An old house often has a locked cabinet full of tools: everything is there, but nobody fixes anything. Aging cells work much the same way. They accumulate the enzyme NAMPT, which kicks off production of the molecule NAD+, a sort of fuel for cellular processes. But in old cells that fuel is burned slowly, and the enzyme sits idle.
Researchers compared young and old human cells using isotopic labels: they fed the cells nicotinamide (a form of vitamin B3) tagged with deuterium and tracked how quickly it turned into NAD+ and back again. It turned out that in old cells the NAD+ turnover is slowed, even though there is more of the enzyme. It is as if the library had installed a second copy of the catalog, but readers are not allowed in.
When old cells were given the activator, they began to die off, while young cells were unharmed. In mice, the activator depleted the nicotinamide supply in the blood, so it was combined with nicotinamide in the feed. That pair raised NAD+ in muscle and heart, dampened age-related inflammation, and lowered levels of the aging marker p16Ink4a. Old mice on this diet grew frail more slowly and held on to the rotating rod longer.
The work shows for the first time that aging cells hold a "dormant" reserve of the enzyme that can be woken up. Previously it was known only that NAMPT accumulates, but it was not clear why. Now it makes sense: the cell prepares its tools but never puts them to work. If we learn to open that cabinet, we can selectively clear out old cells and extend healthy life.
Senescent cells, despite their "old age," contain more of the enzyme NAMPT than young ones, but use it less efficiently, like a library with a huge collection and a closed reading room.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.