[
International Worm Meeting,
2015]
One way to understand aging is to use unbiased approaches to profile molecular changes that occur with age, and determine the cause and effect of these changes. In this study, we identify changes in the proteome during aging in C. elegans using mass spectrometry-based proteomics. We find that secreted proteins and proteins expressed specifically in adult animals tend to increase in abundance with age. A previously uncharacterized subset of these age-increased proteins are expressed solely in the extracellular space of the adult uterus. These uterine proteins dramatically accumulate with age, but this increase in abundance is blunted in animals with an extended reproductive period. This suggests that age-induced infertility, an early event in the aging process, is at least partially responsible for the accumulation of proteins in the uterus. Furthermore, we find that uterine proteins rapidly turn over in young adult animals, but are removed much more slowly in old worms. Uterine proteins are not removed in young vulvaless worms, which indicates that egg laying or another means of exit through the vulva is necessary for the rapid removal observed in wild-type young animals. Finally, we show that uterine protein accumulation is toxic for the animal, as knocking down multiple uterine proteins simultaneously can extend lifespan. These findings represent a novel link between reproductive and somatic aging, in which age-induced infertility contributes to changes in the soma that are detrimental for survival. .
[
International Worm Meeting,
2013]
One way to understand how organisms age is to define the differences between young and old. To identify proteins that are differentially regulated during normal aging in C. elegans, we performed quantitative proteomics by tandem mass spectrometry. In total, we quantified expression of 1797 proteins in at least two of three biological replicates. Of these, 53 proteins show significant changes in levels with age; specifically, 40 were increased and 13 were decreased in old age. These proteins are enriched for expression in the intestine. The proteins that are age-downregulated are strongly enriched for downregulation at the mRNA level, suggesting that decreased RNA expression may be responsible for decreased protein levels in old age. In contrast, the proteins that increase with age do not tend to have age-upregulated mRNAs. This may be due to protein accumulation, or changes in translation or degradation rate with age. Therefore, it may be possible to identify regulators of protein expression (such as miRNAs) that are responsible for driving the changes in the aging proteome that are distinct from the aging transcriptome.