There are twenty or so different proteins in the body that can become altered in ways that cause them to aggregate into solid deposits known as amyloids, spreading and encouraging other molecules of the same protein to do likewise. Amyloids are a phenomenon of old individuals and old tissues, for reasons that are much debated and no doubt quite complex.

Some of these amyloids are well studied and well known to be harmful, such as the amyloid-β involved in Alzheimer’s disease. Others are known but less well studied, and whether or not they are harmful is a question mark. The progression of knowledge over the past decade regarding the damage done by transthyretin amyloid, with new associations with disease states emerging every few years, suggests that looking more closely at any amyloid will turn up ways in which it contributes to age-related tissue dysfunction and disease. The SENS proposals for rejuvenation therapies suggest that all amyloids should be targeted for removal by approaches such as catabodies, firstly on the basis that they are a feature of aging, a distinguishing difference between young and old tissues, and secondly that the amyloids that have been carefully investigated all turned out to be harmful.

Today’s research materials are an example of looking more closely at the biochemistry of one specific amyloid, and as a result finding out that it isn’t innocuous. Medin is the most common human amyloid, which makes it interesting that there has been just about as little investigation of its role in age-related disease as was the case for transthyretin amyloid until quite recently. Researchers have published evidence for medin to be involved in aortic anyeurism and of late vascular dysfunction in the brain. That latter finding is echoed in the research noted below.

Lumpy proteins stiffen blood vessels of the brain

Nearly all people over the age of 50 are known to have tiny lumps of the protein Medin in the walls of their blood vessels. “These deposits are apparently a side effect of the aging process. They are predominantly found in the aorta and in blood vessels of the upper body, including those of the brain. Most surprisingly, in our study we could not only detect Medin particles in brain tissue samples from deceased individuals but also in old mice – despite the limited lifespan of these animals. It has been assumed for quite some time that Medin aggregates have an unfavorable effect on blood vessels and can contribute to vascular diseases. Recent studies support this hypothesis. According to these previous findings, older adults with vascular dementia show increased amounts of Medin deposits compared to healthy individuals.”

However, despite these suspicious signs, there has not yet been conclusive evidence that the protein lumps are actually harmful. A research team has now succeeded in proving this – enabled by their finding that Medin deposits also form in aging mice. In mice, when the brain is active and a higher blood supply is needed, blood vessels with Medin deposits expand more slowly than those without Medin. However, the ability of the vessels to expand rapidly is important for regulating blood flow and providing the brain with an optimal supply of oxygen and nutrients. If this ability is impaired, it can have far-reaching consequences for the functioning of organs. Medin deposits therefore seem to contribute to the deterioration of blood vessel function at an advanced age, and this is probably not only the case in the brain, because the deposits also occur in other blood vessels and could therefore lead not only to vascular dementia but also to cardiovascular disease.

Medin aggregation causes cerebrovascular dysfunction in aging wild-type mice

Vascular dysfunction, as it develops either during normal aging or vascular disease, remains a major medical problem. The amyloid Medin, which is derived from its precursor protein MFG-E8 (through unknown mechanisms), forms insoluble aggregates in the vasculature of virtually anybody over 50 years of age, and it has been hypothesized that Medin aggregation could contribute to age-associated vascular decline; however, mechanistic analyses have so far been lacking. Our data now demonstrate that reminiscent of humans, mice also develop Medin deposits in an age-dependent manner. Importantly, mice that genetically lack Medin show reduced vascular dysfunction in the aged brain. Therefore, the prevention of Medin accumulation should be investigated as a novel therapeutic approach to preserve vascular health in the aging population.