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Exogenous Hsp70 delays senescence and improves cognitive function in aging mice
Open accessAbstract
Significance: The compromised ability of neurons to express Heat Shock Protein 70 (Hsp70) correlates with aging-related neurodegeneration. In this study, middle-aged and old mice were treated chronically until death with human Hsp70 delivered intranasally and were investigated after 5 or 9 mo of Hsp70 treatment for their cognitive ability and synaptic density. Hsp70 treatment extended mean and maximum lifespan, improved learning and memory in old animals, increased curiosity, decreased anxiety, and helped maintain synaptic structures that degrade with age. These results provide evidence that intranasal administration of Hsp70 could have significant therapeutic potential in preserving brain tissue and memory for middle-age and old individuals and could be applied either as unique self-contained treatment or in combination with other pharmacological therapies.
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“Intranasal application of recombinant human HSP70 protein to mice enhances proteasome activity, reduces brain lipofuscin levels, enhances cognitive functions and extends lifespan 93 .”
From Hallmarks of aging: An expanding universe (2023) · cites this paper as [93]
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“There are 4 core genes significantly downregulated in astrocytes in all brain regions, 2 of which are heat shock proteins (Figure 2G), protective molecular chaperones that prevent protein damage (Bobkova et al., 2015).”
From The aging astrocyte transcriptome from multiple regions of the mouse brain. (2018) · cites this paper as Bobkova et al., 2015
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Metadata
- Authors
- Bobkova, N. V., Evgen’ev, M., Garbuz, D. G., Kulikov, A. M., Morozov, A., Samokhin, A., Velmeshev, D., Medvinskaya, N., Nesterova, I., Pollock, A., & Nudler, E.
- Affiliations
- Russian Academy of Sciences (RU)
- Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow, 142290, Russia;
- Engelhardt Institute of Molecular Biology (RU)
- Institute of Developmental Biology, Moscow, 124319, Russia;
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia;
- Howard Hughes Medical Institute (US)
- Corresponding author
- Nudler, Evgeny
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-12-14
- Volume
- 112
- Issue
- 52
- Pages
- 16006-16011
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4702952
- OpenAlex
- W2270421926
- Cited by
- 118
- References
- 59
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 11 · 2023: 10 · 2022: 8 · 2021: 12 · 2020: 7 · 2019: 17 · 2018: 16 · 2017: 6 · 2016: 6
- FWCI
- 4.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute (NA)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Antioxidants, Aging, Portulaca oleracea
- Keywords
- HSP70, intranasal administration, aging, lifespan extension, cognitive function, learning and memory, neurodegeneration, synaptophysin, lipofuscin accumulation, proteasome activity, synaptic integrity, neuroprotection
- MeSH terms
- Aging, Animals, Brain, Cognition, Exploratory Behavior, Humans, Lipofuscin, Longevity, Male, Memory, Mice, Inbred Strains, Microscopy, Fluorescence, Motor Activity, Recombinant Proteins, Blotting, Western, Synaptophysin, Maze Learning, HSP70 Heat-Shock Proteins, Protein Subunits, Proteasome Endopeptidase Complex
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