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

Yael H. Edrey, Diana Casper, Dorothee Huchon, James Mele, Jonathan A. Gelfond, Deborah M. Kristan, Eviatar Nevo, Rochelle Buffenstein

Research output: Contribution to journalArticle

41 Scopus citations

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 1day to 26years 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 (4-32year) 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.

Original languageEnglish (US)
Pages (from-to)213-222
Number of pages10
JournalAging Cell
Volume11
Issue number2
DOIs
StatePublished - Apr 1 2012

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Keywords

  • Aging
  • Cerebellum
  • ErbB4
  • HIF1α
  • Maximum lifespan
  • Naked mole-rat
  • Neuregulin-1
  • Neurotrophic factors
  • Spalax

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Edrey, Y. H., Casper, D., Huchon, D., Mele, J., Gelfond, J. A., Kristan, D. M., Nevo, E., & Buffenstein, R. (2012). Sustained high levels of neuregulin-1 in the longest-lived rodents; A key determinant of rodent longevity. Aging Cell, 11(2), 213-222. https://doi.org/10.1111/j.1474-9726.2011.00772.x