| Autor: |
Harrison BR; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Partida-Aguilar M; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Marye A; University of Utah, Department of Microbiology and Immunology, Salt Lake City, UT, USA., Djukovic D; Center for Studies in Ecology and Demography, University of Washington, Seattle, WA, USA., Kauffman M; Center for Studies in Ecology and Demography, University of Washington, Seattle, WA, USA., Dunbar MD; Center for Studies in Ecology and Demography, University of Washington, Seattle, WA, USA., Mariner BL; School of Life Sciences, Arizona State University, Tempe, AZ, USA., McCoy BM; School of Life Sciences, Arizona State University, Tempe, AZ, USA., Algavi YM; Department of Clinical Microbiology and Immunology, Tel Aviv University, Tel Aviv, Israel., Muller E; Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel., Baum S; Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel., Bamberger T; Department of Clinical Microbiology and Immunology, Tel Aviv University, Tel Aviv, Israel., Raftery D; Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA., Creevy KE; Department of Small Animal Clinical Sciences, Texas A&M University, College Station, TX, USA., Avery A; College of Veterinary Medicine and Biomedical Sciences, Colorado State University, CO, USA., Borenstein E; Department of Clinical Microbiology and Immunology, Tel Aviv University, Tel Aviv, Israel.; Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel.; Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel., Snyder-Mackler N; School of Life Sciences, Arizona State University, Tempe, AZ, USA., Promislow DE; Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. |
| Abstrakt: |
Our understanding of age-related physiology and metabolism has grown through the study of systems biology, including transcriptomics, single-cell analysis, proteomics and metabolomics. Studies in lab organisms in controlled environments, while powerful and complex, fall short of capturing the breadth of genetic and environmental variation in nature. Thus, there is now a major effort in geroscience to identify aging biomarkers and to develop aging interventions that might be applied across the diversity of humans and other free-living species. To meet this challenge, the Dog Aging Project (DAP) is designed to identify cross-sectional and longitudinal patterns of aging in complex systems, and how these are shaped by the diversity of genetic and environmental variation among companion dogs. Here we surveyed the plasma metabolome from the first year of sampling of the Precision Cohort of the DAP. By incorporating extensive metadata and whole genome sequencing information, we were able to overcome the limitations inherent in breed-based estimates of genetic and physiological effects, and to probe the physiological and dietary basis of the age-related metabolome. We identified a significant effect of age on approximately 40% of measured metabolites. Among other insights, we discovered a potentially novel biomarker of age in the post-translationally modified amino acids (ptmAAs). The ptmAAs, which can only be generated by protein hydrolysis, covaried both with age and with other biomarkers of amino acid metabolism, and in a way that was robust to diet. Clinical measures of kidney function mediated about half of the higher ptmAA levels in older dogs. This work identifies ptmAAs as robust indicators of age in dogs, and points to kidney function as a physiological mediator of age-associated variation in the plasma metabolome. |
