Indeed, many studies have already shown a link between stress during development and later behavioural effects, such as sexual signalling, longevity, breeding behaviour, learning and memory (Henriksen et al., 2011; Lupien et al., 2009; Monaghan, 2008; Monaghan et al., 2012; Sachser et al., 2011; Spencer and Verhulst, 2007; Weinstock, 2008).
One caveat of the IGF-1 pathway is that reduced signaling increases longevity, whereas, enhanced signaling promotes cancer.
The signal for longevity in our data is strongest in D4a because it has the greatest number of protective mutations.
Thus, it deserves further studies on the roles of RAS-RAF-MEK signaling in longevity and neuronal atrophy with models of higher animals, such as rodents or monkeys.
An interesting question remains to be fully addressed is whether activation of autophagy mediates the beneficial effects of suppressing insulin/IGF-1 or mTOR signaling on longevity.
However, to avoid compromising brain function of higher animals (Fig. 2 4), our results raise caution about inhibiting RAS-RAF-MEK signaling for longevity.
Insulin signaling influences longevity in Drosophila [3], [12], [40].
There are two possibilities about how Wnt signaling regulates longevity.
The link between reduced IIS signaling and longevity was subsequently also observed in D. melanogaster.
Genetic suppression of IIS signaling extends longevity in worms, insects, and mammals [ 1].
