Resumen de la plática

Aging is characterized by a progressive decline in physiological function that contributes to chronic disease. Biological clocks derived from high-dimensional clinical and multi-omics data offer a promising approach for more precise tracking of aging processes and disease outcomes. Yet existing biological clocks are often limited in cross-ancestry generalizability and in their ability to capture organ- and pathway-specific dimensions of aging. To address these limitations, our lab has developed multimodal biological clocks at multiple levels of resolution, integrating clinical markers, proteomics, metabolomics, and imaging data across diverse populations. We assessed the predictive utility of these clocks for disease outcomes in large biobanks, including UK Biobank, All of Us, and the Canadian Longitudinal Study on Aging (CLSA). Genome-wide association analyses across multiple populations further revealed ancestry-specific and pathway-specific genetic architectures underlying these clocks. Notably, NPRL3 emerged in both European and African GWAS of clinical biological clocks. As a negative regulator of the mTORC1 pathway, NPRL3 points to a biologically compelling mechanism linked to cellular senescence and neurodegeneration. Our findings demonstrate the value of multimodal biological clocks for disease tracking and therapeutic target discovery.

Sirui Zhou. Human Genetics, McGill University, Canada

https://szhoulab.github.io/
https://www.mcgill.ca/sbms/sirui-zhou

Frontiers in Genomics