Multimodal brain cell atlas across the adult macaque lifespan

Zhang, X., Lai, G., Guo, X., Ma, W., Yuan, Y., Zhang, H., Fan, P., Liu, X., Guo, P., An, J., Li, J., Huang, K., Zuo, J., Wu, L., Shangguan, S., Yu, F., Xiang, Y., Hu, Y., Huang, Y., Lin, Y., He, D., Pan, M., Chen, L., Li, B., Yang, W., Yin, P., Li, S., Zhang, X., Yang, T., Chen, J., Zhong, Q., Lv, Y., Qin, B., Qing, X., Deng, Q., Huang, Y., Liu, C., Han, L., Liu, S., Qin, D., Liu, Z., Zhou, Y., Qiao, L., Li, C., Zhang, Y., Volpe, G., Graf, S., Diks, I. F., Flotho, M., Krol, R. P., Mulder, J., Hutchins, A. P., Keller, A., Maxwell, P. H., Rubinsztein, D. C., Liu, X., Tse, H.-F., Poo, M., Wang, B

BGI Research, Shenzhen 518083, China · biorxiv

Paper

Abstract

High-throughput single-cell omics of non-human primate tissues present a remarkable opportunity to study primate brain aging. Here, we introduce a transcriptomic and chromatin accessibility landscape of 1,985,317 cells from eight brain regions of 13 cynomolgus female monkeys spanning adult lifespan including exceptionally old individuals up to 29-years old. This dataset uncovers dynamic molecular changes in critical brain functions such as synaptic communication and axon myelination, exhibiting a high degree of cell type and brain region specificity. We identify the multicellular networks of the pons and medulla as a previously unrecognized hotspot for aging. Furthermore, comparative analyses with human neurodegeneration datasets highlight both shared and distinct mechanisms contributing to aging and disease. In addition, we uncover transcription factors implicated in monkey brain aging and pinpoint aging-regulated loci linked to longevity and neurodegeneration. This spatiotemporal atlas will advance our understanding of primate brain aging and its broader implications for health and disease.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper presents a comprehensive atlas of molecular changes in the primate brain across the adult lifespan, highlighting mechanisms of aging and neurodegeneration. This research is relevant as it addresses the biological underpinnings of aging and longevity, potentially informing strategies for lifespan extension and understanding age-related diseases.

Author of this paper? Send a correction.