Dietary restriction and gonadal signaling differentially regulate post‐development quality control functions in Caenorhabditis elegans

Abstract

Protein homeostasis is remodeled early in Caenorhabditis elegans adulthood, resulting in a sharp decline in folding capacity and reduced ability to cope with chronic and acute stress. Endocrine signals from the reproductive system can ameliorate this proteostatic collapse and reshape the quality control network. Given that environmental conditions, such as food availability, impact reproductive success, we asked whether conditions of dietary restriction (DR) can also reverse the decline in quality control function at the transition to adulthood, and if so, whether gonadal signaling and dietary signaling remodel the quality control network in a similar or different manner. For this, we employed the eat‐2 genetic model and bacterial deprivation protocol. We found that animals under DR maintained heat shock response activation and high protein folding capacity during adulthood. However, while gonadal signaling required DAF‐16, DR‐associated rescue of quality control functions required the antagonistic transcription factor, PQM‐1. Bioinformatic analyses supported a role for DAF‐16 in acute stress responses and a role for PQM‐1 in cellular maintenance and chronic stress. Comparing the stress activation and folding capacities of dietary‐ and gonadal‐signaling mutant animals confirmed this prediction and demonstrated that each differentially impacts cellular quality control capabilities. These data suggest that the functional mode of cellular quality control networks can be differentially remodeled, affecting an organism's ability to respond to acute and chronic stresses during adulthood.

HSF-1: Guardian of the Proteome Through Integration of Longevity Signals to the Proteostatic Network

“…This cell non-autonomous mechanism is specific to germline to Soma signaling, as these functions are not required for ILS-mediated longevity or DAF-16 activation (Berman and Kenyon 2006). Similarly, endocrine germline signals and DR differentially regulate protein quality control mechanisms (Shpigel et al, 2019). For a recent review on cell non-autonomous signaling in longevity see (Miller et al, 2020).…”

Proteostasis collapse is a driver of cell aging and death

“…Yet, oddly, this stress response is turned off very early in C. elegans adulthood (69). Other stress-response pathways such as the mitochondrial unfolded protein response and the endoplasmic reticulum unfolded protein response are also strongly down-regulated (59) by a mechanism that can be modulated by gonadal signaling (70–72) and dietary restriction (73). Given that a single temperature was used to raise the worms (61), our model therefore uses a single, constant chaperone level for all adult temperature conditions and ages (12).…”

Transcellular chaperone signaling is an intercellular stress-response distinct from the HSF-1 mediated HSR

“…Transcription factors other than HSF-1 are known to be involved in the regulation of heat shock proteins and molecular chaperones, including FOXO/DAF-16, SKN-1/NRF2, PHA-4 and PQM-1 (Blackwell et al, 2015; Hsu et al, 2003; Lindquist, 1986; O’Brien et al, 2018; Shpigel et al, 2019; Tepper et al, 2013). Although CEH-58 has previously not been implicated in chaperone expression, the hsp-70 promoter contains a CEH-58 consensus sequence and our data suggests that CEH-58 genetically interacts with HSF-1.…”