Understanding how different methods of DR induce lifespan extension is pivotal for the identification of all the components of the gene network that orchestrates maximal longevity extension in response to nutrient deprivation.
Rapamycin, an inhibitor of mTOR kinase, increased median lifespan of genetically heterogeneous mice by 23% (males) to 26% (females) when tested at a dose threefold higher than that used in our previous studies; maximal longevity was also increased in both sexes.
Reduction of maximal longevity was detected only in females.
While the male dwarf GH + T4 treatment group had no significant effect on lifespan, the female dwarfs undergoing treatment showed a decrease in maximal longevity.
The most intriguing finding was that the complete elimination of normal RasGrf1 increased both average and maximal longevity independent of a role in cancer.
35 Whether similar disease prevention and maximal longevity extension will be present in the CR monkeys is not yet established, but additional interim results for mortality are expected in the near term (1 3 years).
From a fundamental point of view, these results are strongly consistent with a relationship between species maximal longevity and mitochondrial mutation rate, in agreement with the mitochondrial theory of ageing.
Data in this paper show that ATF4 levels, levels of proteins controlled by ATF4, and levels of three mRNAs regulated directly by ATF4 are elevated in liver of mice exposed to each of five interventions shown elsewhere to increase maximal longevity: the drugs acarbose and rapamycin, diets low in calories or methionine, or transient milk deprivation limited to the suckling period.
In birds, GC3* correlates negatively with maximal longevity (R = −0.36, PP = 0.03), but not with body mass and age at sexual maturity.
DOI: http://dx.doi.org/10.7554/eLife.01098.013 Kaplan Meier survival curves indicate that in GHRH-KO mice, CR produced significant increase in overall survival, average, median, and maximal longevity when the data from both sexes were combined (log-rank test, p<0.0001).
