“The clock is ticking: timing in worms elucidates the ageing process”
Prof. Adam Antebi
Prof. Adam Antebi did his undergraduate studies at Swarthmore College (Swarthmore, PA) from 1979-83, where he received a Bachelors degree with distinction in Biochemistry. He performed his Ph.D. research at Massachusetts Institute of Technology (Cambridge, MA) from 1985-92 in yeast genetics, and went on with his post-doctoral studies at the Johns Hopkins University (Baltimore, MD) from 1992-97 in C. elegans (worm) development. He was an independent group leader at the Max Planck Institute for Molecular Genetics (Berlin) from 1997-2004, where he began studies on worm ageing.
In 2004, Antebi returned to the USA where he was promoted to associate professor at the Huffington Center on Ageing, Baylor College of Medicine (Houston, TX). During this time, he also won the prestigious American Federation for Ageing Research Breakthrough in Gerontology Award and the Ellison Medical Foundation Senior Scholar Award in Ageing Research. Since 2008, he has served as a Director at the newly founded Max Planck Institute for Biology of Ageing (Cologne), continuing work on endocrine regulation of life span using worm as the model system.
- Developmental timing
- Endocrine regulation of longevity
Previous scientific achievements
- Discovered that nuclear receptor signal transduction links circuits governing developmental timing and longevity.
- De-orphanized the first nuclear receptor in worms, showing ligands for DAF-12 nuclear receptor to be bile acid-like steroids.
- Elucidated an entire nuclear receptor signal transduction cascade in vivo, from upstream environmental inputs, to hormone synthesis, transcriptional complexes and outputs for reproduction and longevity.
- Provided the first critical evidence that bile acids working through nuclear receptors regulate metazoan lifespan.
- Showed that these same signalling pathways can regulate the infective stage of distantly related parasitic nematodes.
- Discovered a nuclear receptor-microRNA switch that triggers stage transitions in epidermal stem cells in response to growth signals.
A remarkable finding over the last two decades is the discovery of conserved gene signalling pathways that enhance longevity in C. elegans and other species. Life extension is triggered by several different manipulations including a modest reduction of insulin/IGF signalling, removal of the germline, reduced mitochondrial activity, increased HIF1-α activity as well as dietary restriction. Although these pathways appear to behave somewhat independently of one another, whether they converge on common mechanisms is currently unknown. Within Sybacol the Antebi group will join forces with other C. elegans laboratories, as well as mathematicians and physicists, and use global genomic approaches to dissect the transcriptome of these long-lived mutants. By focusing on time courses of mRNA and microRNA profiles, these researchers will derive dynamic network models that describe the comparative structure and output of these various pathways. Models will then be used to formulate testable hypotheses on functional modules that mediate longevity.
Wollam, J., Magomedova, L., Magner, D.B., Shen, Y., Rottiers, V., Motola, D.L., Mangelsdorf, D.J., Cummins, C.L., and Antebi, A.: The Rieske oxygenase DAF-36 functions as a cholesterol 7-desaturase in steroidogenic pathways governing longevity. Aging Cell. (2011).
Bethke, A., Fielenbach, N., Wang, Z., Mangelsdorf, D.J., and Antebi, A.: Nuclear hormone receptor regulation of microRNAs controls developmental progression. Science. (2009); 324(5923): 95-98.
Gerisch, B., Rottiers, V., Li, D., Motola, D.L., Cummins, C.L., Lehrach, H., Mangelsdorf, D.J., and Antebi, A.: A bile acid-like steroid modulates Caenorhabditis elegans lifespan through nuclear receptor signaling. Proc Natl Acad Sci U S A. (2007); 104(12): 5014-5019.
Rottiers, V., Motola, D.L., Gerisch, B., Cummins, C.L., Nishiwaki, K., Mangelsdorf, D.J., and Antebi, A.: Hormonal control of C. elegans dauer formation and life span by a Rieske-like oxygenase. Dev Cell. (2006); 10(4): 473-482.
Motola, D.L., Cummins, C.L., Rottiers, V., Sharma, K.K., Li, T., Li, Y., Suino-Powell, K., Xu, H.E., Auchus, R.J., Antebi, A., and Mangelsdorf, D.J.: Identification of ligands for DAF-12 that govern dauer formation and reproduction in C. elegans. Cell. (2006); 124(6): 1209-1223.