Imagine a neighborhood slowly deteriorating over time. The houses become dilapidated, the streets crumble, and everything starts to fall apart. Well, that’s kind of what happens in our bodies as we age. But instead of houses and streets, it’s our proteins that suffer the consequences. Just like misbehaving neighbors, misfolded protein aggregates start to accumulate and cause trouble. These aggregates are responsible for many age-related diseases and neurodegenerative disorders. In this study, researchers explored how protein misfolding and aggregation affect aging in different organisms. They found that as time goes by, the amount of insoluble proteins increases in senescent cells, roundworms (Caenorhabditis elegans), and mouse tissues. These pesky aggregates possess all the characteristics of disease-related clusters – they’re stubborn, resistant to cleaning agents, and even show up under special staining. The results also shed light on which specific proteins are involved in the aging process, revealing a potential link between protein misfolding and disrupted cellular pathways. So if you’re curious to learn more about how these protein hooligans accelerate aging, make sure to dive into the fascinating details of this study!

Accumulation of misfolded protein aggregates is a hallmark event in many age-related protein misfolding disorders, including some of the most prevalent and insidious neurodegenerative diseases. Misfolded protein aggregates produce progressive cell damage, organ dysfunction, and clinical changes, which are common also in natural aging. Thus, we hypothesized that aging is associated to the widespread and progressive misfolding and aggregation of many proteins in various tissues. In this study, we analyzed whether proteins misfold, aggregate, and accumulate during normal aging in three different biological systems, namely senescent cells, Caenorhabditis elegans, and mouse tissues collected at different times from youth to old age. Our results show a significant accumulation of misfolded protein aggregates in aged samples as compared to young materials. Indeed, aged samples have between 1.3 and 2.5-fold (depending on the biological system) higher amount of insoluble proteins than young samples. These insoluble proteins exhibit the typical characteristics of disease-associated aggregates, including insolubility in detergents, protease resistance, and staining with amyloid-binding dye as well as accumulation in aggresomes. We identified the main proteins accumulating in the aging brain using proteomic studies. These results show that the aged brain contain large amounts of misfolded and likely non-functional species of many proteins, whose soluble versions participate in cellular pathways that play fundamental roles in preserving basic functions, such as protein quality control, synapsis, and metabolism. Our findings reveal a putative role for protein misfolding and aggregation in aging.

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