Sustained high levels of neuregulin-1 in the longest-lived rodents; a key determinant of rodent longevity
Yael H. Edrey
Department of Biology, The City College of New York, 138 st @Convent Ave, New York, NY 10031, USA
Department of Epidemiology and Biostatistics, UTHSCSA, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
Barshop Institute for Longevity and Aging Studies, UTHSCSA 15355 Lambda drive, San Antonio, TX 78245, USA
Search for more papers by this authorDiana Casper
Neurosurgery lab, The Albert Einstein College of Medicine and Montefiore Medical Center, Moses 3, 111 East 210th Street, The Bronx, NY 10467, USA
Search for more papers by this authorDorothee Huchon
Department of Zoology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel
National Evolutionary Synthesis Center, 2024 W. Main St., Suite A200, Durham, NC 27705, USA
Search for more papers by this authorJames Mele
Department of Epidemiology and Biostatistics, UTHSCSA, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
Barshop Institute for Longevity and Aging Studies, UTHSCSA 15355 Lambda drive, San Antonio, TX 78245, USA
Search for more papers by this authorJonathan A. Gelfond
Department of Epidemiology and Biostatistics, UTHSCSA, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
Department of Epidemiology and Biostatistics, UTHSCSA 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
Search for more papers by this authorDeborah M. Kristan
Department of Biological Sciences, California State University San Marcos, 333 S. Twin Oaks Valley Rd. San Marcos, CA 92096, USA
Search for more papers by this authorEviatar Nevo
Institute of Evolution, University of Haifa, Mount Carmel, Haifa 31905, Israel
Search for more papers by this authorRochelle Buffenstein
Department of Biology, The City College of New York, 138 st @Convent Ave, New York, NY 10031, USA
Department of Epidemiology and Biostatistics, UTHSCSA, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
Barshop Institute for Longevity and Aging Studies, UTHSCSA 15355 Lambda drive, San Antonio, TX 78245, USA
Search for more papers by this authorYael H. Edrey
Department of Biology, The City College of New York, 138 st @Convent Ave, New York, NY 10031, USA
Department of Epidemiology and Biostatistics, UTHSCSA, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
Barshop Institute for Longevity and Aging Studies, UTHSCSA 15355 Lambda drive, San Antonio, TX 78245, USA
Search for more papers by this authorDiana Casper
Neurosurgery lab, The Albert Einstein College of Medicine and Montefiore Medical Center, Moses 3, 111 East 210th Street, The Bronx, NY 10467, USA
Search for more papers by this authorDorothee Huchon
Department of Zoology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel
National Evolutionary Synthesis Center, 2024 W. Main St., Suite A200, Durham, NC 27705, USA
Search for more papers by this authorJames Mele
Department of Epidemiology and Biostatistics, UTHSCSA, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
Barshop Institute for Longevity and Aging Studies, UTHSCSA 15355 Lambda drive, San Antonio, TX 78245, USA
Search for more papers by this authorJonathan A. Gelfond
Department of Epidemiology and Biostatistics, UTHSCSA, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
Department of Epidemiology and Biostatistics, UTHSCSA 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
Search for more papers by this authorDeborah M. Kristan
Department of Biological Sciences, California State University San Marcos, 333 S. Twin Oaks Valley Rd. San Marcos, CA 92096, USA
Search for more papers by this authorEviatar Nevo
Institute of Evolution, University of Haifa, Mount Carmel, Haifa 31905, Israel
Search for more papers by this authorRochelle Buffenstein
Department of Biology, The City College of New York, 138 st @Convent Ave, New York, NY 10031, USA
Department of Epidemiology and Biostatistics, UTHSCSA, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
Barshop Institute for Longevity and Aging Studies, UTHSCSA 15355 Lambda drive, San Antonio, TX 78245, USA
Search for more papers by this authorSummary
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.
References
- Andziak B, Buffenstein R (2006) Disparate patterns of age-related changes in lipid peroxidation in long-lived naked mole-rats and shorter-lived mice. Aging Cell 5, 525–532.
- Arieli R (1979) The atmospheric environment of the fossorial mole-rat (Spalax ehrenbergi): effects of season, soil texture, rain, temperature and activity. Comp. Biochem. Physiol. 63A, 569–575.
- Aristotle On Longevity and Shortness of Life ( Ross GRT, ed.) http://classics.mit.edu/Aristotle/longev_short.html [accessed on 6 December 2011]..
