The functions of many important tissues in the body depend on physical properties such as elasticity or ability to bear load. These properties derive from the particular structure of the extracellular matrix formed by a tissue, an arrangement of proteins constructed as a mesh to surround and support the cells it holds. The structural properties of the extracellular matrix are increasingly degraded over the course of aging, however, such as by the formation of advanced glycation end-products (AGEs) that can link together proteins of the extracellular matrix in ways that alter the physical properties of the tissue. In the case of blood vessels, rising levels of these cross-links lead to a progressive loss of elasticity, and that in turn causes a whole range of issues in the cardiovascular system that start at hypertension and culminate in catastrophic structural failure of the heart or important blood vessels.

Biochemistry is as a rule always more complicated than we'd like it to be, and so there are many areas of open investigation when it comes to the chemistry of stiffening blood vessels. Metabolic waste products come in many varieties, and it isn't always the case that any given class is actually doing what it is thought to do. Small consensus positions are quietly overturned on a daily basis at the edges of the field, given the falling costs of performing the necessary work, and the foundations of tomorrow are being built beneath the notice of even most researchers.

One of the more important lines of research at the moment, for all that is has little funding and is paid little attention, is to create the means for more research groups to work on glucosepane in human tissues. This appears to be the most prevalent type of AGE forming cross-links in our species - and here it is worth noting that a part of the complexity of this issue is that the chemistry of extracellular matrix cross-linking is very different in various different mammalian species. Lessons learned in mice are only relevant in a very general sense. You'll see few papers on glucosepane despite its importance in our biochemistry, as good tools for working with the class of compounds that glucosepane belongs to in the context of cells and tissues really don't exist yet. For a variety of not-so-good reasons no major research establishment has yet turned its eyes to building them, and so it has fallen on forward-thinking philanthropy to bridge the gap.

As I said, however, there are a lot of different waste products: it is a large space to explore. Those researchers not working on glucosepane are putting in time on other chemicals thought to be relevant to the issue of blood vessel stiffening, but they often draw a blank or find that presence of waste in cells doesn't necessarily correspond to a significant impact on the function of the extracellular matrix, as is the case here. That may not always be the case, of course, and there are certainly good reasons to think that stiffening isn't just AGEs. Science is as much a process of opening doors to empty rooms as it is of finding the one that hides the goal.

Elastin aging and lipid oxidation products in human aorta