Reduction of glucose, which is the preferred carbon source of most microbes, has a wide spectrum of effects in the variety of established microbial life span models, ranging from nearly 100-fold life span extension (van Diepeningen et al. 2010) to threefold life span reduction (Oliveira et al. 2008).
Furthermore, we recently reported that expression of exogenous Bmi-1 in NHOK led to significant extension (2.7 fold) of replicative life span but did not efficiently downregulate the expression of p16INK4A (Kim et al, 2006).
We noted that the flies with increased dSir2 expression from the Sir2-3 and Sir2-4 transgexpresspress dSir2 to a similar extent, from 2-5 fold increased, when life span is extended, while some of the conditions that we had tested had much higher levels of dSir2, and rarely extended life span.
KP1339 monotherapy led to a 2.4-fold increase in life span and, thus, was superior to sorafenib, which induced a 1.9-fold prolonged survival.
This pronounced anticancer activity resulted in life prolongation in all treated groups (Fig. 5B): KP1339 treatment induced a 2.4-fold increase in life span with a mean survival of 80 days as compared to 33 days in the control group.
Expression below this range (less than 2-fold increase), or slightly above it (between 5-10 fold increase) inconsistently extends life span, while higher levels of expression are detrimental to life span and can induce JNK signaling and dnaJ-H expression.
This finding suggests that in these conditions, a modest ~1.5-fold and significantly higher ~11-fold elevation of dSir2 can extend life span.
Maximal life span, for example, varies 5,000 fold among insects, 100 fold among mammals, and 15 fold among birds (Calder, 1984).
In addition, very high dSir2 expression (greater than 30-fold increase) is associated with shortened life span, suggesting that such high levels of dSir2 may have a toxic effect.
The three yeast mutants sch9Δ, ras2Δ, tor1Δ show extended chronological life span up to three folds.
In budding yeast inactivation of sch9, homolog of mammalian serine/threonine protein kinase Akt, extends chronological life span by nearly three folds [6].
