Extracellular junk is different from extracellular cross-linking -- it means aggregates of stuff that do not have any function (not even a biophysical one) and should ideally have been destroyed, but have proven resistant to destruction. There are two main examples of such junk. One is the acellular lipid core of mature atherosclerotic plaques, but that doesn't really count, because macrophages are constantly arriving and eating bits of that core, and the only problem is that they can't then break it down after eating it, and eventually they die and become part of the problem. So this would be completely fixed if we could make the intracellular degradation machinery more powerful, as explained here. The other big problem of extracellular junk is called amyloid. Amyloid forms into big globules called plaques in the brain of Alzheimer's disease patients, and the same thing happens (more slowly) in everyone's brains. We don't actually yet know for sure that amyloid is what makes Alzheimer's sufferers lose cognitive function, but we can be pretty sure that the plaques aren't doing any good (though some researchers think that the individual protein molecules do do some good before they aggregate into plaques), so to be on the safe side we should try to get rid of them. The same applies to a variety of similar aggregates that form in other tissues during aging and age-related diseases, of which the best-known is islet amyloid in type 2 diabetes.

A strategy for indefinitely postponing the accumulation of such material is being pursued by Elan Pharmaceuticals: vaccination to stimulate the immune system (specifically, microglia) to engulf the material. When it has been internalised, it may still be resistant to degradation, but if so its degradation can be achieved by the approach necessary for naturally intracellular aggregates described here. The early clinical trials of the Elan vaccine had to be stopped prematurely because of side-effects, but they're working on a better vaccine.

Another strategy is to use small molecules to dissolve the plaques. It seems that the surface of the plaque can be disrupted by small peptides that winkle their way into it, and this makes it less stable, so whole protein molecules float off the surface. These small peptides are called beta-breakers.

Talks on this topic at IABG 10:
Nitsch

Talks on this topic at SENS2:
Lemere      Pepys