title: Long-lived species have improved proteostasis compared to phylogenetically-related shorter-lived species.
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.
authors.affiliation: Linus Pauling Institute, Oregon State University, USA.
authors.forename: Harrison
authors.initials: H
authors.lastname: Pride
authors.affiliation: Linus Pauling Institute, Oregon State University, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Linus Pauling Institute, Oregon State University, USA.
authors.forename: Bharath
authors.initials: B
authors.lastname: Sunchu
authors.affiliation: Linus Pauling Institute, Oregon State University, USA.
authors.forename: Jillian
authors.initials: J
authors.lastname: Mochnick
authors.affiliation: Department of Chemistry and Biochemistry, University of Michigan-Flint, MI 48502, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Coles
authors.affiliation: Department of Physiology, The University of Texas Health Science Center, San Antonio, TX, USA; Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology, The University of Texas Health Science Center, San Antonio, TX, USA; Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Rochelle
authors.initials: R
authors.lastname: Buffenstein
authors.affiliation: Department of Physiology, The University of Texas Health Science Center, San Antonio, TX, USA; Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center, San Antonio, TX, USA; South Texas Veteran's Health Care System, Audie L Murphy Division, San Antonio, TX 78249, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hornsby
authors.affiliation: Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center, San Antonio, TX, USA; Department of Cell and Structural Biology, The University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Steven N
authors.initials: SN
authors.lastname: Austad
authors.affiliation: Linus Pauling Institute, Oregon State University, USA; Department of Biochemistry and Biophysics, Corvallis, OR 97331, USA. Electronic address: viviana.perez@oregonstate.edu.
authors.forename: Viviana I
authors.initials: VI
authors.lastname: Pérez
mesh_terms: D000818:Animals; D001343:Autophagy; D005075:Biological Evolution; D002478:Cells, Cultured; D002685:Chiroptera; D005347:Fibroblasts / Q000378:metabolism; D018869:Heat-Shock Response; D008136:Longevity; D008394:Marsupialia; D051379:Mice; D019577:Mole Rats; D018384:Oxidative Stress; D010802:Phylogeny; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis; D054875:Ubiquitination
chemical_list: D046988:Proteasome Endopeptidase Complex
keywords: Autophagy; Heat shock response; Long-lived species; Proteasome; Protein homeostasis