Chinese scholars have made progress in the research of aging mechanism and intervention

Figure Mechanism and intervention strategies of endogenous archaeal virus revival driving aging

With the support of the National Natural Science Foundation of China (approval numbers: 81921006, 82125011, 92149301, 92168201, 91949209, 92049116), researchers Liu Guanghui and Qu Jing of the Institute of Zoology, Chinese Academy of Sciences and Zhang Weiqi, a researcher at the Beijing Institute of Genomics, Chinese Academy of Sciences, have made progress
in the research of aging mechanism and intervention 。 The research results, titled "Resurrection of endogenous retroviruses during aging reinforces senescence", were published online in the journal
Cell on January 6, 2023.
Link to paper: https://doi.
org/10.
1016/j.
cell.
2022.
12.
017
.

In the history of human evolution, viruses and humans have evolved
in tandem.
Among them, endogenous retrovirus (ERV) elements are relics of ancient retrovirus invasion and integration into the human genome millions of years ago, accounting for about
8% of the human genome sequence.
In the later stages of embryonic development, ERV elements in the genome are usually in a state
of silent inhibition due to epigenetic and other factors.
Aging is the biggest risk factor for human chronic diseases, and cellular aging is an important cause
for the occurrence and development of aging and various aging-related diseases.
But during aging, it is unknown
whether these ERV elements sleeping in the human genome can escape the host's surveillance and be reawakened.
If awakened, what is the role of ERV elements in aging and its mechanisms? Can ERVs be used as a target to provide new strategies for assessing and intervening in aging-related diseases? These key scientific questions need to be addressed
urgently.

Based on the self-established systematic aging research system, the team comprehensively used multidimensional epigenome, transcriptional targeted manipulation, single-molecule imaging, virology, immunology, chemical biology and molecular pathology to reveal the process of epigenetic activation of ERV elements to promote their transcription, translation and packaging into virus-like particles
。 On the one hand, the reverse transcription products of ERV in senescent cells induce cellular senescence and inflammation by activating the cGAS-STING natural immune pathway; On the other hand, ERV virus particles released by senescent cells can effectively transmit and amplify aging signals between cells, tissues and even organs through paracrine or humor-mediated methods, promoting the aging
of young cells 。 Further, through targeted interventions in different life cycle links such as ERV latency, resurrection, and cell-to-cell transmission, researchers proposed a variety of strategies to effectively inhibit ERV revival and infection, including CRISPR gene silencing system based on ERV regulatory elements, small molecule drugs targeting reverse transcriptase, neutralizing antibodies targeting viral envelope proteins, etc.
, blocking ERV transcription, reverse transcription, viral cascade infection and other processes, thereby delaying the aging of cells, tissues and even systems (Figure
。

This study systematically revealed that aging-induced resurrection of endogenous retrovirus (AIR-ERV) can be used as the cause and marker of aging in cells, organs and even the body, providing ideas for the evaluation and intervention of
aging-related diseases.