Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2015, Article ID 351698, 14 pages
Research Article

L-Lactate Protects Skin Fibroblasts against Aging-Associated Mitochondrial Dysfunction via Mitohormesis

1Institute of Physiology, Czech Academy of Sciences, Vídeňská 1083, 142 20 Prague, Czech Republic
2Department of Biochemistry and Microbiology, Institute of Chemical Technology Prague, Technická 5, 166 28 Prague, Czech Republic

Received 11 March 2015; Revised 25 May 2015; Accepted 27 May 2015

Academic Editor: Liang-Jun Yan

Copyright © 2015 Jaroslav Zelenka et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


A moderate elevation of reactive oxygen species (ROS) production and a mild inhibition of mitochondrial respiratory chain have been associated with a health promotion and a lifespan extension in several animal models of aging. Here, we tested whether this phenomenon called mitohormesis could be mediated by L-lactate. The treatment with 5 mM L-lactate significantly increased H2O2 production and slightly inhibited the respiration in cultured skin fibroblasts and in isolated mitochondria. The L-lactate exposure was associated with oxidation of intracellular glutathione, phosphorylation of 5′AMP-activated protein kinase (AMPK), and induction of peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) transcription. A replicative aging of fibroblasts (L0) with a constant (LC), or intermittent 5 mM L-lactate (LI) in media showed that the high-passage LI fibroblasts have higher respiration, lower H2O2 release, and lower secretion of L-lactate compared to L0 and LC. This protection against mitochondrial dysfunction in LI cells was associated with lower activity of mechanistic target of rapamycin complex 1 (mTORC1), less signs of cellular senescence, and increased autophagy compared to L0 and LC. In conclusion, we demonstrated that intermittent but not constant exposure to L-lactate triggers mitohormesis, prevents aging-associated mitochondrial dysfunction, and improves other markers of aging.