![DEGs that are involved in TE silencing according to results for D. melanogaster. (A) Shown is a simplified version of the ping-pong amplification cycle [after Czech and Hannon (24)] of the piRNA pathway, which is involved in silencing TEs in the germline of animals. Ago3 with its sense piRNA recognizes and cleaves piRNA cluster transcripts, which are loaded into Aub1, probably assisted by a Tudor protein and Qin, which prevents Aub1/Aub1 pairings. Maturation of piRNAs involves several proteins, including Mino, Zuc, Papi, and Hen1, and results in mature antisense piRNA-Aub1 complexes. Methylation by Capsuleen (Csul) is essential for stable Ago3 and Aub proteins (36). These complexes can detect and slice transposon RNAs. The 3′ cleaved product is then loaded in Ago3 and, after modification, the cycle can restart. The expression of the following genes involved in the ping-pong cycle was down-regulated in old major workers compared with young ones (mean ± SEM): (B) aub1 (C) zuc, (D) qin, and (E) csul.](https://www.researchgate.net/publication/325035320/figure/fig2/AS:635485231796224@1528522894001/DEGs-that-are-involved-in-TE-silencing-according-to-results-for-D-melanogaster-A_Q320.jpg)
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Longevity and transposon defense, the case of termite reproductives
Abstract and Figures
Significance
Social insects such as honey bees or termites are promising new models for aging research. In contrast to short-lived models like the fruit fly or mouse, the reproductives of an insect colony have exceptionally long lifespans. This offers important new avenues for gerontology, especially as mechanisms underlying aging are highly conserved among animals. We studied aging in a termite from the wild. Our results suggest that aging in this species, as in other animals, is related to the activity of transposable elements (TEs; also known as “jumping genes”). Yet reproductives seem to be protected by a process that normally silences TEs in the germline of animals. This suggests that natural selection used a mechanism from the germline to protect whole animals.
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... Caste differences in social insects have been associated with differential expression of these pathways (e.g., Chandra et al. 2018;Corona et al. 2007;Libbrecht et al. 2013;Lin, Werle, and Korb 2021;Séité et al. 2022;Yan et al. 2022). In addition, ageing in termites seems to be associated with a breakdown of TE defence and an associated increase in TE activity (Elsner, Meusemann, and Korb 2018;Monroy Kuhn, Meusemann, and Korb 2021;Post et al. 2023). ...
... TEs, and especially the break-down of TE defence, has been associated with ageing in termites (Elsner, Meusemann, and Korb 2018;Monroy Kuhn, Meusemann, and Korb 2021;Post et al. 2023) and other animals (De Cecco et al. 2013;Gorbunova et al. 2021;Sturm, Ivics, and Vellai 2015). We observed an upregulation of TE defence genes following HDAC3 silencing (e.g., Csec_G05156 (Csec-ago2; argonaute2) and Csec-G04420 (E3 SUMO-protein ligase PIAS3)). ...
... HDAC3 silencing was associated with an upregulated TE defence system, indicative of fostered lifespan maintenance. The breakdown of TE defence has been associated with ageing in termites and other animals (e.g., De Cecco et al. 2013;Elsner, Meusemann, and Korb 2018;Sturm, Ivics, and Vellai 2015;Wood et al. 2016;Monroy Kuhn, Meusemann, and Korb 2021;Post et al. 2023). Ago2, a post-transcriptional regulator that facilitates siRNA-and miRNA-mediated mRNA degradation (Tomari, Du, and Zamore 2007), was upregulated after HDAC3 silencing. ...
The role of epigenetics in regulating caste polyphenism in social insects has been debated. Here, we tested the importance of histone de/acetylation processes for the maintenance of queen hallmarks like a high fecundity and a long lifespan. To this end, we performed RNA interference experiments against histone deacetylase 3 ( HDAC3 ) in the termite Cryptotermes secundus . Fat body transcriptomes and chemical communication profiles revealed that silencing of HDAC3 leads to signals indicative of queen hallmarks. This includes fostering of queen signalling, defence against ageing and a reduction of life‐shortening IIS (insulin/insulin‐like growth factor signalling) and endocrine JH (juvenile hormone) signalling via Kr‐h1 (Krüppel‐homologue 1). These observed patterns were similar to those of a protein‐enriched diet, which might imply that histone acetylation conveys nutritional effects. Strikingly, in contrast to solitary insects, reduced endocrine JH signalling had no negative effect on fecundity‐related vitellogenesis in the fat bodies. This suggests an uncoupling of longevity pathways from fecundity in fat bodies, which can help explain queens' extraordinary lifespans combined with high fecundity.
