ArticleAging cell2016
Regional metabolic heterogeneity of the hippocampus is nonuniformly impacted by age and caloric restriction.
Article in Aging cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
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- Targeting the Electron Transport System for Enhanced Longevity.Biomolecules · 2025Review
- Neuron-specific isoform of PGC-1α regulates neuronal metabolism and brain aging.Nature communications · 2025Article
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- Maternal Calorie Restriction Induces a Transcriptional Cytoprotective Response in Embryonic Liver Partially Dependent on Nrf2.Antioxidants (Basel, Switzerland) · 2022Article
- The Role of Astrocytes in the Mechanism of Perioperative Neurocognitive Disorders.Brain sciences · 2022Article
- Age-Dependent Decline of NADNutrients · 2021Review
- Article
- Review
- Does calorie restriction improve cognition?IBRO reports · 2020Article
- Age-Related Cognitive Impairment: Role of Reduced Synaptobrevin-2 Levels in Deficits of Memory and Synaptic Plasticity.The journals of gerontology. Series A, Biological sciences and medical sciences · 2020Article
- Senescent neurophysiology: CaNeurobiology of learning and memory · 2019Review
- Real-Time Monitoring of Exosome Enveloped-AAV Spreading by Endomicroscopy Approach: A New Tool for Gene Delivery in the Brain.Molecular therapy. Methods & clinical development · 2019Article
- An expanding GSK3 network: implications for aging research.GeroScience · 2019Review
- Age- and AD-related redox state of NADH in subcellular compartments by fluorescence lifetime imaging microscopy.GeroScience · 2019Article
- Fornix white matter glia damage causes hippocampal gray matter damage during age-dependent limbic decline.Scientific reports · 2019Article
- Non-human primates as a model for aging.Biochimica et biophysica acta. Molecular basis of disease · 2018Review
- GSK3β Regulates Brain Energy Metabolism.Cell reports · 2018Article
- Aging and caloric restriction impact adipose tissue, adiponectin, and circulating lipids.Aging cell · 2017Article
- Loss of protohaem IX farnesyltransferase in mature dentate granule cells impairs short-term facilitation at mossy fibre to CA3 pyramidal cell synapses.The Journal of physiology · 2017Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The hippocampus is critical for cognition and memory formation and is vulnerable to age-related atrophy and loss of function. These phenotypes are attenuated by caloric restriction (CR), a dietary intervention that delays aging. Here, we show significant regional effects in hippocampal energy metabolism that are responsive to age and CR, implicating metabolic pathways in neuronal protection. In situ mitochondrial cytochrome c oxidase activity was region specific and lower in aged mice, and the impact of age was region specific. Multiphoton laser scanning microscopy revealed region- and age-specific differences in nicotinamide adenine dinucleotide (NAD)-derived metabolic cofactors. Age-related changes in metabolic parameters were temporally separated, with early and late events in the metabolic response to age. There was a significant regional impact of age to lower levels of PGC-1α, a master mitochondrial regulator. Rather than reversing the impact of age, CR induced a distinct metabolic state with decreased cytochrome c oxidase activity and increased levels of NAD(P)H. Levels of hippocampal PGC-1α were lower with CR, as were levels of GSK3β, a key regulator of PGC-1α turnover and activity. Regional distribution and colocalization of PGC-1α and GSK3β in mouse hippocampus was similar in monkeys. Furthermore, the impact of CR to lower levels of both PGC-1α and GSK3β was also conserved. The studies presented here establish the hippocampus as a highly varied metabolic environment, reveal cell-type and regional specificity in the metabolic response to age and delayed aging by CR, and suggest that PGC-1α and GSK3β play a role in implementing the neuroprotective program induced by CR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.