Laboratory of Telomere Research
Cellular processes, such as incomplete DNA replication or oxidative damage, lead to a gradual loss of chromosome termini, ultimately resulting in cell cycle arrest (known as cell senescence). Telomeres are the nucleoprotein structures at chromosome ends that are essential for solving the chromosome shortening. The most common mechanism of compensation for telomere shortening is the activity of telomerase, an enzyme that adds short repetitive DNA sequences to the chromosome ends. The activity of telomerase is strictly regulated. In humans, telomerase is the most active during embryogenesis, but later it is downregulated and present in limited cell types, such as the stem or germ cells, endothelial cells, or peripheral lymphocytes. If telomerase activity in somatic cells is insufficient, it might limit the regenerative capacity of the organisms and trigger age-related diseases and excessive aging.
Our research is mainly focused on the role of telomerase in the regulation of aging in social insects. It is known that social life plays a significant role in lifespan regulation via its effects on neuroendocrine and antioxidant systems. Eusocial insects are used as great model systems for research of aging. Firstly, eusocial insect species display large plasticity in the lifespan regulation depending on social contexts, such as population density or age distribution in the colony. Secondly, they show extraordinary caste-related lifespan differences, which contradict the common fecundity/lifespan trade-off. It is believed that the negative correlation between lifespan and reproduction rate/capacity (known as the cost of reproduction) is one of the fundamental trade-offs to cope with the competitive allocation of limited resources. Reproductive individuals of eusocial species, known as kings and queens, are associated with a 100-fold increase in lifespan compared to workers or soldiers, or solitary insects.
Role of telomerase in eusocial insects
Using the cockroach Periplaneta americana (a representative of solitary hemimetabolous insects) and workers of honeybees (Apis mellifera, a representative of eusocial holometabolous insects), we showed that development and aging in insects associate with a decline of telomerase activity (Chromosome Research (2014) 22:455-503; Korandova and Frydrychová (2016) Chromosoma 125: 405-411). Nevertheless, telomerase activity in the somatic tissues of honeybee queens and reproductive individuals in termites is strongly upregulated compared to that in workers or soldiers of the same species. It suggests that upregulation of telomerase activity may be linked to the caste differentiation process and lifespan extension of kings and queens in eusocial insects (Korandova and Frydrychová (2016); in press).
Bombus terrestris (Hymenoptera: Bombini) is a hymenopteran species with primitive social organization and, compared to advanced social insects such as A. mellifera, have several distinct features. For instance, colonies of B. terrestris are annual and have smaller population sizes than those of more advanced social insects. After a relatively long diapause, their queens undergo both solitary and social phases. In general, bumblebee queens are only slightly morphologically different from workers. We studied telomerase activity in B. terrestris to see if this species, despite its primitive social organization, has the same pattern in telomerase activity as observed in A. mellifera. Among tested somatic tissues of B. terrestris, telomerase activity was found only in the fat bodies of young pre-diapause queens and associated with increased DNA synthesis (Figure 1). We speculate that the upregulation of telomerase activity and DNA synthesis in the queens are essential for rapid intensification of metabolic activity in the fat body to build up a sufficient energy reserve prior to diapause. Our data support the hypothesis that the lifespan differences between B. terrestris workers and queens are simply related to the long diapause period. We propose that there are differences in lifespan regulation between primitive and eusocial insect species (Koubová et al. (2019) IBMB 115:103241).
Currently, the role of telomerase in eusocial insects is investigated in more detail.
Seasonal effects on telomerase activity and aging in honeybees
In honeybees, the rate of aging is modulated through social interactions and seasonal effects. Winter generation workers, which hatch at the end of summer, have remarkably extended lifespans as an adaptation to the cold season when the resources required for the growth and reproduction of colonies are limited and the bees need to maintain the colony until the next spring. In contrast, the summer bees only live for several weeks. To better understand the lifespan differences between summer and winter bees, we studied the fat bodies of honeybee workers and identified several parameters that fluctuate in a season-dependent manner. We reported that telomerase activity, DNA replication, fat body mass, and vitellogenin levels gradually increased as the winter season proceeded (Figure 2). Our study showed that although the fat bodies of winter bees differ significantly from those of summer bees, these differences are not a priori set when bees hatch at the end of summer or in early autumn but instead gradually evolve throughout the season, depending on environmental factors (Koubová et al. (2021) Scientific Reports 11:1-11).
Currently, we investigate effects of various environmental factors on honeybee aging in more detail.