Author summary Survival in extreme environments for prolonged periods is a challenge that only a few organisms, are capable of. It is not well understood, which molecular and biochemical pathways are utilized by such cryptobiotic organisms, and how long they might suspend life. Here, we show that a soil nematode Panagrolaimus kolymaensis, suspended life for 46,000 years in the Siberian permafrost. Through comparative analysis, we find that P. kolymaensis and model organism C. elegans utilize similar adaptive mechanisms to survive harsh environmental conditions for prolonged periods. Our findings here are important for the understanding of evolutionary processes because generation times could be stretched from days to millennia, and long-term survival of individuals of species can lead to the refoundation of otherwise extinct lineages.