Centenarian hippocampus displays high levels of astrocytic metallothioneins

Centenarian hippocampus displays high levels of astrocytic metallothioneins

The hippocampus is a brain area linked to cognition. The mechanisms that maintain cognitive activity in humans are poorly understood. Centenarians display extreme longevity which is generally accompanied by better quality of life, lower cognitive impairment, and reduced incidence of pathologies incl...

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Published in:Aging cell Vol. 23; no. 8; pp. e14201 - n/a
Main Authors: Saenz‐Antoñanzas, Ander, Muñoz‐Culla, Maider, Rigo, Piero, Ruiz‐Barreiro, Leire, Moreno‐Valladares, Manuel, Alberro, Ainhoa, Cruces‐Salguero, Sara, Arroyo‐Izaga, Marta, Arranz, Amaia M., Otaegui, David, Guillemot, François, Matheu, Ander
Format: Journal Article
Language:English
Published: England John Wiley & Sons, Inc 01-08-2024
John Wiley and Sons Inc
Subjects:
Age
Aging
Alzheimer's disease
Astrocytes
Biobanks
Brain
Centenarians
Cognitive ability
Dementia
Gene expression
Geriatrics
Hippocampus
Homeostasis
Isoforms
Metabolism
metallothioneins
Nervous system
Neurodegenerative diseases
Neurons
Oldest old people
Quality of life
transcriptomic
Transcriptomics
astrocytes
metallothioneins
hippocampus
transcriptomic
centenarians
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Summary:The hippocampus is a brain area linked to cognition. The mechanisms that maintain cognitive activity in humans are poorly understood. Centenarians display extreme longevity which is generally accompanied by better quality of life, lower cognitive impairment, and reduced incidence of pathologies including neurodegenerative diseases. We performed transcriptomic studies in hippocampus samples from individuals of different ages (centenarians [≥97 years], old, and young) and identified a differential gene expression pattern in centenarians compared to the other two groups. In particular, several isoforms of metallothioneins (MTs) were highly expressed in centenarians. Moreover, we identified that MTs were mainly expressed in astrocytes. Functional studies in human primary astrocytes revealed that MT1 and MT3 are necessary for their homeostasis maintenance. Overall, these results indicate that the expression of MTs specifically in astrocytes is a mechanism for protection during aging. Higher levels of MT1 and MT3 are detected in hippocampus of very old individuals (over 90) compared with old and young individuals. MTs colocalize with astrocytic markers.
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ISSN:1474-9718
1474-9726
1474-9726
DOI:10.1111/acel.14201