Role in ageing
Almost every protein in your body is broken down and replaced by new synthesis, sometimes dozens of times each day. This ensures a constant supply of new, undamaged proteins. But many proteins exist tightly bound to other proteins, which can ‘remember’ any changes in conformation in their binding partners induced by proteome instability. When the new, undamaged protein enters the complex, it can adopt the altered conformation even without, itself, being damaged. We have termed this phenomenon ‘tertiary structural memory’. It is very similar to the way prions, such as CJD or scrapie, propagate and cause disease. Methuselah Health believes this same process underlies ageing.
Nature or nurture?
Why do some people develop age-related diseases and others do not? Some of the variability may come from their environment - exposure to radiation or UV light from the sun, for example, may accelerate proteome instability (just as it accelerates DNA damage). But the majority of the variation most likely results from the genetic sequence encoding the protein. Many different variations (called single nucleotide polymorphisms) can subtly alter the protein conformation rendering it more susceptible to post-translational damage, and hence altered function. The protein thats most susceptible to such instability will determine which late-onset disease an individual suffers from.
Creating treatments
Understanding the role of proteome instability in ageing and disease provides a unique insight into the pathogenesis of diseases such as autoimmunity and neurodegeneration. By examining which proteins carry the most post-translational damage, we can highlight the pathways that actually cause these diseases. Once such targets have been identified, we can design agents that protect those proteins from damage (by maintaining them in their optimal conformation). These new agents should prevent or treat these late-onset degenerative diseases, where current drugs merely address their symptoms. This insight has the potential to revolutionise 21st Century medicine.
