Telomerase is upregulated in the long-lived eusocial reproductives
The common presumption that telomerase activity is a marker of aging and advancing organismal development, even in insects, is supported by observations in hemimetabolous insects such as cockroaches and termites (Korandová et al. 2014; Koubová et al. 2021a). Hemimetabolous insects exhibit incomplete metamorphosis, where ontogenetic development lacks larval and pupal stages and instead includes several nymphal stages that eventually molt into adults. Recent phylogenetic studies indicate that termites evolved from cockroaches, and along with cockroaches, they form the order Blattodea (Inward et al. 2007). But, in contrast to cockroaches, termites are eusocial insects. Both cockroaches and termites exhibit upregulated telomerase activity in young instars, which gradually declines during development. However, there were two exceptions for the decline: germline cells in both insects and somatic tissues in the long-lived reproductives (Korandová et al. 2014; Koubová et al. 2021a). Telomerase activity is also increased in adult somatic tissues of long-lived honeybee queens (Korandová and Frydrychová 2016; Koubová and Čapková Frydrychová 2021) and ant queens (our unpublished data), both of which are holometabolous insects with adult growth largely determined by metamorphosis. These findings suggest that telomerase upregulation is important in caste differentiation in eusocial insects (both holometabolous and hemimetabolous) and in the extended longevity of their reproductive individuals.
It is well established that where telomerase is required for the maintenance of telomeres, it is active during DNA replication stage (S-phase), and while high levels of telomerase activity are found in S-phase, telomerase activity is virtually absent in G2/M or G0 phases (Zhu et al. 1996; Holt et al. 1997). Surprisingly, no DNA synthesis was detected in telomerase-positive somatic tissues of honeybee queens (Koubová and Čapková Frydrychová 2021) or the termiteProrhinotermes simplex (our unpublished data). Furthermore, there were no differences in telomere length between the long-lived and short-lived castes of honeybees or the tested ant (Lasius niger ) or termite (P. simplex ) (Jemielity et al. 2007; Korandová and Frydrychová 2016).
To explain the role of telomerase in the caste system of eusocial insects and to identify its possible engagement in the disparity between fertility and life expectancy, research was further conducted examining the bumblebee Bombus terrestris (Koubová et al. 2019). Bumblebees are members of the group of insects possessing a primitive social organization, and there are significant differences in the life expectancies of their female castes. Workers of the bumblebee speciesB. terrestris typically live for 2-3 months, however, the queens can live up to one year. Nevertheless, the lifespan comparison is not unbiased, as bumblebee queens spend the majority of their lives (approximately 6-9 months) in diapause, in which most biological processes take place at only low-cost levels. Thus, bumblebee queens cannot provide an example of a full-bodied extension of life expectancy, or at least they cannot provide it in the way that exists in advanced eusocial species. In contrast to eusocial reproductive individuals, the only adult somatic tissue of B. terrestris showing upregulated telomerase was the fat body of very young and pre-diapause queens (Koubová et al. 2019). Additionally, telomerase activity in fat body was co-localized with the DNA endoreduplication cycles that were followed by a massive increase in fat body mass and nutrient content, which suggests that the upregulation of telomerase activity in the fat body is tightly linked to the ability of queens to survive upcoming diapause (Koubová et al. 2019). A similar observation was obtained in honeybee workers, where telomerase activity, DNA synthesis, and nutrient content were reinforced in the fat body cells of winter-generation workers (Koubová et al. 2021b).
As there is very little cell turnover or DNA synthesis in most adult insect soma, we can expect that the caste-related differences in telomerase activity in eusocial insects such as honeybees or termites are not linked to telomere maintenance mechanisms, and instead, they can be associated with some non-canonical telomerase role, i.e. a role of telomerase without the typical telomerase catalytic activity that directly serves to elongate telomeres.