Researchers flip the switch between development and aging in C. elegans

July 5, 2011

When researchers at the Buck Institute dialed back activity of a specific mRNA translation factor in adult nematode worms they saw an unexpected genome-wide response that effectively increased activity in specific stress response genes that could help explain why the worms lived 40 percent longer under this condition. The study, appearing in the July 6, 2011 edition of Cell Metabolism, highlights the importance of mRNA translation in the aging process. mRNA translation occurs after genetic messages have been transcribed in cells, when the encoded messages of genes are actually translated into functional proteins.

"This study gives us a much more comprehensive picture of the aging process," said Buck faculty Pankaj Kapahi, PhD, the principle investigator of the study. "Our work may help explain the relationship between development and aging."

Scientists have identified a number of so-called "longevity" genes active in many species. However, the mechanisms by which those genes impact lifespan remain poorly understood. According to Kapahi, the majority of research involving those genes has focused on transcription, the first level of whereby DNA produces RNA. This research focuses on translation, whereby RNA specifies the production of proteins.

First-author Aric N. Rogers, Ph. D., a Buck Institute postdoctoral fellow, inhibited expression of the mRNA translation factor, IFG-1, in adult worms. IFG-1 is important for growth and development, and has a homolog (eIF4G) in humans.. According to Rogers turning down IFG-1 right after the animals reached maturity set off a genome-wide change in the type of messages that were being translated. He said this causes a shift towards increased somatic maintenance by increasing the activity of genes involved in stress responses thereby enhancing longevity. Rogers said. "Turning down ifg-1 expression flips a switch that turned down growth and reproduction, but increased their healthspan as well as their lifespan."

Analysis of genes that were upregulated and downregulated pointed to processed transcript length as a determinant of altered translation. The next phase of the research will involve a closer look at small conserved sequences within the genetic code that may also contribute to changes in protein expression"Our primary interest is to understand the biological basis of aging," said Kapahi. "This will help identify molecular targets that can be used to develop therapeutics that would slow age-related diseases and extend the healthy years of life."

Explore further: Aging: Worms, Flies & Yeast Are More Like Us than Previously Expected

More information: Lifespan extension via eIF4G inhibition is mediated by post-transcriptional remodeling of stress response gene expression in C. elegans, Cell Metabolism.

Related Stories

New insights into cardiac aging

September 14, 2009

Investigators at Burnham Institute for Medical Research (Burnham) have found that the conserved protein d4eBP modulates cardiac aging in Drosophila (fruit flies). The team also found that d4eBP, which binds to the protein ...

'Anti-Atkins' low protein diet extends lifespan in flies

October 1, 2009

Flies fed an "anti-Atkins" low protein diet live longer because their mitochondria function better. The research, done at the Buck Institute for Age Research, shows that the molecular mechanisms responsible for the lifespan ...

Recommended for you

How bees naturally vaccinate their babies

July 31, 2015

When it comes to vaccinating their babies, bees don't have a choice—they naturally immunize their offspring against specific diseases found in their environments. And now for the first time, scientists have discovered how ...

Researchers design first artificial ribosome

July 29, 2015

Researchers at the University of Illinois at Chicago and Northwestern University have engineered a tethered ribosome that works nearly as well as the authentic cellular component, or organelle, that produces all the proteins ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.