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 #
5R01AG029631-04
Application #
8019996
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
2011-02-15
Budget End
2012-01-31
Support Year
4
Fiscal Year
2011
Total Cost
$355,485
Indirect Cost
Name
Buck Institute for Age Research
Department
Type
DUNS #
786502351
City
Novato
State
CA
Country
United States
Zip Code
94945
Lucanic, Mark; Plummer, W Todd; Chen, Esteban et al. (2017) Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects. Nat Commun 8:14256
Leonoudakis, Dmitri; Rane, Anand; Angeli, Suzanne et al. (2017) Anti-Inflammatory and Neuroprotective Role of Natural Product Securinine in Activated Glial Cells: Implications for Parkinson's Disease. Mediators Inflamm 2017:8302636
Mark, Karla A; Dumas, Kathleen J; Bhaumik, Dipa et al. (2016) Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1. Cell Rep 17:1227-1237
Martins, Rute; Lithgow, Gordon J; Link, Wolfgang (2016) Long live FOXO: unraveling the role of FOXO proteins in aging and longevity. Aging Cell 15:196-207
Lucanic, Mark; Garrett, Theo; Yu, Ivan et al. (2016) Chemical activation of a food deprivation signal extends lifespan. Aging Cell 15:832-41
Kumar, Jitendra; Barhydt, Tracy; Awasthi, Anjali et al. (2016) Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans. PLoS One 11:e0153513
Chaudhuri, Jyotiska; Bose, Neelanjan; Gong, Jianke et al. (2016) A Caenorhabditis elegans Model Elucidates a Conserved Role for TRPA1-Nrf Signaling in Reactive ?-Dicarbonyl Detoxification. Curr Biol 26:3014-3025
Siddiqui, Almas; Bhaumik, Dipa; Chinta, Shankar J et al. (2015) Mitochondrial Quality Control via the PGC1?-TFEB Signaling Pathway Is Compromised by Parkin Q311X Mutation But Independently Restored by Rapamycin. J Neurosci 35:12833-44
Klang, Ida M; Schilling, Birgit; Sorensen, Dylan J et al. (2014) Iron promotes protein insolubility and aging in C. elegans. Aging (Albany NY) 6:975-91
Lucanic, Mark; Graham, Jill; Scott, Gary et al. (2013) Age-related micro-RNA abundance in individual C. elegans. Aging (Albany NY) 5:394-411

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