Cellular Oncology Group, Biodonostia Health Research Institute, San Sebastian, Spain.
Multiple Sclerosis Group, Biodonostia Health Research Institute, San Sebastian, Spain.
Aging Cell. 2024 Aug;23(8):e14201. doi: 10.1111/acel.14201. Epub 2024 May 20.
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.
海马体是与认知相关的大脑区域。人类维持认知活动的机制还不太清楚。百岁老人表现出极端的长寿，通常伴随着更好的生活质量、更低的认知障碍以及包括神经退行性疾病在内的发病减少。我们对来自不同年龄段的个体（百岁老人[≥97 岁]、老年人和年轻人）的海马体样本进行了转录组研究，发现与其他两组相比，百岁老人存在差异表达的基因模式。特别是，几种金属硫蛋白 (MT) 的同工型在百岁老人中高度表达。此外，我们发现 MT 主要在星形胶质细胞中表达。在人类原代星形胶质细胞中的功能研究表明，MT1 和 MT3 对于它们的稳态维持是必需的。总的来说，这些结果表明 MT 特异性在星形胶质细胞中的表达是衰老过程中保护的一种机制。