... Termites are the sister group of cockroaches and common models to study eusociality with phenotypically and behaviorally differentiated morphs [95]. In the highly social termite Macrotermes bellicosus, genes related to piRNA biogenesis, including ping-pong factors, were found to be highly expressed in brain transcriptomes [96]. Interestingly, the authors found several of those genes, including aub1, qin, and zuc highly abundant in transcriptomes from heads. ...
... These observations suggested that piRNAs might be active in the termite's brain as an anti-aging mechanism. This hypothesis could explain the long life of queens, which is up to 20 years, compared to workers who live only a few months and have higher TE activity in the brain [96]. ...
PIWI-interacting RNAs (piRNAs) were discovered in the early 2000s and became known for their role in protecting the germline genome against mobile genetic elements. Successively, piRNAs were also detected in the somatic cells of gonads in multiple animal species. In recent years, piRNAs have been reported in non-gonadal tissues in various arthropods, contrary to the initial assumptions of piRNAs being exclusive to gonads. Here, we performed an extensive literature review, which revealed that reports on non-gonadal somatic piRNA expression are not limited to a few specific species. Instead, when multiple studies are considered collectively, it appears to be a widespread phenomenon across arthropods. Furthermore, we systematically analyzed 168 publicly available small RNA-seq datasets from diverse tissues in 17 species, which further supported the bibliographic reports that piRNAs are expressed across tissues and species in Arthropoda.
... TEs continue to spread through the genome throughout an organism's lifetime (25), which may result in fitness costs for long-lived species (13,23,77). Selection should then favor an increase in TE-silencing mechanisms among the eusocial Hymenoptera, whose reproductives have a longer adult lifespan than their solitary counterparts. ...
... A second line of support for the prediction that TE suppression has larger fitness benefits among long-lived organisms than their short-lived relatives comes from patterns of TE suppression in social insect queens. In a species of eusocial termite, microRNAs that interfere with TE expansion throughout the genome were found expressed in long-lived reproductive individuals but not in shorter-lived workers (25). Additionally, in a comparison of PIWI-interacting RNAs (piRNAs) that target TEs in the tissues of Temnothorax rugatulus queens and foragers, there were many more significantly upregulated piRNAs in queens than in foragers (111). ...
Social insects have the highest rates of meiotic recombination among Metazoa, but there is considerable variation within the Hymenoptera. We synthesize the literature to investigate several hypotheses for these elevated recombination rates. We reexamine the long-standing Red Queen hypothesis, considering how social aspects of immunity could lead to increases in recombination. We examine the possibility of positive feedback between gene duplication and recombination rate in the context of caste specialization. We introduce a novel hypothesis that recombination rate may be driven up by direct selection on recombination activity in response to increases in lifespan. Finally, we find that the role of population size in recombination rate evolution remains opaque, despite the long-standing popularity of this hypothesis. Moreover, our review emphasizes how the varied life histories of social insect species provide an effective framework for advancing a broader understanding of adaptively driven variation in recombination rates.
... Research on natural anti-aging in model organisms to find natural compounds with anti-aging effects in their diets may yield breakthroughs. Although traditional model organisms facilitate experiments due to their extreme generational characteristics, their excessively short lives render them unsuitable as samples for this study [29,30]. Social insects share a common set of genetic templates throughout the nesting colony, but reproductive and worker classes differ dramatically in longevity. ...
