7. ABSTRACT 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 #
2R01AG029631-06A1
Application #
8632793
Study Section
Cellular Mechanisms in Aging and Development Study Section (CMAD)
Program Officer
Guo, Max
Project Start
2006-12-01
Project End
2019-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Buck Institute for Age Research
Department
Type
DUNS #
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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