Via EurekAlert!, we note that Sinclair's research team are exploring the role of SIRT3 and SIRT4 in calorie restriction biochemistry: "Mitochondria, a kind of cellular organ that lives in the cytoplasm, are often considered to be the cell's battery packs. When mitochondria stability starts to wane, energy is drained out of the cell, and its days are numbered. ... SIRT3 and SIRT4 play a vital role in a longevity network that maintains the vitality of mitochondria and keeps cells healthy when they would otherwise die. When cells undergo caloric restriction, signals sent in through the membrane activate a gene called NAMPT. As levels of NAMPT ramp up, a small molecule called NAD begins to amass in the mitochondria. This, in turn, causes the activity of enzymes created by the SIRT3 and SIRT4 genes - enzymes that live in the mitochondria - to increase as well. As a result, the mitochondria grow stronger, energy-output increases, and the cell's aging process slows down significantly. (Interestingly, this same process is also activated by exercise.) ... We're not sure yet what particular mechanism is activated by these increased levels of NAD, and as a result SIRT3 and SIRT4, but we do see that normal cell-suicide programs are noticeably attenuated."