L-Lactate Protects Skin Fibroblasts against Aging-Associated Mitochondrial Dysfunction via Mitohormesis
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 medi...
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Series: | Oxidative Medicine and Cellular Longevity |
Online Access: | http://dx.doi.org/10.1155/2015/351698 |
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doaj-bbc6d9e22ed84f0baec273d80f13bb422020-11-24T22:24:23ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942015-01-01201510.1155/2015/351698351698L-Lactate Protects Skin Fibroblasts against Aging-Associated Mitochondrial Dysfunction via MitohormesisJaroslav Zelenka0Aleš Dvořák1Lukáš Alán2Institute of Physiology, Czech Academy of Sciences, Vídeňská 1083, 142 20 Prague, Czech RepublicInstitute of Physiology, Czech Academy of Sciences, Vídeňská 1083, 142 20 Prague, Czech RepublicInstitute of Physiology, Czech Academy of Sciences, Vídeňská 1083, 142 20 Prague, Czech RepublicA 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.http://dx.doi.org/10.1155/2015/351698 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jaroslav Zelenka Aleš Dvořák Lukáš Alán |
spellingShingle |
Jaroslav Zelenka Aleš Dvořák Lukáš Alán L-Lactate Protects Skin Fibroblasts against Aging-Associated Mitochondrial Dysfunction via Mitohormesis Oxidative Medicine and Cellular Longevity |
author_facet |
Jaroslav Zelenka Aleš Dvořák Lukáš Alán |
author_sort |
Jaroslav Zelenka |
title |
L-Lactate Protects Skin Fibroblasts against Aging-Associated Mitochondrial Dysfunction via Mitohormesis |
title_short |
L-Lactate Protects Skin Fibroblasts against Aging-Associated Mitochondrial Dysfunction via Mitohormesis |
title_full |
L-Lactate Protects Skin Fibroblasts against Aging-Associated Mitochondrial Dysfunction via Mitohormesis |
title_fullStr |
L-Lactate Protects Skin Fibroblasts against Aging-Associated Mitochondrial Dysfunction via Mitohormesis |
title_full_unstemmed |
L-Lactate Protects Skin Fibroblasts against Aging-Associated Mitochondrial Dysfunction via Mitohormesis |
title_sort |
l-lactate protects skin fibroblasts against aging-associated mitochondrial dysfunction via mitohormesis |
publisher |
Hindawi Limited |
series |
Oxidative Medicine and Cellular Longevity |
issn |
1942-0900 1942-0994 |
publishDate |
2015-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2015/351698 |
work_keys_str_mv |
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