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Resurrection of endogenous retroviruses during aging reinforces senescence

sasp aging theory senescence retroviruses

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#1 albedo

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Posted 09 January 2023 - 10:33 AM

I found this fascinating:


Liu X, Liu Z, Wu Z, et al. Resurrection of endogenous retroviruses during aging reinforces senescence. Cell. 2023;0(0).


"Whether and how certain transposable elements with viral origins, such as endogenous retroviruses
(ERVs) dormant in our genomes, can become awakened and contribute to the aging process is largely
unknown. In human senescent cells, we found that HERVK (HML-2), the most recently integrated
human ERVs, are unlocked to transcribe viral genes and produce retrovirus-like particles (RVLPs).
These HERVK RVLPs constitute a transmissible message to elicit senescence phenotypes in young
cells, which can be blocked by neutralizing antibodies. The activation of ERVs was also observed in
organs of aged primates and mice as well as in human tissues and serum from the elderly.
Their repression
alleviates cellular senescence and tissue degeneration and, to some extent, organismal aging. These
findings indicate that the resurrection of ERVs is a hallmark and driving force of cellular senescence and tissue


Attached File  retrovirus aging sasp.jpg   133.99KB   0 downloads

"In this study, using various primate and rodent aging models, we
discovered a positive feedback loop between endogenous retrovirus
activation and aging. Our comprehensive analysis unraveled
the causal relationship between HERVK and aging in multiple
and was supported by pioneering studies showing
increased expression of ERVs concomitant with aging in yeast,
fly, and rodent models.73–75 For instance, the activation of gypsy,
a transposable element in Drosophila showing homology with
vertebrate ERVs, was reported in aged flies.76 In addition,
emerging studies suggested a correlation between awakened
ERVs and aging-related disorders, such as rheumatoid arthritis
and neurodegenerative diseases.42,77–81 More importantly, we
successfully employed multiple strategies to block the prosenescence
effect of ERVs, demonstrating the alleviation of aging
defects across cellular models and multiple tissues in vivo.
line with our results, attempts to alleviate neurodegenerative disorders
including amyotrophic lateral sclerosis (ALS) via the inhibition
of HERVK were reported.82,83 Thus, ERVs represent druggable
targets for alleviating aspects of aging and improving
overall organismal health
" (blue mine)

Edited by albedo, 09 January 2023 - 10:57 AM.

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