Long-lived species have improved proteostasis compared to phylogenetically-related shorter-lived species

Harrison Pride, Zhen Yu, Bharath Sunchu, Jillian Mochnick, Alexander Coles, Yiqiang Zhang, Rochelle Buffenstein, Peter J. Hornsby, Steven N. Austad, Viviana I. Pérez

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40 Scopus citations


Our previous studies have shown that the liver from Naked Mole Rats (NMRs), a long-lived rodent, has increased proteasome activity and lower levels of protein ubiquitination compared to mice. This suggests that protein quality control might play a role in assuring species longevity. To determine whether enhanced proteostasis is a common mechanism in the evolution of other long-lived species, here we evaluated the major players in protein quality control including autophagy, proteasome activity, and heat shock proteins (HSPs), using skin fibroblasts from three phylogenetically-distinct pairs of short- and long-lived mammals: rodents, marsupials, and bats. Our results indicate that in all cases, macroautophagy was significantly enhanced in the longer-lived species, both at basal level and after induction by serum starvation. Similarly, basal levels of most HSPs were elevated in all the longer-lived species. Proteasome activity was found to be increased in the long-lived rodent and marsupial but not in bats. These observations suggest that long-lived species may have superior mechanisms to ensure protein quality, and support the idea that protein homeostasis might play an important role in promoting longevity.

Original languageEnglish (US)
Pages (from-to)669-675
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - Feb 20 2015



  • Autophagy
  • Heat shock response
  • Long-lived species
  • Proteasome
  • Protein homeostasis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Pride, H., Yu, Z., Sunchu, B., Mochnick, J., Coles, A., Zhang, Y., Buffenstein, R., Hornsby, P. J., Austad, S. N., & Pérez, V. I. (2015). Long-lived species have improved proteostasis compared to phylogenetically-related shorter-lived species. Biochemical and Biophysical Research Communications, 457(4), 669-675. https://doi.org/10.1016/j.bbrc.2015.01.046