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


ABSTRACT: 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.

SUBMITTER: Edrey YH 

PROVIDER: S-EPMC4399559 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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

Edrey Yael H YH   Casper Diana D   Huchon Dorothee D   Mele James J   Gelfond Jonathan A JA   Kristan Deborah M DM   Nevo Eviatar E   Buffenstein Rochelle R  

Aging cell 20111229 2


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 the  ...[more]

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