Open AccessThe neuronal receptor tyrosine kinase Alk is a target for longevity
Author(s) -
Woodling Nathaniel S.,
Aleyakpo Benjamin,
Dyson Miranda Claire,
Minkley Lucy J.,
Rajasingam Arjunan,
Dobson Adam J.,
Leung Kristie H. C.,
Pomposova Simona,
Fuentealba Matías,
Alic Nazif,
Partridge Linda
Publication year - 2020
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.13137
Subject(s) - biology , receptor tyrosine kinase , anaplastic lymphoma kinase , receptor protein tyrosine kinases , insulin receptor , signalling , tyrosine kinase , receptor , signal transduction , kinase , microbiology and biotechnology , cancer research , genetics , insulin , endocrinology , medicine , insulin resistance , pleural effusion , malignant pleural effusion
Inhibition of signalling through several receptor tyrosine kinases (RTKs), including the insulin‐like growth factor receptor and its orthologues, extends healthy lifespan in organisms from diverse evolutionary taxa. This raises the possibility that other RTKs, including those already well studied for their roles in cancer and developmental biology, could be promising targets for extending healthy lifespan. Here, we focus on anaplastic lymphoma kinase (Alk), an RTK with established roles in nervous system development and in multiple cancers, but whose effects on aging remain unclear. We find that several means of reducing Alk signalling, including mutation of its ligand jelly belly (jeb), RNAi knock‐down of Alk, or expression of dominant‐negative Alk in adult neurons, can extend healthy lifespan in female, but not male, Drosophila . Moreover, reduced Alk signalling preserves neuromuscular function with age, promotes resistance to starvation and xenobiotic stress, and improves night sleep consolidation. We find further that inhibition of Alk signalling in adult neurons modulates the expression of several insulin‐like peptides, providing a potential mechanistic link between neuronal Alk signalling and organism‐wide insulin‐like signalling. Finally, we show that TAE‐684, a small molecule inhibitor of Alk, can extend healthy lifespan in Drosophila , suggesting that the repurposing of Alk inhibitors may be a promising direction for strategies to promote healthy aging.