title: Freeze-thaw Caenorhabditis elegans freeze-thaw stress response is regulated by the insulin/IGF-1 receptor daf-2.
abstract: BACKGROUND
  Adaption to cold temperatures, especially those below freezing, is essential for animal survival in cold environments. Freezing is also used for many medical, scientific, and industrial purposes. Natural freezing survival in animals has been extensively studied. However, the underlying mechanisms remain unclear. Previous studies demonstrated that animals survive in extremely cold weather by avoiding freezing or controlling the rate of ice-crystal formation in their bodies, which indicates that freezing survival is a passive thermodynamic process.
  
  
  RESULTS
  Here, we showed that genetic programming actively promotes freezing survival in Caenorhabditis elegans. We found that daf-2, an insulin/IGF-1 receptor homologue, and loss-of-function enhanced survival during freeze-thaw stress, which required the transcription factor daf-16/FOXO and age-independent target genes. In particular, the freeze-thaw resistance of daf-2(rf) is highly allele-specific and has no correlation with lifespan, dauer formation, or hypoxia stress resistance.
  
  
  CONCLUSIONS
  Our results reveal a new function for daf-2 signaling, and, most importantly, demonstrate that genetic programming contributes to freezing survival.
authors.affiliation: The Department of Geriatrics, Ren-Ji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China. hujpsh@163.com.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Hu
authors.affiliation: The Department of Geriatrics, Ren-Ji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China. xsally79@163.com.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Xu
authors.affiliation: The Department of Geriatrics, Ren-Ji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China. liying1769@163.com.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Huang
authors.affiliation: The Division of Translational Medicine, Minhang Hospital, Fudan University, Shanghai, China. lishunwang@fudan.edu.cn.
authors.forename: Li-shun
authors.initials: LS
authors.lastname: Wang
authors.affiliation: The Department of Geriatrics, Ren-Ji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China. fangnysh@126.com.
authors.forename: Ning-Yuan
authors.initials: NY
authors.lastname: Fang
mesh_terms: D000483:Alleles; D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D048430:Cell Shape; D005615:Freezing; D017238:Genes, Helminth; D007328:Insulin / Q000378:metabolism*; D007814:Larva / Q000502:physiology; D008136:Longevity / Q000235:genetics; D021381:Protein Transport; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D016019:Survival Analysis
chemical_list: D029742:Caenorhabditis elegans Proteins; D007328:Insulin; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin