Combating Ageing Beyond The Cell: Emerging Roles Of Extracellular Proteostasis
Our bodies rely on a sophisticated system called proteostasis to keep proteins healthy and functioning correctly. Think of proteins as tiny machines that perform almost all tasks in our cells. Proteostasis ensures these machines are built right, stay in good shape, and are cleared away when they’re no longer needed. This system is crucial for overall health, but its efficiency naturally declines as we age.
While we know a lot about how proteostasis works inside our cells, the mechanisms that maintain protein health in the space between cells – the extracellular environment – have been less explored. This “extracellular proteostasis network” faces unique challenges because it lacks some of the cellular machinery found inside cells, like certain energy-dependent helper proteins called chaperones. Instead, it relies on specialized secreted chaperones, enzymes that break down proteins (proteases), and systems that clear proteins from the body.
As we get older, changes in the extracellular environment, such as altered fluid dynamics and shifts in chemical properties, can create conditions where proteins are more likely to misfold and clump together. Interestingly, recent research has shown an unexpected increase in the components of this extracellular proteostasis network with age. This network also plays a role in “inflammaging,” which is chronic, low-grade inflammation associated with aging.
Understanding and strengthening this extracellular proteostasis network offers a promising new frontier for developing strategies to extend our healthy lifespan, reduce age-related protein aggregation, and restore the balance of the extracellular matrix, which provides structural support to tissues.
Source: link to paper