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Barshop Institute investigator James Nelson, Ph.D., notes that some mice were unaffected or died on the restricted diet. He cautions people who intentionally restrict their food intake in order to live longer to be careful with this practice.
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SAN ANTONIO (Dec. 3, 2009) — Experts have long considered lowering food intake to be an effective way to extend life span in mice. However, new evidence suggests only some rodents actually benefit from eating fewer calories.

The findings, from The University of Texas Health Science Center at San Antonio and The University of Colorado at Boulder, may temper the enthusiasm of people who seek to live longer by substantially limiting their eating.

At the Barshop Institute for Longevity and Aging Studies, part of the UT Health Science Center, researchers fed a restricted diet to 41 genetically different, inbred strains of mice. The scientists expected that each strain would respond differently, producing a range of life span-lengthening responses.

Results showed many mice were unaffected or harmed by the restricted diet
“To our surprise not only did we find great variation, but we found that more than half of the strains either showed no response to dietary restriction or showed shortened life span in response to it,” said Barshop Institute investigator James Nelson, Ph.D., professor of physiology at the Health Science Center.

A survey of the history of research on dietary restriction “revealed hints of negative effects before, but these effects seem to have been overlooked,” Dr. Nelson said. An unbiased screen of many different mice with genetic variations was lacking in the literature, the study authors report in an upcoming issue of the journal Aging Cell.

“This study dramatically illustrates that there is a very fine line between life extension and life shortening under dietary restriction,” said collaborator Brad Rikke, Ph.D., of the Institute for Behavioral Genetics at the University of Colorado. “There is a critical need to identify early predictors of the life span response if we are going to apply the benefits of dietary restriction — or therapies that mimic it — to humans.”

Biochemical pathways
It is possible that dietary restriction adjusts biochemical pathways, such as oxidative stress, that are implicated in aging. Oxidative stress is cumulative damage — caused by molecules called free radicals — that is not adequately countered by other molecules called antioxidants.

Some strains of mice may not need the adjustment.

“This finding raises the possibility that, inherently, long-lived mice already have increased activity in biochemical pathways that are activated by dietary restriction,” Dr. Nelson said. “These mice may also have reduced activity in pathways that are repressed by dietary restriction. Further study is needed to explore this question.”

More study likewise is needed to determine whether mice with shortened life spans would be impacted as negatively by smaller levels of diet restriction.

Restricting calories to live longer remains an unproven theory
The Aging Cell article noted that “members of an organization, the Calorie Restriction Society, practice self-imposed dietary restriction in an effort to extend their lives.” Dr. Nelson said: “The results raise a cautionary note to those people who are self-restricting in the hope of having a longer and healthier life.”

Dr. Rikke noted an important implication beyond studies of dietary restriction. “I think many investigators using rodent models would find, as we did, that you get an eye-opening amount of variation when you conduct studies across a large number of different genetic strains,” he said. “It is frightening how much of our knowledge has been built on studies of just one or two strains.”

Dr. Rikke first proposed the idea of studying dietary restriction in so many genetically different mice. Study collaborators included Thomas Johnson, Ph.D., of the University of Colorado; Chen-Yu Liao, Ph.D., who collected and analyzed study data for his doctoral dissertation at the UT Health Science Center; and Vivian Diaz of the Nathan Shock Animal Core, also at the Health Science Center.

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