title: 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.
authors: Department of Biology, The City College of New York, New York, NY 10031, USA.
authors: Yael H
authors: YH
authors: Edrey
authors: Diana
authors: D
authors: Casper
authors: Dorothee
authors: D
authors: Huchon
authors: James
authors: J
authors: Mele
authors: Jonathan A
authors: JA
authors: Gelfond
authors: Deborah M
authors: DM
authors: Kristan
authors: Eviatar
authors: E
authors: Nevo
authors: Rochelle
authors: R
authors: Buffenstein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008136:Longevity; D019577:Mole Rats / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D020890:Neuregulin-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D066247:Receptor, ErbB-4; D016415:Sequence Alignment
chemical_list: D020890:Neuregulin-1; C587689:ERBB4 protein, human; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; C587691:Erbb4 protein, rat; D066247:Receptor, ErbB-4