Aging is the single most important risk factor in human disease in developed countries, and it is thought that an understanding of aging mechanisms would prompt design of rational therapies against age-related diseases. A corollary is that a pharmacological agent that slows aging itself is likely to be effective against a wide spectrum of diseases. To discover what classes of chemical compounds slow aging, we will screen a large and diverse chemical library for extension in the lifespan of the nematode C. elegans. We have developed a number of automated screening methods that exploit C. elegans handling technology. We will also screen a library of compounds generally recognized as safe (GRAS) for extended lifespan to bias our search towards compounds that will prove useful in mammals. We will establish whether the compounds extend lifespan by acting on known pathways and determine their impact on general metabolism and stress resistance. We expect some compounds will prolong lifespan by novel mechanisms in which case we will identify the target proteins. Overall, we aim to identify a range of compounds that slow aging;these compounds will be leads for the development of therapeutics against a range of age-related diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG029631-05
Application #
8220806
Study Section
Cellular Mechanisms in Aging and Development Study Section (CMAD)
Program Officer
Guo, Max
Project Start
2008-02-15
Project End
2013-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
5
Fiscal Year
2012
Total Cost
$355,485
Indirect Cost
$128,726
Name
Buck Institute for Age Research
Department
Type
DUNS #
786502351
City
Novato
State
CA
Country
United States
Zip Code
94945
Angeli, Suzanne; Klang, Ida; Sivapatham, Renuka et al. (2013) A DNA synthesis inhibitor is protective against proteotoxic stressors via modulation of fertility pathways in Caenorhabditis elegans. Aging (Albany NY) 5:759-69
Chinta, Shankar J; Ganesan, Abirami; Reis-Rodrigues, Pedro et al. (2013) Anti-inflammatory role of the isoflavone diadzein in lipopolysaccharide-stimulated microglia: implications for Parkinson's disease. Neurotox Res 23:145-53
Monroy, Adriana; Lithgow, Gordon J; Alavez, Silvestre (2013) Curcumin and neurodegenerative diseases. Biofactors 39:122-32
Lucanic, Mark; Graham, Jill; Scott, Gary et al. (2013) Age-related micro-RNA abundance in individual C. elegans. Aging (Albany NY) 5:394-411
Alavez, Silvestre; Lithgow, Gordon J (2012) Pharmacological maintenance of protein homeostasis could postpone age-related disease. Aging Cell 11:187-91
Page, Kathryn E; White, Keith N; McCrohan, Catherine R et al. (2012) Aluminium exposure disrupts elemental homeostasis in Caenorhabditis elegans. Metallomics 4:512-22
Lucanic, Mark; Held, Jason M; Vantipalli, Maithili C et al. (2011) N-acylethanolamine signalling mediates the effect of diet on lifespan in Caenorhabditis elegans. Nature 473:226-9
Alavez, Silvestre; Vantipalli, Maithili C; Zucker, David J S et al. (2011) Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature 472:226-9
McColl, Gawain; Rogers, Aric N; Alavez, Silvestre et al. (2010) Insulin-like signaling determines survival during stress via posttranscriptional mechanisms in C. elegans. Cell Metab 12:260-72
Benedetti, Michael G; Foster, Amanda L; Vantipalli, Maithili C et al. (2008) Compounds that confer thermal stress resistance and extended lifespan. Exp Gerontol 43:882-91