Molecular characterization of the transition to mid-life in Caenorhabditis elegans

Abstract

We present an initial molecular characterization of a morphological transition between two early aging states. In previous work, an age score reflecting physiological age was developed using a machine classifier trained on images of worm populations at fixed chronological ages throughout their lifespan. The distribution of age scores identified three stable post-developmental states and transitions. The first transition occurs at day 5 post-hatching, where a significant percentage of the population exists in both state I and state II. The temperature dependence of the timing of this transition (Q 10~1 .17) is too low to be explained by a stepwise process with an enzymatic or chemical rate-limiting step, potentially implicating a more complex mechanism. Individual animals at day 5 were sorted into state I and state II groups using the machine classifier and analyzed by microarray expression profiling. Despite being isogenic, grown for the same amount of time, and indistinguishable by eye, these two morphological states were confirmed to be molecularly distinct by hierarchical clustering and principal component analysis of the microarray results. These molecular differences suggest that pharynx morphology reflects the aging state of the whole organism. Our expression profiling yielded a gene set that showed significant overlap with those from three previous age-related studies and identified several genes not previously implicated in aging. A highly represented group of genes unique to this study is involved in targeted ubiquitin-mediated proteolysis, including Skp1-related (SKR), F-box-containing, and BTB motif adaptors.

High transcript levels of heat-shock genes are associated with shorter lifespan of Caenorhabditis elegans

“…In agreement with our hypothesis that the induction of these genes can be considered as an indication of advanced senescence, published transcriptome analysis of the aging C. elegans showed that the expression of heat-shock protein genes increased after the reproductive period, even at 20°C (Eckley et al, 2013;Lund et al, 2002). On the other hand, genes coding for the transcription factors DAF-16 and HSF-1 were more expressed in the fast than in the slow category.…”

“…A useful biomarker must be a better predictor of lifespan than chronological age. Different biomarkers have been used to determine biological age of C. elegans nematodes: accumulation of lipofuscin in the gut, rate of pharyngeal pumping, pharyngeal morphology, defecation rates, internal growth of food bacteria, ability to induce heat-shock response, induction of certain genes (e.g., sod-3), and muscle-function decline that results in reduction of motility with age (Eckley et al, 2013;Pincus and Slack, 2010).…”

Cockayne syndrome group A and B proteins converge on transcription-linked resolution of non-B DNA

“…4 G-I). Accelerated aging was also found when using a machine classifier to quantify morphological changes that occur with aging in the head of nematodes (32)(33)(34) (Fig. 4J).…”

Tomatidine enhances lifespan and healthspan in C. elegans through mitophagy induction via the SKN-1/Nrf2 pathway

“…We previously showed that pharynx muscle morphology reflects the aging state of the whole organism, and based on this mechanism in combination with machine-learning software, we analyzed the effects of tomatidine on age stage scoring of pharynx in accordance to the previous publications3536. We defined C. elegans pharynx scoring from stage 0 (young) to stage 3 (old): stage 0  C. elegans are predominantly found in the first 2 days of adulthood and are developing fecundity.…”