With the rapid increase in global population aging, the incidence and mortality rates of age-related diseases are rising, becoming a worldwide issue. Therefore, researching and discovering natural compounds with anti-aging properties is crucial. Social insects such as termites exhibit significant differences in lifespan between reproductive and non-reproductive castes. Reproductive castes are exclusively fed by worker termites through trophallaxis, providing a convenient model for the discovery of natural anti-aging compounds. This thesis systematically investigates the trophallactic fluid among different caste members of termite Reticulitermes labralis. A total of 1028 metabolites were identified in the trophallactic fluid, seven of which have been validated in the KEGG database to possess anti-aging functions. This indicates that the trophallactic fluid of termites indeed contains natural compounds that promote longevity. Using the “fishing method”, we successfully screened out potential life-extending compounds, including IDA (trans-3-indoleacrylic acid). Preliminary experimental results showed that IDA influences lifespan by modulating the IIS (insulin/insulin-like growth factor signaling) pathway and the RAS pathway. Notably, the modulation of the IIS pathway by IDA does not require the involvement of foxoa. Our research findings suggest that the extended lifespan of reproductive termites is diet-related and that the lifespan-extending effects of these nutritionally regulated natural compounds are conserved across different taxa.
... This study reveals that reproducing queens and kings can live for decades without a substantial rise in TE expression levels. On the other hand, major workers, with a lifespan of only a few weeks, exhibit an up-regulation of TEs as they age [193]. Recent studies have shown that both calorie restriction (CR) and anti-aging drugs like rapamycin can decrease TE transcript levels, while aging and age-accelerating interventions can also increase TE expression [194]. ...
Aging is a spontaneous and permanent physiological process that leads to declines in tissue and cell functions, along with an increased risk of developing various age-related diseases. The primary driving force associated with aging is the accumulation of damaged genetic material in the cell, such as DNA. DNA damage can be caused by endogenous and exogenous factors, which leads to genome instability, mitochondrial dysfunction, epigenetic modifications, and proteostatic disturb. Another driving force associated with aging is the disruption of cellular metabolism. This disruption is closely linked to alterations in the role of metabolic pathways, including insulin/IGF-1 and mTOR, which regulate crucial cellular processes like cell growth, cell proliferation, and apoptosis. The activation of the insulin/IGF-1 signaling pathway highly promotes cell growth and proliferation, while also inhibits autophagy and increasing ROS production. This ultimately leads to accelerated aging. Another crucial signaling pathway is the mTOR signaling pathway. It is responsible for detecting nutrient availability and controlling cell growth and metabolism. The dysregulation of mTOR function can lead to the development of neurodegenerative diseases, which are characterized by the aggregation of protein. Activation of transposable elements is the other driving force of aging, caused by changes in DNA methylation and the loss of heterochromatin. As a result, this leads to DNA damage, genomic instability, and inflammation. The aim of this review is to elucidate the consequence of DNA damage and other associated factors drive aging.
... Hence, I will summarize only some major findings. TE activity has been associated with caste-specific ageing, where queens and kings seem to be better protected against these jumping genes especially by the PIWI-interacting RNA ( piRNA; see Glossary) defence pathway (Elsner et al., 2018;Monroy Kuhn et al., 2019;Post et al., 2023). In addition, improved protection against oxidative stress by queens and kings might play a role in some termites, but probably not all (Tasaki et al., 2017(Tasaki et al., , 2018(Tasaki et al., , 2021Rau and Korb, 2021;Kramer et al., 2021). ...
Social insects (termites, ants and some bees and wasps) are emerging model organisms of ageing research. In this Commentary, I outline which advantages they offer compared with other organisms. These include the co-occurrence of extraordinarily long-lived, highly fecund queens together with short-lived workers within colonies that share the same genetic background. I then summarize which new insights have been gained so far from social insect studies. Research on social insects has led to the development of a universal mechanistic framework underlying the regulation of ageing and other life-history trade-offs in insects: the TI-J-LiFe network (short for TOR/IIS–juvenile hormone–lifespan/fecundity). Because of its conservative nature, this network can be extended to also incorporate vertebrates. Current data for social insect models suggest that molecular re-wirings along the I-J-Fe (IIS–juvenile hormone–fecundity) axis of the network can explain the concurrent long lifespans and high fecundity of queens. During social evolution, pathways that foster a high fecundity have apparently been uncoupled from mechanisms that shorten lifespan in solitary insects. Thus, fecundity-related vitellogenesis is uncoupled from life-shortening high juvenile hormone (JH)-titres in the honeybee and from insulin/insulin-like growth factor signalling (IIS) activity in ants. In termites, similarly, vitellogenesis seems tissue-specifically unlinked from JH signalling and IIS activity might have lost life-shortening consequences. However, as in solitary animals, the downstream processes (Li of the TI-J-LiFe network) that cause actual ageing (e.g. oxidative stress, transposable element activity, telomere attrition) seem to differ between species and environments. These results show how apparently hard-wired mechanisms underlying life-history trade-offs can be overcome during evolution.
