Longevity and transposon defence, the case of termite queens

生物体衰老，但它们以不同的速度衰老。是什么导致了衰老，这是一个对科学家和公众都具有根本重要性的重大问题。对模式生物的研究，如线虫、果蝇或小鼠的研究，揭示了对衰老机制的重要认识。然而，最近的研究，这些r-选择实验室物种以外的要求，以解决自然条件下的老化和不同的生活史的物种。蜜蜂、蚂蚁和白蚁等社会性昆虫是研究衰老的新途径。在一个群体中，具有相同遗传背景的巢友在寿命上可以相差两个数量级。虽然繁殖的蚁后（在白蚁中也是国王）可以活20多年，但工蚁的寿命通常只有几个月。除了社会性昆虫之外，只有在差异很大的物种之间才能发现类似的衰老速度差异，比较起来要困难得多。通过研究一种高度社会化的白蚁，Macrotermes bellicosus，我们最近发现了一种通常保护动物生殖系免受衰老的机制，这可能解释了种姓之间的寿命差异。老白蚁工人的特点是高表达的转座因子（TEs）。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。皇后和国王似乎通过皮尔纳（PIWI相互作用RNA）途径来保护免受TE的影响，该途径通常保护动物的种系免受TE活性的影响。虽然这一途径的基因在蚁后和蚁王中一直高度表达，但它们在年老的工蚁中表达下调。在目前的项目中，我们的目标是更详细地分析这种TE-piRNA机制，以测试功能链接。在目标1中，我们将提高研究物种的测序基因组的质量，以获得高质量的基因组，特别是适合于TE分析。目的2主要旨在测试TE活性的后果，即它们是否导致基因组内不同位点的TE转座。我们将在老年工人的两个组织中测试这一点。最后，在目标3中，我们将通过对M中的必需皮尔纳基因进行RNA干扰实验来测试皮尔纳表达与（i）TE活性、（ii）TE转座和（iii）寿命之间的因果关系。好战的女王我们的项目将有助于更好地了解衰老和长寿的原因，特别是因为TE活性和皮尔纳通路最近被老年学家讨论为衰老的主要机制原因，而这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.