Much of the current effort in sensory neuroscience research has been directed to investigating sensory regulation of behavior. This has greatly advanced our understanding of the neural and genetic basis of behavior. Nevertheless, it should be noted that sensory environment not just regulates behavior. For instance, environmental cues have a profound impact on longevity. However, unlike behavior, relatively little is known about sensory regulation of longevity. Temperature is one of the two primary environmental factors that affect lifespan; however, the underlying mechanisms remain largely elusive. It was reported nearly a century ago that poikilothermic (cold-blooded) animals, such as worms, flies, and fish, live longer at lower temperatures. Recent work demonstrates that lowering the body temperature of homeothermic (warm-blooded) animals, such as mice, also extends lifespan, highlighting a general role of temperature reduction in lifespan extension. One prominent model argues that cold temperatures would reduce the rate of chemical reactions, thereby leading to a slower pace of living. This model suggests that the extended lifespan observed at low temperatures is simply a passive thermodynamic process. However, our recent work challenges this century-old view. We find that genetic pathways actively promote longevity at low temperatures in C. elegans, one of the most commonly used model organism for aging research. We show that TRPA-1, a conserved cold-sensitive TRP channel, acts as a thermal sensor to detect temperature drop in the environment to initiate a pro-longevity genetic program. Interestingly, human TRPA1 can functionally substitute for worm TRPA-1 in lifespan extension at cold temperatures. These results identify a novel function for TRP family channels in regulating longevity. More importantly, they demonstrate that cold-induced lifespan extension is not simply a passive thermodynamic process but rather an active process that is regulated by genes. Nevertheless, many unanswered questions remain. For example, how animals detect temperature drop in the environment is not very well understood. Particularly, the identity of the thermosensory neurons that sense cold temperatures remains elusive. It is also unclear how these cold-sensitive neurons, if present, mediate lifespan extension at low temperatures. In addition, though we have identified a genetic program that mediates lifespan extension at cold temperatures, are there other genes involved in the pathway? Here, we propose to address these questions by testing several hypotheses. We will take a combination of genetic and neurophysiological approaches. As very little is known about temperature modulation of lifespan, our work will fill in a critical gap in both the sensory neuroscience and aging fields. A aging mechanisms are known to be evolutionarily conserved from worms to mammals, the proposed work will also provide novel insights into our understanding of similar phenomena in mammals.
Thermosensation is essential for the survival and longevity of animals and humans. Dysregulation of thermosensation contributes to age-dependent neurological and neurodegenerative diseases. Our work will lead to a better understanding of how sensory environment affects longevity and age-dependent neurological and neurodegenerative diseases.
|Li, Zhaoyu; Iliff, Adam J; Xu, X Z Shawn (2016) An Elegant Circuit for Balancing Risk and Reward. Neuron 92:933-935
|Chaudhuri, Jyotiska; Bose, Neelanjan; Gong, Jianke et al. (2016) A Caenorhabditis elegans Model Elucidates a Conserved Role for TRPA1-Nrf Signaling in Reactive ?-Dicarbonyl Detoxification. Curr Biol 26:3014-3025
|Li, Ling-Bo; Lei, Haoyun; Arey, Rachel N et al. (2016) The Neuronal Kinesin UNC-104/KIF1A Is a Key Regulator of Synaptic Aging and Insulin Signaling-Regulated Memory. Curr Biol 26:605-15
|Xiao, Rui; Chun, Lei; Ronan, Elizabeth A et al. (2015) RNAi Interrogation of Dietary Modulation of Development, Metabolism, Behavior, and Aging in C. elegans. Cell Rep 11:1123-33
|Zhang, Bi; Xiao, Rui; Ronan, Elizabeth A et al. (2015) Environmental Temperature Differentially Modulates C. elegans Longevity through a Thermosensitive TRP Channel. Cell Rep 11:1414-24
|Xiao, Rui; Liu, Jianfeng; Xu, X Z Shawn (2015) Thermosensation and longevity. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 201:857-67
|Chun, Lei; Gong, Jianke; Yuan, Fengling et al. (2015) Metabotropic GABA signalling modulates longevity in C. elegans. Nat Commun 6:8828
|Yadlapalli, Swathi; Wani, Khursheed A; Xu, X Z Shawn (2014) Past experience resets behavior: CaMK takes the heat. Neuron 84:883-5