There is an old saying that when you are old, diseases are coming. Aging is considered the principal risk factor for the onset of a number of neurodegenerative disorders associated with aggregate deposition, such as Alzheimer’s, Huntington’s, and Parkinson’s diseases. Here, by a large scale of proteome analysis, we found that ageing lead to proteome aggregation in C.elegans.
Firstly, we take C. elegans as a model, for it is one of the most extensively studied model organisms in aging research, its relatively short lifespan and the availability of genetic tools to identify pathways that regulate longevity. We proﬁled more than 5,000 proteins along.
Next, we ﬁnd that one-third of proteins change in abundance at least 2-fold during aging, resulting in a severe proteome imbalance. The proteins that increased by at least 2-fold amounted to approximately 50% of total protein in aged animals, as determined by label free absolute quantiﬁcation.
Finally, we compared the physic-chemical properties of the insoluble proteins. Strikingly, the proteins that aggregate most in the daf-2 mutant animals are predicted to have signiﬁcantly lower aggregation Z scores, display more structural disorder.
To summary, aging in C. elegans is associated with a progressive loss of proteome balance, which drives the accumulation of surplus and aberrant protein species that overburden the proteostasis system.