is complex and influenced by genetics, environmental exposures, and modifiable lifestyle factors across multiple organ systems. Understanding the phenotypic landscape and genetic architecture of biological aging in multiple human organ systems is crucial for precision medicine, including identifying vulnerability and resilience factors. Previous research has made progress in studying the interconnectedness of multiorgan systems in human health. The study expands on prior research by depicting the genetic architecture underlying biological aging across nine human organ systems, including the brain, cardiovascular, eye, hepatic, immune, metabolic, musculoskeletal, pulmonary, and renal BAGs. The study's results illustrate the potential for improving human organ health through a multiorgan network, including lifestyle interventions and drug repurposing strategies. The findings also highlight the importance of considering the genetic covariance of age-related diseases in clinical practice. The study found a bidirectional causal relationship between the hepatic and musculoskeletal BAGs, suggesting that liver function and metabolic health significantly impact musculoskeletal health. The study also identified potential causal effects of chronic diseases, body weight, and sleep duration on the nine BAGs. The results provide insights into the shared mechanisms underlying the nine BAGs, their relationships with chronic diseases, and cognition. The study underscores the importance of understanding the complex, multifaceted nature of biological aging and its impact on organ health.