Artificially stimulating retrotransposon activity increases mortality and accelerates a subset of aging phenotypes in Drosophila.
Artificially stimulating retrotransposon activity increases mortality and accelerates a subset of aging phenotypes in Drosophila.
复制标题
DOI：
10.7554/elife.80169
复制
发表时间：
2022-08-18
期刊：
影响因子：
7.7
通讯作者：
Marr, Michael T.
中科院分区：
文献类型：
--
作者：
Rigal, Joyce;Anduaga, Ane Martin;Bitman, Elena;Rivellese, Emma;Kadener, Sebastian;Marr, Michael T.
转座元件 (TE) 是可移动的 DNA 序列，随着动物年龄的增长，其转录活性会变得活跃。 TE 活性是否只是异染色质分解的副产品，或者是否有助于衰老过程，目前尚不清楚。在这里，我们将 TE 吉普赛人置于 UAS GAL4 系统的控制下，以模拟衰老过程中的 TE 激活。我们发现，TE 活性增加会缩短雄性果蝇的寿命。该效果仅在中年动物中明显。在幼龄动物中并未观察到死亡率的增加。完整的逆转录酶对于寿命的缩短是必要的，这暗示着 DNA 介导的过程。活跃的吉普赛果蝇寿命的缩短伴随着一部分衰老表型的加速。 TE 活性增加对氧化应激的敏感性并促进昼夜节律的下降。 Forkhead-box O 家族 (FOXO) 应激反应转录因子的过度表达可以部分缓解 TE 活性增加对寿命的不利影响。我们的结果提供了证据，表明活性 TE 在衰老过程中可以充当效应器，并表明 dFOXO 在促进黑腹果蝇寿命方面具有潜在的新作用。
Transposable elements (TEs) are mobile sequences of DNA that can become transcriptionally active as an animal ages. Whether TE activity is simply a by-product of heterochromatin breakdown or can contribute toward the aging process is not known. Here, we place the TE gypsy under the control of the UAS GAL4 system to model TE activation during aging. We find that increased TE activity shortens the life span of male Drosophila melanogaster. The effect is only apparent in middle-aged animals. The increase in mortality is not seen in young animals. An intact reverse transcriptase is necessary for the decrease in life span, implicating a DNA-mediated process in the effect. The decline in life span in the active gypsy flies is accompanied by the acceleration of a subset of aging phenotypes. TE activity increases sensitivity to oxidative stress and promotes a decline in circadian rhythmicity. The overexpression of the Forkhead-box O family (FOXO) stress response transcription factor can partially rescue the detrimental effects of increased TE activity on life span. Our results provide evidence that active TEs can behave as effectors in the aging process and suggest a potential novel role for dFOXO in its promotion of longevity in D. melanogaster.