The insulin-like growth factor system in the long-lived naked mole-rat

Malene Brohus, Vera Gorbunova, Chris G. Faulkes, Michael T. Overgaard, Cheryl A Conover

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Naked mole-rats (Heterocephalus glaber) (NMRs) are the longest living rodents known. They show negligible senescence, and are resistant to cancers and certain damaging effects associated with aging. The insulin-like growth factors (IGFs) have pluripotent actions, influencing growth processes in virtually every system of the body. They are established contributors to the aging process, confirmed by the demonstration that decreased IGF signaling results in life-extending effects in a variety of species. The IGFs are likewise involved in progression of cancers by mediating survival signals in malignant cells. This report presents a full characterization of the IGF system in the NMR: ligands, receptors, IGF binding proteins (IGFBPs), and IGFBP proteases. A particular emphasis was placed on the IGFBP protease, pregnancy-associated plasma protein-A (PAPP-A), shown to be an important lifespan modulator in mice. Comparisons of IGF-related genes in the NMR with human and murine sequences indicated no major differences in essential parts of the IGF system, including PAPP-A. The protease was shown to possess an intact active site despite the report of a contradictory genome sequence. Furthermore, PAPP-A was expressed and translated in NMRs cells and retained IGF-dependent proteolytic activity towards IGFBP-4 and IGF-independent activity towards IGFBP-5. However, experimental data suggest differential regulatory mechanisms for PAPP-A expression in NMRs than those described in humans and mice. This overall description of the IGF system in the NMR represents an initial step towards elucidating the complex molecular mechanisms underlying longevity, and how these animals have evolved to ensure a delayed and healthy aging process.

Original languageEnglish (US)
Article numbere0145587
JournalPLoS One
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2015

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Mole Rats
Heterocephalus glaber
somatomedins
Somatomedins
Rats
insulin-like growth factor binding proteins
Pregnancy-Associated Plasma Protein-A
Nuclear magnetic resonance
Insulin-Like Growth Factor Binding Proteins
blood proteins
Peptide Hydrolases
proteinases
Aging of materials
pregnancy
mice
Genes
Insulin-Like Growth Factor Binding Protein 5
Insulin-Like Growth Factor Binding Protein 4
neoplasms
Protein Binding

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

The insulin-like growth factor system in the long-lived naked mole-rat. / Brohus, Malene; Gorbunova, Vera; Faulkes, Chris G.; Overgaard, Michael T.; Conover, Cheryl A.

In: PLoS One, Vol. 10, No. 12, e0145587, 01.12.2015.

Research output: Contribution to journalArticle

Brohus, M, Gorbunova, V, Faulkes, CG, Overgaard, MT & Conover, CA 2015, 'The insulin-like growth factor system in the long-lived naked mole-rat', PLoS One, vol. 10, no. 12, e0145587. https://doi.org/10.1371/journal.pone.0145587
Brohus, Malene ; Gorbunova, Vera ; Faulkes, Chris G. ; Overgaard, Michael T. ; Conover, Cheryl A. / The insulin-like growth factor system in the long-lived naked mole-rat. In: PLoS One. 2015 ; Vol. 10, No. 12.
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