Three mice in a cage, each with her own schedule. One sniffs the bedding, another gnaws a grain, the third freezes by the water bottle. A month later, one of them will get an injection that temporarily stops her internal clock, while the other two continue living by the timetable. Thus begins the test: how a single drug affects ovarian aging.
The drug is called tamoxifen. It works like a customs officer who holds passengers at the border for five days and then lets them go. In mouse ovaries, this drug switches on the desired genes but pretends to be a hormone. The ovary is highly sensitive to hormones, so after the injection the cycle goes haywire. The scientists gave mice tamoxifen at three months and then tracked their cycles until one year.
At six and twelve months, the ovaries were compared under a microscope and by RNA composition. Age left its usual marks: connective tissue grew, and large cells with multiple nuclei accumulated. But in mice that had gone through customs, these marks were the same as in those that had lived without delays. Only three genes in the young and three in the old changed their activity after tamoxifen, and none of them is linked to aging. So customs delays passengers for a short time but does not change their route. Now biologists know: after tamoxifen, one must wait three months before drawing conclusions about the ovaries.
In humans, a 6-month-old mouse roughly corresponds to a 20-year-old woman, and a 12-month-old to a 40-year-old. So the experiment spans the period from peak fertility to the onset of age-related decline.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.