We have discovered a series of chemical compounds that delay the onset of age-related pathology and extend lifespan. These compounds were identified in focused chemical screens and high throughput screens of both synthetic compounds and natural products. Here we propose to identify the mechanism of lifespan extension with a focus on vitamin D which we have shown maintains protein homeostasis and extends lifespan in C. elegans. This will uncover novel mechanisms for interventions in aging and age-related disease.

Public Health Relevance

The development of preventative therapies aimed at reducing or delaying age-related disease must be a priority for the biomedical community. We and others have proposed that targeting aging mechanisms contribute to a number of age-related diseases. We have identified molecules, including vitamin D in the nematode C. elegans that slow aging. We propose to elucidate the mechanisms at play.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG029631-10
Application #
9471758
Study Section
Cellular Mechanisms in Aging and Development Study Section (CMAD)
Program Officer
Guo, Max
Project Start
2008-02-15
Project End
2019-04-30
Budget Start
2018-05-01
Budget End
2019-04-30
Support Year
10
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Buck Institute for Age Research
Department
Type
DUNS #
786502351
City
Novato
State
CA
Country
United States
Zip Code
94945
Peters, Theodore W; Nelson, Christopher S; Gerencser, Akos A et al. (2018) Natural Genetic Variation in Yeast Reveals That NEDD4 Is a Conserved Modifier of Mutant Polyglutamine Aggregation. G3 (Bethesda) 8:3421-3431
Lucanic, Mark; Garrett, Theo; Gill, Matthew S et al. (2018) A Simple Method for High Throughput Chemical Screening in Caenorhabditis Elegans. J Vis Exp :
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
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
Lithgow, Gordon J; Driscoll, Monica; Phillips, Patrick (2017) A long journey to reproducible results. Nature 548:387-388
Lucanic, Mark; Garrett, Theo; Yu, Ivan et al. (2016) Chemical activation of a food deprivation signal extends lifespan. Aging Cell 15:832-41
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
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
Kumar, Jitendra; Barhydt, Tracy; Awasthi, Anjali et al. (2016) Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans. PLoS One 11:e0153513

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