We suggest that long-living species may also feature higher levels of lifespan-limiting molecules and that metabolome remodeling upon dietary interventions activates compensatory mechanisms.
Thus, an urgent need to either confirm or rebut these effects of Sir2 expression levels on lifespan exists.
This is nevertheless consistent with a non-linear relationship between ATP levels and extension of lifespan in different RNAi-mediated Mit mutants (Fig. S2E and Dillin et al., 2002).
In addition, studies in C. elegans have highlighted the fact that the ratio of AMP ATP levels is predictive of lifespan and that AMPK activation promotes longevity (Apfeld et al., 2004; Curtis et al., 2006; Greer et al., 2007; Mair et al., 2011).
Mice lacking Klotho have a short lifespan [ 54] while high levels of Klotho increase lifespan [ 58].
Several models have been proposed to explain how different levels of stress influence lifespan [ 25, 26, 64, 65].
Our study showed that the elevated levels of autophagy and lifespan extension induced by β‐GPA were abolished by Atg1‐RNAi.
In Caenorhabditis elegans, increased levels of Sir2 increase lifespan in a mechanisms dependent on the insulin/IGF-1 pathway (i.e., FOXO transcription factors) (Tissenbaum & Guarente, 2001).
While the oxidative stress theory of aging has been explored, except in limited examples using gene knockout or overexpression of antioxidant enzymes, there is a general lack of correlation between the levels of antioxidants and lifespan.
Together, these results suggest that a balance in neurotransmission from the primary olfactory neurons is crucial to an animal's longevity; both higher than normal and lower than normal levels of neurotransmission extend lifespan.
