Abstract
In brief
Social insect queens display both extraordinary longevity and fertility. In this point of view, we describe their distinctive traits that make them useful models for reproductive longevity, holding implications for human health discoveries.
Abstract
Social insects present an extraordinary opportunity as models for reproductive longevity because they challenge the conventional patterns of aging and reproduction seen in other model organisms. Their queens are simultaneously long-lived and highly fecund, and understanding how these traits co-occur may lead to discoveries with important implications for human health.
A common life history trade-off in animals is that life expectancy is at the expense of reproduction. In this sense, having the capacity to live longer has a direct cost to organisms’ fertility, and conversely, having a more fertile life leads to a decrease in life expectancy. However, social insects like ants, bees, and wasps defy this general pattern. In these highly social species, reproductives, particularly the queens, challenge the conventional trade-off by showcasing both very high fecundity and remarkably long life spans. In this point of view, we delve into the unique characteristics of social insects and their potential to unlock the mysteries of reproductive longevity in long-living animals.
While the power of social insects for the study of aging has long been recognized (Keller & Genoud 1997, Jemielity et al. 2005, Parker 2010), their extraordinary extended fertility has yet to receive similar attention (Korb et al. 2021). The unique reproductive biology of social insects such as ants, bees, wasps, and termites makes them good models for such research. Thus, social insects provide a unique opportunity to explore the molecular and cellular mechanisms allowing for the co-occurrence of high fecundity and long life span in animals and to identify novel candidate genes and cellular pathways regulating fecundity, longevity, and aging that may be unique to long-lived species, furthering our understanding of the proximate mechanisms of reproductive longevity.
Social insects, exemplified by species like the African driver ant Dorylus wilverthi and the red harvester ant Pogonomyrmex barbatus, display an astoundingly high lifetime fecundity along with remarkable longevity. D. wilverthi queens lay up to 4 million eggs every 25 days, setting a record in insect fecundity (Raignier 1955). Meanwhile, P. barbatus queens can live for more than 30 years and remain fertile throughout their lives (Jemielity et al. 2005, Ingram et al. 2013). In some species of ants, queens increase reproductive output with age (Heinze & Schrempf 2012). This stark contrast with the short life spans and relatively more modest egg production of solitary insects like flies, mosquitoes, and moths underscores the uniqueness of social insect reproductive biology.
In social insects, there is extreme variation in fecundity and longevity between the reproductive and non-reproductive castes within species, with female reproductives living in some instances up to 30 times longer than female workers and, in the case of ants, 500 times longer than males (Keller & Genoud 1997, Jemielity et al. 2005). This allows for a direct comparison of the underlying mechanisms of high fecundity and longevity in individuals with essentially the same genetic makeup (Fig. 1). This disparity appears to arise from variations in development, nutrition, epigenetics, the social environment, and mating status (Heinze & Schrempf 2008). In certain species, both longevity and fertility manifest as plastic traits, and changes can be induced by alterations in the social environment. In the Indian jumping ant Harpegnathos saltator, certain workers, called gamergates, retain reproductive potential, but their ovarian development is suppressed by queen pheromones. When the queen of the colony dies or is removed, gamergates undergo continuous duels to replace her. The victorious ant becomes a pseudo-queen, and in addition to activating its ovaries and laying viable eggs, increases its life expectancy by up to five times. Remarkably, this process is reversible, with the pseudo-queen transitioning back into a worker-like phenotype, with the associated shorter life span, upon reintroduction of the queen (Yan et al. 2022). Increased ovary size and life span in worker ants upon removal of the queen from the colony, observed in Temnothorax ant colonies, align with this notion too, and similar phenomena have been documented in bees and termites (Majoe et al. 2021). The plasticity of senescence and fertility phenotypes in social insects reinforces their potential as valuable models for understanding the intricate interplay of genetic and physiological factors influencing reproductive longevity.
Differences between reproductive and non-reproductive castes of social insects. (A) Life span variability between the reproductive and non-reproductive castes in ants of the species Pogonomyrmex barbatus (Gordon & Hölldobler 1984, Jemielity et al. 2005) and Harpegnathos saltator (Yan et al. 2022), the honey bee Apis mellifera (Haddad et al. 2007), and the termite Macrotermes bellicosus (Elsner et al. 2018). (B) Scheme of the morphology of an ant ovariole. Oocytes develop from stem cells in the germarium which form egg follicles, composed of oocytes and nurse cells. (C) Ovarian activity correlates with longevity in ants. Queen and worker Pogonomyrmex barbatus ant ovarioles that show developing egg follicles stained for nuclei (blue), actin (magenta), and histone H4K12ac (green). Note the difference in the size of the mature oocyte in the queen and the size of the largest oocyte in the worker. Queens also have many more ovarioles than workers.
Citation: Reproduction 167, 6; 10.1530/REP-24-0020
Evolutionary and physiological hypotheses that seek to explain the relationship between life expectancy and reproduction often frame it as a trade-off, where both traits compete for limited resources. However, this competing allocation of energy resources appears not to hold true in social insects, where reproduction does not appear to shorten life span and may, in fact, lengthen it (Edward & Chapman 2011). The hyperfunction hypothesis suggests that aging results from an accumulation of excessively biosynthesized molecules, while the damage accumulation hypothesis attributes aging to DNA damage resulting from reactive oxygen species. However, these theories face challenges when applied to social insects. For instance, we might expect the queen to accumulate many waste products of biosynthesis during her lifetime because of her high reproduction rate, but this is not the case, with excess products being eliminated through egg production. Despite the well-established link between antioxidants and delayed aging, ant and honeybee queens exhibit lower levels of antioxidants. Furthermore, queens appear to neglect telomere maintenance, yet they possess longer telomeres than workers, contradicting the telomere shortening hypothesis of aging (de Verges & Nehring 2016). These intriguing deviations from conventional aging theories in social insects raise questions that current research has yet to answer, and the unique characteristics of social insects make them valuable models for future investigations.
