Adaptations to a Subterranean Environment and Longevity Revealed by the Analysis of Mole Rat Genomes

Abstract

SUMMARY Subterranean mammals spend their lives in dark, unventilated environments rich in carbon dioxide and ammonia, and low in oxygen. Many of these animals are also long-lived and exhibit reduced aging-associated diseases, such as neurodegenerative disorders and cancer. We sequenced the genome of the Damaraland mole rat (DMR, Fukomys damarensis) and improved the genome assembly of the naked mole rat (NMR, Heterocephalus glaber). Comparative genome analysis, along with transcriptomes of related subterranean rodents, reveal candidate molecular adaptations for subterranean life and longevity, including a divergent insulin peptide, expression of oxygen-carrying globins in the brain, prevention of high CO2-induced pain perception, and enhanced ammonia detoxification. Juxtaposition of the genomes of DMR and other more conventional animals with the genome of NMR revealed several truly exceptional NMR features: unusual thermogenesis, aberrant melatonin system, pain insensitivity, and novel processing of 28S rRNA. Together, the new genomes and transcriptomes extend our understanding of subterranean adaptations, stress resistance and longevity.

Hypoxia potentially promotes Tibetan longevity

“…In addition, wild mammals with hypoxic habitats, such as the naked mole rat that lives in burrow, and whales that must hold their breath as they dive, seem to live longer [3][4][5]. In stark contrast with observations in the laboratory, humans living under natural hypoxic environment of the Tibetan Plateau have generally been thought to have much shorter lifespans compared with people living at lower altitudes.…”

“…On the other hand, hypoxia might induce longevity in Tibetans, as has been stated for model animals under laboratory experimentation [1,2], as well as wild mammals that live in natural hypoxic environments, such as the naked mole rat and whales [3][4][5]. Considering the strongly significant greater frequency of interaction between aging-associated genes and hypoxia response genes (Supplementary information, Figure S1F and Data S1), and the fact that 18 genes were shared between these two groups of genes, it is likely that hypoxia stress would accelerate the evolution of aging-associated genes.…”

“…This result suggests that genes downregulated during aging tend to be upregulated under hypoxia, and vice versa. Hypoxia, thus, might offset the effect of aging and therefore extend lifespan, as observed in model and wild animals [1][2][3][4][5].…”

Molecular signatures of longevity: Insights from cross-species comparative studies

“…For example, despite being smallest mammals (~5–20 g), microbats can live for more than 40 years (compared to < 4 years in shrews and small rodents) (Seim et al, 2013). The naked mole rat ( Heterocephalus glaber ) lives 10 times longer than other rodents of comparable size (Buffenstein, 2008; Fang et al, 2014b; Kim et al, 2011). Humans are also considered long-lived: Jeanne Calment of France holds the longevity record of 122 years and 164 days (Whitney, 1997), whereas many other similarly sized mammals live only about 30 years.…”

Redox Pioneer: Professor Vadim N. Gladyshev

“…The author will mention, although briefly, Gladyshev's contributions to the area of aging, including mechanisms of aging and control of lifespan, in addition to the application of redox biology to understanding aging discussed earlier. The Gladyshev lab also sequenced and characterized the genomes, transcriptomes, and/or metabolomes of several exceptionally long-lived mammals, most notably the naked mole rat, Brandt's bat, and bowhead whale (11,32,53,54), providing numerous insights into the biology of these animals, their adaptations, and the associated molecular mechanisms involved (many of which were related to selenium and redox biology) (Fig. 5).…”