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Ketone Supplementation Reduces Superoxide Production in Cultured Primary Human Dermal Fibroblasts: Comparison of Young vs Aged Cells
Author(s) -
Kesl Shan Lynn,
Moor Andrea Nichole,
Jung Michelle Yung,
Poff Angela M,
Gould Lisa,
D'Agostino Dominic Paul
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1144.8
Subject(s) - reactive oxygen species , cytosol , mitochondrial ros , oxidative stress , hydrogen peroxide , chemistry , mitochondrion , andrology , superoxide , medicine , endocrinology , biochemistry , enzyme
In the United States, it is estimated that there are 1.8 million new cases of chronic wounds annually, with the majority occurring in the elderly. Reactive oxygen species (ROS) damage is augmented in aged patients leading to redox imbalance and is a key characteristic in impaired wound healing. Ketones are an energy substrate that reduce ROS production in the brain and heart, and thus may augment wound healing. We hypothesized that Beta‐Hydroxybutyrate (BHB; 5mM) would reduce cytosolic and mitochondrial ROS production in both young and aged primary human dermal fibroblasts. Primary human dermal fibroblasts (HDFs, passaged 2–8) from young and aged donors (24 to 88 years) were incubated in the absence or presence of BHB for 72 hours prior to stress with 100uM tert‐buytl‐hydrogen peroxide for 3 hours. ROS production was measured fluorescently with dihydroethidium (DHE, cytosolic) and Mitosox Red (mitochondrial) in triplicate, N=6. In the cytosol, aged HDFs produced 28% (p=<0.001)) more ROS basally compared to their young counterparts. When incubated in BHB for 72 hours, ROS production in the young HDFs decreased by 40% (p=<0.0001) and by 41% (p=<0.0001) in the aged. In the mitochondria, aged HDFs produced 27% (p=<0.0001) more ROS at baseline than the young HDFs, consistent with observations in cytosol. When incubated in BHB, ROS production was reduced in the young by 29% (p<0.0001) and in the aged by 51% (p<0.0001); the aged ROS production was no longer significantly different from the young. Ketone supplementation did not significantly change proliferation in the HDFs, but did increase migration in both young and aged HDFs. We conclude that ketone supplementation may protect against redox stress and augment wound healing, shifting redox homeostasis in HDFs, especially in the elderly. Funding: ONR, VA Merit Review.