Greer EL, Maures TJ, Ucar D, Hauswirth AG, Mancini E, Lim JP, Benayoun BA, Shi Y, Brunet A. Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature. 2011 Nov 17;479(7373):365-71. PubMed.
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Picower Institute for Learning and Memory, MIT
What if the elixir of life is encoded in the epigenome and longevity is transmitted in a hereditary fashion? The study by Greer and colleagues certainly seems to indicate that this concept holds true, and provides the first example of transgenerational epigenetic inheritance of a complex trait such as longevity. Given that plastic chromatin-mediated changes in gene expression are required throughout the lifespan, it is not surprising that epigenetic mechanisms, such as post-translational histone modifications that specifically alter chromatin structure, can control the capacity of the organism to adapt. Indeed, a number of chromatin modifiers have already been linked to aging. According to Greer et al., long-term hereditary epigenetic memory of longevity may also be mediated through post-translational modifications of chromatin, thus biologically embedding and transmitting lifespan information from parents to offspring. Importantly, the authors identified components of the methylation machinery responsible for regulating one of the more stable chromatin modifications, histone H3K4me3, as underlying long-term heritable transmission of longevity information.
The authors suggest that the mechanism by which H3K4 methylation machinery regulates lifespan inheritance is associated with epigenetic changes in gene expression. However, as heritable global changes in H3K4me3 levels were not observed, it would be interesting to examine, on a genomewide level, heritable local changes in H3K4me3 levels and how they correlate to the corresponding gene expression changes. It is also very intriguing that lifespan extension can only be inherited for a limited number of generations, suggesting a potential dosage effect. In that context, an interesting question is whether heterozygotes exhibit intermediate longevity phenotype as compared to their wild-type and homozygous mutant siblings. Whether hereditary lifespan is indeed regulated via H3K4me3 or indirectly, possibly through other, non-histone targets of the methylation complex, transgenerational epigenetic inheritance of longevity is certainly an exciting concept. One may hope that lessons learned from C. elegans will translate to mammalian models.
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