title: 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.
authors.affiliation: Image Informatics and Computational Biology Unit, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: D Mark
authors.initials: DM
authors.lastname: Eckley
authors.forename: Salim
authors.initials: S
authors.lastname: Rahimi
authors.forename: Sandra
authors.initials: S
authors.lastname: Mantilla
authors.forename: Nikita V
authors.initials: NV
authors.lastname: Orlov
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Coletta
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wilson
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Iser
authors.forename: John D
authors.initials: JD
authors.lastname: Delaney
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: William
authors.initials: W
authors.lastname: Wood
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Wolkow
authors.forename: Ilya G
authors.initials: IG
authors.lastname: Goldberg
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics; D044842:Cullin Proteins / Q000737:chemistry / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D044842:Cullin Proteins