EGF Pathway Found to Influence Nematode Longevity

Researchers have uncovered what might be a new set of genes and protein mechanisms that influence healthy longevity: the epidermal growth factor or EGF pathway. The work was carried out in nematode worms, but the track record of such metabolic influences upon longevity carrying through into higher animals is pretty good so far.

The epidermal growth factor (EGF) peptide induces cellular proliferation through the EGF receptor ... Inhibitors of the EGF receptor are being pursued as potential cancer therapies and EGF may stimulate wound healing. Mutation of the EGF receptor has been associated with cancer in humans.

The best known of the metabolic mechanisms influencing longevity are those involved in insulin metabolism and calorie restriction - there may be some overlap between the two when all is said and done. The researchers here were in fact surprised to find that the results of their work did not point to insulin metabolism. Here's a reference to the paper:

Improving health of the rapidly growing aging population is a critical medical, social, and economic goal. Identification of genes that modulate healthspan, the period of mid-life vigor that precedes significant functional decline, will be an essential part of the effort to design anti-aging therapies. Because locomotory decline in humans is a major contributor to frailty and loss of independence and because slowing of movement is a conserved feature of aging across phyla, we screened for genetic interventions that extend locomotory healthspan of Caenorhabditis elegans.

From a group of 54 genes previously noted to encode secreted proteins similar in sequence to extracellular domains of insulin receptor, we identified two genes for which RNAi knockdown delayed age-associated locomotory decline, conferring a high performance in advanced age phenotype (Hpa). Unexpectedly, we found that hpa-1 and hpa-2 act through the EGF pathway, rather than the insulin signaling pathway, to control systemic healthspan benefits without detectable developmental consequences. Further analysis revealed a potent role of EGF signaling [to] promote healthy aging associated with low lipofuscin levels, enhanced physical performance, and extended lifespan.

This study identifies HPA-1 and HPA-2 as novel negative regulators of EGF signaling and constitutes the first report of EGF signaling as a major pathway for healthy aging. Our data raise the possibility that EGF family members should be investigated for similar activities in higher organisms.

In the present atmosphere of enthusiasm for manipulating metabolism to slow aging, I'm sure that the funding will be raised for further investigation. Now if we could just transfer some of that enthusiasm to the more productive and promising lines of research based upon periodic repair of the damage generated by metabolism rather than changing metabolism to slow down the rate at which damage is caused...

ResearchBlogging.orgIwasa H, Yu S, Xue J, & Driscoll M (2010). Novel EGF Pathway Regulators Modulate C. elegans Healthspan and Lifespan via EGF Receptor, PLC-gamma and IP3R Activation. Aging cell PMID: 20497132

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