反转录转座子是一类可自复制并插入新基因组位置的可移动元件。跨物种研究表明，体细胞内反转录转座子的移动可能导致衰老过程中细胞和组织的功能衰退。反转录转座子广泛存在于各种细胞类型中，并且新的插入与肿瘤形成相关。然而，在正常衰老过程中新的反转录转座子插入的程度及其对细胞和动物功能的影响仍需进一步研究。本文采用果蝇的单核全基因组测序方法直接测试转座子插入是否随着体细胞老化而增加，结果表明在胸部核和间接飞行肌核中，并未发现转座子插入数量随年龄增加而显著增加。尽管如此，通过减少两种不同反转录转座子（412和Roo）的表达，延长了寿命，但并未改变应激抵抗等健康指标。这表明，转座子表达而不是插入在调节寿命方面发挥了关键作用。转录组分析揭示了412和Roo敲除果蝇的基因表达类似，提示编码蛋白降解和免疫功能的基因的变化可能是导致寿命变化的潜在原因。综上所述，我们的数据揭示了反转录转座子表达与衰老之间的明确关联。© 作者（2023），由牛津大学出版社代表遗传学会。保留所有权利。如需授权，请发送电子邮件至：journals.permissions@oup.com。

Retrotransposons are a class of transposable elements capable of self-replication and insertion into new genomic locations. Across species, the mobilization of retrotransposons in somatic cells has been suggested to contribute to the cell and tissue functional decline that occurs during aging. Retrotransposons are broadly expressed across cell types, and de novo insertions have been observed to correlate with tumorigenesis. However, the extent to which new retrotransposon insertions occur during normal aging and their effect on cellular and animal function remains understudied. Here we use a single nucleus whole genome sequencing approach in Drosophila to directly test whether transposon insertions increase with age in somatic cells. Analyses of nuclei from thoraces and indirect flight muscles using a newly developed pipeline, Retrofind, revealed no significant increase in the number of transposon insertions with age. Despite this, reducing the expression of two different retrotransposons, 412 and Roo, extended lifespan, but did not alter indicators of health such as stress resistance. This suggests a key role for transposon expression and not insertion in regulating longevity. Transcriptomic analyses revealed similar changes to gene expression in 412 and Roo knockdown flies and highlighted changes to genes involved in proteolysis and immune function as potential contributors to the observed changes in longevity. Combined, our data show a clear link between retrotransposon expression and aging.© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.