Hippocampal gene expression patterns linked to late-life physical activity oppose age and AD-related transcriptional decline.
Adult
Aged
Aged, 80 and over
Aging
/ genetics
Alzheimer Disease
/ genetics
Axons
/ physiology
Cognition
Energy Metabolism
/ genetics
Exercise
/ physiology
Gene Expression
Hippocampus
/ metabolism
Humans
Microarray Analysis
Middle Aged
Mitochondria
/ metabolism
Neuronal Plasticity
/ genetics
Synaptic Vesicles
/ genetics
Young Adult
Axon
Exercise
Microarray
Mitochondria
Myelin
Plasticity
Synaptic vesicle trafficking
White matter
Journal
Neurobiology of aging
ISSN: 1558-1497
Titre abrégé: Neurobiol Aging
Pays: United States
ID NLM: 8100437
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
07
02
2018
revised:
16
01
2019
accepted:
12
02
2019
pubmed:
31
3
2019
medline:
10
7
2019
entrez:
31
3
2019
Statut:
ppublish
Résumé
Exercise has emerged as a powerful variable that can improve cognitive function and delay age-associated cognitive decline and Alzheimer's disease (AD); however, the underlying mechanisms are poorly understood. To determine if protective mechanisms may occur at the transcriptional level, we used microarrays to investigate the relationship between physical activity levels and gene expression patterns in the cognitively intact aged human hippocampus. In parallel, hippocampal gene expression patterns associated with aging and AD were assessed using publicly available microarray data profiling hippocampus from young (20-59 years), cognitively intact aging (73-95 years) and age-matched AD cases. To identify "anti-aging/AD" transcription patterns associated with physical activity, probesets significantly associated with both physical activity and aging/AD were identified and their directions of expression change in each condition were compared. Remarkably, of the 2210 probesets significant in both data sets, nearly 95% showed opposite transcription patterns with physical activity compared with aging/AD. The majority (>70%) of these anti-aging/AD genes showed increased expression with physical activity and decreased expression in aging/AD. Enrichment analysis of the anti-aging/AD genes showing increased expression in association with physical activity revealed strong overrepresentation of mitochondrial energy production and synaptic function, along with axonal function and myelin integrity. Synaptic genes were notably enriched for synaptic vesicle priming, release and recycling, glutamate and GABA signaling, and spine plasticity. Anti-aging/AD genes showing decreased expression in association with physical activity were enriched for transcription-related function (notably negative regulation of transcription). These data reveal that physical activity is associated with a more youthful profile in the hippocampus across multiple biological processes, providing a potential molecular foundation for how physical activity can delay age- and AD-related decline of hippocampal function.
Identifiants
pubmed: 30927700
pii: S0197-4580(19)30059-4
doi: 10.1016/j.neurobiolaging.2019.02.012
pmc: PMC6901108
mid: NIHMS1054644
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
142-154Subventions
Organisme : NINDS NIH HHS
ID : R01 NS078009
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG034667
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG000538
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG017917
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016573
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA062203
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG051807
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG057558
Pays : United States
Informations de copyright
Published by Elsevier Inc.
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