Scientists discover age-regulated cellular activities that protect against protein aggregation

The research, led by Professor Jeffery Kelly of Scripps Research and Professor Andrew Dillin of the Salk Institute's Molecular and Cell Biology Laboratory, is being published August 10, 2006 as an article in an advanced, online edition of the journal Science.

Alzheimer's disease now strikes more than one in 30 Americans, and about half the population that lives past 85 acquires Alzheimer's. Approximately one million Americans have Parkinson's disease, including three out of every 100 people over age 60. Aging is the most important risk factor for both of these diseases.

The new study-conducted in a C. elegans model, a roundworm that expresses a protein whose aggregation appears to cause Alzheimer's disease-showed that toxicity from protein aggregation is "drastically reduced" when aging is slowed by modulating the insulin growth factor (IGF) signaling pathway.

Moreover, the researchers found two novel independent activities promoting this cellular survival. The first protective mechanism disassembles and cuts up protein aggregates. Surprisingly, the second protective mechanism enables the formation of larger aggregates from smaller ones that appear to be more toxic.

Unexpected Findings

Kelly, who is the Lita Annenberg Hazen Professor of Chemistry at The Scripps Research Institute, a member of its Skaggs Institute of Chemical Biology, and dean of graduate and postgraduate studies, stresses that this novel work was a synergetic collaboration between the research groups at the two institutions.

The Dillin lab at Salk was interested in investigating the connection between cell aging and the onset of proteotoxicity. So, the group set out to determine if the aging process in the worm could be slowed by using RNA interference (RNAi), a naturally occurring process known to suppress certain gene activity in living cells, to lower the activity of the IGF signaling pathway. Indeed, this approach worked an

Contact: Keith McKeown
Scripps Research Institute

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