Population aging accelerates in the world and the anti-aging study becomes more and more important. During these decades, anti-aging studies have discovered several regulatory mechanisms of aging, such as mTOR and insulin signals. And clinical studies on anti-aging have launched recently. However, it is still unclear "why we age". To answer the fundamental question, we are now studying slowed aging at low temperatures, as a new anti-aging model. In C. elegans, lifespan and developmental speed are inversely correlated with living temperature even in both long-lived and short-lived mutants. It suggests that aging speed in whole-life, from development to aging, is slowed down at low temperatures. But, the regulatory mechanism of aging at low temperatures is poorly understood. In previous studies, we found components of HSP90 complex, HSP90/hsp-90 and co-chaperone
p23/daf-41, controlled lifespan in response to temperature (PLoS Genet 2015). A mutation of
daf-41 caused short-lived and a gain-of-function mutation of
hsp-90 extremely extended the lifespan at 15°C. The maximum lifespan of the
hsp-90 mutant was longer than 100 days. According to the result, we thought some chaperones are involved in cold adaptation and investigated the functions of chaperones at low temperatures. And, we found the
hsf-1(
sy441) mutants, heat shock response (HSR), stopped development at 9°C and they restarted growing when the mutants were transferred to 20°C. Interestingly, the
hsf-1 mutants could survive at least for 60 days in the diapause at 9°C. Therefore, we named this cold-inducible diapause phenotype "hibernation". Next, we explored mutants that show the hibernation phenotype from known aging mutants and found the
rict-1(
mg451) mutants, in mTORC2 pathway, also stopped growth at 9°C. Although the
rict-1 mutants were mostly killed by severe vulval bursting, approximately 10% of total worms could enter into hibernation and survived longer than 60 days as larvae. We also tested crosstalk between HSR and mTORC2 pathways and found that the gain-of-function mutation of
hsp-90 inhibited the hibernation-entry of the
rict-1 mutants. We found another crosstalk that the overexpression of
skn-1 extending lifespan only at 15°C (H Miller, Aging Cell 2017) also prevented the hibernation-entry of both the
rict-1 and
hsf-1 mutants. With these findings, we hypothesized that there is a crosstalk between the regulation of hibernation-entry and longevity, and it can be used for the screening of novel longevity genes. By EMS mutagenesis, we have already isolated more than 50 hibernation-exit mutants in
hsf-1 and
rict-1 mutants background and now measure the lifespan of the worms.