Ash-2, Another Longevity Gene in Worms

Researchers have been turning up quite the trove of longevity-influencing genes and processes in nematode worms of late. Here is the latest:

Study identifies proteins that modulate life span in worms

The gene with the most pronounced effect, Ash-2, makes a protein that functions as a methyltransferase - meaning it works together with other proteins to add a chemical tag called a methyl group to a component of a cell's DNA packaging machinery, which is known as a histone. The presence or absence of this tag affects whether the DNA remains wound up tightly like thread on a spool, or unfurls to allow its genes to be expressed. Inhibiting Ash-2 activity reduces the number of methyl tags on the histone, which keeps the DNA inaccessible and somehow extends the animal's life by as much as 30 percent.

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The researchers found that Ash-2 is highly expressed in the germline, or reproductive cells, as well as in newly formed eggs. These cells also had high levels of the methyl tag. When Greer blocked the expression of Ash-2 in worms that lacked normal reproductive cells, he found that this no longer extended worm life span, suggesting that an intact germline is necessary for Ash-2 to regulate longevity.

A little more context can be found in the paper itself; this is a discovery found by exploring mechanisms similar to those in which sirtuins play a role:

The plasticity of ageing suggests that longevity may be controlled epigenetically by specific alterations in chromatin state. The link between chromatin and ageing has mostly focused on histone deacetylation by the Sir2 family, but less is known about the role of other histone modifications in longevity. Histone methylation has a crucial role in development and in maintaining stem cell pluripotency in mammals

Given the pace at which new significant metabolic contributions to longevity are emerging, I'd expect this to be far from the last.

ResearchBlogging.orgGreer, E., Maures, T., Hauswirth, A., Green, E., Leeman, D., Maro, G., Han, S., Banko, M., Gozani, O., & Brunet, A. (2010). Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans Nature DOI: 10.1038/nature09195

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