Such aggregates are hallmarks of the disease, but protein aggregation seems to occur with aging throughout the body.

The aging brains of people with Alzheimer’s, Parkinson’s and other neurodegenerative diseases are suffused with telltale aggregates of proteins in or around their neurons.

The new work, which was posted to the biorxiv.org preprint server in March, is the first attempt to quantify how much protein aggregation occurs throughout the body during the natural aging of a vertebrate animal — in this case, a very short-lived fish.

In the aging killifish, they discovered protein aggregates in all the tissues that they looked at: not only the brain but also the heart, gut, liver, muscle, skin and testis.

None of this means that protein aggregation causes aging, but it strongly implies that the two are tightly correlated.

To further probe the relationship between protein aggregation and aging, the Stanford researchers looked more closely at the proteins in a mutant variety of killifish that ages unusually quickly.

Once again, problems with the cell’s control over the quality of its proteins may be the explanation.

If cells lose control over the processes that maintain the quality of their proteins, more damage from aggregates may build up with each cell division.

Worse, some defective proteins not only misfold and aggregate themselves but also cause other proteins of the same type to misfold, leading to a chain reaction of aggregation.

A clear illustration of this emerged in a second preprint posted in March, in which the Stanford team homed in on a protein called DDX5 that aggregates in aging killifish brains.

Aggregates can sometimes act as “sticky blobs” that trap other proteins, indiscriminately interfering with cellular functions, explained John Labbadia, whose laboratory at University College London studies protein quality control and aging.

The Stanford team carefully established which region of the DDX5 protein makes it possible for condensation to control its activity — and it turned out to be the same region that also makes it prone to aggregation.

In 2004, Steve Finkbeiner, a researcher on aging at the Gladstone Institutes and the University of California, San Francisco, was studying aggregation of huntingtin protein in cultured neurons.

His team showed that although all the neurons expressing the abnormal huntingtin protein died over time, the neurons that had aggregates of huntingtin survived longer than those that did not.

Many normal, developmentally important proteins like DDX5 have a tendency to aggregate, and coping with this clumping is a universal challenge that every cell has to address.

Because abundant proteins are prone to aggregation, and mutations increase that tendency, natural selection against mutations in abundant proteins is likely to be very strong.

(That conclusion is supported by the observation that in young animals, more abundant proteins tend to have lower mutation rates.) So scarce proteins may evolve more quickly than abundant proteins, and a faster evolutionary rate should correlate with a propensity to aggregate.

Different jobs demand different proteins, which means the evolved strategies for coping with protein aggregation will vary from tissue to tissue and from animal to animal

Because the vertebrate brain has in the relatively recent past evolved so much more extensively and quickly than, say, the muscles, its protein quality control machinery may not yet have had enough time to evolve adequate protections against the aggregation of relatively new proteins

The prionlike DDX5 and similar proteins “have an intrinsic propensity to aggregate, and the organism strives to protect itself against the aggregation,” David said

And the fact that protein aggregation throughout the body is a factor in the aging of organisms as disparate as yeast, worms, flies, fish, mice and humans, she added, “means that we, as a field, should be paying a lot more attention to this.”