TitleLong-lived species have improved proteostasis compared to phylogenetically-related shorter-lived species.
Publication TypeJournal Article
Year of Publication2015
AuthorsPride H, Yu Z, Sunchu B, Mochnick J, Coles A, Zhang Y, Buffenstein R, Hornsby PJ, Austad SN, Perez VI
JournalBiochem Biophys Res Commun
Date Published2015 Feb 20
KeywordsAnimals, Autophagy, Biological Evolution, Cells, Cultured, Chiroptera, Fibroblasts, Heat-Shock Response, Longevity, Marsupialia, Mice, Mole Rats, Oxidative Stress, Phylogeny, Proteasome Endopeptidase Complex, Proteolysis, Ubiquitination

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.

Alternate JournalBiochem. Biophys. Res. Commun.
PubMed ID25615820
Grant ListR01 AG022891 / AG / NIA NIH HHS / United States
R03 AG052394 / AG / NIA NIH HHS / United States