Voluntary Wheel Running Reverses Age-Induced Changes in Hippocampal Gene Expression

Normal aging alters expression of numerous genes within the brain. Some of these transcription changes likely contribute to age-associated cognitive decline, reduced neural plasticity, and the higher incidence of neuropathology. Identifying factors that modulate brain aging is crucial for improving quality of life. One promising intervention to counteract negative effects of aging is aerobic exercise. Aged subjects that exercise show enhanced cognitive performance and increased hippocampal neurogenesis and synaptic plasticity. Currently, the mechanisms behind the anti-aging effects of exercise are not understood. The present study conducted a microarray on whole hippocampal samples from adult (3.5-month-old) and aged (18-month-old) male BALB/c mice that were individually housed with or without running wheels for 8 weeks. Results showed that aging altered genes related to chromatin remodeling, cell growth, immune activity, and synapse organization compared to adult mice. Exercise was found to modulate many of the genes altered by aging, but in the opposite direction. For example, wheel running increased expression of genes related to cell growth and attenuated expression of genes involved in immune function and chromatin remodeling. Collectively, findings show that even late-onset exercise may attenuate age-related changes in gene expression and identifies possible pathways through which exercise may exert its beneficial effects.

• Publication year

  2011

• Venue

  PLoS ONE

• Publication date

  2011-08-08

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0022654PMID 21857943PMCID 3152565
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Age-dependent alterations in nerve growth factor (NGF)-related proteins, sortilin, and learning and memory in rats.

  2011cited by this paper
• Chromatin structure as a mediator of aging

  2011influential reference
• CHD7 functions in the nucleolus as a positive regulator of ribosomal RNA biogenesis.

  2010cited by this paper
• Deletion of the nuclear isoform of poly(ADP-ribose) glycohydrolase (PARG) reveals its function in DNA repair, genomic stability and tumorigenesis.

  2010cited by this paper
• Brain-Derived Neurotrophic Factor Is Associated with Age-Related Decline in Hippocampal Volume

  2010cited by this paper
• Regulation of cyclin D1 gene expression.

  2010cited by this paper
• Physical activities and future risk of Parkinson disease

  2010cited by this paper
• Hippocampal gene expression patterns underlying the enhancement of memory by running in aged mice.

  2010cited by this paper
• Elevated histone expression promotes life span extension.

  2010cited by this paper
• Exercise and Alzheimer's disease biomarkers in cognitively normal older adults

  2010cited by this paper
• Chromatin Remodeling in Development and Disease: Focus on CHD7

  2010cited by this paper
• Regular voluntary exercise cures stress-induced impairment of cognitive function and cell proliferation accompanied by increases in cerebral IGF-1 and GST activity in mice.

  2010influential reference
• Regulation of hippocampal progenitor cell survival, proliferation and dendritic development by BDNF

  2009cited by this paper
• Exercise enhances hippocampal‐dependent learning in the rat: Evidence for a BDNF‐related mechanism

  2009cited by this paper
• Mitochondrial function as a determinant of life span

  2009cited by this paper
• RVB1/RVB2: running rings around molecular biology.

  2009cited by this paper
• Exercise, inflammation, and innate immunity.

  2009cited by this paper
• Neural Stem and Progenitor Cells Retain Their Potential for Proliferation and Differentiation into Functional Neurons Despite Lower Number in Aged Brain

  2009cited by this paper
• Aerobic fitness is associated with hippocampal volume in elderly humans

  2009cited by this paper
• Intact neurogenesis is required for benefits of exercise on spatial memory but not motor performance or contextual fear conditioning in C57BL/6J mice.

  2008cited by this paper
• Molecular Bases of Caloric Restriction Regulation of Neuronal Synaptic Plasticity

  2008cited by this paper
• PUMA, a potent killer with or without p53

  2008cited by this paper
• Caloric restriction and age affect synaptic proteins in hippocampal CA3 and spatial learning ability.

  2008cited by this paper
• Central Mechanisms of HPA Axis Regulation by Voluntary Exercise

  2008cited by this paper
• Aging hippocampus and amygdala

  2008cited by this paper
• Model-based variance-stabilizing transformation for Illumina microarray data

  2008cited by this paper
• Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources

  2008cited by this paper
• Aging, microglial cell priming, and the discordant central inflammatory response to signals from the peripheral immune system

  2008cited by this paper
• NTACT NEUROGENESIS IS REQUIRED FOR BENEFITS OF EXERC N SPATIAL MEMORY BUT NOT MOTOR PERFORMANCE OR ONTEXTUAL FEAR CONDITIONING IN C 57 BL / 6

  2008cited by this paper
• lumi: a pipeline for processing Illumina microarray

  2008cited by this paper
• Exercising Our Brains: How Physical Activity Impacts Synaptic Plasticity in the Dentate Gyrus

  2008cited by this paper
• Growth Factors as Mediators of Exercise Actions on the Brain

  2008cited by this paper
• Protein hormones and immunity.

