Histone 3 lysine 4 methylation (H3K4me) is an epigenetic mark regulating transcription, metabolism, and longevity. H3K4me necessitates, in addition to KMT2 enzymes, the conserved core components WDR5, ASH2, and RBBP5. In C. elegans, deficiency in WDR-5 or ASH-2 reduces H3K4me3 levels and extends lifespan. Transgenerational experiments whereby only the parental generation is deficient in WDR-5 or ASH-2 leads to incomplete reprogramming of the next generation resulting in long-lived descendants. Whether RBBP-5 has similar functions remains unclear. Herein, using spike in ChIP-seq, we show that RBBP-5 is required for H3K4 mono- and multi-methylation and adults lacking RBBP-5 are short-lived. In contrast with WDR-5 or ASH-2 deficiencies, our transgenerational experiments show that reprogramming of the next wild type generation is normal. Instead, we revealed that RBBP-5-deprived descendants originating from mothers heterozygous for the
rbbp-5 deficiency inherit a wild type lifespan. However, at the fifth generation the
rbbp-5(-) short-lived phenotype fully manifest. Using RNA-seq and reporter assays, we found that RBBP-5 is important to maintain mitochondrial bioenergetic and core translational functions. We also show that restoring RBBP-5 expression in the soma is sufficient to recapitulate the wild type lifespan, hence ruling out the germlines as the primary site for H3K4me longevity promoting functions. Collectively, this work shows RBBP-5 regulated H3K4me promotes longevity and wild type lifespan can be epigenetically transmitted to H3K4me-depleted descendants most likely by a mechanism alleviating mitochondrial and translational dysfunctions in somatic cells.