[Editors] MIT on aging: calorie cuts, endocrine function linked to lengthy lives

[Elizabeth Thomson]

MIT News Office
Massachusetts Institute of Technology
Room 11-400
77 Massachusetts Avenue
Cambridge, MA  02139-4307
Phone: 617-253-2700
http://web.mit.edu/newsoffice/www

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MIT biologists link calorie restriction, endocrine function in worm longevity

--Work advances study of aging
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For Immediate Release
WEDNESDAY, JUNE 13, 2007
Contact: Elizabeth A. Thomson, MIT News Office
Phone: 617-258-5402
Email: thomson at mit.edu

PHOTO AVAILABLE

CAMBRIDGE, Mass.--The link between calorie restriction and a longer, 
healthier life may lie in the head, not in the gut, MIT biologists 
report.

Dietary restriction extends lifespan and retards age-related disease 
in many species, although the phenomenon's underlying mechanisms 
remain a mystery. Underfeeding an organism such as the ordinary 
roundworm alters its endocrine function, which regulates hormones 
instrumental in metabolism. But no connection between the longevity 
induced by calorie restriction and the endocrine system has been 
found-until now.

In a recent issue of Nature, Leonard P. Guarente, Novartis Professor 
of Biology, and postdoctoral associate Nicholas A. Bishop show that a 
particular pair of neurons in the heads of underfed worms may play an 
essential role in their lengthy lives. When these two individual 
neurons were killed by a laser beam, the worms could not enjoy the 
longevity normally associated with calorie restriction.

"This study directs our attention to the brain as a center for 
mediating the beneficial effects of calorie restriction in higher 
organisms, potentially including us," Guarente said. "A complete 
molecular understanding of calorie restriction may lead to new drugs 
for the major diseases of aging."

Restricting calories activates a gene in two neurons, Guarente and 
Bishop report. The gene, called skn-1, is found in a particular pair 
of sensory neurons in the head of the nematode worm Caenorhabditis 
elegans. These neurons are critical in translating information about 
food availability into endocrine signals. The neurons lead peripheral 
tissues to increase their metabolic activity, and this enhanced 
metabolism makes the worms live longer than normally fed counterparts.

In the study, the researchers also confirmed the results with a 
genetic test: They showed that skn-1 genes expressed only in these 
two cells support dietary-restriction longevity; without the genes, 
the longevity increase on dietary restriction disappeared. At the 
same time, the lack of skn-1 genes had little or no effect on the 
lifespan of worms whose calorie intake was not restricted, Guarente 
said.

"We suspect that the two neurons sense dietary restriction and 
secrete a hormone that increases metabolism-and life span-in the 
animal," he said.

Guarente, who published "Ageless Quest: One Scientist's Search for 
Genes that Prolong Youth" in 2003, discovered in 2000 that calorie 
restriction activates the silenced information regulator (SIR2) gene, 
which has the apparent ability to slow aging. This gene makes a 
protein called Sir2, which Guarente has shown is integrally tied to 
extending life span in yeast and in the roundworm. Humans carry a 
similar gene. How Sir2 relates to the two neurons identified in the 
findings is not yet clear, Guarente said.

Guarente suggests that the first commercial products based on 
manipulating Sir2 to slow aging will appear in the next 10 to 20 
years. It is only a matter of time, he said, before aging itself is 
declared a disease.

This work is supported by the National Institutes of Health and the 
Glenn Foundation.

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Written by Deborah Halber, MIT News Office Correspondent