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

Biochem Biophys Res Commun. 2015 Feb 20;457(4):669-75. doi: 10.1016/j.bbrc.2015.01.046. Epub 2015 Jan 21.

Abstract

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.

Keywords: Autophagy; Heat shock response; Long-lived species; Proteasome; Protein homeostasis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Biological Evolution
  • Cells, Cultured
  • Chiroptera
  • Fibroblasts / metabolism
  • Heat-Shock Response*
  • Longevity*
  • Marsupialia
  • Mice
  • Mole Rats
  • Oxidative Stress
  • Phylogeny
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteolysis
  • Ubiquitination

Substances

  • Proteasome Endopeptidase Complex