It was discovered only comparatively recently that epigenetic alterations, decorations attached to the genome rather than changes to the genome itself, can produce changes in offspring longevity. Not all epigenetic changes are erased during early embryonic development; some are retained and go on to influence development and metabolism throughout life. This is a mechanism by which species can improve their reproductive fitness via producing offspring better suited to the environment experienced by the parents. One of the best examples is that calorie restriction affects the metabolism and longevity of the offspring of animals, not just the calorie restricted parents. The research here is an example of ongoing investigations into this aspect of epigenetic regulation, focused on a single epigenetic mark that is shown to produce greater longevity in parents and offspring.
It is commonly accepted that genetic sequences coded within DNA are passed down through generations and can influence characteristics such as appearance, behavior, and health. However, emerging evidence suggests that some traits can also be inherited 'epigenetically' from information that is independent of the DNA sequence. One of the ways characteristics may be epigenetically passed down is through the temporary modification of histone proteins which help to package DNA into the cell. Histones are adorned with chemical marks that can regulate how and when a gene is expressed by changing how tightly the DNA is wrapped. These marks are typically removed before genetic information is passed on to the next generation, but some sites escape erasure.
It has previously been reported that genetic mutations in an enzyme complex called COMPASS increase the lifespan of tiny worms called Caenorhabditis elegans. This complex acts on histones and creates a chemical mark called H3K4me, which is typically associated with less compact DNA and higher gene expression. When these mutants mate with wild-type worms they generate descendants that no longer have COMPASS mutations. Although these wild-type offspring recover normal levels of H3K4me, they still inherit the long-lived phenotype which they sustain for several generations.
Previous work showed that one of the COMPASS complex mutants, known as wdr-5, has increased levels of another histone mark called H3K9me2. This epigenetic mark generally promotes DNA compaction and appears to antagonize the action of H3K4me. Researchers found that homozygous wdr-5 mutants, which had descended from ancestors carrying one copy of the mutated wdr-5 gene and one wild-type copy for multiple generations, did not live for longer than their non-mutant counterparts. This indicates that the mutation carried by wdr-5 worms did not immediately cause a lifespan change. However, future generations of worms that maintained the homozygous wdr-5 mutation had an increasingly longer lifespan, suggesting that the accumulation of an epigenetic signal across generations promotes longer living. These late generation wdr-5 mutants had higher levels of H3K9me2, and they were able to pass on this extended longevity to their progeny following mating with wild-type worms as previously reported.