Centenarian hippocampus displays high levels of astrocytic metallothioneins.
Ander Saenz-AntoñanzasMaider Muñoz-CullaPiero RigoLeire Ruiz-BarreiroManuel Moreno-ValladaresAinhoa AlberroSara Cruces-SalgueroMarta Arroyo-IzagaAmaia M ArranzDavid OtaeguiFrançois GuillemotAnder MatheuPublished in: Aging cell (2024)
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.
Keyphrases
- cognitive impairment
- gene expression
- cerebral ischemia
- prefrontal cortex
- single cell
- endothelial cells
- white matter
- case control
- poor prognosis
- dna methylation
- climate change
- risk factors
- mild cognitive impairment
- induced pluripotent stem cells
- brain injury
- subarachnoid hemorrhage
- rna seq
- resting state
- binding protein
- middle aged
- multiple sclerosis
- pluripotent stem cells