In the barracks of an aging body, muscle stem cells behave like reservists who have taken off their uniforms but never left the base. It used to seem that their numbers dwindled with age: a roll call by ID tags showed a decline. But when scientists tagged every single cell with a permanent yellow mark for life, it turned out that the soldiers are all still there. They simply stopped answering to the old call signs.
These cells, named GERI-MuSCs, lose the proteins VCAM1 and Pax7, by which they are usually found, and go silent. They don't turn into muscle fibers, but when transplanted they still take part in repairing damaged muscle, though they produce smaller fibers. Inside them, genes linked to aging switch on, for example Cdkn2a, but the full set of hallmarks of irreversible decrepitude is absent. This is not a discharge, but a transfer to the reserves.
The drugs dasatinib and quercetin, which usually kill senescent cells, selectively wipe out precisely these quiet reservists. And the male hormone dihydrotestosterone restores their lost markers and improves muscle repair. It turns out that rejuvenation may work not by replacing cells, but by waking up the body's own sleeping reserves.
The discovery changes how we view muscle aging: instead of a simple depletion of the stem cell pool, we see the emergence of a special "quiet" state that is reversible. This forces a rethink of the criteria for aging in quiescent cells, which spend most of their lives not dividing. Perhaps drugs will emerge that don't kill senescent cells but wake the sleeping ones.
Mice at the age of 28 months correspond to humans of about 90 years. Yet even in such deeply old animals, stem cells retain the ability to repair muscle if they are woken up by a hormone.
In the novel "Elysium," aging people gain access to medical pods that rejuvenate tissues. The discovery of GERI-MuSCs hints that rejuvenation may work not by replacing cells but by awakening the body's own dormant reserves.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.