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
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
Siddiqui, Almas; Bhaumik, Dipa; Chinta, Shankar J et al. (2015) Mitochondrial Quality Control via the PGC1α-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
Lucanic, Mark; Lithgow, Gordon J; Alavez, Silvestre (2013) Pharmacological lifespan extension of invertebrates. Ageing Res Rev 12:445-58
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
Alavez, Silvestre; Lithgow, Gordon J (2012) Pharmacological maintenance of protein homeostasis could postpone age-related disease. Aging Cell 11:187-91

Showing the most recent 10 out of 16 publications