Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Zelenka 2015 Oxid Med Cell Longev

From Bioblast
Publications in the MiPMap
Zelenka J, Dvořák A, Alán L (2015) L-lactate protects skin fibroblasts against aging-associated mitochondrial dysfunction via mitohormesis. Oxid Med Cell Longev 2015:351698.

» PMID: 26171114 Open Access

Zelenka J, Dvorak A, Alan L (2015) Oxid Med Cell Longev

Abstract: 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 1α (PGC1α) 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.


O2k-Network Lab: CZ Prague Jezek P


Labels: MiParea: Respiration, mtDNA;mt-genetics  Pathology: Aging;senescence  Stress:Oxidative stress;RONS  Organism: Rat  Tissue;cell: Liver, Endothelial;epithelial;mesothelial cell, Fibroblast  Preparation: Intact cells, Isolated mitochondria 


Coupling state: LEAK, ROUTINE, ET  Pathway: N, S  HRR: Oxygraph-2k