Single‐worm quantitative proteomics reveals aging heterogeneity in isogenic Caenorhabditis elegans

The heterogeneity of aging has been investigated at cellular and organic levels in the mouse model and human, but the exploration of aging heterogeneity at whole‐organism level is lacking. C. elegans is an ideal model organism for studying this question as they are self‐fertilized and cultured in the same chamber. Despite the tremendous progress made in single‐cell proteomic analysis, there is few single‐worm proteomics studies about aging. Here, we apply single‐worm quantitative mass spectrometry to quantify the heterogenous proteomic changes during aging across individuals, a total of 3524 proteins from 157 C. eleagns individuals were quantified. A reconstructed C. elegans aging trajectory and proteomic landscape of fast‐aging individuals were used to analyze the heterogeneity of C. elegans aging. We characterized inter‐individual proteomic variation during aging and revealed contributing factors that distinguish fast‐aging individuals from their siblings. This study quantitatively analyzed the proteomes of more than 150 worms during the aging process with a high temporal resolution. A reconstructed C. elegans aging trajectory reveals the dynamic aging process with heterogeneity among individuals. We characterized inter‐individual proteomic variation among isogenic individuals and revealed contributing factors that distinguish fast‐aging individuals from their siblings.