Stem cells and cancer, forget everything you know

I was pretty happy with the theory of cancer being a trade off for longevity, and now this nature paper comes and changes everything. It used to be simple, we have evolved a system of balances and checkpoints, which prevents stem cells from growing uncontrollably and turning into cancer as a result of induced or spontaneous mutations. This balance creates a condition where the stronger the system is, the more stem cells get purged and longevity is diminished to the benefit of being cancer free. Conversely a balance which tolerates more errors, has the benefit of conferring longer longevity to the detriment of getting cancer. It was so nice and simple. All the experiments so far such as overexpressing p53 agreed with that hypothesis. But now this team in Spain show that if you add an additional copy of p53, within its natural promoter, you get to have your cake and eat it too, longer longevity by 16% while the animal appear more youthfull and have reduced incidence of cancer. It seems the key is to express p53 when it's appropriate... It reminds me how ras expression in some system, depending on whether it's from a strong promoter, or it's endogenous promoter, gives diametrically opposed results, senescence vs transformation...

On a somewhat related topic, a new twist to the old oct4/c-myc/sox2/flf4 induced stem cells is that if you select for nanog, you can get the formation of germ cells. The drawback is that 20% of the offspring develop tumour, most likely because of c-myc. Is the change induced by c-myc permanent? if it was expressed only transiently, could we get around this problem? Somehow I suspect not, but I've recently been obsessed with generation-skipping epigenetic effects carried in the germline (hopefully more on this subject later...).

The smell of food can kill you

We have previously discussed the subject of caloric restriction and longevity to great lengths. However, in a surprising twist, it seems that just the smell of food can reverse the anti-aging benefits of dieting: "Smell is an ancient sensory system present in organisms from bacteria to humans. In the nematode Caeonorhabditis elegans, gustatory and olfactory neurons regulate aging and longevity. Using the fruit fly, Drosophila melanogaster, we showed that exposure to nutrient-derived odorants can modulate life span and partially reverse the longevity-extending effects of dietary restriction. Furthermore, mutation of odorant receptor Or83b resulted in severe olfactory defects, altered adult metabolism, enhanced stress resistance, and extended life span. Our findings indicate that olfaction affects adult physiology and aging in Drosophila, possibly through the perceived availability of nutritional resources, and that olfactory regulation of life span is evolutionarily conserved.^"