Abstract
Protein turnover rates severely decline in aging organisms, including C. elegans However, limited information is available on turnover dynamics at the individual protein level during aging. We followed changes in protein turnover at one-day resolution using a multiple-pulse 15N-labeling and accurate mass spectrometry approach. Forty percent of the proteome shows gradual slowdown in turnover with age, whereas only few proteins show increased turnover. Decrease in protein turnover was consistent for only a minority of functionally related protein subsets, including tubulins and vitellogenins, whereas randomly diverging turnover patterns with age were the norm. Our data suggests increased heterogeneity of protein turnover of the translation machinery, whereas protein turnover of ubiquitin-proteasome and antioxidant systems are well-preserved over time. Hence, we presume that maintenance of quality control mechanisms is a protective strategy in aging worms, although the ultimate proteome collapse is inescapable.
Highlights
The downturn of protein homeostasis, including the commonly observed slowdown of protein synthesis and degradation, is a major hallmark of aging [1, 2]
To monitor age-dependent changes in protein turnover, we used Stable Isotope Labeling by Nitrogen in Caenorhabditis elegans (SILeNCe), a metabolic labeling approach that has been shown to be efficient in C. elegans [21, 34, 35]
Pulsing of new subcultures was continued until day 7 and the last sample was collected at day 9, which coincides with mean lifespan of the population under these culture conditions (Fig. 1A, supplemental Table S2)
Summary
The downturn of protein homeostasis (proteostasis), including the commonly observed slowdown of protein synthesis and degradation (protein turnover), is a major hallmark of aging [1, 2]. These studies point out shifts in protein synthesis rates in old worms, the gradual change in turnover of individual proteins with increasing chronological age has not been investigated previously. We analyzed the change of individual protein half-lives in aging worms using a multiple-pulse metabolic 15N-labeling method.
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