  2007cited by this paper
• Role of complement in neurodegeneration and neuroinflammation.

  2007cited by this paper
• Physical activity in prevention and treatment of the metabolic syndrome.

  2007cited by this paper
• Aging, plasticity and environmental enrichment: structural changes and neurotransmitter dynamics in several areas of the brain.

  2007cited by this paper
• The CNS glycoprotein Shadoo has PrPC-like protective properties and displays reduced levels in prion infections

  2007cited by this paper
• Exercise builds brain health: key roles of growth factor cascades and inflammation.

  2007cited by this paper
• Age‐related alterations in hippocampal spines and deficiencies in spatial memory in mice

  2006cited by this paper
• Impaired trace and contextual fear conditioning in aged rats.

  2006cited by this paper
• Exercise, inflammation, and innate immunity.

  2006cited by this paper
• Neurobiology of exercise

  2006cited by this paper
• Doublecortin-like kinase controls neurogenesis by regulating mitotic spindles and M phase progression.

  2006cited by this paper
• TAF10 is required for the establishment of skin barrier function in foetal, but not in adult mouse epidermis.

  2005cited by this paper
• Exercise Enhances Learning and Hippocampal Neurogenesis in Aged Mice

  2005cited by this paper
• Exaggerated neuroinflammation and sickness behavior in aged mice after activation of the peripheral innate immune system

  2005cited by this paper
• Neurogenesis in a rat model of age‐related cognitive decline

  2004cited by this paper
• Altered hippocampal transcript profile accompanies an age-related spatial memory deficit in mice.

  2004influential reference
• From hormones to immunity: the physiology of immunology.

  2004cited by this paper
• Region-specific alterations in insulin-like growth factor-I receptor in the central nervous system of nNOS knockout mice.

  2004cited by this paper
• Experimental validation of novel and conventional approaches to quantitative real-time PCR data analysis.

  2003influential reference
• Gene Microarrays in Hippocampal Aging: Statistical Profiling Identifies Novel Processes Correlated with Cognitive Impairment

  2003cited by this paper
• Exercise increases hippocampal neurogenesis to high levels but does not improve spatial learning in mice bred for increased voluntary wheel running.

  2003cited by this paper
• DAVID: Database for Annotation, Visualization, and Integrated Discovery

  2003cited by this paper
• DAVID: Database for Annotation, Visualization, and Integrated Discovery

  2003cited by this paper
• Differential effects of acute and chronic exercise on plasticity‐related genes in the rat hippocampus revealed by microarray

  2002cited by this paper
• Characterization of Human RNA Polymerase III Identifies Orthologues for Saccharomyces cerevisiae RNA Polymerase III Subunits

  2002cited by this paper
• Immune response gene expression increases in the aging murine hippocampus.

  2002cited by this paper
• Pre‐mRNA splicing modulations in senescence

  2002cited by this paper
• The human mitochondrial ribosomal protein genes: mapping of 54 genes to the chromosomes and implications for human disorders.

  2001cited by this paper
• Effects of exercise on gene-expression profile in the rat hippocampus.

  2001cited by this paper
• Body temperatures of house mice artificially selected for high voluntary wheel-running behavior: repeatability and effect of genetic selection.

  2000cited by this paper
• Gene-expression profile of the ageing brain in mice

  2000cited by this paper
• Spontaneous classical pathway activation and deficiency of membrane regulators render human neurons susceptible to complement lysis.

  2000cited by this paper
• Behaviour of house mice artificially selected for high levels of voluntary wheel running.

  1999cited by this paper
• Mammalian Mitochondrial Ribosomal Proteins (2)

  1999cited by this paper
• Running enhances neurogenesis, learning, and long-term potentiation in mice.

  1999cited by this paper
• Dietary Supplementation with Vitamin E Reverses the Age-related Deficit in Long Term Potentiation in Dentate Gyrus*

  1998cited by this paper
• Mammalian mitochondrial ribosomal proteins. N-terminal amino acid sequencing, characterization, and identification of corresponding gene sequences.

  1998cited by this paper
• Complement gene expression in mouse microglia and astrocytes in culture: comparisons with mouse peritoneal macrophages.

