Blood-forming cells are like cooks in the kitchen of the blood. In youth they prepare a varied menu: immune cells and inflammation cells alike. With age, the cooks start making the same spicy dish over and over, inflammation cells, and forget about immunity. That is why older people get sick more often. But what if the cooks were sent on a short master class once, and remembered for life how to cook a balanced meal?
That is exactly the master class the mice got. At the age of two to three months, four proteins were switched on in them for 16 days, proteins that usually turn a mature cell into a stem cell, that is, into a blank-slate cell capable of becoming anything. Here the proteins were switched on only briefly, so the cells would not transform but merely "remember their youth."
The result was surprising: when the mice grew old, their blood stayed young. They had no skew toward inflammation, and their stem cells worked like those of young animals when transplanted. The proteins themselves had long stopped acting, but the cells had remembered something. It turned out they had learned to package their DNA better. In youth, DNA is wound tightly, like thread on a spool, and extra stretches stay silent. With age, the winding loosens, and "junk" stretches of DNA start making noise. Reprogramming restored the tight packaging and the silence.
This experiment is like a vaccine: one short procedure in youth protects for many years. So far it works only in mice, but if it can be repeated in humans, we could prepare blood cells for old age in advance instead of treating them once they have already aged.
A single 16-day course of doxycycline in youth protected mice from the age-related decline in blood formation for almost their entire lives, even though the Yamanaka factors themselves stopped being expressed after just a month.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.