- Bernstein HG, Lendeckel U, Bertram I, Bukowska A, Kanakis D, Dobrowolny H, Stauch R, Krell D, Mawrin C, Budinger E, Keilhoff G, Bogerts B. (2006) Localization of neuregulin-1alpha (heregulin-alpha) and one of its receptors, ErbB-4 tyrosine kinase, in developing and adult human brain. Brain Res. Bull. 69, 546–559.
- Blanga-Kanfi S, Miranda H, Penn O, Pupko T, DeBry R, Huchon D (2009) Rodent phylogeny revised: analysis of six nuclear genes from all major rodent clades. BMC Evol. Biol. 9, 71.
- Buffenstein R (2005) The naked mole-rat: a new long-living model for human aging research. J. Gerontol. A Biol. Sci. Med. Sci. 60, 1369–1377.
- Buonanno A (2010) The neuregulin signaling pathway and schizophrenia: from genes to synapses and neural circuits. Brain Res. Bull. 83, 122–131.
- Chaudhury A, Gerecke K, Wyss J, Morgan D, Gordon M, Carroll S (2003) Neuregulin-1 and erbB4 immunoreactivity is associated with neuritic plaques in Alzheimer disease brain and in a transgenic model of Alzheimer disease. J. Neuropathol. Exp. Neurol. 62, 42–54.
- Cho H, Leahy D (2002) Structure of the extracellular region of HER3 reveals an interdomain tether. Science 297, 1330–1333.
- Dickstein D, Kabaso D, Rocher A, Luebke J, Wearne S, Hof P (2007) Changes in the structural complexity of the aged brain. Aging Cell 6, 275–284.
- Edrey Y, Park T, Kang H, Biney A, Buffenstein R (2011) Endocrine function and neurobiology of the longest-living rodent, the naked mole-rat. Exp. Gerontol. 46, 116–123.
- Ehrlichman R, Luminais S, White S, Rudnick N, Ma N, Dow H, Kreibich A, Abel T, Brodkin E, Hahn C et al. (2009) Neuregulin 1 transgenic mice display reduced mismatch negativity, contextual fear conditioning and social interactions. Brain Res. 1294, 116–127.
- Esper R, Pankonin M, Loeb J (2006) Neuregulins: versatile growth and differentiation factors in nervous system development and human disease. Brain Res. Rev. 51, 161–175.
- Fischbach G (2007) NRG1 and synaptic function in the CNS. Neuron 54, 495–497.
- Garland JT, Ives A (2000) Using the past to predict the present: confidence intervals for regression equations in phylogenetic comparative methods. Am. Nat. 155, 346–364.
- Gerecke K, Wyss J, Karavanova I, Buonanno A, Carroll S (2001) ErbB transmembrane tyrosine kinase receptors are differentially expressed throughout the adult rat central nervous system. J. Comp. Neurol. 433, 86–100.
- Hahn C, Wang H, Cho D, Talbot K, Gur R, Berrettini W, Bakshi K, Kamins J, Borgmann-Winter K, Siegel S et al. (2006) Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia. Nat. Med. 12, 824–828.
- Harrison D, Strong R, Sharp Z, Nelson J, Astle C, Flurkey K, Nadon N, Wilkinson J, Frenkel K, Carter C et al. (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460, 392–395.
- Hayakawa N, Abe M, Eto R, Kato H, Araki T (2008) Age-related changes of NGF, BDNF, parvalbumin and neuronal nitric oxide synthase immunoreactivity in the mouse hippocampal CA1 sector. Metab. Brain Dis. 23, 199–211.
- Heath T, Hedtke S, Hillis D (2008) Taxon sampling and the accuracy of phylogenetic analyses. J. Syst. Evol. 46, 239–257.
- Huchon D, Chevret P, Jordan U, Kilpatrick C, Ranwez V, Jenkins P, Brosius J, Schmitz J (2007) Multiple molecular evidences for a living mammalian fossil. Proc. Natl Acad. Sci. USA 104, 7495–7499.
- Hulbert AJ, Else PL (2004) Basal metabolic rate: history, composition, regulation, and usefulness. Physiol. Biochem. Zool. 77, 869–876.
- Hulbert A, Pamplona R, Buffenstein R, Buttemer W (2007) Life and death: metabolic rate, membrane composition, and life span of animals. Physiol. Rev. 87, 1175–1213.
- Hwang I, Yoo K, Jung B, Cho J, Kim D, Kang T, Kwon Y, Kim Y, Won M (2006) Correlations between neuronal loss, decrease of memory, and decrease expression of brain-derived neurotrophic factor in the gerbil hippocampus during normal aging. Exp. Neurol. 201, 75–83.
- Kelly K, Nadon N, Morrison J, Thibault O, Barnes C, Blalock E (2006) The neurobiology of aging. Epilepsy Res. 68(Suppl 1), S5–S20.
