LIFE SCIENCE

New research reveals that the resurrection of archaea drives brain aging


On June 1, Liu Guanghui’s research group and collaborators published an article online in Cell Reports, revealing for the first time that endogenous retrovirus revival caused by wear of the nuclear fiber layer can be used as a driving force and biomarker of human frontal lobe aging, which provides new clues for the scientific assessment and early warning of brain aging and the prevention and treatment of related neurodegenerative diseases.

Mechanism and intervention strategy of endogenous retroviral revival induced by lamellar wear to drive neuronal aging

The frontal lobe is an important part of the brain involved in cognitive and behavioral control. At present, the understanding of the cellular and molecular mechanisms that drive frontal senescence in primates is still very limited, which seriously restricts the clinical evaluation and intervention strategy development of brain aging and neurodegenerative diseases.

Through the systematic analysis of the aging process of the frontal lobe of cynomolgus monkeys, the researchers found that the wear of the nuclear fiber layer and the loss of heterochromatin in senescent neurons can lead to the transcriptional activation of endogenous retrovirus (ERV) transcription in the genome and the expression of viral proteins, which in turn form viral particles. In the cytoplasm of senescent neurons, the reverse transcript of ERV induces the aging and inflammatory response of neurons by activating the cGAS-STING natural immune pathway.

The researchers also established an in vitro senescence model of neurons derived from human embryonic stem cells, and based on this, verified that the deletion of lamin LaminB1 and LaminB2 and their induced ERV revival are the initiating events in the neuronal aging cascade. Further, the researchers achieved inhibition of human neuronal aging by developing a siRNA gene silencing system based on targeting ERV or cGAS pathways.

The study also found that the anti-AIDS drug abacavir can effectively inhibit the aging of human neurons by inhibiting ERV reverse transcriptase. In addition, elderly mice with oral abacavir also showed delayed aging of frontal lobe neurons and improved cognitive performance.

Qu Jing, co-corresponding author of the paper and researcher of the Institute of Zoology, introduced that the research system revealed a new molecular pathway that mediates frontal aging and cognitive decline in primates, provides a new biomarker for the scientific evaluation and early warning of human brain aging and neurodegenerative diseases, and lays a theoretical foundation for the development of targeted drugs to intervene in brain aging and neurodegenerative diseases. (Source: Liu Runan, China Science News)

Related paper information:https://doi.org/10.1016/j.celrep.2023.112593



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