Differential Regulation of the Heat Shock Factor 1 and DAF-16 by Neuronal nhl-1 in the Nematode C. elegans

Abstract

In the nematode Caenorhabditis elegans, insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) reduction hyperactivates the transcription factors DAF-16 and heat shock factor 1 (HSF-1), creating long-lived, stress-resistant worms that are protected from proteotoxicity. How DAF-16 executes its distinct functions in response to IIS reduction is largely obscure. Here, we report that NHL-1, a member of the TRIM-NHL protein family, acts in chemosensory neurons to promote stress resistance in distal tissues by DAF-16 activation but is dispensable for the activation of HSF-1. The expression of nhl-1 is regulated by the IIS, defining a neuronal regulatory circuit that controls the organismal stress response. The knockdown of nhl-1 protects nematodes that express the Alzheimer-disease-associated Aβ peptide from proteotoxicity but has no effect on lifespan. Our findings indicate that DAF-16- and HSF-1-regulated heat-responsive mechanisms are differentially controlled by neurons and show that one neuronal protein can be involved in the activation of different stress responses in remote tissues.

Modulation of caveolae by insulin/ IGF ‐1 signaling regulates aging of Caenorhabditis elegans

“…These observations support the notion that the ability to resist heat stress is separable from lifespan [36,37]. These observations support the notion that the ability to resist heat stress is separable from lifespan [36,37].…”

Heterotypic Signals from Neural HSF-1 Separate Thermotolerance from Longevity

“…The ability of increased neural hsf-1 to modulate sod-3 levels in a daf-16 dependent manner correlates with its ability to extend animal lifespan. Although daf-16 possesses thermal protective properties (Volovik et al, 2014), daf-16 was not required for neural hsf-1 overexpressing worms to protect against heat stress (Figure 3E). Moreover, expression of the sod-3 stress responsive gene was not heat inducible and likely represents a distinct stress response pathway utilized by neural hsf-1 during the aging process (Figure S4B, S4C and S4D).…”

Ultraviolet-A triggers photoaging in model nematode Caenorhabditis elegans in a DAF-16 dependent pathway

“…Moreover, this DAF-16 dependent protein plays a pivotal role against oxidative stress (Honda and Honda 1999), invading pathogens and their subcellular components (Sivamaruthi et al 2015b;JebaMercy et al 2013), and heat shock (Volovik et al 2014). All these factors help HSF-1 to play a role in the lifespan extension of the nematode (Kenyon et al 1993;Antebi 2007).…”