In a large orchestra, every musician knows their part: the violinist carries the melody, the cello holds the bass, the flute comes in during the pauses. If the violinist suddenly started playing the horn part, the music would fall apart, even though the instruments themselves would remain intact. The network of blood vessels works in much the same way: the cells lining them from the inside play a distinct role in each organ. In the lungs, they make sure the capillary walls do not let the wrong things through; in the liver, they capture waste; in the heart, they help new vessels grow.
With age, this orchestra starts to go out of tune. Scientists studied 258 574 endothelial cells from the lungs, kidneys, liver, heart, and brain of mice of different ages and watched aging cells gradually forget their parts and drift into a common melody. Instead of organ-specific genes, they switch on the same inflammatory programs, as if all the musicians suddenly started playing the same motif.
This loss of specialization has concrete consequences. In the lungs, cells that once maintained the barrier begin showing fragments of proteins to immune cells, as if a border guard, instead of protecting the frontier, started handing out flyers to passersby. After the introduction of a substance that damages the lungs, more dye leaked through the vessel walls in old mice than in young ones. In the liver, cells responsible for cleaning the blood turned into ordinary capillary cells, and in the heart the ability to grow new vessels declined.
Vascular aging used to be seen as simple wear and tear on the pipes through which blood flows. Now it looks more like a loss of specialization: each organ is stripped of its tailored endothelium and gets a universal but less skilled worker in return. Functional decline begins before clear signs of cellular senescence appear, which means there is a chance to intervene at an early stage. The orchestra has not fallen apart yet, but it is already playing the wrong music.
In old mice, after interferon-gamma was neutralized, MHC-II levels on the endothelium of the lungs and kidneys dropped, but MHC-I stayed unchanged. This suggests that different components of antigen presentation are regulated differently. What is more, in germ-free old mice the age-related induction of MHC genes persisted, meaning the microbiota is not an obligatory trigger of this process.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.