... This study reveals that reproducing queens and kings can live for decades without a substantial rise in TE expression levels. On the other hand, major workers, with a lifespan of only a few weeks, exhibit an up-regulation of TEs as they age (Elsner et al., 2018). Recent studies have shown that both calorie restriction (CR) and anti-aging drugs like rapamycin can decrease TE transcript levels, while aging and age-accelerating interventions can also increase TE expression (Wahl et al., 2021). ...
Aging is a gradual and irreversible physiological process that leads to declines in tissue and cell functions, along with an increased risk of developing various age-related diseases. The primary driving force associated with aging is the accumulation of damaged genetic material in the cell, such as DNA. DNA damage can be caused by endogenous and exogenous factors, which leads to genome instability, mitochondrial dysfunction, epigenetic modifications, and proteostatic disturb. Another driving force associated with aging is the disruption of cellular metabolism. This disruption is closely linked to alterations in the function of metabolic pathways, including insulin/IGF-1 and mTOR, which regulate crucial cellular processes like cell growth, cell proliferation, and apoptosis. The activation of the insulin/IGF-1 signaling pathway highly promotes cell growth and proliferation, while also inhibits autophagy and increasing ROS production. This ultimately leads to accelerated aging. Another crucial signaling pathway is the mTOR signaling pathway. It is responsible for detecting nutrient availability and controlling cell growth and metabolism. The dysregulation of mTOR function can lead to the development of neurodegenerative diseases, which are characterized by the aggregation of protein. Activation of transposable elements is the other driving force of aging, caused by changes in DNA methylation and the loss of heterochromatin. As a result, this leads to DNA damage, genomic instability, and inflammation. The aim of this review is to elucidate the consequence of DNA damage and other associated factors drive aging.
The dream of eternal youth and immortality has always fascinated human societies. Even today, this quest is the source of major financial investments, particularly for the development of anti-ageing drugs. To unravel the mysteries of longevity, scientists have long been observing and quantifying the lifespan of animals. These decades of extensive comparative biology research have documented the extreme diversity of lifespan on Earth and identified key ecological and life history factors driving this diversity and, more recently, molecular pathways that might modulate it. However, the maximum lifespan of a species is far from being an accurate representation of a species’ ageing trajectory, both biologically and demographically. For a given species, the changes in mortality risk over the life course can be complex, and the ageing process is much more accurately described by ageing parameters, such as the age of onset of actuarial senescence and the rate of actuarial senescence. This chapter argues that current research in the comparative biology of ageing should now focus on the diversity of actuarial senescence patterns documented across the tree of life, as well as the species-specific causes of death, to identify key genetic and physiological determinants associated with delayed actuarial senescence or low actuarial senescence rate. Just a few years ago, such research projects would have seemed unrealistic, but the recent development of omics tools, coupled with the increased availability of demographic data for a wide range of species with contrasting life histories, lifestyles and habitats make such exciting comparative analyses now achievable and full of promise.
Kings and queens of termites are endowed with an extraordinary longevity coupled with lifelong fecundity. We recently reported that termite kings and queens display a dramatically increased enzymatic activity and abundance of telomerase in their somatic organs when compared to short‐lived workers and soldiers. We hypothesized that this telomerase activation may represent a noncanonical pro‐longevity function, independent of its canonical role in telomere maintenance. Here, we explore this avenue and investigate whether the presumed noncanonical role of telomerase may be due to alternative splicing of the catalytic telomerase subunit TERT and whether the subcellular localization of TERT isoforms differs among organs and castes in the termite Prorhinotermes simplex . We empirically confirm the expression of four in silico predicted splice variants ( psTERT1‐A , psTERT1‐B , psTERT2‐A , psTERT2‐B ), defined by N‐terminal splicing implicating differential localizations, and C‐terminal splicing giving rise to full‐length and truncated isoforms. We show that the transcript proportions of the psTERT are caste‐ and tissue‐specific and that the extranuclear full‐length isoform TERT1‐A is relatively enriched in the soma of neotenic kings and queens compared to their gonads and to the soma of workers. We also show that extranuclear TERT protein quantities are significantly higher in the soma of kings and queens compared to workers, namely due to the cytosolic TERT. Independently, we confirm by microscopy the extranuclear TERT localization in somatic organs. We conclude that the presumed pleiotropic action of telomerase combining the canonical nuclear role in telomere maintenance with extranuclear functions is driven by complex TERT splicing.
