It will be important to test this possibility and determine whether or not CR induces feminizing gene expression changes in organisms that have a clear female lifespan advantage, such as humans, and whether such changes might influence lifespan.
Moreover, SIRT6 is the only mammalian sirtuin which displayed clear increase in lifespan when overexpressed in the whole body of mice (Kanfi et al., 2012).
It is now clear that the lifespan of an organism is determined by a combination of environmental conditions, stochastic factors (such as lifestyle) and genetic background.
In marked contrast, on PASM containing 2% glucose PaGlo1_OEx, PaGlo1/ Pando2_OEx and Δ PaGlo1 strains are characterized by clear differences in lifespan.
Looking only at the measured control and treatment, the conclusion is a clear increase in lifespan when overexpressing dFOXO, and further studies (Hwangbo et al., 2004; Giannakou et al., 2008) support the general statement that dFOXO overexpression can extend lifespan.
This may even be relevant in terms of longevity, since IGF-1R signalling inhibition does not appear to have clear effects on lifespan in male mice (44), leading these authors to suggest that the effects of inhibiting this pathway in mammals may not be as straightforward as has been predicted by invertebrate studies (44).
In summary, there are several well-known species that show clear plasticity of lifespan due to changes in gene expression and hormonal levels, which appear to have evolved as an adaptation to a specific environment and result in at least two distinct routes to death.
While it remains unclear whether or not female mice live longer in general than males, lifespans of both male and female mice are extended by CR and it is quite clear that their lifespans are greatly influenced by sex-associated variables, including hormonal status and reproductive history [23], [24].
In Drosophila, the expression of hMGS-9A induced the accumulation of large glycogen deposits which correlated with a dramatic reduction in lifespan and clear locomotion defects.
This might still seem like a lot for those living on $2 a day, but when you factor in the health and productivity costs for poor families of traditional cook stoves, the return on investment of a clean cookstove with a three- to five-year lifespan becomes clearer.
