Open AccessReduced bone morphogenic protein signaling along the gut–neuron axis by heat shock factor promotes longevity
Author(s) -
Arneaud Sonja L. B.,
McClendon Jacob,
Tatge Lexus,
Watterson Abigail,
Zuurbier Kielen R.,
Madhu Bhoomi,
Gumienny Tina L.,
Douglas Peter M.
Publication year - 2022
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13693
Subject(s) - biology , microbiology and biotechnology , rab , bone morphogenetic protein , signal transduction , smad , caenorhabditis elegans , gtpase , genetics , gene
Aging is a complex and highly regulated process of interwoven signaling mechanisms. As an ancient transcriptional regulator of thermal adaptation and protein homeostasis, the Heat Shock Factor, HSF‐1, has evolved functions within the nervous system to control age progression; however, the molecular details and signaling dynamics by which HSF‐1 modulates age across tissues remain unclear. Herein, we report a nonautonomous mode of age regulation by HSF‐1 in the Caenorhabditis elegans nervous system that works through the bone morphogenic protein, BMP, signaling pathway to modulate membrane trafficking in peripheral tissues. In particular, HSF‐1 represses the expression of the neuron‐specific BMP ligand, DBL‐1, and initiates a complementary negative feedback loop within the intestine. By reducing receipt of DBL‐1 in the periphery, the SMAD transcriptional coactivator, SMA‐3, represses the expression of critical membrane trafficking regulators including Rab GTPases involved in early (RAB‐5), late (RAB‐7), and recycling (RAB‐11.1) endosomal dynamics and the BMP receptor binding protein, SMA‐10. This reduces cell surface residency and steady‐state levels of the type I BMP receptor, SMA‐6, in the intestine and further dampens signal transmission to the periphery. Thus, the ability of HSF‐1 to coordinate BMP signaling along the gut–brain axis is an important determinate in age progression.