1. Nature. 2011 Apr 14;472(7342):226-9. doi: 10.1038/nature09873. Epub 2011 Mar 30.

Amyloid-binding compounds maintain protein homeostasis during ageing and extend
lifespan.

Alavez S(1), Vantipalli MC, Zucker DJ, Klang IM, Lithgow GJ.

Author information: 
(1)Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, California
94945, USA.

Comment in
    Rejuvenation Res. 2011 Jun;14(3):335-9.
    Nat Methods. 2011 May;8(5):376.

Genetic studies indicate that protein homeostasis is a major contributor to
metazoan longevity. Collapse of protein homeostasis results in protein misfolding
cascades and the accumulation of insoluble protein fibrils and aggregates, such
as amyloids. A group of small molecules, traditionally used in histopathology to 
stain amyloid in tissues, bind protein fibrils and slow aggregation in vitro and 
in cell culture. We proposed that treating animals with such compounds would
promote protein homeostasis in vivo and increase longevity. Here we show that
exposure of adult Caenorhabditis elegans to the amyloid-binding dye Thioflavin T 
(ThT) resulted in a profoundly extended lifespan and slowed ageing. ThT also
suppressed pathological features of mutant metastable proteins and human
β-amyloid-associated toxicity. These beneficial effects of ThT depend on the
protein homeostasis network regulator heat shock factor 1 (HSF-1), the stress
resistance and longevity transcription factor SKN-1, molecular chaperones,
autophagy and proteosomal functions. Our results demonstrate that pharmacological
maintenance of the protein homeostatic network has a profound impact on ageing
rates, prompting the development of novel therapeutic interventions against
ageing and age-related diseases.

DOI: 10.1038/nature09873 
PMCID: PMC3610427
PMID: 21451522  [Indexed for MEDLINE]