Why do damaged proteins accumulate in your cells as you age?
With age, the systems that clear damaged proteins become less and less efficient, while damage to proteins actually increases. It is worth knowing that good sleep supports the glymphatic system, which helps drain protein waste from the brain.
Two major 'clean-up systems' normally keep your proteins healthy: molecular guardians (chaperones) that fold proteins into the right shape, and breakdown machines that shred damaged ones. Both systems become less efficient with age. Multiple independent review studies confirm this consistently. The result is that misfolded proteins keep lingering and building up.
At the same time, the production of damaged proteins increases. Sugar molecules spontaneously attach themselves to proteins and form so-called advanced glycation end-products. These chemically altered proteins stick together into clumps that the breakdown machines can no longer handle. On top of that, they trigger inflammatory responses, which in turn cause even more damage.
Cells also use temporary liquid droplets of proteins to direct certain processes. Under prolonged stress or during ageing, these droplets can harden into solid clumps. This has been demonstrated for the protein involved in ALS, and is suspected to occur in more proteins as well. Once hardened, these clumps are virtually impossible to clear away.
In the brain, the glymphatic system also plays a role: a kind of drainage channel that flushes protein waste away during sleep. This system deteriorates with age, causing waste products to remain in the brain. This is associated with a higher risk of dementia.
The consequences are far-reaching. Accumulating protein aggregates are toxic to cells and are identified as a central mechanism behind Alzheimer's and Parkinson's disease. Some of these clumps can even jump from cell to cell and infect healthy proteins, in a manner comparable to how prion diseases spread. The precise details of that last mechanism are still being investigated.
Based on multiple review studies and laboratory experiments (PMIDs: 25784053, 21776078, 27365453, 26317470, 33510441, 33004510, 24624331, 24698014). The core of the story, the decline of the clean-up system during ageing, is well supported. The glymphatic system and condensate hardening are less mature areas and have not yet been directly demonstrated quantitatively in humans on a large scale.