Nanoparticle–Protein Corona-Based Tissue Proteomics for the Aging Mouse Proteome Atlas

Highly abundant proteins present in biological fluids
and tissues
significantly interfere with low-abundance protein identification
by mass spectrometry (MS), limiting proteomic depth and hindering
protein biomarker discovery. Herein, to enhance the coverage of tissue
proteomics, we developed a nanoparticle–protein corona (NP-PC)–based
method for the aging mouse proteome atlas. Based on this method, we
investigated the complexity of life process of 5 major organs, including
the heart, liver, spleen, lungs, and kidneys, from 4 groups of mice
at different ages. Compared with the conventional strategy, NP-PC–based
proteomics significantly increased the number of identified protein
groups in the heart (from 3007 to 3927; increase of 30.6%), liver
(from 2982 to 4610; increase of 54.6%), spleen (from 5047 to 7351;
increase of 45.7%), lungs (from 4984 to 6903; increase of 38.5%),
and kidneys (from 3550 to 5739; increase of 61.7%), and we identified
a total of 10 104 protein groups. The overall data indicated
that 3-week-old mice showed more differences compared with the other
three age groups. The proteins of amino acid–related metabolism
were increased in aged mice compared with those in the 3-week-old
mice. Protein-related infections were increased in the spleen of the
aged mice. Interestingly, the spliceosome-related pathway significantly
changed from youth to elders in the liver, spleen, and lungs, indicating
the vital role of the spliceosome during the aging process. Our established
aging mouse organ proteome atlas provides comprehensive insights into
understanding the aging process, and it may help in prevention and
treatment of age-related diseases.