Longevity and transposon defence, the case of termite queens

生物体会衰老，但它们的衰老速度不同。对科学家和普通大众来说，是什么导致衰老是一个具有根本性重要性的重大问题。对模式生物的研究，如线虫秀丽线虫、果蝇黑腹果蝇或老鼠，揭示了对衰老机制的重要见解。然而，最近要求在这些r选择的实验室物种之外进行研究，以解决自然条件下的老化问题和具有不同生活史的物种。蜜蜂、蚂蚁和白蚁等群居昆虫有望成为衰老研究的新途径。在一个群体内，拥有相同遗传背景的筑巢伙伴的寿命可能会相差两个数量级。虽然繁殖蚁后(白蚁也是国王)的寿命超过20年，但工蚁的寿命通常只有几个月。在群居昆虫之外，只有在差异很大的物种之间才会发现衰老速度的巨大差异，而这些物种之间的比较要困难得多。通过研究一种高度社会化的白蚁，我们最近发现，一种通常保护动物种系不受衰老影响的机制，可能解释了不同种姓之间的寿命差异。老白蚁工蚁具有高表达转座因子(TES)的特点。这种“跳跃基因”会干扰基因组的完整性和基因功能，它们与包括人类在内的许多动物的衰老有关。女王和国王似乎受到piRNA(PIWI-相互作用RNA)途径的保护，该途径通常保护动物种系免受TE活动的影响。虽然这一途径的基因在王后和国王身上持续高表达，但在老年工蚁中表达下调。在本项目中，我们的目标是更详细地分析这种TE-piRNA机制，以测试功能联系。在目标1中，我们将改进所研究物种的测序基因组的质量，以获得高质量的基因组，特别适合于TE分析。目标2主要是测试TE活性的后果，即它们是否导致基因组内不同位置的TE转座。我们将在老年工人身上测试两种组织。最后，在目标3中，我们将通过对钟乳杆菌皇后体内必需的piRNA基因进行RNA干扰实验，来测试piRNA表达与(I)TE活性、(Ii)TE转座和(Iii)寿命之间的因果关系。我们的项目将有助于更好地了解衰老和长寿的原因，特别是TE活动和piRNA途径最近被老年学家讨论为衰老的主要机制原因，但在很大程度上被忽视了。

Organisms age but they do so at different pace. What causes ageing is a major question of fundamental importance for scientists and the general public alike. Work on model organisms, such as the nematode Caenorhabditis elegans, the fly Drosophila melanogaster, or mice, reveal important insights into the mechanisms underlying ageing. Yet, more recently studies outside these r-selected laboratory species are requested to address ageing under natural conditions and for species with different life histories. Social insects, like the honeybee, ants and termites, are promising new avenues for ageing research. Within a single colony, nestmates that share the same genetic background can differ by two orders of magnitude in lifespan. While the reproducing queens (and in termites also kings) live for more than 20 years, workers often have a lifespan of a few months only. Outside of social insects similar large differences in rates of ageing are only found between widely divergent species, where comparisons are far more difficult. Studying a highly social termite, Macrotermes bellicosus, we recently uncovered that a mechanism, which normally protects the germline of animals against ageing, might explain these longevity differences between castes. Old termite workers were characterized by a high expression of transposable elements (TEs). Such 'jumping genes' can interfere with genome integrity and gene functioning and they have been associated with ageing in many animals, including humans. Queens and kings seem to be protected against TEs by the piRNA (PIWI-interacting RNA) pathway that normally protects the germline of animals against TE activity. While genes for this pathway were constantly highly expressed in queens and kings, they were downregulated in old workers. In the current project, we aim to analyse this TE-piRNA mechanism in more detail to test functional links. In Objective 1 we will improve the quality of the sequenced genome of the study species to obtain a high quality genome, especially suitable for TE analyses. Objective 2 mainly aims at testing the consequences of TE activity, namely whether they result in TE transposition at different sites within the genome. We will test this for two tissues in old workers. Finally, in Objective 3 we will test for a causal relationship between piRNA expression and (i) TE activity, (ii) TE transposition, and (iii) longevity by performing a RNA interference experiment against an essential piRNA gene in M. bellicosus queens. Our project will contribute towards a better understanding of the causes of ageing and longevity, especially as TE activity and the piRNA pathway have been recently discussed by gerontologists to be a major mechanistic cause of ageing that has largely been neglected.