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Elixir Researchers Identify Molecular Sensor Linking Energy Levels and Insulin-Like Signals to Lifespan

Posted on: Thursday, 2 December 2004, 12:00 CST

- Research Findings with Broad Implications for Human Aging Research Are Published in Genes & Development -

Elixir Pharmaceuticals announced today that Company researchers have identified a molecular sensor in the nematode, C. elegans, that links lifespan to the organism's energy level and insulin-like signaling. Research conducted over the last decade has suggested that limiting energy availability, for example, by dietary restriction, extends the lifespan of different organisms. Elixir's study, published today in the online version of Genes & Development, sheds new light on how aging is actively regulated at a molecular level and has broad implications for human aging research.

The sensor, AAK-2 is a protein kinase that is highly conserved between nematodes and man and correlates to the human enzyme, AMP-1. AAK-2 is part of a molecular circuit that is very similar in both species, suggesting that AMP-1 may also regulate aging in humans. Further identification of the targets of AMP-1 will be important in understanding how lifespan is regulated in humans.

Peter DiStefano, Ph.D., Chief Scientific Officer at Elixir commented, "This work supports our premise that aging is highly regulated and extends our list of molecular targets in pathways that affect lifespan by controlling metabolic processes. These findings will facilitate development of new drugs for metabolic disorders, and are encompassed in recent patent filings by the Company."

About the Study:

The paper titled, "The AMP-Activated Protein Kinase AAK-2 Links Energy Levels and Insulin-like Signals to Lifespan in C. elegans," (Genes & Development, vol. 18, issue 24, pages 3004-3009) was authored by a team of Elixir researchers led by Senior Scientist, Javier Apfeld, Ph.D. The team's research suggests that at a molecular level, animals actively sense changes in energy levels and these changes can result in alterations in lifespan. Using an array of genetic and molecular manipulations of C. elegans, researchers found that an increased cellular ratio of two small molecules, AMP and ATP, correlates well with increased lifespan. Humans and other organisms routinely use ATP as a source of energy and generate AMP as a by-product. Elixir researchers focused on a specific AMP-activated protein kinase, AAK-2, which, when activated by high levels of AMP, stimulates a variety of pathways that work to conserve energy stores.

The research findings highlight AAK-2 as a key component of a circuit in C. elegans that regulates lifespan in response to environmental stressors and insulin-like signaling. The findings suggest that this circuit may also be influenced by signals from sensory neurons and the reproductive system, as these inputs modulate the activity of the insulin-like signaling pathway that contains the known aging genes, daf-2 and daf-16.

About Elixir

Elixir Pharmaceuticals is focused on discovering and developing new drugs for metabolic disorders based on a unique understanding of the genetics of aging. Elixir scientists have identified many important genes that regulate aging and the proteins encoded by those genes are the targets of the company's drug discovery efforts. More information about Elixir is available at www.elixirpharm.com.

Source: Business Wire

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