Chromosome dosage as a life span determinant in Caenorhabiditis elegans.

Caenorhabiditis elegans males live longer than hermaphrodites when cultured individually. Since hermaphrodites contain a pair of X chromosomes (XX) and males are XO (there is no Y chromosome in C. elegans), we questioned whether chromosomal differences per se might impact life span. The use of mutations in the sex-determination genes tra-1 and her-1 allowed us to uncouple sexual phenotype from the normal X chromosomal composition and demonstrate that possession of two X chromosomes limits hermaphrodite life span. We also provide evidence that diplo-X animals live shorter than haplo-X animals because faulty dosage compensation results in inappropriately high expression of X-linked genes in geriatric animals. First, three dosage-compensation-defective Dpy mutants were short lived, but four other Dpy mutants with wild-type dosage compensation had normal life spans. Second, we employed the microarray data generated by Lund and coworkers to show that X-linked gene expression in the roughly 10% of geriatric worms that were still alive between 16 and 19 days was almost 20% higher than autosomal gene expression. While this increase was statistically insignificant owing to wide variation in the gene-to-gene expression, our collective data suggest that age-related reductions in dosage compensation may occur in this nematode and, as a consequence, limit the life span of XX animals.