  1996cited by this paper
• Controlling the false discovery rate: a practical and powerful approach to multiple testing

  1995cited by this paper
• Characterization by cDNA cloning of two new human protein kinases. Evidence by sequence comparison of a new family of mammalian protein kinases.

  1994cited by this paper
• Comparison of Protein Synthesis in Brain and Peripheral Tissue during Aging: Relationship to Insulin‐like Growth Factor‐1 and Type 1 IGF Receptors

  1993cited by this paper
• Reversal of age-related cognitive impairments by an M1 cholinergic agonist, AF102B.

  1990cited by this paper
• Journal of Neuroinflammation Exercise Alters the Immune Profile in Tg2576 Alzheimer Mice toward a Response Coincident with Improved Cognitive Performance and Decreased Amyloid

  year unknowncited by this paper

• Aging reprograms the response to chronic stress

  2026cites this paper
• Hippocampal Neurogenesis via Light-Intensity Running and Its Mechanism.

  2025cites this paper
• Contributions of mouse genetic strain background to age-related phenotypes in physically active HET3 mice.

  2024cites this paper
• Mechanisms underlying the effect of voluntary running on adult hippocampal neurogenesis

  2023cites this paper
• Remembering how to run: A descriptive wheel run analysis in CF1 male and female mice

  2022cites this paper
• Restoring Age-Related Cognitive Decline through Environmental Enrichment: A Transcriptomic Approach

  2022cites this paper
• Exercise duration differentially effects age-related neuroinflammation and hippocampal neurogenesis.

  2022cites this paper
• Digital biomarkers enable automated, longitudinal monitoring in a mouse model of aging.

  2021cites this paper
• Microglia and modifiable life factors: Potential contributions to cognitive resilience in aging.

  2021cites this paper
• Sedentary Life and Reduced Mastication Impair Spatial Learning and Memory and Differentially Affect Dentate Gyrus Astrocyte Subtypes in the Aged Mice

  2021cites this paper
• Long-term voluntary running modifies the levels of proteins of the excitatory/inhibitory system and reduces reactive astrogliosis in the brain of Ts65Dn mouse model for Down syndrome.

  2021cites this paper
• Different genes may be involved in distal and local sensitization: A genome‐wide gene‐based association study and meta‐analysis

  2021influential citation
• Creation of a gene expression portrait of depression and its application for identifying potential treatments

  2021cites this paper
• Epigenetic Mechanisms of Learning and Memory: Implications for Aging

  2020cites this paper
• Neurobiological effects of aerobic exercise, with a focus on patients with schizophrenia

  2019cites this paper
• Hippocampal gene expression patterns linked to late-life physical activity oppose age and AD-related transcriptional decline.

  2019cites this paper
• Ceasing exercise induces depression-like, anxiety-like, and impaired cognitive-like behaviours and altered hippocampal gene expression.

  2019cites this paper
• Voluntary wheel running delays brain atrophy in aged mice

  2019cites this paper
• Diversity of CD28null T Cells in the Elderly: A Glimpse in a Biological Adaptation of Aging

  2019cites this paper
• Rabbits and Rodents (Glires )

  2018cites this paper
• Sequence analysis and structure prediction of ABHD16A and the roles of the ABHD family members in human disease

  2018cites this paper
• Exercise Training Protects Against Aging-Induced Cognitive Dysfunction via Activation of the Hippocampal PGC-1α/FNDC5/BDNF Pathway

  2018cites this paper
• Assessing Healthspan and Lifespan Measures in Aging Mice: Optimization of Testing Protocols, Replicability, and Rater Reliability

  2018cites this paper
• Sex‐related differences in the wheel‐running activity of mice decline with increasing age

  2017cites this paper
• Impact of exercise and a complex environment on hippocampal dendritic morphology, Bdnf gene expression, and DNA methylation in male rat pups neonatally exposed to alcohol

  2017cites this paper
• Mechanisms of Hippocampal Aging and the Potential for Rejuvenation.

  2017cites this paper
• Indomethacin Increases Neurogenesis across Age Groups and Improves Delayed Probe Trial Difference Scores in Middle-Aged Rats

  2017cites this paper
• Treatment of intermittent hypoxia increases phosphorylated tau in the hippocampus via biological processes common to aging

  2017influential citation
• Chronic purple grape juice consumption induces age-dependent changes on cognitive function in elderly women

  2017influential citation
• Identifying molecular mediators of environmentally enhanced neurogenesis

  2017cites this paper
• Widespread cerebellar transcriptome changes in Ts65Dn Down syndrome mouse model after lifelong running.

