sut-2 loss of function mutants protect against tau-driven shortened lifespan and hyperactive pharyngeal pumping in a C. elegans model of tau toxicity.

ABSTRACT

Expression of human tau in C. elegans neurons causes progressive, age-associated loss of motor coordination, selective neurodegeneration, and shortened lifespan. Loss of function (LOF) mutations in the conserved gene sut-2 protects against progressive motor uncoordination and neurodegeneration in models of tauopathy. To determine whether sut-2 LOF also protects against shortened lifespan of tau transgenic C. elegans , we conducted lifespan assays comparing four different alleles of sut-2 . We found that sut-2 LOF robustly suppresses the shortened lifespan of tau transgenic animals. We also demonstrate that tau transgenic C. elegans exhibit hyperactive pharyngeal pumping, which is restored by sut-2 LOF.