Abstract: As we age, the rate of protein aggregation rises along with the incidence of degenerative conditions, and it is widely accepted that loss of proteostasis is a hallmark of aging. But what is the relationship between protein aggregation and “normal” aging?
Experimental work on this question in model systems evolutionarily close to humans has been hampered by the fact that vertebrates have such long lifespans—but enter the killifish, which lives only 6 months, enabling lifespan studies to be completed much more quickly than in conventional model systems.
Using killifish, Chen has detected age-associated changes in aggregation for particular proteins, identifying one or a few dozen proteins in each tissue that exhibit a significant age-related increase in aggregation propensity.
In functional terms, each tissue seems to exhibit aggregation in specific pathways, e.g., RNA binding proteins tend to aggregate in liver, but not in other parts of the body. However, not all of these aggregated proteins are inherently toxic.Strikingly, in brain, the proteins that aggregate have a strong tendency to be prion-like.
Pioneer: Yiwen Chen (Jarosz lab/Stanford)
Agent: Chris Patil (Hourglass)