Darwin famously described special difficulties in explaining social evolution in insects. More than a century later, the evolution of sociality - defined broadly as cooperative group living - remains one of the most intriguing problems in biology. Providing a unique perspective on the study of social evolution, this volume synthesizes the features of animal social life across the principle taxonomic groups in which sociality has evolved. The chapters explore sociality in a range of species, from ants to primates, highlighting key natural and life history data and providing a comparative view across animal societies. In establishing a single framework for a common, trait-based approach towards social synthesis, this volume will enable graduate students and investigators new to the field to systematically compare taxonomic groups and reinvigorate comparative approaches to studying animal social evolution.
The trade-off between reproduction and longevity is known in wide variety of animals. Social insect queens are rare organisms that can achieve a long lifespan without sacrificing fecundity. The extended longevity of social insect queens, which contradicts the trade-off, has attracted much attention because it implies the existence of an extraordinary anti-aging mechanism. Here, we show that queens of the termite Reticulitermes speratus incur significantly lower oxidative damage to DNA, protein and lipid and have higher activity of antioxidant enzymes than non-reproductive individuals (workers and soldiers). The levels of 8-hydroxy-2’-deoxyguanosine (oxidative damage marker of DNA) were lower in queens than in workers after UV irradiation. Queens also showed lower levels of protein carbonyls and malondialdehyde (oxidative damage markers of protein and lipid, respectively). The antioxidant enzymes of insects are generally composed of catalase (CAT) and peroxiredoxin (Prx). Queens showed more than two times higher CAT activity and more than seven times higher expression levels of the CAT gene RsCAT1 than workers. The CAT activity of termite queens was also markedly higher in comparison with other solitary insects and the queens of eusocial Hymenoptera. In addition, queens showed higher expression levels of the Prx gene RsPRX6. These results suggested that this efficient antioxidant system can partly explain why termite queens achieve long life. This study provides important insights into the evolutionary linkage of reproductive division of labor and the development of queens’ oxidative stress resistance in social insects.
OrthoDB is a comprehensive catalog of orthologs, genes inherited by extant species from a single gene in their last common ancestor. In 2016 OrthoDB reached its 9th release, growing to over 22 million genes from over 5000 species, now adding plants, archaea and viruses. In this update we focused on usability of this fast-growing wealth of data: updating the user and programmatic interfaces to browse and query the data, and further enhancing the already extensive integration of available gene functional annotations. Collating functional annotations from over 100 resources, and enabled us to propose descriptive titles for 87% of ortholog groups. Additionally, OrthoDB continues to provide computed evolutionary annotations and to allow user queries by sequence homology. The OrthoDB resource now enables users to generate publication-quality comparative genomics charts, as well as to upload, analyze and interactively explore their own private data. OrthoDB is available from http://orthodb.org.
RNA interference (RNAi) refers to the set of molecular processes found in eukaryotic organisms in which small RNA molecules mediate the silencing or down-regulation of target genes. In insects, RNAi serves a number of functions, including regulation of endogenous genes, anti-viral defense, and defense against transposable elements. Despite being well studied in model organisms, such as Drosophila, the distribution of core RNAi pathway genes and their evolution in insects is not well understood. Here we present the most comprehensive overview of the distribution and diversity of core RNAi pathway genes across 100 insect species, encompassing all currently recognized insect orders. We inferred the phylogenetic origin of insect-specific RNAi pathway genes and also identified several hitherto unrecorded gene expansions using whole-body transcriptome data from the international 1KITE (1000 Insect Transcriptome Evolution) project as well as other resources such as i5K (5000 Insect Genome Project). Specifically, we traced the origin of the double stranded RNA binding protein R2D2 to the last common ancestor of winged insects (Pterygota), the loss of Sid-1/Tag-130 orthologs in Antliophora (fleas, flies and relatives, and scorpionflies in a broad sense), and confirm previous evidence for the splitting of the Argonaute proteins Aubergine and Piwi in Brachyceran flies (Diptera, Brachycera). Our study offers new reference points for future experimental research on RNAi-related pathway genes in insects.
