Longevity and transposon defence, the case of termite queens

生物体衰老，但它们衰老的速度不同。是什么导致了衰老，这是一个对科学家和公众都至关重要的重大问题。对模式生物的研究，如秀丽隐杆线虫、黑腹果蝇或小鼠，揭示了衰老机制的重要见解。然而，最近在这些r选择的实验室物种之外的研究被要求解决自然条件下和具有不同生活史的物种的衰老问题。蜜蜂、蚂蚁和白蚁等群居昆虫有望成为衰老研究的新途径。在一个群体中，具有相同遗传背景的同伴在寿命上可能会有两个数量级的差异。虽然繁殖的蚁后（在白蚁中也有蚁王）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类似的衰老速度的巨大差异，在这些物种之间进行比较要困难得多。通过研究一种高度社会化的白蚁——巨白蚁（Macrotermes bellicosus），我们最近发现了一种通常保护动物生殖细胞不衰老的机制，或许可以解释种姓之间的寿命差异。老年白蚁工蚁具有转座因子（te）高表达的特点。这种“跳跃基因”可以干扰基因组的完整性和基因功能，并且它们与包括人类在内的许多动物的衰老有关。女王和国王似乎通过piRNA （piwi相互作用RNA）途径保护动物免受TE活性的侵害。虽然这条通路的基因在女王和国王身上一直高度表达，但在老工人身上却被下调。在当前的项目中，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，我们将提高所研究物种的基因组测序质量，以获得高质量的基因组，特别适合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转位。我们将对老年工人的两种组织进行测试。最后，在目标3中，我们将测试piRNA表达与(i) TE活性、（ii） TE转位和（iii）寿命之间的因果关系，方法是对M. bellicosus queens中一种必需的piRNA基因进行RNA干扰实验。我们的项目将有助于更好地理解衰老和长寿的原因，特别是因为老年学家最近讨论了TE活性和piRNA途径是很大程度上被忽视的衰老的主要机制原因。

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.