While questions regarding how and why social insect reproductives exhibit such high fecundity and longevity remain unanswered, it is evident that further research in these species could provide crucial insights. Reproductive senescence, a decline in fecundity as an individual ages, is observed in most animals, including humans and the well-studied invertebrate models Caenorhabditis elegans and Drosophila melanogaster. In C. elegans, reproductive aging is a genetically regulated process that is normally coupled to, but also distinct from somatic aging (Luo & Murphy 2011). In C. elegans, as well as in humans, the fertile capacity of oocytes declines with age. For example, developmentally programmed germ cell death is a mechanism involved in maintaining the quality of oocytes, and a slight disruption in this process has negative effects on egg quality (Andux & Ellis 2008). In D. melanogaster, there are also age-related changes in fecundity, offspring viability, and egg production (Miller et al. 2014). Molecular analyses have implicated insulin and TGF-β signaling in regulating germline stem cell maintenance and proliferation during aging, which may cause reproductive senescence, while reduced signaling of insulin-like peptides has been associated with increased life span (Tatar 2010).
In ants, evidence suggests the involvement of the insulin signaling pathway in regulating ovarian activity. However, in contrast to D. melanogaster and C. elegans, where higher insulin signaling is associated with shorter life spans, queens, the most long-lived individuals, show higher levels of insulin-like peptide (Ilp2) gene expression in the brain than workers. Furthermore, pharmacologically increasing ILP2 levels in workers of the queenless clonal raider ant, Ooceraea biroi, increases ovary activation (Chandra et al. 2018). Recent work in H. saltator suggests a connection between increased insulin expression in the gamergate brain and amplified lipid synthesis, along with increased vitellogenin (Vg) production in the fat body, crucial for egg development. In the gamergate’s developing ovary, the anti-insulin protein Imp-L2 is expressed. This suggests that Imp-L2 may be inhibiting insulin in some manner in certain tissues to counteract the aging effect of insulin, allowing for extended longevity in gamergates (Yan et al. 2022). Interestingly, in the honeybee Apis mellifera, higher Vg levels correlate with increased life span and high fecundity of queens. However, in C. elegans and D. melanogaster, Vg is involved in reducing longevity (Murphy et al. 2003, Ren & Hughes 2014).
Notably, the longevity and fertility differences observed in social insects surpass the effects of mutations in specific genes associated with longevity studied in other organisms. In mice and flies, the NAD+ -dependent deacetylases Sirt6 and dSirt6, respectively, are implicated in regulating metabolism and aging pathways (Roichman et al. 2021). In C. elegans, a mutation in daf-2, an insulin/insulin-like growth factor (IGF-1) receptor, doubles its life span (Kenyon et al. 1993). DAF-2 prevents DAF-16, a transcription factor involved in life span extension, from accumulating in the nucleus leading to a shorter life span (Lin et al. 2001). Genetic interventions have shown limited extension of longevity, possibly due to inherent biological constraints. Therefore, studying social insects is incredibly valuable because the huge differences in longevity and fertility within the same species, the magnitude of which has not been attained through manipulations in model systems, may make it easier to identify the mechanisms involved.
The parallels between social insects and humans, being both long-lived and influenced by their social environment, emphasize the relevance of social insects in the study of reproductive aging. In humans, menopause is associated with various adverse health effects, and insights from basic research in social insects could pave the way for understanding and mitigating the negative effects associated with fertility decline during a significant portion of women’s lives. Therefore, studies on aging in social insects could provide insights into how reproductive senescence can be prevented or reversed and will give clues as to how this research can be translated to mammalian models and humans. Additionally, non-insect eusocial species, such as the naked mole rat and the Damaraland mole rat or some shrimps in the genus Synalpheus, also feature long-lived fertile individuals. In the case of mole rats, they may act as bridges between discoveries in social insects and humans and may yield interesting discoveries in themselves.
In conclusion, social insects serve as extraordinary models for studying the mechanisms underlying the coincidence of high fecundity and long life span. The unconventional aging patterns observed in these species challenge existing paradigms and expand our understanding of aging and senescence. As we continue to explore the molecular and cellular mechanisms underlying reproductive longevity, social insects offer fresh perspectives that may extend beyond their realm, influencing our understanding of aging in diverse species. The plasticity and reversibility observed in their senescence patterns and the distinct regulation of known signaling pathways suggest the potential for innovative approaches to understanding and addressing reproductive longevity in humans and other animals. The rich field of research in social insects promises to unlock the secrets of reproductive longevity, providing valuable insights for both scientific exploration and potential applications in human health.
Declaration of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the study reported.
Funding
This work was supported by the Global Consortium for Reproductive Longevity and Equality at the Buck Institute for Research on Aging, made possible by the Bia-Echo Foundation (GCRLE-0620 Junior Scholar Award) to IF-P, and by Consejo Nacional de Humanidades, Ciencia y Tecnología, CONAHCyT (NUM CVU 1249398) to MFV-M.
Author contribution statement
MFV-M and IF-P conceptualized and wrote the paper. BO-D generated the images presented in Figure 1 and revised the manuscript.
Acknowledgements
We thank Dr Ian AE Butler for providing valuable feedback on the manuscript and Carlos López Salinas for making the ovariole illustration. This article serves as a requirement for the MSc degree of MFV-M in Posgrado en Ciencias Biológicas UNAM.
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