Since 1992, FlyBase (flybase.org) has been an essential online resource for the Drosophila research community. Concentrating on the most extensively studied species, Drosophila melanogaster, FlyBase includes information on genes (molecular and genetic), transgenic constructs, phenotypes, genetic and physical interactions, and reagents such as stocks and cDNAs. Access to data is provided through a number of tools, reports, and bulk-data downloads. Looking to the future, FlyBase is expanding its focus to serve a broader scientific community. In this update, we describe new features, datasets, reagent collections, and data presentations that address this goal, including enhanced orthology data, Human Disease Model Reports, protein domain search and visualization, concise gene summaries, a portal for external resources, video tutorials and the FlyBase Community Advisory Group.
Significance
Most eukaryotic genomes contain abundant transposable elements (TEs), mobile DNA elements that can replicate and move within the genome. Because of the deleterious nature of active TEs, cells have mechanisms to suppress and prevent TE activation, including formation of repressive heterochromatin. In this report, we show that many TEs become activated with age in Drosophila , and this activation is prevented by dietary restriction, an intervention known to extend life span. We also show TE activation is blocked by genetic manipulations that stabilize heterochromatin and increase life span. This study provides evidence that a breakdown in TE silencing and repression may be a contributing factor to aging, and preventing TE activation may be a significant method of ameliorating the diseases of aging.
Understanding why organisms senesce is a fundamental question in biology. One common explanation is that senescence results from an increase in macromolecular damage with age. The tremendous variation in lifespan between genetically identical queen and worker ants, ranging over an order of magnitude, provides a unique system to study how investment into processes of somatic maintenance and macromolecular repair influence lifespan. Here we use RNAseq to compare patterns of expression of genes involved in DNA and protein repair of age-matched queens and workers. There was no difference between queens and workers in 1-day-old individuals, but the level of expression of these genes increased with age and this up-regulation was greater in queens than in workers, resulting in significantly queen-biased expression in 2-month-old individuals in both legs and brains. Overall, these differences are consistent with the hypothesis that higher longevity is associated with increased investment into somatic repair.
Transposable elements or transposons are DNA pieces that can move around within the genome and are, therefore, potential threat to genome stability and faithful transmission of the genetic information in the germline. Accordingly, self-defense mechanisms have evolved in the metazoan germline to silence transposons, and the primary mechanism requires the germline-specific non-coding small RNAs, named Piwi-interacting RNA (piRNAs), which are in complex with Argonaute family of PIWI proteins (the piRNA–RISC complexes), to silence transposons. piRNA-mediated transposon silencing occurs at both transcriptional and post-transcriptional levels. With the advantages of genetic manipulation and advances of sequencing technology, much progress has been made on the molecular mechanisms of piRNA-mediated transposon silencing in Drosophila melanogaster, which will be the focus of this review. Because piRNA-mediated transposon silencing is evolutionarily conserved in metazoan, model organisms, such as Drosophila, will continue to be served as pioneer systems towards the complete understanding of transposon silencing in the metazoan germline.
The common approach to the multiplicity problem calls for controlling the familywise error rate (FWER). This approach, though, has faults, and we point out a few. A different approach to problems of multiple significance testing is presented. It calls for controlling the expected proportion of falsely rejected hypotheses — the false discovery rate. This error rate is equivalent to the FWER when all hypotheses are true but is smaller otherwise. Therefore, in problems where the control of the false discovery rate rather than that of the FWER is desired, there is potential for a gain in power. A simple sequential Bonferronitype procedure is proved to control the false discovery rate for independent test statistics, and a simulation study shows that the gain in power is substantial. The use of the new procedure and the appropriateness of the criterion are illustrated with examples.
