Worms with Genes for Long Life Pass on Longevity to Offspring…Even Without the Genes

Epigenetic changes in your parents’ chromosomes could affect your lifespan. At least, that is, if you’re a simple roundworm.

Recent research has shown that some epigenetic changes in plant DNA can be inherited. (See here, here). However, these changes aren’t robust, and tend to drop out after a few generations.

The epigenetic changes in plants that were heritable involved DNA methylation. The new research on roundworms (Caenorhabditis elegans) concerned a slightly different type of epigenetic change: methylation of a histone protein. Histones make up chromatin, the scaffolding around which DNA is wrapped around in chromosomes. There are four different histones, and two copies of each of these form a nucleosome. About 146 base pairs of DNA are wrapped around each nucleosome. The expression of genes whose DNA is wrapped around a nucleosome can be affected by the methylation state of the H3 histone.

Previous research had found that decreased levels of methylation of a specific part of the H3 histone resulted in longevity extensions of C. elegans by up to 30%. More specifically, a protein complex called H3K4me3 does the job of methylating the critical location in the H3 histone. Mutations of certain components of H3K4me3 were known to bring about the longevity extension effect.

How Longevity Is Passed On

Anne Brunet, an associate professor of genetics at the Stanford School of Medicine, found that mutations in a chromatin-modifying complex also significantly increased lifespan in C. elegans. The complex, known as the histone H3 lysine 4 trimethylation (H3K4me3) complex, is responsible for methylating a chromatin packaging protein called histone H3. This methylation is often associated with the increased expression of genes in the vicinity.

When Brunet and her colleagues knocked down members of the H3K4me3 complex—such as the WDR-5 and SET-2—they extended C. elegans life by up to 30 percent, suggesting that the epigenetic changes regulated by the complex controlled genes related to lifespan.

“Basically we think that the reason why those worms live longer is because they have less of this H3K4 mark at specific loci in the genome,” Brunet explained. “That probably results in changes in the expression of some genes,” such as those that regulate the aging process, she added.

That much was understood before the latest research. The new and rather surprising thing the new research has shown is that even if the mutations affecting H3K4me3 levels are eliminated in succeeding generations, the longevity extending effect persists for two more generations. The research found that expression of certain genes affecting metabolism – which often in turn affects longevity – persisted across generations, suggesting that other, as yet unknown, epigenetic changes occurred due to the original changes in H3 methylation.

The research paper itself concludes:

Our observations are consistent with the notion that H3K4me3 at specific loci may not be completely erased and replenished. Alternatively, the ASH-2/WDR-5/SET-2 complex could control the expression of the genes responsible for the erasure and replenishment of histone methylation marks between generations. Modulation of H3K4me3 modifiers in parents may also affect an unidentified protein or RNA that could in turn be inherited and cause lifespan changes.

Further reading:

Long life passed down through generations

Live long, pass it on

Worms with Genes for Long Life Pass on Longevity to Offspring…Even Without the Genes

Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans

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