Abstract

Comparative biological approaches will provide novel insights into aging. We propose a """"""""functional comparative' approach to the biology of aging in a range of animal models to test the hypothesis that """"""""aging is strongly influenced by an ancient and conserved genetic pathway that coordinately regulates cell cycle progression, cell death and stress response."""""""" The study is prompted by our unexpected observation that the lifespan and stress resistance of Caenorhabditis elegans is under the influence of cell cycle checkpoint components. This taken together with recent speculation on the role of the tumor suppression and apoptosis p53 protein in aging, we believe it is timely to undertake a inter-specific comparative study of p53 and checkpoint functions. As these factors appear to affect aging in both simple invertebrates and mammals, we expect to define broad mechanisms by which cellular and organismal aging are co-regulated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG022868-03
Application #
6929286
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5 (O1))
Program Officer
Sierra, Felipe
Project Start
2003-09-30
Project End
2008-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
3
Fiscal Year
2005
Total Cost
$388,000
Indirect Cost

  Institution

Name
Buck Institute for Age Research
Department
Type
DUNS #
786502351
City
Novato
State
CA
Country
United States
Zip Code
94945

  Publications

Lucanic, Mark; Lithgow, Gordon J; Alavez, Silvestre (2013) Pharmacological lifespan extension of invertebrates. Ageing Res Rev 12:445-58
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
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
McColl, Gawain; Killilea, David W; Hubbard, Alan E et al. (2008) Pharmacogenetic analysis of lithium-induced delayed aging in Caenorhabditis elegans. J Biol Chem 283:350-7
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
Fisher, Alfred L; Page, Kathryn E; Lithgow, Gordon J et al. (2008) The Caenorhabditis elegans K10C2.4 gene encodes a member of the fumarylacetoacetate hydrolase family: a Caenorhabditis elegans model of type I tyrosinemia. J Biol Chem 283:9127-35
Scott, Gary K; Goga, Andrei; Bhaumik, Dipa et al. (2007) Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem 282:1479-86
Olsen, Anders; Vantipalli, Maithili C; Lithgow, Gordon J (2006) Checkpoint proteins control survival of the postmitotic cells in Caenorhabditis elegans. Science 312:1381-5

Showing the most recent 10 out of 12 publications