CGC Bibliography Paper 5475

Transcriptional profile of aging in C. elegans.

Lund J, Tedesco P, Duke K, Wang J, Kim SK, Johnson TE

Medline:

12372248

Citation:

Current Biology 12: 1566-1573 2002

Type:

ARTICLE

Genes:

act-4 age-1 daf-2 emb-27 fer-15 hsp-1 hsp-2 hsp-3 hsp-4 hsp-16 ins-2 ins-3 ins-4 ins-5 ins-6 ins-7 ins-11 ins-17 ins-18 ins-21 ins-22 ins-23 mup-2 sip-1 sir-2.1 spe-9

Abstract:

Background: Numerous gerontogene mutants leading to dramatic life extensions have been identified in the nematode Caenorhabditis elegans over the last 20 years. Analysis of these mutants has provided a basis for understanding the mechanisms driving the aging process(es). Several distinct mechanisms including an altered rate of aging, increased resistance to stress, decreased metabolic rate, or alterations in a program causing organismic aging and death have been proposed to underlie these mutants. Results: Whole-genome analysis of gene expression during chronological aging of the worm provides a rich database of age-specific changes in gene expression and represents one way to distinguish among these models. Using a rigorous statistical model with multiple replicates, we find that a relatively small number of genes (only 164) show statistically significant changes in transcript levels as aging occurs (<1 % of the genome). Expression of heat shock proteins decreases, while expression of certain transposases increases in older worms, and these findings are consistent with a higher mortality risk due to a failure in homeostenosis and destabilization of the genome in older animals. Finally, a specific subset of genes is coordinately altered both during chronological aging and in the transition from the reproductive form to the dauer, demonstrating a mechanistic overlap in aging between these two processes. Conclusions: We have performed a whole-genome analysis of changes in gene expression during aging in C. elegans that provides a molecular description of C. elegans senescence.