TY - JOUR
T1 - Testing the oxidative stress hypothesis of aging in primate fibroblasts
T2 - Is there a correlation between species longevity and cellular ROS production?
AU - Csiszar, Anna
AU - Podlutsky, Andrej
AU - Podlutskaya, Natalia
AU - Sonntag, William E.
AU - Merlin, Steven Z.
AU - Philipp, Eva E.R.
AU - Doyle, Kristian
AU - Davila, Antonio
AU - Recchia, Fabio A.
AU - Ballabh, Praveen
AU - Pinto, John T.
AU - Ungvari, Zoltan
N1 - Funding Information:
This work was supported by grants from the American Diabetes Association (to Z . U . ), American Federation for Aging Research (to A . C . ), the American Heart Association (to A . C . ), the Oklahoma Center for the Advancement of Science and Technology (to A . C . and Z . U . ), the University of Oklahoma College of Medicine Alumni Association (to A . C . ), the San Antonio Area Foundation (to A P.), and the National Institutes of Health (AG031085 to A . C . , AT006526 to Z . U . , AG022873, and AG025063 to S.N.A.).
PY - 2012/8
Y1 - 2012/8
N2 - The present study was conducted to test predictions of the oxidative stress theory of aging assessing reactive oxygen species production and oxidative stress resistance in cultured fibroblasts from 13 primate species ranging in body size from 0.25 to 120 kg and in longevity from 20 to 90 years. We assessed both basal and stress-induced reactive oxygen species production in fibroblasts from five great apes (human, chimpanzee, bonobo, gorilla, and orangutan), four Old World monkeys (baboon, rhesus and crested black macaques, and patas monkey), three New World monkeys (common marmoset, red-bellied tamarin, and woolly monkey), and one lemur (ring-tailed lemur). Measurements of cellular MitoSox fluorescence, an indicator of mitochondrial superoxide (O2 •-) generation, showed an inverse correlation between longevity and steady state or metabolic stress - induced mitochondrial O2 •- production, but this correlation was lost when the effects of body mass were removed, and the data were analyzed using phylogenetically independent contrasts. Fibroblasts from longer-lived primate species also exhibited superior resistance to H2O2-induced apoptotic cell death than cells from shorter-living primates. After correction for body mass and lack of phylogenetic independence, this correlation, although still discernible, fell short of significance by regression analysis. Thus, increased longevity in this sample of primates is not causally associated with low cellular reactive oxygen species generation, but further studies are warranted to test the association between increased cellular resistance to oxidative stressor and primate longevity.
AB - The present study was conducted to test predictions of the oxidative stress theory of aging assessing reactive oxygen species production and oxidative stress resistance in cultured fibroblasts from 13 primate species ranging in body size from 0.25 to 120 kg and in longevity from 20 to 90 years. We assessed both basal and stress-induced reactive oxygen species production in fibroblasts from five great apes (human, chimpanzee, bonobo, gorilla, and orangutan), four Old World monkeys (baboon, rhesus and crested black macaques, and patas monkey), three New World monkeys (common marmoset, red-bellied tamarin, and woolly monkey), and one lemur (ring-tailed lemur). Measurements of cellular MitoSox fluorescence, an indicator of mitochondrial superoxide (O2 •-) generation, showed an inverse correlation between longevity and steady state or metabolic stress - induced mitochondrial O2 •- production, but this correlation was lost when the effects of body mass were removed, and the data were analyzed using phylogenetically independent contrasts. Fibroblasts from longer-lived primate species also exhibited superior resistance to H2O2-induced apoptotic cell death than cells from shorter-living primates. After correction for body mass and lack of phylogenetic independence, this correlation, although still discernible, fell short of significance by regression analysis. Thus, increased longevity in this sample of primates is not causally associated with low cellular reactive oxygen species generation, but further studies are warranted to test the association between increased cellular resistance to oxidative stressor and primate longevity.
KW - Comparative biology
KW - Free radical
KW - Oxidative stress
KW - Primates
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U2 - 10.1093/gerona/glr216
DO - 10.1093/gerona/glr216
M3 - Article
C2 - 22219516
AN - SCOPUS:84866426621
SN - 1079-5006
VL - 67 A
SP - 841
EP - 852
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 8
ER -