<i>PAK1</i>-deficiency/down-regulation reduces brood size, activates <i>HSP16.2</i> gene and extends lifespan in <i>Caenorhabditis elegan</i><i>s </i>
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- Yanase Sumino
- Daito-Bunka University
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- Luo Yuan
- Center for Scientific Review (CSR), National Institutes of Health (NIH)
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- Maruta Hiroshi
- NF/TSC Cure Org.
Bibliographic Information
- Other Title
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- PAK1-deficiency/down-regulation reduces brood size, activates HSP16.2 gene and extends lifespan in Caenorhabditis elegans
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Abstract
There is an increasing evidence that the oncogenic kinase PAK1 is responsible not only for malignant transformation, but also for several other diseases such as inflammatory diseases (asthma and arthritis), infectious diseases including malaria, AIDS, and flu, as well as a series of neuronal diseases/disorders (neurofibromatosis, tuberous sclerosis, Alzheimer's diseases, Huntington's disease, epilepsy, depression, learning deficit, etc.) which often cause premature death. Interestingly, a few natural PAK1-blockers such as curcumin, caffeic acid (CA) and rosmarinic acid (RA) extend the lifespan of the nematode Caenorhabditis elegans or fruit flies. Here, to explore the possibility that C. elegans could provide us with a quick and inexpensive in vivo screening system for a series of more potent but safe (non-toxic) PAK1-blocking therapeutics, we examined the effects of PAK1-deficiency or down-regulation on a few selected functions of this worm, including reproduction, expression of HSP16.2 gene, and lifespan. In short, we found that PAK1 promotes reproduction, whereas it inactivates HSP16.2 gene and shortens lifespan, as do PI-3 kinase (AGE-1), TOR, and insulin-like signalling /ILS (Daf-2) in this worm. These findings not only support the "trade-off" theory on reproduction versus lifespan, but also suggest the possibility that the reduced reproduction (or HSP16.2 gene activation) of this worm could be used as the first indicator of extended lifespan for a quick in vivo screening for PAK1-blockers.
Journal
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- Drug Discoveries & Therapeutics
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Drug Discoveries & Therapeutics 7 (1), 29-35, 2013
International Research and Cooperation Association for Bio & Socio-Sciences Advancement
