Could fasting allow older women to have children? That''s the implication of two new studies which suggest that restricting food may offset some of the loss of egg quality and quantity that comes with ageing. The findings may even enable new eggs to be created from scratch.
It''s not yet clear whether the findings extend to humans, but a better understanding of the mechanisms involved might eventually make it easier for older women to bear children.
In the first study, Jonathan Tilly and his colleagues at Harvard Medical School reduced the calorie intake of adult female mice by 40 per cent and found that significantly fewer of their eggs had abnormal chromosomes once the mice reached the age of 12 months – advanced reproductive years in mouse terms – compared with mice that were allowed to eat as much as they liked.
Such abnormalities in eggs are known to increase the risk of miscarriage and birth defects in older mothers, both mouse and human.
Calorie-restricted mice also produced more eggs than normal mice when their ovaries were artificially stimulated, and their eggs were more likely to develop into embryos upon fertilisation.
"Our data show that adult-onset caloric restriction prevents the age-related decline in oocyte [egg precursor cell] quality and quantity," says Tilly, who is presenting his results at a meeting organised by the SENS (Strategies for Engineered Negligible Senescence) Foundation in Cambridge, UK, next week.
Last year, Tilly''s team announced that restricting the calorie intake of adult mice extended the mice''s reproductive lifespan and increased the chances of their offspring surviving after birth.
"It continues to show how little we know about the mechanisms that are involved in regulating [egg] growth, development and quality," says Evelyn Telfer of the University of Edinburgh, UK, who also researches egg development. "Manipulating nutrition is clearly modifying underlying signalling pathways."
One possibility is that restricting food intake affects the interactions between developing eggs and their support cells, says Telfer. Or it could alter the activity of germ-line stem cells, which some think could replenish depleted ovaries under the right conditions.
That''s where the second study may provide insights. Marc Van Gilst and Giana Angelo at the Fred Hutchinson Cancer Research Centre in Seattle have shown that during starvation, adult nematode worms can put reproduction on hold – destroying any existing sex cells and regenerating a new crop of healthy eggs from a few remaining stem cells once conditions improve.
Worms that undergo this process also seem to extend their lifespan up to threefold.
Van Gilst suspects that a signalling protein called NHR-49, already known to be involved in the metabolic response to fasting, is involved: "In worms that contained an inactive NHR-49 gene, reproductive recovery and fertility after starvation were severely impaired," says Van Gilst.
From worm to human
He thinks a similar process might exist in humans. This is yet to be tested, however, and the trigger needed to activate such a signalling pathway has not been identified. "It might have evolved to help our ancestors preserve fertility during times of famine," he says.
One protein that might do the job in humans is called PPAR gamma, which is analogous to NHR-49 and appears to control the rate of ovulation.
It is also unclear how much caloric restriction would be needed to turn on such a system in humans – assuming we have it at all. But if the underlying signalling molecules could be identified, and ways found to manipulate them, it could help treat a variety of fertility problems and even extend female reproductive lifespan, says Telfer.
"Fundamentally, if you can understand how eggs initiate into the growing population and you can slow it down, then you would be extending female fertility."