Nanoproteomics analysis reveals single C. elegans heterogeneity during aging

Aging was long assumed to be a passive and stochastic process caused by random damage accumulation, however，such theories fail to explain the program-like features of the aging process. Measuring the aging process in C. elegans at individual level provides an opportunity to analyze both the programmed (age-related changes at population level) and stochastic (inter-individual differences in isogenic population) components during the aging process. Here, we performed quantitative proteomic analyses on more than 150 worm individuals of different ages and aged individuals with different mobility. The analysis of inter-individual variations helps dissect the programmed and stochastic components during the aging process, and key proteins underlying the lifespan plasticity among the genetically identical worm individuals. Using a high temporal resolution single worm proteomic landscape, we found that the aging process was non-linearly progressed, with each stage marked by distinct age-related changes. The fast-aging individuals are depleted with such secreted proteins and over-activation of lysosome degradation processes, providing a first molecular link for the programmed enhanced offspring growth and death of the parent individual. This mechanistic link indicates that programmed events at least in part explain the heterogeneity of adult aging.