Age-related changes in the proteostasis network in the brain of the naked mole-rat: Implications promoting healthy longevity

Judy C. Triplett, Antonella Tramutola, Aaron Swomley, Jessime Kirk, Kelly Grimes, Kaitilyn Lewis, Miranda Orr, Karl Rodriguez, Jian Cai, Jon B. Klein, Marzia Perluigi, Rochelle Buffenstein, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

The naked mole-rat (NMR) is the longest-lived rodent and possesses several exceptional traits: marked cancer resistance, negligible senescence, prolonged genomic integrity, pronounced proteostasis, and a sustained health span. The underlying molecular mechanisms that contribute to these extraordinary attributes are currently under investigation to gain insights that may conceivably promote and extend human health span and lifespan. The ubiquitin-proteasome and autophagy-lysosomal systems play a vital role in eliminating cellular detritus to maintain proteostasis and have been previously shown to be more robust in NMRs when compared with shorter-lived rodents. Using a 2-D PAGE proteomics approach, differential expression and phosphorylation levels of proteins involved in proteostasis networks were evaluated in the brains of NMRs in an age-dependent manner. We identified 9 proteins with significantly altered levels and/or phosphorylation states that have key roles involved in proteostasis networks. To further investigate the possible role that autophagy may play in maintaining cellular proteostasis, we examined aspects of the PI3K/Akt/mammalian target of rapamycin (mTOR) axis as well as levels of Beclin-1, LC3-I, and LC3-II in the brain of the NMR as a function of age. Together, these results show that NMRs maintain high levels of autophagy throughout the majority of their lifespan and may contribute to the extraordinary health span of these rodents. The potential of augmenting human health span via activating the proteostasis network will require further studies.

Original languageEnglish (US)
Pages (from-to)2213-2224
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1852
Issue number10
DOIs
StatePublished - Oct 1 2015

Keywords

  • Aging
  • MTOR
  • Naked mole-rat
  • Phosphoproteomics
  • Proteomics
  • Proteostasis networks

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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