Stress as a key player in telomere homeostasis maintenance
Although organisms have evolved a set of stress responses to protect against adverse environmental conditions, protracted stressful conditions and long-term activation of the stress response negatively impact health and lifespan (Monaghan 2014). It is now broadly accepted that chronic stress and lifestyle factors such as oxidative stress, psychosocial stress, and improper health conditions can affect telomere dynamics (Epel et al. 2004; Kotrschal et al. 2007; Lin et al. 2012; Monaghan 2014; Korandová et al. 2018). Reproduction is an energetically costly activity that increases metabolic rates, ROS production, and susceptibility to oxidative stress, and it is hypothesized that oxidative stress may represent a mechanistic link for the inverse relationship between reproduction and lifespan in both vertebrate and invertebrate models that acts independently of energy allocation (Alonso-Alvarez et al. 2004; Wiersma et al. 2004; Krůček et al. 2015; Sharick et al. 2015; Colominas-Ciuró et al. 2017; Costantini 2018). It has been demonstrated that resistance to oxidative stress is decreased during reproduction and that breeding activity increases susceptibility to oxidative stress (Alonso-Alvarez et al. 2004; Wiersma et al. 2004). Additionally, resistance to oxidative stress plays a significant role in shaping fecundity, as a higher fecundity rate was observed in individuals with higher oxidative protection (Bize et al. 2008). It is well established that oxidative stress in humans is implicated in pathological processes in the reproductive tract that contribute to infertility and poor pregnancy outcomes, and treatments based on strategies to boost the exhausted antioxidant defense of the reproductive microenvironment have been suggested (Adeoye et al. 2018).
DNA molecules represent an important target of oxidative damage in cells, and the most common DNA damage caused by free oxygen radicals is oxidative modifications of DNA bases such as the formation of 8-oxoguanin. Oxidative DNA lesions are associated with the production of single-strand breaks that are induced directly or as an intermediate step in the repair of oxidative base modifications. Due to their high content of guanine, telomeres are highly sensitive to oxidative damage and induction of single-strand breaks that interfere with the replication fork and thus lead to telomere attrition (von Zglinicki 2002; Houben et al. 2007; Coluzzi et al. 2019). In agreement with the assumption that breeding individuals are more susceptible to oxidative damage, engaging organisms in reproduction accelerates telomere loss (Kotrschal et al. 2007; Heidinger et al. 2011).
Bypassing the common negative association between fecundity and longevity in eusocial reproductives may explain their enhanced oxidative protection coupled with the fecundity rate. As demonstrated in ants, young founding queens exhibit immunity and resistance against environmental and physiological stress, while established older queens exhibit stimulated oxidative protection (Lucas and Keller 2018; Negroni et al. 2019). Similarly, data suggesting a role for antioxidant genes in modulating the lifespan of long-lived reproductives were identified in Adélie penguins that exhibit an increased antioxidant defense in response to breeding efforts, while oxidative damage and telomere length remained unchanged (Beaulieu et al. 2011). When we compared a few-day-old termite reproductives (with no or very low mating experience) to greater than 1-year-old reproductives, the old individuals exhibited highly upregulated oxidative defenses in their somatic tissues in combination with telomerase activity (Koubová et al. 2021a; our unpublished data).