These results showed that different genes control the life span of C. elegans and the length of reproductive time. In her latest work, Murphy wanted to know whether reproduction and life span were two aspects of the same overall genetic pathway or completely separate entities. To answer this question, Murphy tracked which genes were turned on and off over time in the oocytes and somatic cells in C. elegans IGF-1 and TGF-β mutants, as well as wild-type worms.
Murphy found that the normal pattern of gene activation seen in aging wild-type C. elegans was reversed in the body cells and oocytes of IGF-1 mutants. Gene activation was also reversed in the oocytes of TGF-β mutants. With genes that helped them produce higher-quality eggs for a longer period of time, the TGF-β mutants had double the reproductive span as control worms. When Murphy compared the genes turned off and on in oocytes and body cells of the same worm, however, she saw that two completely different sets of genes controlled oocyte and body-cell aging in C. elegans. Those genes that helped somatic cells live longer and age more slowly maintained the quality of the cell's membranes and proteins. The genes linked to oocyte longevity, however, preserved the integrity of chromosomes and DNA.
"The TGF-β have a longer reproductive span by better maintaining their DNA, chromosomes and chromatin structure—all these things that have to do with the DNA components of the cell. That's a completely non-overlapping pathway with the kind of genes we see regulating somatic aging," Murphy says. Genes maintaining protein and cell membrane quality help drive body cell longevity, because the priority of these cells is to preserve existing function rather than produce large numbers of new cells.
"What drives the decline in oocyte quality in human females is chromosome abnormalities," Hassold says. "The likelihood of a woman in her twenties conceiving a chromosomally abnormal embryo is under 5 percent. For a woman in her forties, the likelihood may be as high as 50 percent." As with humans, he says, the oocytes of C. elegans also show an increase in chromosome abnormalities with aging.
With more women delaying childbirth until their thirties or even later, understanding how oocytes age is crucial to helping women have healthy babies. But the importance of Murphy's work extends beyond fertility and childbirth. By understanding how different cells age, Murphy says, researchers may one day not only extend reproduction, but also life span and organ function.