Fibroblasts From Longer-Lived Species of Primates, Rodents, Bats, Carnivores, and Birds Resist Protein Damage

Abstract

Species differ greatly in their rates of aging. Among mammalian species life span ranges from 2 to over 60 years. Here, we test the hypothesis that skin-derived fibroblasts from long-lived species of animals differ from those of short-lived animals in their defenses against protein damage. In parallel studies of rodents, nonhuman primates, birds, and species from the Laurasiatheria superorder (bats, carnivores, shrews, and ungulates), we find associations between species longevity and resistance of proteins to oxidative stress after exposure to H(2)O(2) or paraquat. In addition, baseline levels of protein carbonyl appear to be higher in cells from shorter-lived mammals compared with longer-lived mammals. Thus, resistance to protein oxidation is associated with species maximal life span in independent clades of mammals, suggesting that this cellular property may be required for evolution of longevity. Evaluation of the properties of primary fibroblast cell lines can provide insights into the factors that regulate the pace of aging across species of mammals.

Lifespan of mice and primates correlates with immunoproteasome expression

“…In some cases, primate cell lines were generated from skin biopsies obtained from the New England Regional Primate Research Center (Harvard University, Cambridge, Massachusetts, USA) and Southwest National Primate Research Center (Texas Biomedical Research Institute, San Antonio, Texas, USA). Cell lines were generated from these biopsies as described previously (1). In most instances the same cell lines were used for each set of experiments, but inconsistencies in cell growth sometimes led to substitution within a species or omission of a species from a specific data set.…”

Mitochondrial thioredoxin reductase 2 is elevated in long‐lived primate as well as rodent species and extends fly mean lifespan

“…For most experiments, cells were seeded at 300 000 cells mL −1 in either 6‐well plates or T75 flasks 48 h prior to assay. In most cases, media were replaced with serum free media 24 h prior to assay as described previously (Pickering et al ., , ). All cell lines used in experiments were primary cell fibroblast lines either developed by the University of Michigan or acquired from Coriell Cell Repository (Camden, NJ, USA) as described in more detail previously (Pickering et al ., , ).…”

“…Comparative analysis of cultured cells from species that vary in lifespan provides a powerful tool to identify factors which may regulate the rate of aging. This approach has documented systematic variation, among species of rodents, birds, and/or primates, in proteasome structure and function (Pickering et al ., ), telomere length (Gomes et al ., ), stress kinase activation (Elbourkadi et al ., ), cadmium exclusion (Dostál et al ., ), and resistance to oxidant injury (Harper et al ., , ; Pickering et al ., ). Comparisons between pairs of short‐ and long‐lived species, such as comparisons between laboratory mice and the naked mole rat (Rodriguez et al ., ) or long‐ and short‐lived species of clams (Ungvari et al ., ), have also been informative.…”

“…Genetic, dietary, or drug manipulations that extend lifespan in mice, flies, and worms often increase oxidative stress resistance (Larsen, ; Landis et al ., ; Salmon et al ., ; Lithgow & Miller, ). Cells from longer‐lived species are often more resistant to oxidative stress than cells derived from shorter‐lived species of the same clade (Harper et al ., , ; Pickering et al ., ). In contrast, augmentation or knockdown of cellular antioxidant defenses seldom affects lifespan in mice (Perez et al ., ).…”

High throughput small molecule screening reveals NRF2-dependent and - independent pathways of cellular stress resistance

“…In this regard, cellular resistance to environmental stressors is a frequent correlate of longevity 23 . In mammals, dermal fibroblasts derived from longerlived species, or from long-lived mouse mutants, show resistance to some forms of lethal injury [24][25][26][27][28][29][30] . Similarly, in C. elegans, many long-lived mutants show resistance to a variety of environmental insults 31 , including oxidative stress, a phenotype that has been used to screen for longevity mutants 32 .…”