A mouse with progeria ages at an accelerated pace: by five weeks it already shows damage in the aorta and skin. Scientists built a switch into its genome that, on command, turns on production of the Δ133p53α protein. This protein is a shortened version of the famous guardian of the genome, p53, which can both halt cell division and set their repair in motion. Flip the switch, and aging slowed down as if someone had pressed a brake.
In the aorta, the number of smooth muscle cells and the thickness of the wall were restored; in the skin, so were the thickness of the dermis and the work of hair follicle stem cells. The level of the inflammatory protein IL-6 dropped to normal. Kyphosis, a curvature of the spine, developed less often and later. Median lifespan rose by 11%: from 349 to 387 days.
In human skin, the level of Δ133p53α declines with age, while the level of the protein p21, which triggers senescence, rises. There is an inverse correlation between them. So the same brake that worked in mice is gradually being released in us as well. Learning to press it again is a job for future drugs.
A mouse with progeria got a reprieve. Its aorta and skin became younger, its spine straighter, and its life longer. A brake that does not disable protection is a rare stroke of luck in the biology of aging.
Δ133p53α got its name because it starts at the 133rd amino acid residue of p53, while the letter Δ (delta) means a deletion of the first 132 amino acids. This isoform occurs naturally in human cells, and its levels fall with age.
In Aldous Huxley's novel Brave New World, people age more slowly thanks to genetic manipulation. Work on Δ133p53α is a step in the same direction, but without the dystopian undertone: the goal is not immortality but a longer healthy life.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.