A study of 41 mouse strains found that 40% dietary restriction had different effects on lifespan; each strain’s response to milder restriction remains to be tested
A study of 41 mouse strains found that 40% dietary restriction had different effects on lifespan; each strain’s response to milder restriction remains to be tested
On September 15, biomedical researcher Avi Roy discussed a 2010 experiment in which mice of different strains and sexes responded differently to the same reduction in food intake. The experiment tested one level of restriction; each strain’s response to milder restriction requires a separate test.
Caloric restriction, a reduction in food intake, is often used in lifespan experiments. In a 2010 experiment, researchers asked whether genetics influences the response to one such regimen. They compared unrestricted feeding with food intake restricted to 60% of that amount across 41 mouse strains, each with its own fixed set of inherited variants.
When food intake was reduced by 40%, lifespan increased significantly in males from 5% of strains and females from 21% of strains; it decreased significantly in males from 27% of strains and females from 26% of strains. These figures describe how different strains and sexes responded to the same level of restriction.
The authors tested only this level of restriction and identified a question for further study: “It remains to be established whether strains that showed no response to 40% restriction would live longer under a less restrictive regimen.” In his September reply, Roy raised the same question for the full panel:
“Until someone tests a milder level of restriction across the full panel, ‘beneficial for all’ remains an assumption.”
A review of dose selection for exercise, heat and caloric restriction proposed using the body’s ability to recover from stress as a criterion for choosing the intensity of an intervention. For the mouse strains in the 2010 experiment, this criterion provides a hypothesis that requires a separate test.
The original study typically used five mice for each combination of strain, sex and feeding regimen. In a 2021 replication study, researchers selected four strains with the largest reductions in lifespan in the original study and increased group sizes to 30–45 animals. Seven of the eight original findings for these combinations of strain and sex were not replicated. In strain 107, median lifespan, the age by which half the group has died, increased by 24% in females and decreased by 22% in males.
In a 2024 study, 937 genetically diverse female mice were assigned to five feeding regimens. With 40% restriction, median lifespan was approximately 36% longer than with unrestricted feeding. Statistical analysis attributed 23,6% of the variation in lifespan to genetics and 7,4% to feeding regimen.
The average result in a large, genetically diverse group of females and the differences between strains and sexes address different questions. Selecting a feeding regimen for the full panel of 41 strains requires an experiment testing several levels of restriction in both males and females.