  2016cites this paper
• Functionally Diverse NK-Like T Cells Are Effectors and Predictors of Successful Aging

  2016cites this paper
• Voluntary wheel running reduces voluntary consumption of ethanol in mice: identification of candidate genes through striatal gene expression profiling

  2016influential citation
• Can Exercise Ameliorate Aromatase Inhibitor-Induced Cognitive Decline in Breast Cancer Patients?

  2016cites this paper
• Cerebellum Transcriptome of Mice Bred for High Voluntary Activity Offers Insights into Locomotor Control and Reward-Dependent Behaviors

  2016cites this paper
• Efectos del envejecimiento en la maduración e integración funcional de células granulares nacidas en el hipocampo adulto

  2015cites this paper
• Effects of Microglia on Neurogenesis

  2015cites this paper
• Physical activity and cognitive vitality.

  2015cites this paper
• Running rescues a fear-based contextual discrimination deficit in aged mice

  2015influential citation
• Mouse models rarely mimic the transcriptome of human neurodegenerative diseases: A systematic bioinformatics-based critique of preclinical models.

  2015cites this paper
• Some hormone, cytokine and chemokine levels that change across lifespan vary by cognitive status in male Fischer 344 rats.

  2015cites this paper
• Alleviation of central accumulation of amyloid-beta and prevention of cognitive dysfunction following peripheral inflammation

  2014cites this paper
• Microglial modulation as a mechanism behind the promotion of central nervous system well‐being by physical exercise

  2014cites this paper
• A bout of voluntary running enhances context conditioned fear, its extinction, and its reconsolidation

  2014cites this paper
• De-regulation of gene expression and alternative splicing affects distinct cellular pathways in the aging hippocampus

  2014cites this paper
• Addiction and reward-related genes show altered expression in the postpartum nucleus accumbens

  2014cites this paper
• The Value of Exercise Training for Prevention and Complementary Treatment of Brain Aging and Neurodegeneration

  2014cites this paper
• DNA microarray‐based analysis of voluntary resistance wheel running reveals novel transcriptome leading robust hippocampal plasticity

  2014cites this paper
• Preconditioned muscle-derived mesenchymal stem cells revitalize growth and function in aged skeletal muscle

  2014cites this paper
• Caractérisation des facteurs de régulation de la prolifération des cellules souches neurales dans le cerveau adulte

  2013influential citation
• Adult hippocampal neurogenesis inversely correlates with microglia in conditions of voluntary running and aging

  2013cites this paper
• Daily exercise improves memory, stimulates hippocampal neurogenesis and modulates immune and neuroimmune cytokines in aging rats.

  2013cites this paper
• Exercise reduces activation of microglia isolated from hippocampus and brain of aged mice

  2013cites this paper
• Mammalian alpha beta hydrolase domain (ABHD) proteins: Lipid metabolizing enzymes at the interface of cell signaling and energy metabolism.

  2013cites this paper
• Dependence-induced changes in opioid-receptor gene expression

  2013cites this paper
• Enhancement of cognitive function in models of brain disease through environmental enrichment and physical activity.

  2013cites this paper
• Long-term running alleviates some behavioral and molecular abnormalities in Down syndrome mouse model Ts65Dn.

  2013cites this paper
• Bridging animal and human models of exercise-induced brain plasticity.

  2013cites this paper
• Exercise induces age-dependent changes on epigenetic parameters in rat hippocampus: a preliminary study.

  2013cites this paper
• Activity-dependent, stress-responsive BDNF signaling and the quest for optimal brain health and resilience throughout the lifespan.

  2013influential citation
• Long-Term Exercise Modulates Hippocampal Gene Expression in Senescent Female Mice

  2013cites this paper
• The Ets Transcription Factor EHF as a Regulator of Cornea Epithelial Cell Identity*

  2013cites this paper
• Identity Regulator of Cornea Epithelial Cell The Ets Transcription Factor EHF as a Gene Regulation :

  2013cites this paper
• AQP9: a novel target for bone loss induced by microgravity.

  2012cites this paper
• Neurobiological studies of fatigue.

  2012cites this paper
• Aging microglia: relevance to cognition and neural plasticity.

  2012cites this paper
• Brain Aging: A Critical Reappraisal

  2012cites this paper
• Age-related cognitive decline: Can neural stem cells help us?

  2012cites this paper
• Wnt Signaling in Neurogenesis during Aging and Physical Activity

  2012cites this paper
• Smith ScholarWorks Smith ScholarWorks

  year unknowncites this paper