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Updated: Jul 28, 2025

Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence
Published on: January 17, 2025
Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging
Hui Zhang1, Jiaming Li2, Yang Yu3
1State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Abstract:
The primate frontal lobe (FL) is sensitive to aging-related neurocognitive decline. However, the aging-associated molecular mechanisms remain unclear. Here, using physiologically aged non-human primates (NHPs), we depicted a comprehensive landscape of FL aging with multidimensional profiling encompassing bulk and single-nucleus transcriptomes, quantitative proteome, and DNA methylome. Conjoint analysis across these molecular and neuropathological layers underscores nuclear lamina and heterochromatin erosion, resurrection of endogenous retroviruses (ERVs), activated pro-inflammatory cyclic GMP-AMP synthase (cGAS) signaling, and cellular senescence in post-mitotic neurons of aged NHP and human FL. Using human embryonic stem-cell-derived neurons recapitulating cellular aging in vitro, we verified the loss of B-type lamins inducing resurrection of ERVs as an initiating event of the aging-bound cascade in post-mitotic neurons. Of significance, these aging-related cellular and molecular changes can be alleviated by abacavir, a nucleoside reverse transcriptase inhibitor, either through direct treatment of senescent human neurons in vitro or oral administration to aged mice.
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