Thioflavin T Extends Life in Nematode Worms

Another hit in the search for compounds that extend life in lower animals: "Basic Yellow 1, a dye used in neuroscience laboratories around the world to detect damaged protein in Alzheimer's disease - [also] known as Thioflavin T, (ThT) - extended lifespan in healthy nematode worms by more than 50 percent and slowed the disease process in worms bred to mimic aspects of Alzheimer's. The research, conducted at the Buck Institute for Research on Aging, could open new ways to intervene in aging and age-related disease. The study highlights a process called protein homeostasis - the ability of an organism to maintain the proper structure and balance of its proteins, which are the building blocks of life. Genetic studies have long indicated that protein homeostasis is a major contributor to longevity in complex animals. Many degenerative diseases have been linked to a breakdown in the process. ... this study points to the use of compounds to support protein homeostasis, something that ThT, did as the worms aged. ThT works as a marker of neurodegenerative diseases because it binds amyloid plaques - the toxic aggregated protein fragments associated with Alzheimer's. In the nematodes ThT's ability to not only bind, but also slow the clumping of toxic protein fragments, may be key to the compound's ability to extend lifespan ... We have been looking for compounds that slow aging for more than ten years and ThT is the best we have seen so far. But more exciting is the discovery that ThT so dramatically improves nematode models of disease-related pathology as well. ThT allows us to manipulate the aging process, it has the potential to be active in multiple disease states and it enhances the animal's innate ability to deal with changes in its proteins."

Link: http://www.eurekalert.org/pub_releases/2011-03/bifa-nss032411.php

Comments

I believe that prevention of protein aggregation/misfolding and clearance of aggregates by autophagy are complementary.
Would combining both approaches be synergistic?

Several simple substances upregulate autophagy
- rapamycin, trehalose, lithium (also maybe caffeine)
"CHEMICAL INDUCERS OF AUTOPHAGY THAT ENHANCE THE CLEARANCE OF..."
http://www.jbc.org/content/early/2010/02/10/jbc.R109.072181.full.pdf

So do eight other small molecule drugs which are already FDA approved
"Small molecule regulators of autophagy identified..."
http://www.pnas.org/content/104/48/19023.full

Other common inhibitors of aggregation may exist, e.g., proline derivatives
http://www.pnas.org/content/103/36/13357
http://www.ncbi.nlm.nih.gov/pubmed/17764077
- also, some polyphenols
http://www.tau.ac.il/lifesci/departments/biotech/members/gazit/documents/52.pdf

Since some in vitro experiments show that combining several weak aggregation inhibitors are more than additive, it would be very interesting to see in vivo results of aggregation inhibitors + autophagy inducers.

Posted by: Lou Pagnucco at March 31st, 2011 8:55 PM

i would not just want to live a longer life but forever live and be healthy and stay young.....its a shame that we as human beings should have to die period aging is a desease and should be treated like one................

Posted by: hasan... at March 14th, 2016 9:38 AM

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