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Reproductive Signals Affect Lifespan In Roundworm C. Elegans, Offering Possible Insight Into Human Aging Process

suspect that at least one may be a small peptide hormone similar to insulin or IGF-1.

In work that laid the groundwork for the current finding, the investigators determined that when the DAF-2 receptor receives a signal from its insulin/IGF-like hormone, it inhibits the activity of the DAF-16 gene, which normally signals cells to continue to live long and productively. When the DAF-2 gene is mutated, DAF-16's activity increases, and the animal remains active and youthful much longer than normal and lives more than twice as long. In the current study, the researchers' findings suggest that germ cell signals decrease lifespan by down-regulating, or inhibiting, DAF-16, while somatic gonad signals increase life span by repressing the activity of DAF-2.

Just as DAF-16 and DAF-2 normally counteract each other to produce a consistent lifespan in C. elegans, the signals from the reproductive system normally counteract each other by modulating these two opposing proteins in the IGF/insulin-like pathway.

In addition to regulating the lifespan of adult animals, the DAF-2/DAF-16 pathway allows young worms to enter a hibernation-like state if food is limited. The new findings, said the senior author of the study, Cynthia Kenyon, PhD, the Herbert Boyer Professor of Biochemistry and Biophysics at UCSF, indicate that lifespan is not a fixed and immutable process but instead a very plastic one, subject to change by hormonal signals. These new findings imply that the roundworm's insulin/IGF-1 system integrates multiple signals to define the rate of aging of the animal.

"We suspect," she said, "that the DAF-2/DAF-16 system acts as a master regulator to regulate development and aging in response to environmental signals, such as food, as well as internal signals that reflect the state of the reproductive system."

External factors affecting the rate at which reproductive cells develop could, in turn, influence the aging of the individual animal.

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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
26-May-1999


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