title: Exogenous Hsp70 delays senescence and improves cognitive function in aging mice.
abstract: Molecular chaperone Heat Shock Protein 70 (Hsp70) plays an important protective role in various neurodegenerative disorders often associated with aging, but its activity and availability in neuronal tissue decrease with age. Here we explored the effects of intranasal administration of exogenous recombinant human Hsp70 (eHsp70) on lifespan and neurological parameters in middle-aged and old mice. Long-term administration of eHsp70 significantly enhanced the lifespan of animals of different age groups. Behavioral assessment after 5 and 9 mo of chronic eHsp70 administration demonstrated improved learning and memory in old mice. Likewise, the investigation of locomotor and exploratory activities after eHsp70 treatment demonstrated a significant therapeutic effect of this chaperone. Measurements of synaptophysin show that eHsp70 treatment in old mice resulted in larger synaptophysin-immunopositive areas and higher neuron density compared with control animals. Furthermore, eHsp70 treatment decreased accumulation of lipofuscin, an aging-related marker, in the brain and enhanced proteasome activity. The potential of eHsp70 intranasal treatment to protect synaptic machinery in old animals offers a unique pharmacological approach for various neurodegenerative disorders associated with human aging.
authors.affiliation: Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow, 142290, Russia;
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Bobkova
authors.affiliation: Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow, 142290, Russia; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia;
authors.forename: Mikhail
authors.initials: M
authors.lastname: Evgen'ev
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia;
authors.forename: David G
authors.initials: DG
authors.lastname: Garbuz
authors.affiliation: Institute of Developmental Biology, Moscow, 124319, Russia;
authors.forename: Alexei M
authors.initials: AM
authors.lastname: Kulikov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia;
authors.forename: Alexei
authors.initials: A
authors.lastname: Morozov
authors.affiliation: Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow, 142290, Russia;
authors.forename: Alexander
authors.initials: A
authors.lastname: Samokhin
authors.affiliation: Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow, 142290, Russia;
authors.forename: Dmitri
authors.initials: D
authors.lastname: Velmeshev
authors.affiliation: Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow, 142290, Russia;
authors.forename: Natalia
authors.initials: N
authors.lastname: Medvinskaya
authors.affiliation: Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow, 142290, Russia;
authors.forename: Inna
authors.initials: I
authors.lastname: Nesterova
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016; Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016.
authors.forename: Andrew
authors.initials: A
authors.lastname: Pollock
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016; Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016 evgeny.nudler@nyumc.org.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Nudler
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism; D008136:Longevity / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D009043:Motor Activity / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D008062:Lipofuscin; D021122:Protein Subunits; D011994:Recombinant Proteins; D016708:Synaptophysin; D046988:Proteasome Endopeptidase Complex
keywords: Hsp70; aging; memory; proteasome; therapy