Spermidine Enhances Mitochondrial Bioenergetics in Young and Aged Human-Induced Pluripotent Stem Cell-Derived Neurons

The accumulation of damaged mitochondria has long been considered a hallmark of the aging process. Among various factors, age-related mitochondrial alterations comprise bioenergetic impairments and disturbances in reactive oxygen species (ROS) control, thereby negatively affecting mitochondrial perf...

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Main Authors: Leonora Szabo, Imane Lejri, Amandine Grimm, Anne Eckert
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/13/12/1482
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author Leonora Szabo
Imane Lejri
Amandine Grimm
Anne Eckert
author_facet Leonora Szabo
Imane Lejri
Amandine Grimm
Anne Eckert
author_sort Leonora Szabo
collection DOAJ
description The accumulation of damaged mitochondria has long been considered a hallmark of the aging process. Among various factors, age-related mitochondrial alterations comprise bioenergetic impairments and disturbances in reactive oxygen species (ROS) control, thereby negatively affecting mitochondrial performance and ultimately accelerating aging. Previous studies have revealed that polyamine spermidine appears to exert health-protective and lifespan-promoting effects. Notably, recent findings have also described a spermidine-induced improvement in age-associated mitochondrial dysfunction, but the beneficial effects of spermidine on aged mitochondria have not been entirely examined yet. Here, we show that spermidine positively regulates several parameters related to mitochondrial bioenergetics and mitochondrial redox homeostasis in young and aged human-induced pluripotent stem cell-derived neurons. We report that spermidine treatment increases adenosine triphosphate production and mitochondrial membrane potential, which is accompanied by an attenuation in mitochondrial ROS levels in both age groups. Furthermore, we demonstrate a spermidine-mediated amelioration in mitochondrial respiration in both young and aged neurons. Overall, our findings suggest that nutritional spermidine supplementation might represent an attractive therapeutic approach to enhance mitochondrial function, consequently decelerating aging.
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spelling doaj-art-e27b159a282c4bf9a163fae18da4ab6f2025-08-20T02:53:34ZengMDPI AGAntioxidants2076-39212024-12-011312148210.3390/antiox13121482Spermidine Enhances Mitochondrial Bioenergetics in Young and Aged Human-Induced Pluripotent Stem Cell-Derived NeuronsLeonora Szabo0Imane Lejri1Amandine Grimm2Anne Eckert3Research Cluster Molecular and Cognitive Neurosciences, University of Basel, 4002 Basel, SwitzerlandResearch Cluster Molecular and Cognitive Neurosciences, University of Basel, 4002 Basel, SwitzerlandResearch Cluster Molecular and Cognitive Neurosciences, University of Basel, 4002 Basel, SwitzerlandResearch Cluster Molecular and Cognitive Neurosciences, University of Basel, 4002 Basel, SwitzerlandThe accumulation of damaged mitochondria has long been considered a hallmark of the aging process. Among various factors, age-related mitochondrial alterations comprise bioenergetic impairments and disturbances in reactive oxygen species (ROS) control, thereby negatively affecting mitochondrial performance and ultimately accelerating aging. Previous studies have revealed that polyamine spermidine appears to exert health-protective and lifespan-promoting effects. Notably, recent findings have also described a spermidine-induced improvement in age-associated mitochondrial dysfunction, but the beneficial effects of spermidine on aged mitochondria have not been entirely examined yet. Here, we show that spermidine positively regulates several parameters related to mitochondrial bioenergetics and mitochondrial redox homeostasis in young and aged human-induced pluripotent stem cell-derived neurons. We report that spermidine treatment increases adenosine triphosphate production and mitochondrial membrane potential, which is accompanied by an attenuation in mitochondrial ROS levels in both age groups. Furthermore, we demonstrate a spermidine-mediated amelioration in mitochondrial respiration in both young and aged neurons. Overall, our findings suggest that nutritional spermidine supplementation might represent an attractive therapeutic approach to enhance mitochondrial function, consequently decelerating aging.https://www.mdpi.com/2076-3921/13/12/1482spermidineaginginduced pluripotent stem cell-derived neuronsmitochondriabioenergeticsoxidative stress
spellingShingle Leonora Szabo
Imane Lejri
Amandine Grimm
Anne Eckert
Spermidine Enhances Mitochondrial Bioenergetics in Young and Aged Human-Induced Pluripotent Stem Cell-Derived Neurons
Antioxidants
spermidine
aging
induced pluripotent stem cell-derived neurons
mitochondria
bioenergetics
oxidative stress
title Spermidine Enhances Mitochondrial Bioenergetics in Young and Aged Human-Induced Pluripotent Stem Cell-Derived Neurons
title_full Spermidine Enhances Mitochondrial Bioenergetics in Young and Aged Human-Induced Pluripotent Stem Cell-Derived Neurons
title_fullStr Spermidine Enhances Mitochondrial Bioenergetics in Young and Aged Human-Induced Pluripotent Stem Cell-Derived Neurons
title_full_unstemmed Spermidine Enhances Mitochondrial Bioenergetics in Young and Aged Human-Induced Pluripotent Stem Cell-Derived Neurons
title_short Spermidine Enhances Mitochondrial Bioenergetics in Young and Aged Human-Induced Pluripotent Stem Cell-Derived Neurons
title_sort spermidine enhances mitochondrial bioenergetics in young and aged human induced pluripotent stem cell derived neurons
topic spermidine
aging
induced pluripotent stem cell-derived neurons
mitochondria
bioenergetics
oxidative stress
url https://www.mdpi.com/2076-3921/13/12/1482
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AT amandinegrimm spermidineenhancesmitochondrialbioenergeticsinyoungandagedhumaninducedpluripotentstemcellderivedneurons
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