Infertility induced by auxin in PX627 Caenorhabditis elegans does not affect mitochondrial functions and aging parameters

Abstract

Caenorhabditis elegans is widely used for aging studies. 5-Fluoro-2´-deoxyuridine (FUdR) is commonly used to control offspring. While larvae are stopped from further development, also mitochondrial DNA and function may be affected. Since mitochondria and longevity are closely related, the use of FUdR may falsify possible studies. PX627, an auxin inducible infertility strain to control offspring, allows mitochondrial investigations during senescence without FUdR toxicity. Longevity and health parameters were assessed in 2-and 10-day old nematodes wild-type N2 and PX627 treated with FUdR or auxin, respectively. Mitochondrial membrane potential, energetic metabolites and reactive oxygen species levels, were determined. mRNA expression levels of key genes involved were quantified using quantitative real-time PCR. FUdR significantly increased lifespan and health parameters, as well as, mitochondrial function compared to untreated controls and auxin treated PX627. Although a decrease in all parameters could be observed in aged nematodes, this was less severe after FUdR exposure. Glycolysis was significantly up-regulated in aged PX627 compared to N2. Expression levels of daf-16, sir-2.1, aak-2, skn-1, atp-2 and atfs-1 were regulated accordingly. Hence, auxin in PX627 might be a good alternative to control progeny, for mitochondrial-and longevity-related investigations in nematodes.

Auxin confers protection against ER stress in Caenorhabditis elegans

“…Indole at a concentration range of 0.1 – 0.25 mM was found to promote healthy aging (Sonowal et al, 2017) while at concentrations higher than 0.5 mM it was found to reduce survival (Lee et al, 2017). By contrast, 1 mM IAA was reported to have no effect on either lifespan or mitochondrial functions (Dilberger et al, 2020; Kasimatis et al, 2018). The reasons for these different responses when using closely-related molecules are unclear.…”

Auxin confers protection against ER stress in Caenorhabditis elegans

“…Indole at a concentration range of 0.1–0.25 mM was found to promote healthy aging ( Sonowal et al, 2017 ) while concentrations higher than 0.5 mM were found to reduce survival ( Lee et al, 2017 ). By contrast, 1 mM IAA was reported to have no effect on either lifespan or mitochondrial functions ( Dilberger et al, 2020 ; Kasimatis et al, 2018 ). The reasons for these different responses when using closely-related molecules are unclear.…”

Auxin treatment increases lifespan in Caenorhabditis elegans

“…In PX627, TIR1 expression is driven in the germline using the germ-cell specific pie-1 promoter . PX627 has been characterized for mitochondrial and health span parameters but mainly in comparison to the effects produced by fluoro-deoxy uridine (fUDR), an alternative sterility-induction treatment ( Dilberger, et al, 2020 ). Dilberger et al found PX627 to show similar lifespan upon supplementation with 1 mM auxin versus FUdR ( Dilberger, et al, 2020 ).…”

“…PX627 has been characterized for mitochondrial and health span parameters but mainly in comparison to the effects produced by fluoro-deoxy uridine (fUDR), an alternative sterility-induction treatment ( Dilberger, et al, 2020 ). Dilberger et al found PX627 to show similar lifespan upon supplementation with 1 mM auxin versus FUdR ( Dilberger, et al, 2020 ). However, Kasimatis et al found that the strain exhibited lower late life mortality on auxin as compared to unsupplemented animals ( Kasimatis, et al, 2018 ).…”

“…However, Kasimatis et al found that the strain exhibited lower late life mortality on auxin as compared to unsupplemented animals ( Kasimatis, et al, 2018 ). PX627 adults were also reported to exhibit remarkably greater mobility during old age ( Dilberger, et al, 2020 ). These observations merit attention because two of the AID transgenic strains we examined also express TIR1 within the germline albeit using a different promoter, and degron tags associated with germline proteins ( Zhang, et al, 2018 ).…”