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Sustained high levels of neuregulin‐1 in the longest‐lived rodents; a key determinant of rodent longevity

Summary Naked mole‐rats (Heterocephalus glaber), the longest‐lived rodents, live 7–10 times longer than similarly sized mice and exhibit normal activities for approximately 75% of their lives. Little is known about the mechanisms that allow them to delay the aging process and live so long. Neuregulin‐1 (NRG‐1) signaling is critical for normal brain function during both development and adulthood. We hypothesized that long‐lived species will maintain higher levels of NRG‐1 and that this contributes to their sustained brain function and concomitant maintenance of normal activity. We monitored the levels of NRG‐1 and its receptor ErbB4 in H. glaber at different ages ranging from 1 day to 26 years and found that levels of NRG‐1 and ErbB4 were sustained throughout development and adulthood. In addition, we compared seven rodent species with widely divergent (4–32 year) maximum lifespan potential (MLSP) and found that at a physiologically equivalent age, the longer‐lived rodents had higher levels of NRG‐1 and ErbB4. Moreover, phylogenetic independent contrast analyses revealed that this significant strong correlation between MLSP and NRG‐1 levels was independent of phylogeny. These results suggest that NRG‐1 is an important factor contributing to divergent species MLSP through its role in maintaining neuronal integrity. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Aging Cell Wiley

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