A genetic program promotes C. elegans longevity at cold temperatures via a thermosensitive TRP channel

Cell. 2013 Feb 14;152(4):806-17. doi: 10.1016/j.cell.2013.01.020.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Signaling
  • Cold Temperature
  • Forkhead Transcription Factors
  • Humans
  • Intestinal Mucosa / metabolism
  • Longevity*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Kinase C / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • TRPA1 Cation Channel
  • Thermosensing*
  • Transcription Factors / metabolism
  • Transient Receptor Potential Channels / genetics
  • Transient Receptor Potential Channels / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Calcium Channels
  • Forkhead Transcription Factors
  • Nerve Tissue Proteins
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • Transcription Factors
  • Transient Receptor Potential Channels
  • daf-16 protein, C elegans
  • trpa-1 protein, C elegans
  • Protein-Serine-Threonine Kinases
  • Sgk-1 protein, C elegans
  • PKC-2 protein, C elegans
  • Protein Kinase C