Royalactin induces copious longevity via increased translation and proteasome activity in C. elegans

Abstract

As demonstrated in various animal models, organismal longevity can be achieved via interventions that at the mechanistic level could be considered to entail 'defensive' responses: most long-lived mutants focus on somatic maintenance, while reducing growth pathway signalling and protein translation and turnover. We here provide evidence that the opposite mechanism can also lead to longevity and improved health.We report on the mode of action of royalactin, a glycoprotein activator of epidermal growth factor signalling, capable of extending lifespan in several animals. We show that in Caenorhabditis elegans, royalactin-induced longevity depends on increased protein translation and entails increased proteasome activity. We propose the term 'copious longevity' to describe this newly-elucidated mechanism. In contrast to what is true for many other lifespan-extending interventions, we observed no obvious trade-offs between royalactininduced longevity and several life history traits. Our data point towards increased protein turnover to support healthy ageing, and provide a means for future comparative studies of defensive vs. copious mechanisms.

Royal Jelly and Its Components Promote Healthy Aging and Longevity: From Animal Models to Humans

“…Still, the exact mechanism through which RJ affects EGFR to promote longevity is not clear. However, it has been recently reported that, royalactin-related EGFR signaling induces longevity in C. elegans via upregulation of elongation factors and chaperonins, which increase protein translation and proteasome activity—a mechanism that entails rebuilding cellular components and enhancement of cellular detoxification, ribosomal function, and muscle maintenance—rather than stabilizing the existing proteome [113]. Furthermore, activation of MAPK —which is stimulated by EGF —increases the lifespan of daf-2 mutants and thus controls the expression of pathogen response genes ( C-type lectins , ShK toxins , and CUB-like genes); such increased resistance to pathogens increases lifespan in C. elegans [114].…”

Feeding recombinant Royalactin: Measures of improved lifespan and mitochondrial function inCaenorhabditis elegans

“…RA appears to exert its effects, in part at least, through signalling of the Epidermal Growth Factor (EGFR) pathway, in both honeybees and C. elegans [12,22]. RA was reported to improve longevity by also maintaining protein translation and proteasome activity following upregulation of chaperonins and elongation factors [23]. More recently, RA was found to act as a pluripotency factor, conferring self-renewal and promotion of a pluripotent gene network in mouse embryonic stem cells (mESC) [24].…”