A Transition From Interindividual Uniformity to Diversity in Appearance and Transcriptional Features at Midlife in...

During embryogenesis, organisms function as a robust system that ensures uniformity within individuals, but they lose robustness and develop variations at advanced ages. However, when and how organisms lose this robustness remains largely elusive. Here, we identified a sharp transition from interindividual uniformity to diversity in the appearance and transcriptional features of age-matched Caenorhabditis elegans in midlife. Convolutional neural network analysis of individual appearance alterations revealed that the transition occurs in midlife, which coincides with the cessation of egg-laying activity and increased motility defects. This period represents the transition from the young state, marked by shared homogeneous features among same-age individuals, to the old state, marked by shared among old individuals. Transcriptional coherence within the age-matched individuals shows essentially the same transition, coinciding with the appearance features. These findings provide a new framework for understanding the aging trajectory in C. elegans, demonstrating the occurrence of the loss of robust control over appearance and transcriptional homeostasis in midlife.