Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans

Abstract

Chromatin modifiers regulate lifespan in several organisms, raising the question of whether changes in chromatin states in the parental generation could be incompletely reprogrammed in the next generation and thereby affect the lifespan of descendents. The histone H3 lysine 4 trimethylation (H3K4me3) complex composed of ASH-2, WDR-5, and the histone methyltransferase SET-2 regulates C. elegans lifespan. Here we show that deficiencies in the H3K4me3 chromatin modifiers ASH-2, WDR-5, or SET-2 in the parental generation extend the lifespan of descendents up until the third generation. The transgenerational inheritance of lifespan extension by members of the ASH-2 complex is dependent on the H3K4me3 demethylase RBR-2, and requires the presence of a functioning germline in the descendents. Transgenerational inheritance of lifespan is specific for the H3K4me3 methylation complex and is associated with epigenetic changes in gene expression. Thus, manipulation of specific chromatin modifiers only in parents can induce an epigenetic memory of longevity in descendents.

Mutation of C. elegans demethylase spr-5 extends transgenerational longevity

“…It is interesting to note that the previous example of trans-generational epigenetic inheritance of longevity that we identified [10] was caused by deletion of an H3K4 trimethylase complex while the example presented here was caused by deletion of an H3K4 mono/dimethyl demethylase. These two examples are very different in that in the first case longevity extension occurs immediately upon deletion of the H3K4 trimethylase complex [14] and persists even when WT copies of the H3K4 trimethylase complex are returned and then reverts only after three WT generations to WT longevity [10].…”

“…Longevity is regulated by genetic and environmental factors [9] and has recently been shown, in C. elegans, to be regulated by transgenerational epigenetic inheritance [10,11]. How epigenetic information is inherited in these instances and how it regulates longevity is still unknown.…”

Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice

“…Epigenetic inheritance has been demonstrated in several species including worm (2), fly (3) and mouse species (4,5). Epigenetic inheritance can be modulated by environmental factors and transmitted to subsequent generations via germline cells (6,7).…”

When is incomplete epigenetic resetting in germ cells favoured by natural selection?

“…Recent data from both animals and plants indicate that epigenetic resetting is not always complete and hence that acquired epigenetic states may be transmitted from parents to offspring ('germ-line epigenetic inheritance' or 'incomplete epigenetic resetting' or 'incomplete epigenetic reprogramming'; e.g. [6][7][8][9][10][11][12][13][14] reviewed in [4,5,[15][16][17][18][19]). …”