Why do damaged proteins accumulate in your cells as you age?

Your cells continuously run a protein clean-up system called autophagy, which breaks down damaged or misfolded proteins. As you age, this system loses its strength. The result is a self-reinforcing spiral: accumulated proteins hinder the clean-up system, which in turn causes even more accumulation.

At the same time, a broader network of 'guardians' that keep proteins in the right shape, known as chaperones, grows weaker. These are normally responsible for folding new proteins and recognising misshapen ones. When they perform less effectively, more damaged proteins escape clean-up. Researchers link this to the development of diseases such as Alzheimer's and Parkinson's.

A third mechanism is also at play. Some proteins naturally form temporary, liquid, droplet-like clusters inside the cell. This is normal and functional. Over time, however, those clusters can 'solidify' into fixed, irreversible accumulations that the cell can no longer get rid of. In certain neurological diseases, such as ALS, this process is accelerated by specific changes in the protein concerned.

Cells that have become 'old' and no longer divide but also do not die off (sometimes called senescent cells) make the problem worse. They make less use of the clean-up system, and in doing so contribute to the overall accumulation in the surrounding tissue.

Researchers are investigating how accumulation can be targeted directly. Scientists developed an experimental molecule that specifically recognises and breaks down clumped tau proteins (involved in Alzheimer's) without affecting normal tau proteins. It works in cell cultures and in animals, but applications in humans are still a long way off.