Unraveling the interplay between sleep, redox metabolism, and aging: implications for brain health and longevity

The relationship between sleep and metabolism has emerged as a critical factor in aging and age-related diseases, including Alzheimer’s disease and dementia. Mitochondrial oxidative phosphorylation, essential for neuronal energy production, also generates reactive oxygen species (ROS), which increas...

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Main Authors: Fayaz A. Mir, Arianna R. S. Lark, Christa J. Nehs
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Aging
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fragi.2025.1605070/full
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author Fayaz A. Mir
Fayaz A. Mir
Arianna R. S. Lark
Arianna R. S. Lark
Christa J. Nehs
Christa J. Nehs
author_facet Fayaz A. Mir
Fayaz A. Mir
Arianna R. S. Lark
Arianna R. S. Lark
Christa J. Nehs
Christa J. Nehs
author_sort Fayaz A. Mir
collection DOAJ
description The relationship between sleep and metabolism has emerged as a critical factor in aging and age-related diseases, including Alzheimer’s disease and dementia. Mitochondrial oxidative phosphorylation, essential for neuronal energy production, also generates reactive oxygen species (ROS), which increase with age and contribute to oxidative stress. Sleep plays a vital role in modulating redox balance, facilitating the clearance of free radicals, and supporting mitochondrial function. Disruptions in sleep are closely linked to redox imbalances, and emerging evidence suggests that pharmacological interventions, such as dual orexin receptor antagonists and antioxidant-based therapies, may help restore redox homeostasis. Furthermore, antioxidant-rich diets and supplements have shown promise in improving both sleep quality and metabolic health in aging populations. Neurons, with their high energy demands, are particularly vulnerable to oxidative damage, making redox regulation crucial in maintaining brain integrity. This review explores the bidirectional relationship between sleep and redox metabolism through five key areas: (1) sleep’s role in free radical regulation, (2) ROS as mediators of age-related sleep disturbances, (3) feedback loops between impaired sleep and brain metabolism, (4) sleep, redox, and aging in peripheral systems, and (5) therapeutic strategies to restore redox balance and improve aging outcomes. Understanding these mechanisms may provide new targets for interventions aimed at mitigating age-associated diseases.
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spelling doaj-art-b1a78fbe2d4c4ab1a1c0ac759817e60a2025-08-20T03:47:27ZengFrontiers Media S.A.Frontiers in Aging2673-62172025-05-01610.3389/fragi.2025.16050701605070Unraveling the interplay between sleep, redox metabolism, and aging: implications for brain health and longevityFayaz A. Mir0Fayaz A. Mir1Arianna R. S. Lark2Arianna R. S. Lark3Christa J. Nehs4Christa J. Nehs5Mass General Brigham Department of Anesthesiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDivision of Sleep Medicine, Harvard Medical School, Boston, MA, United StatesMass General Brigham Department of Anesthesiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDivision of Sleep Medicine, Harvard Medical School, Boston, MA, United StatesMass General Brigham Department of Anesthesiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDivision of Sleep Medicine, Harvard Medical School, Boston, MA, United StatesThe relationship between sleep and metabolism has emerged as a critical factor in aging and age-related diseases, including Alzheimer’s disease and dementia. Mitochondrial oxidative phosphorylation, essential for neuronal energy production, also generates reactive oxygen species (ROS), which increase with age and contribute to oxidative stress. Sleep plays a vital role in modulating redox balance, facilitating the clearance of free radicals, and supporting mitochondrial function. Disruptions in sleep are closely linked to redox imbalances, and emerging evidence suggests that pharmacological interventions, such as dual orexin receptor antagonists and antioxidant-based therapies, may help restore redox homeostasis. Furthermore, antioxidant-rich diets and supplements have shown promise in improving both sleep quality and metabolic health in aging populations. Neurons, with their high energy demands, are particularly vulnerable to oxidative damage, making redox regulation crucial in maintaining brain integrity. This review explores the bidirectional relationship between sleep and redox metabolism through five key areas: (1) sleep’s role in free radical regulation, (2) ROS as mediators of age-related sleep disturbances, (3) feedback loops between impaired sleep and brain metabolism, (4) sleep, redox, and aging in peripheral systems, and (5) therapeutic strategies to restore redox balance and improve aging outcomes. Understanding these mechanisms may provide new targets for interventions aimed at mitigating age-associated diseases.https://www.frontiersin.org/articles/10.3389/fragi.2025.1605070/fullsleepmitochondriaoxidative stressmetabolicantioxidantsketones
spellingShingle Fayaz A. Mir
Fayaz A. Mir
Arianna R. S. Lark
Arianna R. S. Lark
Christa J. Nehs
Christa J. Nehs
Unraveling the interplay between sleep, redox metabolism, and aging: implications for brain health and longevity
Frontiers in Aging
sleep
mitochondria
oxidative stress
metabolic
antioxidants
ketones
title Unraveling the interplay between sleep, redox metabolism, and aging: implications for brain health and longevity
title_full Unraveling the interplay between sleep, redox metabolism, and aging: implications for brain health and longevity
title_fullStr Unraveling the interplay between sleep, redox metabolism, and aging: implications for brain health and longevity
title_full_unstemmed Unraveling the interplay between sleep, redox metabolism, and aging: implications for brain health and longevity
title_short Unraveling the interplay between sleep, redox metabolism, and aging: implications for brain health and longevity
title_sort unraveling the interplay between sleep redox metabolism and aging implications for brain health and longevity
topic sleep
mitochondria
oxidative stress
metabolic
antioxidants
ketones
url https://www.frontiersin.org/articles/10.3389/fragi.2025.1605070/full
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