A Genetic Program Promotes C. elegans Longevity at Cold Temperatures via a Thermosensitive TRP Channel

• Published in: Cell 2013-02, Vol.152 (4), p.806-817
• Main Authors: Xiao, Rui, Zhang, Bi, Dong, Yongming, Gong, Jianke, Xu, Tao, Liu, Jianfeng, Xu, X.Z. Shawn
• Format: Article
• Language: English
• Subjects: Aging; Animals; Animals, Genetically Modified; body temperature; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - metabolism; calcium; Calcium Channels - genetics; Calcium Channels - metabolism; Calcium Signaling; chemical reactions; cold; Cold Temperature; Forkhead Transcription Factors; Humans; Intestinal Mucosa - metabolism; Longevity; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; protein kinase C; Protein Kinase C - metabolism; Protein-Serine-Threonine Kinases - metabolism; temperature; Thermosensing; transcription factors; Transcription Factors - metabolism; Transient Receptor Potential Channels - genetics; Transient Receptor Potential Channels - metabolism; TRPA1 Cation Channel
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2013.01.020

Both poikilotherms and homeotherms live longer at lower body temperatures, highlighting a general role of temperature reduction in lifespan extension. However, the underlying mechanisms remain unclear. One prominent model is that cold temperatures reduce the rate of chemical reactions, thereby slowing the rate of aging. This view suggests that cold-dependent lifespan extension is simply a passive thermodynamic process. Here, we challenge this view in C. elegans by showing that genetic programs actively promote longevity at cold temperatures. We find that TRPA-1, a cold-sensitive TRP channel, detects temperature drop in the environment to extend lifespan. This effect requires cold-induced, TRPA-1-mediated calcium influx and a calcium-sensitive PKC that signals to the transcription factor DAF-16/FOXO. Human TRPA1 can functionally substitute for worm TRPA-1 in promoting longevity. Our results reveal a previously unrecognized function for TRP channels, link calcium signaling to longevity, and, importantly, demonstrate that genetic programs contribute to lifespan extension at cold temperatures. [Display omitted] ► Cold-dependent lifespan extension is not a passive thermodynamic process ► A genetic program actively contributes to lifespan extension at cold temperatures ► This program includes a cold-sensitive TRP channel, Ca2+ influx, PKC, SGK, and FOXO ► The intestine, a nonexcitable tissue, can also act as a cold receptor A cold-sensitive ion channel detects temperature drops in the environment and actively promotes longevity in worms, suggesting that lifespan extension in response to cold temperatures is under genetic control.