- Kraus M, Issing W, Miki T, Popescu N, Aaronson S (1989) Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors. Proc. Natl Acad. Sci. USA 86, 9193–9197.
- Law AJ, Shannon Weickert C, Hyde TM, Kleinman JE, Harrison PJ (2004) Neuregulin-1 (NRG-1) mRNA and protein in the adult human brain. Neuroscience 127, 125–136.
- Liang S, Mele J, Wu Y, Buffenstein R, Hornsby J (2010) Resistance to experimental tumorigenesis in cells of a long-lived mammal, the naked mole-rat (Heterocephalus glaber). Aging Cell 9, 626–635.
- Masoro E (2005) Overview of caloric restriction and ageing. Mech. Ageing Dev. 126, 913–922.
- Min SS, An J, Lee JH, Seol GH, Im JH, Kim HS, Baik TK, Woo RS (2011) Neuregulin-1 prevents amyloid β-induced impairment of long-term potentiation in hippocampal slices via ErbB4. Neurosci. Lett. 505, 6–9.
- Montero J, Rodríguez-Barrueco R, Ocaña A, Díaz-Rodríguez E, Esparís-Ogando A, Pandiella A (2008) Neuregulins and cancer. Clin. Cancer Res. 14, 3237–3241.
- Nadri C, Belmaker R, Agam G (2007) Oxygen restriction of neonate rats elevates neuregulin-1alpha isoform levels: possible relationship to schizophrenia. Neurochem. Int. 51, 447–450.
- O’Tuathaigh C, Babovic D, O’Sullivan G, Clifford J, Tighe O, Croke D, Harvey R, Waddington J (2007) Phenotypic characterization of spatial cognition and social behavior in mice with ‘knockout’ of the schizophrenia risk gene neuregulin 1. Neuroscience 147, 18–27.
- Paradis E, Claude J, Strimmer K (2004) APE: analyses of phylogenetics and evolution in R language. Bioinformatics, 20, 289–290.
- Peles E, Yarden Y (1993) Neu and its ligands: from an oncogene to neural factors. Bioessays 15, 815–824.
- Plowman G, Culouscou J, Whitney G, Green J, Carlton G, Foy L, Neubauer M, Shoyab M (1993) Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family. Proc. Natl Acad. Sci. USA 90, 1746–1750.
- Role L, Talmage D (2007) Neurobiology: new order for thought disorders. Nature 448, 263–265.
- Sambrook J, Fritsch E, Maniatis T (2001) Molecular Cloning: A Laboratory Manual. 3rd edn. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press.
- Springer M, DeBry R, Douady C, Amrine H, Madsen O, de Jong W, Stanhope M (2001) Mitochondrial versus nuclear gene sequences in deep level mammalian phylogeny reconstruction. Mol. Biol. Evol. 18, 132–143.
- Stanhope MM, Smith MR, Waddell VG, Porter CA, Shivji MS, Goodman M (1996) Mammalian evolution and the interphotoreceptor retinoid binding protein (IRBP) gene: convincing evidence for several superordinal clades. J. Mol. Evol. 43, 83–92.
- Sullivan J, Abdo Z, Joyce P, Swofford D (2005) Evaluating the performance of a successive-approximations approach to parameter optimization in maximum-likelihood phylogeny estimation. Mol. Biol. Evol. 22, 1386–1392.
- Swofford D (2003) PAUP*: Phylogenetic Analysis Using Parsimony (*and Other Methods). Sunderland, Massachusetts: Sinauer Associates.
- Tzahar E, Yarden Y (1998) The ErbB-2/HER2 oncogenic receptor of adenocarcinomas: from orphanhood to multiple stromal ligands. Biochim. Biophys. Acta 1377, M25–M37.
- Ungvari Z, Buffenstein R, Austad S, Podlutsky A, Kaley G, Csiszar A (2008) Oxidative stress in vascular senescence: lessons from successfully aging species. Front. Biosci. 13, 5056–5070.
- Weigi R (2005) Longevity of Mammals in Captivity; from the Living Collections of the World. KleineSenckenberg-Reihe 48: Stuttgart.
-
Wilson D,
Reeder D (2005) Mammal Species of the World. A Taxonomic and Geographic Reference, 3rd edn.
Baltimore: Johns Hopkins University Press.
10.56021/9780801882210 Google Scholar
- Woodley R, Buffenstein R (2002) Thermogenic changes with chronic cold exposure in the naked mole-rat (Heterocephalus glaber). Comp. Biochem. Physiol. A Mol. Integr. Physiol. 133, 827–834.
