Prof. Guang-hui Liu and his colleagues from the Institute of Zoology and the Beijing Institute of Genomics, Chinese Academy of Sciences, have collaborated to reveal a novel role of APOE in destabilizing heterochromatin and driving senescence in human stem cells, which was published in Nature Aging on March 28th, 2022.
APOE is well known as a classical lipid-transport protein that mediates lipid transport. Despite of accumulating evidence showing that it is closely implicated in Alzheimer's disease, atherosclerosis, and human longevity, the role of APOE in the regulation of aging is largely unknown.
The researchers found that the expression of APOE protein increased in aging human stem cells and that human stem cell senescence was accelerated upon APOE overexpression and attenuated by APOE knockout.
Mechanistically, the researchers revealed that nuclear-localized APOE interacted with the nuclear envelope and heterochromatin-associated proteins to promote their degradation via the autophagy-lysosomal pathway, thus facilitating heterochromatin destabilization and contributing to human stem cell senescence.
Last but not least, the researchers also discovered that knockdown of APOE delayed cellular senescence in multiple human cell models.
For the first time, this study uncovers a role of APOE as an epigenetic mediator, expanding our understanding of an entirely new function of APOE in mediating senescence. Collectively, this study provides a potential target with novel mechanistic insights for the development of therapeutic strategies against aging and aging-related disorders.
Figure. Nuclear-localized APOE promotes human stem cell senescence (Image courtesy of Guang-Hui Liu's lab)
28 March 2022 at 16:00 (London time), 28 March 2022 at 11:00 (US Eastern Time)
Institute of Zoology Chinese Academy of Sciences