Sci. Aging Knowl. Environ., 28 May 2003
Young ovaries rejuvenate old mice
Key Words: ovariectomy somatic tissue
Some elderly people wish for the body they had in their 20s, but they might need only certain parts in order to live longer, according to a new study. Ovaries apparently govern aging of the entire organism--at least in mice. The results imply that the mammalian reproductive system might disseminate a longevity-determining signal similar to one found in nematodes.
Conventional evolutionary wisdom says that postponing reproduction increases life span, whereas procreating hastens death--and experimental observations back up that idea. For instance, Medflies that are denied protein, and thereby prevented from reproducing, live longer than those allowed to reproduce at will. Furthermore, destroying a nematode's germ line cells (equivalent to mammalian eggs or sperm) extends life span; however, removing the entire egg-producing organ--known as the gonad--eliminates the longevity gain, suggesting that the gonad somehow counteracts germ line cells' influence on aging. Previous work suggested that mammals also trade reproductive capacity for longevity (see "Aging Research Grows Up"), but no one knows how signals from mammalian gonads affect life span. James Carey, an entomologist at the University of California (UC), Davis, teamed up with UC Davis physiologist Shelley Cargill, who had experience performing mouse ovary transplants, to test whether gonads control how quickly rodents age.
The researchers transplanted ovaries from 2-month-old mice, which had passed puberty, into older animals. The recipients, whose own ovaries had been removed prior to puberty, received the organs at 5 months, 8 months, or 11 months of age. Eleven-month-old mice are typically postreproductive, but 5- and 8-month-olds are able to bear young. The older recipients benefited the most: Refreshing the creatures' reproductive organs increased average life expectancy by 60% over that of animals without ovaries and by 40% compared to females with their original ovaries. The rejuvenated mice remained frisky and healthy until shortly before they died, says Cargill. In contrast, the 5-month-old and 8-month-old recipients had only small gains in average life span. Those mice aren't yet old enough to need the boost that the young ovaries bring, the researchers suggest.
Perhaps, as in worms, competing signals from ovaries and eggs determine life expectancy. The ovary transplant might produce an effect similar to killing germ line cells in nematodes, they reason. The temporary halt of blood flow to the transplanted ovary damages the eggs more than the surrounding cells. If the ovaries churn out a revitalizing signal and eggs issue a life-shortening cue, then crippling eggs without severely damaging the rest of the gonad would enhance the relative strength of the life-extending signal, says Carey.
"It's really intriguing," says molecular geneticist Cynthia Kenyon of the University of California, San Francisco. "The really great thing about it is it tells you that the reproductive system can have a longevity effect in the mammal. Now the question is, does it use a mechanism that's fundamentally the same as the one in the worm, or is it fundamentally different?" The key, she says, will be identifying the signaling system that the ovaries use to slow aging. Manipulating that signal might someday transport the elderly back to their youthful prime.
May 28, 2003
Science of Aging Knowledge Environment. ISSN 1539-6150